This paper reports a novel, minimally invasive, simple technique for the treatment of a displaced dentoalveolar fracture using a vacuum-formed splint in a 12-year-old pediatric patient. Vacuum formed splints have been reliable treatment options with limited morbidity and discomfort compared to other traditionally used procedures. Traumatic injuries to the dentofacial structures in adolescents due to reasons such as falls, sports injury, or road traffic accidents might often lead to the avulsion of anterior teeth, dentoalveolar, and jaw fractures. The incidence of dentoalveolar injury in children is variable, commonly involving the anterior maxillary segment followed by the anterior mandible.minimally invasive and result in the restoration of occlusion with minimal residual esthetic and functional impairment. The management of dentoalveolar fractures partly relates to the treatment of jaw fracture and partly to that of tooth luxation. As a general rule, conservative therapy with long-term follow-up should be favored when treating facial trauma in adolescents, especially when it involves the tooth-bearing regions. Currently, the various methods of stabilizing displaced dentoalveolar fractures include the application of arch bars and metal (cap) splint or acrylic plates fixed using circum-mandibular wiring under general anaesthesia.1Decision-making in the management of pediatric fractures is more challenging as compared to adults due to factors such as smaller jaw size, centers of active bone growth, and unerupted permanent teeth. The goal in treating pediatric fractures is to restore the underlying bony structure to its pre-injury position as early as possible. The treatment of choice should be 2 in 2001 first reported the use of vacuum-formed splint for the treatment of mandibular fractures. The splint is made up of a transparent thermoplastic sheet with the help of a vacuum-forming machine, which is then adapted to the individual dentition. The splint obtains dentoalveolar support through close adaptation to the teeth and alveolus. The splint attains exact anatomical duplication of the patient’s dentition, thus providing excellent three-dimensional stability at the fracture site. The vacuum-formed splint might be a useful alternative to arch bars in managing dentoalveolar fractures, especially in pediatric patients with primary or mixed dentition, where arch bar adaptation is difficult due to retention problems. This technique is minimally invasive and can be carried out in outpatient settings, thus avoiding hospitalization and general anesthesia procedures. This paper reports the use of a vacuum-formed splint in the management of a dentoalveolar fracture of the anterior mandibular segment in a young male patient. The paper also reviews the literature for the use of this new technique in managing jaw fractures in pediatric patients.Vacuum-formed splints are traditionally used as night guards to prevent occlusal wear in chronic bruxers and temporomandibular joint disorder patients. LloydA 12-year-old boy was referred to the oral and maxillofacial surgery clinic with a chief complaint of bleeding from the mouth as a result of a fall from a bicycle. The patient reported on the same day of the injury and received immediate attention. The child was conscious and cooperative at the time of examination with vital signs within the normal limits. There was no history of loss of consciousness, bleeding from the nose and ears, vomiting, or convulsions. On the extraoral examination, the patient presented a normal (straight) facial profile with swelling over the lower lip and chin. Intraoral examination showed labial ecchymosis in the mandibular anterior region and a step deformity between the distal aspect of #32 and the distal aspect of #83. The anterior dentoalveolar segment was displaced superiorly and lingually, causing a deep bite  and 1b. The clinical findings and diagnosis of mandibular dentoalveolar fracture were explained to the patient’s parents. Various treatment modalities, including arch bar fixation, cap splint, acrylic splint with circum-mandibular wiring, and immobilization with vacuum-formed splints, were discussed. The option of using vacuum-formed splints applied in an outpatient setting was chosen and executed under local anesthesia.Under bilateral inferior alveolar nerve block, the displaced dentoalveolar segment was repositioned with finger pressure . Bilater1 Methods of immobilization by dental splinting and ligature wiring have been effective in treating luxated/avulsed teeth and minimally displaced dentoalveolar segments. Traditionally the two most commonly used modalities for stabilization of displaced dentoalveolar fracture include the application of arch bars fixed with inter-dental wiring and use of metal (cap) splint/acrylic plates fixed using circum-mandibular wiring.2 In pediatric patients with mixed dentition, the height of the contour of deciduous teeth is below the gingival level. Thus, the application of arch bars is not feasible. Arch bars also provide lower stability due to root resorption of deciduous teeth and incomplete formation of the roots of permanent teeth. However, splinting with an acrylic plate requires circum-mandibular/peri-alveolar wiring, necessitating hospitalization to carry out the procedure under general anesthesia.Dentoalveolar fractures are injuries affecting teeth with its supporting alveolar bone. It commonly presents as a displaced dentoalveolar segment, tooth mobility, occlusal disturbance, and hematoma into the adjacent oral mucosa. The management of a dentoalveolar fracture involves the reduction of the displaced dentoalveolar segment and its stabilization for 2‒4 weeks. Various stabilization techniques have been reported in the literature, including arch bar, metal cap splints, acrylic plates fixed with per-alveolar or circum-mandibular wiring, dental splinting , interdental ligature wiring, bone screw-plate fixation, and suturing.2 in 2001 for the management of condylar fracture in a child patient.A review of the English literature for the use of vacuum-formed splints in the treatment of jaw fractures in pediatric patients revealed six reported cases  in the mixed dentition period. They are inexpensive and easy to fabricate and are prepared by molding a transparent thermoplastic foil over the cast of the patient in a vacuum molding machine. The transparency of the material allows visualization of the underlying dentition for easy checking of the adaptation and occlusion.6 The splint was maintained for three weeks. The patient did not report any discomfort during this period. The gingival health was good on the removal of the splint, with stable occlusion and alignment of the dentoalveolar segment.Vacuum-formed splints are advantageous as they are non-invasive and preserve the anatomy of the mandible and the developing tooth buds, permitting mastication and speech without any functional deformity. The closely contoured margins of the plastic splint allow mechanical retention by engaging the dentition and the bone undercuts. However, additional means of stabilization is required when treating a displaced fracture segment, which can be achieved mechanically by cirucum-mandibular wiring or chemically by using a luting cement to bond the splint with the teeth. In the present case, the retention of the splint was attained using glass-ionomer cement. The use of glass-ionomer cement has an additional benefit of fluoride release, thus minimizing the decalcification of the deciduous teeth in younger patients.Selection of the splinting method for the immobilization of jaw fracture in pediatric patients must meet specific criteria, including ease of fabrication, application of only passive forces on the teeth, no injury to the soft tissues, underlying bone, and the developing tooth buds, maintain stable occlusion, allow maintenance of good oral hygiene, and easy removal. Vacuum-formed splints offer various advantages. They are an easy and efficient technique for the management of pediatric fractures, including dentoalveolar injuries, and need to be incorporated more often in routine clinical practice.KN: drafting of the manuscript, conducting the clinical procedure, final approval of the manuscript; AM: participation in conducting the clinical procedure, preparation of the manuscript; ST: conducting the clinical procedure; AVV: Drafting of the manuscript, final approval of the manuscript. All authors have read and approved the final manuscript.None.None.The authors declare that they have no competing interests.Not applicable.


Information causality measures have proven to be very effective in uncovering the connectivity patterns of multivariate systems. The non-uniform embedding (NUE) scheme has been developed to address the “curse of dimensionality”, since the estimation relies on high-dimensional conditional mutual information (CMI) terms. Although the NUE scheme is a dimension reduction technique, the estimation of high-dimensional CMIs is still required. A possible solution is the utilization of low-dimensional approximation (LA) methods for the computation of CMIs. In this study, we aim to provide useful insights regarding the effectiveness of causality measures that rely on NUE and/or on LA methods. In a comparative study, three causality detection methods are evaluated, namely partial transfer entropy (PTE) defined using uniform embedding, PTE using the NUE scheme (PTENUE), and PTE utilizing both NUE and an LA method (LATE). Results from simulations on well known coupled systems suggest the superiority of PTENUE over the other two measures in identifying the true causal effects, having also the least computational cost. The effectiveness of PTENUE is also demonstrated in a real application, where insights are presented regarding the leading forces in financial data. Causality is the relationship between cause and effect. In other words, there is a causal relationship between two situations when it is certain that the second one arose due to the first one. The causal link is not mentioned exclusively in the relationship between two events or situations alone, but a causal chain may exist between causes and effects. The key component of causality is the succession of cause and effect. Reinchenbach  was the Identifying the connectivity pattern in complex multivariate systems is an issue that has seen enormous advances recent years. A variety of methods has been developed and compared, leading sometimes to contradictory conclusions ,5,6,7,8.A traditional way to discover causal relations is to use interventions or randomized experiments. If this is not possible, causal information is revealed by analyzing the statistical properties of purely observational data . ProbabiThe benchmark work of Spirtes et al.  utilizedX Granger causes Y, if all the recent and previous information on X values helps in the better prediction of the Y values.Granger’s concept of causality is based on Wiener’s study , accordiThe notion of Granger causality has been very popular the last few decades, and various extensions of its original form have been introduced and applied in an ensemble of scientific fields. However, such approaches have also been intensively criticized ,20. TempRecently, methods of nonlinear time series analysis ,23 and cPairwise causality measures indicate the direct and indirect causal effects between two time series. In , the autk-nearest neighbors (KNN) being one of the most effective ones ,,53], wheThe most common analyses for constructing financial networks were based on the linear Granger causality ,54, e.g.riterion ), while riterion ). Based In this paper, three conditional causality measures were briefly reviewed and evaluated on artificial datasets. In particular, we examined the performance of partial transfer entropy (PTE) computed based on the standard uniform embedding scheme, PTE estimated using the non-uniform embedding (NUE) scheme, denoted as PTENUE, and PTE using the NUE scheme and also a low-dimensional approximation (LA) method for the computation of conditional mutual information (CMI), denoted as LATE. We assessed the effectiveness of each causality measure in identifying the causal influences among the variables of complex coupled systems based on the extracted sensitivity, specificity, and F1-score. In the simulation analysis, we controlled the dimension of the data, the sample size, the coupling strength, and its nature . The dimensionality of the chaotic simulation system advanced up to 50 variables in order to reflect the complexity of the real data. Finally, the applicability of the three causality measures in real applications was demonstrated using financial time series.Based on the empirical findings, partial transfer entropy (PTE) was mainly efficient in the case of low-dimensional systems. LATE improved the performance of PTE in the case of high-dimensional coupled systems. LATE had an overall good performance and was particularly effective in the case of weak couplings and small time series lengths. However, it was computationally expensive and may indicate spurious causal influences.We should note here that the simulation results displayed in  substantPTENUE outperformed the other measures by accurately identifying the connectivity network of all the examined scenarios and achieving the highest mean F1-score over all the examined scenarios. As the dimension of the examined systems progressively increased, the necessity of using dimension reduction techniques, such as the NUE scheme, was profound. Novel simulation results were presented for both low- and high-dimensional systems, where the number of variables varied from In the financial applications, the connectivity network of CAC40 was examined in order to determine the leading forces. Both PTENUE and LATE indicated the most significant leading variable to be CS.PA , influencing all the other observed variables. PTE failed to identify the connectivity relationships of CAC40, tending to identify a fully coupled network.Subsequently, PTENUE was the most effective causality measure for identifying the connectivity network of multivariate systems among the three examined measures. It was robust, and it was unaffected by the “curse of dimensionality” and the nature, and the strength of the connections. However, the sample size should be sufficiently large, and this should be jointly considered with the dimensionality of the examined data. Finally, it had the least computational cost.The presented outcomes concerned multivariate systems with a sparse causality structure. The examined causality measures were probabilistic approaches that required the stationarity of the time series and could be applied only to time-invariant networks. Additionally, contemporaneous relationships were not considered. Future work involves the identification of the efficiency of PTENUE on multivariate systems of higher dimensions and with denser causality structures, which will be utilized in financial applications, such as for portfolio construction. A forthcoming work will examine the robustness of PTENUE in the case of noisy data, where preliminary results seemed very promising.


Lymphatic disorders have received an increasing amount of attention over the last decade. Sparked primarily by improved imaging modalities and the dawn of lymphatic interventions, understanding, diagnostics, and treatment of lymphatic complications have undergone considerable improvements. Thus, the current review aims to summarize understanding, diagnostics, and treatment of lymphatic complications in individuals with congenital heart disease.The altered hemodynamics of individuals with congenital heart disease has been found to profoundly affect morphology and function of the lymphatic system, rendering this population especially prone to the development of lymphatic complications such as chylous and serous effusions, protein-losing enteropathy and plastic bronchitis.Although improved, a full understanding of the pathophysiology and targeted treatment for lymphatic complications is still wanting. Future research into pharmacological improvement of lymphatic function and continued implementation of lymphatic imaging and interventions may improve knowledge, treatment options, and outcome for affected individuals. The lymphatic vasculature is widely distributed throughout the entire body. In health, it functions as a unidirectional drainage and transport system originating in the interstitial space and terminating with the return of the lymphatic fluid back into the great veins of the neck or thorax. The initial lymphatic capillaries are composed of a single layer of lymphatic endothelial cells with interstitially anchored filaments preventing collapse. For initial uptake and transport, the fluid is dependent on favorable pressure gradients to reach the pre-collecting and collecting lymphatic vessels. From here, an increasing concentration of smooth muscle cells intertwiningly weaved around the lymphatic vessel contract in order to propel the fluid forward –3. The iDue to the structural and functional heterogeneity of congenital heart disease (CHD), incidence and prevalence of lymphatic complications are immensely varying within subtypes of malformations. Being often referred to as the forgotten circulation, the etiology behind the development of lymphatic complications remains poorly understood. Generally, the incidence of effusions and other lymphatic complications tend to increase with increasing venous congestion and more severe congenital heart malformations. Accordingly, individuals with tetralogy of Fallot and univentricular heart disease are excessively overrepresented with regards to lymphatic complications in CHD. Sparked primarily by improved lymphatic imaging modalities and the dawn of the field of lymphatic interventions, understanding, diagnostics, and treatment of lymphatic complications have undergone considerable improvements over the last decade. Thus, the current review aims to summarize understanding, diagnostics, and treatment of lymphatic complications in individuals with CHD.In CHD, hemodynamic changes arising from structural abnormalities or their correction may result in increased hydrostatic pressure in parts of the circulation. In the capillary beds, this causes increased filtration of fluid to the interstitial space increasing the necessity for lymphatic removal. Additionally, the increased central venous pressure (CVP) commonly found in some subgroups impedes the emptying of the thoracic duct, adding additional congestion to the already pressured lymphatic system. Consequently, many individuals with congenital heart defects are especially prone to the development of lymphatic complications Fig. . Thus, eProlonged pericardial or pleural effusions and chylothorax and chylopericardium may all, given the origin of the fluid, be considered as lymphatic complications. Prolonged effusions are most commonly observed following surgical repair of either tetralogy of Fallot or univentricular heart disease . DependiProlonged effusions are reported in between 7.3 and 13.5% of operated tetralogy of Fallot patients and may be viewed as a disruption of the fluid equilibrium , 21. TheSimilarly, during the creation of a bidirectional cavopulmonary connection or total cavopulmonary connection, the blood flow and the hydrostatic pressure in the pulmonary capillary beds tend to increase, augmenting filtration and risk of effusions, the incidence following correction being 12.6% and 37%, respectively . In the Chylothorax and chylopericardium are other postoperative lymphatic complications. They are common following traumatic perforation of the thoracic duct or its tributaries during surgery, with leakage accumulating postoperatively. However, it is also observed more sporadically years after surgery. Here, the proposed mechanism is a combination of increased intralymphatic pressure due to increased uptake and impeded return and structural weakness in the lymphatic vessels. Perforation of the endothelial weakness provides a way of decompression for the congested lymphatic system and reroutes fluid into compartments of lower pressure.Chylothorax occurs with an incidence of 7.4% and 9–24% following surgical repair of tetralogy of Fallot and “surgical palliation” of single ventricles, respectively , 32, 33.The clinical manifestations of effusions and chylothorax may progress from asymptomatic to the experience of dyspnea, coughing, and chest discomfort with gradually increasing amounts of accumulating fluid , 38. PerFollowing symptoms, effusions or chylothorax are normally diagnosed with the finding of fluid during ultrasonography or radiographic examination. Commonly, measurement of triglycerides has been used to categorize the fluid as chyle leaking from the lymphatic system. However, as argued above, also fluid filtered out in the lung and transuded into the pleural space may be considered lymphatic fluid. Thus, the content of triglycerides and ratio of triglycerides or cholesterol in pleural fluid compared with serum should, to a greater extent, be viewed as a way of determining the origin of the lymphatic fluid. Thus, triglycerides above the threshold of 110 mg/dl indicate intestinal origin of the lymphatic fluid, confining the leakage to the thoracic duct or its main tributaries. Similarly, low levels of triglycerides indicate an origin of the lymphatic fluid, before the mixing with the lipid-rich fluid flowing in the central thoracic duct –40. InfoWhile prolonged effusions may resolve following a new steady state between filtration and lymphatic removal, the volume of accumulated fluid may deem treatment necessary. Treatment of effusions and chylothorax evolves around two primary goals: short-term relief of respiratory symptoms by drainage of fluid and long-term prevention of recurrence by treating the underlying cause.Thoracocentesis and placement of a chest tube will secure immediate relief of respiratory symptoms and maintain continuous drainage. Nonsurgical conservative options for chylothorax include a no-fat diet in order to reduce production of chyle. Medium-chain triglycerides may be added, as these are absorbed directly into the portal vein, bypassing the lymphatic system , 44, 45.In patients unresponsive to conservative nutritional therapy, pharmacological agents such as somatostatin or the synthetic analog octreotide have been reported efficient in treatment , 47. TheTraditionally, surgical treatment of chylous leakage has been reliant on thoracic duct ligation or pleurodesis performed via either video-assisted thoracoscopy or open thoracotomy, with pleuroperitoneal shunting reserved for the most persisting cases , 53–55. PLE is characterized by an abnormal and occasionally profound intestinal loss of lymphatic fluid and protein. In addition to CHD, PLE may be observed secondarily to several other diseases ranging from congestive heart failure to infection and inflammatory bowel disease. In CHD, incidence of PLE has been reported as affecting from 4 to 15% of individuals following Fontan palliation –61.The pathophysiology behind the development of PLE is incompletely characterized and with a variety of factors contributing, although the combination and impact of each may vary between cases. Under normal circumstances, the liver and intestines are responsible for the production of 25–50% of the lymphatic fluid flowing in the thoracic duct . In indiOther potential mechanisms thought to be involved in the development of PLE in CHD include diminished mesenteric blood flow causing cellular apoptosis and increased permeability of the intestinal wall . AdditioWhile PLE often manifests when the protein leakage is substantial and resulting in severe morbidity, it may also exist in a subclinical version. In addition, the loss of protein may be transient with alternating asymptomatic and affected periods. Symptomatic progression of PLE is related to the loss of protein and range from the development of chronic diffuse edema to diminished tissue integrity and impaired wound healing . ImpaireMeasurement of an elevated α-1 antitrypsin clearance in a 24-h stool collection is the golden standard for diagnosis of PLE . HoweverThe efficacy of pharmacological treatment of PLE is largely case-based, and the lack of randomized controlled trials is universal. Primary treatment aims at decreasing fluid overload through diuretic therapy and preventing hypoproteinemia and low serum oncotic levels through a high-protein, low-fat diet or parenteral nutrition and intravenous albumin , 78. TraInvasive procedures may secure a more permanent symptomatic relief and should be considered on a case-by-case basis. Late fenestration with the creation of a right to left shunt may increase cardiac output and diminish symptoms at the expense of cyanosis , 90. A lPB is characterized by the formation of thick rubbery casts in the lumen of the airways. Not being exclusively associated with structural CHD, PB may also be observed alongside everything from asthma to various lymphatic diseases, sickle cell disease, and cystic fibrosis. Although rare, and only reported in < 5% of Fontan patients, PB causes severe morbidity in the form of chronic coughing, hypoxemia, expectoration of casts, and asphyxiation .The underlying pathophysiology behind PB in CHD patients is not fully understood. However, recent findings attribute a central role to a pressured and morphologically changed lymphatic system ultimately resulting in lymphatic leakage into the airways –98. SimiChronic coughing, wheezing, dyspnea, pleuritic chest pain, fever, or respiratory symptoms unresponsive to bronchodilators may lead the clinician to consider a possible PB diagnosis –102. CheThe overall treatment of PB should have two primary goals: an initial improvement of respiratory symptoms and hemodynamics and secondary targeting of venous and lymphatic congestion. Because of the rarity and heterogeneity of the condition, the evidence behind treatment for plastic bronchitis is scarce. Removal of any obstruction under diagnostic bronchoscopy may initially relieve respiratory symptoms . OptimizIn addition to pharmacotherapy, dietary changes in form of a low-fat diet in combination with ligation of the thoracic duct have been shown to relieve symptoms or cause resolution in some patients and may be considered . Until rDespite symptomatic relief on specific symptomatic treatment, the detrimental pathophysiology of the Fontan circulation is largely unaltered. Thus, continued pharmacological treatment with pulmonary vasodilators and diuretics may be deemed necessary, or additional surgical interventions to optimize hemodynamics and lymphodynamics may be considered. Late catheter-based fenestration redirects flow and lowers venous congestion . As in pOverall, the cause of interstitial accumulation of fluid or edema can be described as an imbalance between potentially four different factors; the hydrostatic- and the oncotic pressure both intravascularly and in the interstitial space, the permeability of the endothelial glycocalyx, and finally the function of lymphatic vessels in removing fluid and protein. Any disturbance to the equilibrium of these forces resulting in a greater microvascular filtration or an attenuation of the lymphatic removal may cause accumulation of fluid and edema , 111. EdEdema in patients with CHD is thought to be primarily revolving around circulatory pressure changes and a decrease in cardiac function. However, individuals with concurrent Turner or Noonans syndrome may have inherent genetic defects impairing normal lymphatic vessel development .AccordinWhatever the cause, the diagnosis of peripheral edema is predominantly based on patient history and clinical findings. Lymphoscintigraphy, lymphangiography, and NIRF imaging may support the diagnosis and help visualize the abnormal route of the lymphatic flow. In addition, duplex ultrasound may reveal chronic venous insufficiency, a common disposition leading to peripheral edema .Treatment and prevention are cause-dependent; optimizing cardiac function and preventing further renal and hepatic deterioration may be relevant within patients with CHD. Persisting edema may be treated with exercise, decongestive physiotherapy, compression stockings, or pneumatic compression therapy , 117.Although the recent decade has seen a sparked interest in research into the function of the lymphatic system and its involvement in various complications, a full understanding of the pathophysiology behind the majority of lymphatic complications is still wanting. Particularly within the field of CHD, research is challenged by the heterogeneous nature of the primary heart defects, and the low numbers treated at each center. Accordingly, targets for the current pharmacological treatments are speculative, based on a limited number of patients, and the lack of randomized placebo-controlled trials is universal.Future continued implementation of lymphatic interventions and increased experience with pre-operative lymphatic risk stratification may improve patient selection and reduce risk of postoperative development of lymphatic complications . Targete


Severe acute respiratory syndrome caused by the novel coronavirus (SARS-CoV-2) was first reported in China in December 2019 which was later declared to be a public health emergency of international concern by the World Health Organization (WHO). This virus proved to be very contagious resulting in life-threatening respiratory intricacies posing overall public health and governance challenges. Amid the coronavirus pandemic and the unprecedented increase in healthcare demands, only inventive and adaptive practice among healthcare professionals is the need of the hour. Pharmacy services are an important mainstay in the public health and have considerable potential to combat the coronavirus disease 2019 (COVID-19) pandemic. Pharmacists working in several localities and health facilities are linked to patients either directly or indirectly. They can act swiftly in public health response such as drafting professional service guidance to pharmacists working in various healthcare facilities, ensuring effective medicine supply system, monitoring and resolving drug shortage issues, establishing and promoting remote pharmacy services, counseling the public on infection prevention basics, educating about proper use of personal protective equipment, discouraging self-medication, participating in clinical trials, small-scale manufacturing of sanitizers and disinfectants, busting the prevailing myths, and conducting drug evaluation and active surveillance. These interventions will help ease unprecedented burden on healthcare facilities during the ongoing pandemic and eventually will add value to patients and the healthcare system. The current manuscript accentuates the potential roles and activities that pharmacists can initiate in various healthcare facilities to help in relieving pressure on the overwhelmed healthcare system. The information and suggestions offered in this review could help in the restructuring of existing pharmacy services by governments, public health bodies, and policy makers in response to the COVID-19 pandemic. Moreover, this manuscript will underscore any unrealized potential among pharmacists working in various sectors including community, hospital, industry, and drug regulatory authorities. Pharmacists are one of the most trusted professions worldwide alongside firefighters, nurses, teachers, and doctors , 2. DuriDuring the ongoing COVID-19 crisis where clinicians and nurses are overburdened, pharmacists are well-situated to offer collaborative and complementary expertise alongside current models of care. However, the capabilities of pharmacists are under-recognized both by patients and physicians. Practitioners report strong mutual respect for pharmacists as allied health professionals, but communication between them could be strengthened . MoreoveSince community pharmacies, hospitals, pharmaceutical industries, and drug regulatory authorities are exempted from the current lockdown which is being observed by most of the countries, effective utilization of pharmacist's services will be of paramount importance to tackle the quadruple burden associated with the pandemic. A pharmacist, being a most trusted and accessible healthcare professional, can be utilized to combat the chaos attributed to the pandemic , 6.To provide a summary of the potential roles and responsibilities of pharmacists during the COVID-19 pandemic, published data from scholarly articles, organizations, and stakeholders were reviewed. Literature was searched by four independent reviewers  using various electronic databases from inception to July 2020. The end date of the review time generally coincides with the generally accepted end of the first wave of COVID-19 in the Northern Hemisphere.https://www.ncbi.nlm.nih.gov/pubmed), Science Direct (https://www.sciencedirect.com/), Google Scholar (https://scholar.google.com/), Scientific Electronic Library Online (SciELO) (http://www.scielo.org/), Cochrane Library (https://www.cochranelibrary.com/), and Web of Science (http://www.webofknowledge.com/). The study databases were selected on account of their score for health and pharmaceutical journals. These databases covered articles of peer-reviewed journals, books, and supplementary reports covering multilevel engagement of pharmacists in COVID-19.The current review describes the various roles of pharmacists that can be performed during the COVID-19 pandemic to leverage all possible resources in the best interest of patient care and management. Moreover, data from studies providing prospective implications of pharmacy services in the management of COVID-19 pandemic were also included to give insight of the possible roles of pharmacists in combating COVID-19. Relevant data was collected via electronic search of different scientific sources including PubMed  distance between every pharmacy personnel. The floor of the pharmacy can be marked with the signs of 1 m distance to avoid any close contact among the customers. This method will provide actual sense of physical distancing to the customers. The minimum safe distance to avoid viral contract should be displayed at every counter. Customers should be encouraged to maintain at least minimum distance while handling the routine matters. Several studies have suggested to maintain at least 2 m (6 ft) distance to avoid any viral contraction –35. The The use of masks is a basic protective measure to avoid viral contract from the patients . HoweverThe COVID-19 pandemic is accompanied by rapidly prevailing myths on treatment and prevention. Moreover, several conspiracy theories and misleading narratives have sprouted and proliferated in many countries, posing substantial challenges for health officials to contain the disease. Since community pharmacists are considered trusted professionals, they can play a pivotal role in busting these myths by providing reliable information to the public. Pharmacies can make pamphlets on prevailing myths and can distribute to each customer attending the premises. They may ask questions to the customers in order to ascertain their perception toward the disease and can clarify any confusion. The WHO has issued various videos and images to eradicate the myths and the same can be utilized in the pharmacy premises . MoreoveCOVID-19 has changed the use of informational technology in the healthcare system. Telemedicine provides electronic consultations and has reduced the risk of transmission by reducing in-person contact among people. Telepharmacy is one of the practical aspects of telemedicine that refers to providing pharmaceutical services within the scope of a pharmacist's responsibilities, with a temporal and spatial distance between patients as the consumers of health services and healthcare providers. This service will not only be useful for COVID-19 patients but also for chronic patients and the general community experiencing the restricted movements amid lockdown. Moreover, telepharmacy will also reduce the volume of patients seeking care at health facilities . Though Early detection and referral of suspected cases are vital to prevent large-scale community transmission. Community pharmacists, therefore, must remain very vigilant and be able to screen the patients for necessary referrals. The Centers for Disease Control and Prevention (CDC) and the International Pharmaceutical Federation (FIP) have provided guidelines for the investigation of suspected COVID-19 cases . There aThe COVID-19 pandemic has caused shortage of hand sanitizers in many developing and developed country, either due to increased consumption or disruption of raw material supply. Community pharmacists can employ their expertise of compounding and ensure the availability of hand sanitizers and disinfectants all the time at an affordable cost. The WHO recommended the use of ethanol (80%) and isopropyl alcohol (75%) in all kinds of hand rub formulations . PharmacDuring these unprecedented times, the global drug supply could severely get impacted by this pandemic, and the results of this shortage could be catastrophic and may last for an extended period, primarily due to the global economic disruption at unprecedented speed and scale. It must be noted that drug shortage could lead to serious consequences when it comes to patient outcomes . PharmacIn order to ensure appropriate supply of medications especially in small towns where local pharmacies may have closed, community pharmacists can arrange home deliveries or an electronic prescription refill system. Home delivery services will prove to be very helpful for people in quarantine as well as for those with weak immunity, i.e., the elders . PharmacIt is a critical time to convert the traditional role of pharmacists into the extended role to allow them provisional prescribing of medications in collaboration with a physician within some jurisdiction . This fuSince the healthcare system is overwhelmed with the increasing number of COVID-19 cases, any drug-related problems (DRPs) might easily be neglected by healthcare professionals. These DRPs are either related to the ongoing use of chronic medications or self-medication and may associate with adverse outcomes. Pharmacists must keep a vigilant observation on the safety profile of these drugs. As most of the healthcare authorities are engaged in containing the virus, any untoward effect of the drug will get unnoticed . It is aIn public health emergencies, pharmacists play a distinguished role in reducing the burden of disease. Hospital pharmacists provide pharmaceutical care and services to both in-patient and out-patient . During Hospital pharmacists are primarily responsible to ensure the timely provision of medications to the patients . PharmacEffective pharmacovigilance results in reduced cost of care while improving therapeutic outcomes, which are the need of the hour during the ongoing pandemic . CurrentDrug repurposing for COVID-19 is improving the clinical conditions of patients but at the same time posing substantial risks of drug-related problems. The use of these drugs is subjected to careful assessment only if the desired effects overshadow the risks. Pharmacists provide accurate clinical information to the healthcare professionals regarding the drug safety, interactions, and adverse effects . OptimizSince most of the hospitals are conducting clinical trials on the treatment of COVID-19, pharmacists can improvise their roles in the provision of the right administration of drugs and with appropriate documentation. Moreover, pharmacist involvement in these trials will strengthen the findings and aid to minimize the potential bias. The primary areas in which pharmacists can work include safety and efficacy evaluation, provision of drug or placebo, and follow-up of patients to ensure optimal therapy , 50. BeiIn the absence of specific treatments for COVID-19, there is a dire need of clinical guidelines and treatment algorithm to manage the patients. Pharmacists, physicians, and other healthcare professionals can work together to develop these guidelines. Since clinical information is rapidly changing and evolving with ongoing research, these guidelines must follow evidence-based practice. Several organizations have provided the stepwise management of patients with COVID-19 , 60–63. Increasing antimicrobial resistance is an important public health problem. Pharmacists play an integral role in the team to implement antimicrobial stewardship programs (ASPs) along with physicians and nurses. The program typically focuses on the use of evidence-based data and monitors the antibiotic consumption and sensitivity patterns in the patient population to highlight and promote rational antibiotic prescribing . The phaHospital pharmacists interact with patients and their caregivers at the time of hospital discharge to provide advice on the appropriate use of medications. This service can be utilized to educate patients regarding precautionary measures in order to prevent the acquisition of infection. As family members of COVID-19 patients are at high risk of contracting the infection, their education and awareness carries paramount importance. Hospital pharmacists can continue their clinical services for chronic patients through telepharmacy in order to avoid the contact of the patients to the hospitals . PharmacAs most of the physicians and nursing staff are overburdened amid unprecedented cases, pharmacists could act as authenticated and updated source of information. The research on COVID-19 is quite dynamic as numerous new findings are originating every day. As hospital pharmacists are also experts in research interpretation, they can timely disseminate information on the recent advancements in the COVID-19 management and prevention. Moreover, pharmacists can communicate to healthcare providers regarding potential medication-related problems (MRPs) of repurposed drugs in order to ensure the drug safety and optimal therapy .Hospital pharmacists are responsible and strictly advised to adhere to the regulations for infection prevention and control in hospitals and medical institutes. Since COVID-19 demonstrated rapid transmission, disinfection, and sterilization services are of utmost importance to contain the virus. Hospital pharmacists along with the hospital's infection prevention team should ensure the disinfection of all surfaces within the hospital premises , 50, 53.The COVID-19 pandemic caused increased demand of drugs, surgical supplies, personal protective equipments (PPEs), and supportive care appliances. With many countries introducing lockdowns and travel restrictions, the global network for manufacturing and delivering medicines is widely affected. Pharmaceutical industries are experiencing major challenges in securing deliveries of medicines, not only for COVID-19 but also for other diseases. In this context, the responsibilities of industrial pharmacists have much increased. The continuous and timely production of key drugs being utilized during the current pandemic is of paramount importance and contributes substantially to alleviate the disease burden , 50. IndThe worldwide COVID-19 outbreak has highlighted the importance of the timely development of not only vaccines but also broad-spectrum antiviral drugs . CurrentPharmacists working in the industries are well aware of the significance of timely distribution of medications to patients, particularly life-saving and essential drugs during the current emergency circumstances . UnavailIndustrial pharmacists are vigilantly working in the pharmacovigilance centers as the qualified person for pharmacovigilance (QPPV). They receive information from the healthcare authorities and other pharmacists dealing with COVID-19 patients about any adverse events of the proprietary drug. Moreover, it is also the fundamental responsibility of the pharmacist to update these events in the National Pharmacovigilance Database. Pharmaceutical organizations producing investigational drugs should ensure safety reporting according to national legal requirements. Industrial pharmacists are also responsible to collect safety data of their drugs by all means including personnel visit, email, phone, or fax. Pharmacists should develop a smooth and convenient reporting tool for the adverse events . MoreoveThe impact of COVID-19 on pharmaceutical companies has been unique, as organizations had setup emergency management systems to continue their operations. Moreover, healthcare professionals and the general public are also expecting significant contribution of industries against COVID-19. During these unprecedented times, industrial pharmacists need to adopt proactive and active measures to fulfill the legal requirements of production and supply. Since regulatory authorities in many countries provided legal flexibilities , pharmacThe responsibilities of drug regulatory and administrative authorities have increased amid the sharp increase in the demand of medications and drug repurposing applications. A quick response from these authorities is of utmost importance to ensure the appropriate use of medications in the current state of unrest. They can ensure that pharmacists performing in community pharmacies, hospitals, clinics, or in industrial sectors are fully equipped and authorized to respond to the COVID-19 emergency plan , 78. A rSince the COVID-19 pandemic continues to put strain on the healthcare system, pharmacists at administrative levels can develop a COVID-19 emergency preparedness plan to mitigate the disruptions in supply which could lead to drug shortages . SpecifiPharmacists are well-positioned to reduce risks of further medication shortages arising from COVID-19 by reassuring patients and members of the public of the continued availability of OTC and prescription medications based on rational levels of demand and implementing policies to prevent unnecessary stockpiling . Recent Active surveillance to identify the secondary wholesalers involved in stockpiling and price surging activities.Increase supply chain security by working with manufacturers.Shortage of personal protective equipment (PPE) can be prevented at the federal level by identifying and reporting the agents involve in hoarding and should be dealt with an iron hand . MoreoveMonitoring of purchasing trends by the pharmacies and frequent follow-up to ensure the availability of the stock in the premises.Administrative authorities should contact reputable manufacturers and supplier to ramp up production and meet the increased demand needs.In the best interest of patient care, pharmacists and clinicians must be able to access the medication and supplies they need during the current outbreak. Personal protective equipment commonly employed in healthcare facilities are now a scarce commodity. The heightened price of PPE including masks, gloves, respirators, goggles, face shields, and gowns is recorded in the USA and in many other countries around the globe . The demRelaxing regulatory requirements can effectively ease the manufacturers to increase the supply of medicine and equipment needed during the current pandemic. Considering the occasional testing of medications through drug testing laboratories will shorten the time span of drug availability in the market. Such sort of regulatory relaxations will be beneficial for alleviating the shortage of medicines which are being used in supportive care of COVID-19 . HoweverAs part of the surveillance team and contingency planning, administration can stem out the false and misleading claims about products purporting to treat or prevent COVID-19 , 84. DruEasing operational barriers for pharmacists working in any health facility will help in their effective engagement in COVID-19 response . Drug adIt is important to recognize the pharmacists' engagements through interprofessional collaborations, which involves pharmacists and other healthcare professionals from various disciplines working together with shared goals, mutual interest, respect, and understanding about each other's roles, along with the acceptance that patients are team members . It is pCommunity pharmacists along with clinicians can effectively arrange the postdischarge follow-up of COVID-19 patients which could provide greater insight into the recovery pattern of such patients. Hospital pharmacists can optimize patient outcomes through working collaboratively within multidisciplinary teams to achieve the responsible use of medicines. In addition, hospital pharmacists should aid overburdened clinicians and nurses through medication reconciliation in order to minimize DRPs. Furthermore, integrated maneuvers of hospital and industrial pharmacists can assist to solve the issues related to drug shortage and supply. A vigilant contact of industrial pharmacists with hospital administration will be of paramount importance to ensure the adequate and continuous supply of medications. During the current health crisis, drug and health regulatory authorities hold greater responsibilities as the pandemic is accompanied by various malpractices on drug use and disease management. Drug regulatory pharmacists should ensure adequate production of drugs in the industry, good selling practices, rational use of drugs, and quality and standards of medication supply and use. These activities can be effectively accomplished through intra- and interprofessional collaboration of drug regulatory pharmacists with other pharmacists and healthcare professionals. The integration of pharmacists into core healthcare teams during the current pandemic would facilitate positive patient outcomes, better team decision-making around drug therapy, improved continuity of care, and improved patient safety.During the current crisis, innovative and adaptive methods of practicing will be required across all health professions. The roles and activities underscored in the current manuscript are not exhaustive but serve to illustrate a range of areas in which pharmacists at different levels could make substantial contributions. These are currently implemented to varying extents across different countries. The activities of pharmacists during the COVID-19 pandemic widely differ from those have been described in previous pandemics and outbreaks during which pharmacists were primarily engaged in vaccination and disease education. This pandemic put more responsibilities on pharmacists due to disease novelty, its rapid transmission, associated morbidity and mortality, massive infodemic, misleading narratives, lack of vaccine or specific drugs, lack of treatment guidelines, and overwhelmed healthcare system.Pharmacists can give full play to their professional expertise; analyze the current situation rationally; test, treat, and immunize; formulate telehealth policies expeditiously; and guarantee medication safety and rational use of drugs , 85, 88.Since the impact of traditional and extended pharmacy services is not evaluated during the pandemic, well-structured and controlled studies are needed in this regard. Moreover, the extent of preparedness among pharmacists for any future outbreak is required to be ascertained. This review also identifies the poor coordination and collaboration of pharmacists working in different sectors with other frontline healthcare professionals dealing with COVID-19. These shortcomings should be considered while designing future research and implementing health policies for infectious diseases.TM, YK, and NA: conception or design of the work. AAl, AL, and AAb: analysis or interpretation of studies for the work. TM, AL, AAb, and NT: drafted the work. NA, YK, AAl, and NT: revised the manuscript critically for important intellectual content. TM, YK, AL, and AAb: provided approval for publication of the content. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Facing cancer diagnosis during pregnancy constitutes a truly complex and challenging situation for both the patients and the physicians. Cancer diagnosis in a period of hope and joy is an unendurable situation that may affect the psychosocial functioning of the mother, causing depression, anxiety, self-blame, and social isolation. At the same time, a moral dilemma evolves among medical professionals; what is best for the mother in terms of immediate chemotherapy may have detrimental effects on the fetus, and conversely, delaying therapy and protecting the fetus may have a negative impact on the mother as the tumor progresses. Solid data on the safety profile or risks of anti-cancer agents and on the long-term neurodevelopmental outcome of children after in utero exposure to chemotherapy may provide both the patients and the physicians the information necessary for shared decision making when cancer is diagnosed during pregnancy.Pregnancy-related cancer management represents a real challenge for both the patients and the physicians. The long-term neurodevelopmental outcome of children in utero exposed to chemotherapeutic agents has only recently been addressed. This review aims to systematically integrate and highlight all existing data from the literature regarding the effect of prenatal exposure to chemotherapy on fetal brain growth and child development. All eligible studies are based on validated neurodevelopmental testing scales  and/or well-defined questionnaires. Our systematic review including 17 studies demonstrates that no major consequences on the neurodevelopment of children after in utero exposure to anti-cancer drugs have been reported; nevertheless, longer and more thorough follow-up with large-scale multicenter prospective studies is certainly required in order to draw firm conclusions. Facing cancer during pregnancy imposes a complex and challenging situation for patients and physicians. On the one hand, a life-threatening disease and the uncertainty about pregnancy may trigger symptoms of psychological distress in the mother to be. On the other hand, an ethical dilemma evolves among medical professionals; toxic and immediate chemotherapy may have detrimental effects on the developing fetus, whereas delaying cancer treatment may permit further tumor progression and result in inferior oncologic outcome.Pregnancy-related cancer affects approximately 1 in 1000 women every year . Breast Data regarding the long-term outcome of children exposed to maternal cancer with or without treatment during gestation are lacking. Multiple factors, such as maternal illness and nutrition, diagnostic tests, cancer management, and high levels of maternal stress, may negatively influence fetal development. Notably, fetal growth is a multi-aspect process with various stages that may be adversely affected by maternal cancer and its management.Deciding on the optimal treatment approach towards cancer diagnosed during gestation is frequently a real challenge for physicians. An increased awareness of the feasibility and safety of cancer treatment during pregnancy has enabled more women to receive antenatal treatment and has resulted in more live births and less iatrogenic preterm deliveries . Of noteThis review aims to systematically summarize all existing data from the literature regarding the effect of prenatal exposure to chemotherapy on fetal brain growth and child development. All studies evaluating the neurodevelopment of children in utero exposed to antineoplastic agents will be meticulously analyzed. Solid data on the neurocognitive outcome of children after in utero exposure to chemotherapy may provide both the patients and the physicians with the information necessary for shared decision making when cancer is diagnosed during pregnancy.All eligible articles included in this review were identified in the Medline/PubMed bibliographical database and the research was conducted according to the PRISMA guidelines ; the endThe articles included in this systematic review had to meet certain inclusion criteria: (1) studies highlighting the neurodevelopmental outcome of children after in utero exposure to chemotherapy; (2) studies focusing on the developmental testing of children prenatally exposed to anti-cancer agents based on validated scales or questionnaires ; (3) articles written in the English language. Publications were excluded if they met one or more of the following criteria: (1) studies not clearly defining the methodology of neurodevelopmental outcome evaluation of children in utero exposed to chemotherapy; (2) animal studies without subsequent validation in human specimens; (3) reviews of literature, Ph.D. summaries, comments, letters or duplicate publications.In case of overlapping publications emerging from the same study, the larger size study was evaluated, unless additional information was provided in the subsequent manuscripts; in this case, all articles were eligible and were analyzed independently.From each of the eligible studies, data regarding the maternal cancer as well as the neurodevelopmental outcome of children in utero exposed to chemotherapy were extracted, including the following: first author, year of publication, type of maternal cancer diagnosed during pregnancy, chemotherapy schemes administered during pregnancy, number of pregnant patients treated with anti-cancer agents, median maternal age at diagnosis, trimester of prenatal exposure to chemotherapy, number of livebirths evaluated after in utero exposure to chemotherapy, perinatal outcome , median length of follow-up, testing age, neurodevelopmental testing method , and neurodevelopmental outcome.The previously described search strategy retrieved in total 74 articles. Of these, 65 were omitted according to the exclusion criteria and nine were considered eligible. While investigating the references of the relevant reviews and eligible studies, eight more articles were added. Overall, 17 articles were entitled eligible for this systematic review, as illustrated in Breast cancer and hematological cancer  were the most frequently diagnosed malignancies during gestation ,27,28,29As illustrated in Several studies applied the Bayley Scales of Infant Development in children aged 18 and/or 36 months in order to evaluate the neurocognitive outcomes after in utero exposure to cytotoxic chemotherapy ,22,24,26Depending on the testing age, Wechsler Intelligence Scales were used in multiple versions; Wechsler Preschool and Primary Scale of Intelligence, Wechsler Intelligence Scale for Children, Wechsler Adult Intelligence Scale, Wechsler Individual Achievement Test ,27,28,29In order to evaluate the impact of maternal chemotherapy on child behavior and executive function, the Child Behavior Checklist (CBCL) and/or the Behavior Rating Inventory of Executive Function (BRIEF) were completed by the parents or the caregivers ,27,28,29Aiming to define the long-term neurodevelopmental outcome after prenatal exposure to antineoplastic agents, certain studies were based solely on general health and education questionnaires or school performance questionnaires, whereas other studies included those surveys as part of the overall evaluation ,27,28,29Complementary to the neurodevelopmental scales, three particular studies included in the review focused on brain MRI neuroimaging and ERP/EEG testing in order to investigate potentially damaged brain areas and correlate these findings with neurocognitive impairment ,21,26. AFurther data extracted from all eligible studies regarding the long-term neurodevelopmental outcome of children prenatally exposed to chemotherapy are presented in The long-term neurodevelopmental effect of in utero exposure to anti-cancer agents, which is an important aspect of chemotherapy treatment safety, has only recently been addressed. We conducted a comprehensive systematic literature review that resulted in the identification of 17 studies exploring the impact of prenatal exposure to chemotherapy on the neurodevelopment of children. Our results demonstrate that no major consequences on long-term neurodevelopmental outcome of children after in utero exposure to chemotherapy have been detected; specific facets of each individual study should be further discussed.In the past, fear of cytotoxic chemotherapeutic impact on the developing fetus has prevented clinicians from starting oncological management during gestation and resulted in pregnancy termination, medically-induced preterm delivery or delay of maternal treatment . CurrentThe placenta and the fetal blood–brain barrier constitute the primary defense mechanism of the fetus against toxic chemotherapeutic agents. Passive diffusion represents the main transfer mechanism of the placenta; molecule penetration follows its concentration gradient and is determined by its physiochemical characteristics such as lipid solubility, polarity and molecular weight. Additionally, active transport by protein pumps  works against the concentration gradient in the maternal and the fetal blood flow and provides an energy-requiring link between the two circulations . Of noteAdditionally to the preferable chemotherapy scheme, the timing of drug administration during the course of pregnancy and embryogenesis is crucial. When cytotoxic drugs are administered in the first ten days after fertilization, the result is an all-or-nothing phenomenon depending on the number of disrupted cells. When cytotoxic drugs are administered during the phase of organogenesis that starts at day 10 and is completed at week 8, there is high risk of teratogenic effects and increased frequency of major congenital malformations. Hence, chemotherapy is contraindicated during the first trimester of pregnancy . In our Interestingly, central nervous system (CNS) development starting at week 5 remains vulnerable throughout the whole pregnancy, while it continues even during the postnatal period. Thus, potential harmful effect of cytotoxic drugs on fetal brain growth may occur later in pregnancy and result in neurocognitive impairment and poor behavioral or academic performance, known as the “chemo-brain” effect . SimilarOur review demonstrates that no significant impairment in neurocognitive development of children prenatally exposed to anti-cancer drugs has been detected. However, various abnormalities were observed in child behavior and executive function after prenatal exposure to chemotherapy during the second and third trimester; weak emotional regulation, and high rates of internalizing, externalizing, and total behavior problems were observed. These findings may also be attributed to antenatal maternal stress, as several studies have demonstrated that maternal psychosocial functioning during pregnancy is highly associated with child cognition ,38,39. TAmong the limitations of this review, it should be stressed that our conclusions are based on studies evaluating child neurodevelopment at different testing ages using various assessment tools , studies examining children exposed to different types of maternal cancer and chemotherapy treatment plans, and studies based on small cohorts, some of which do not include control groups or have short follow-up periods. Furthermore, the number of eligible studies was limited due to the rarity of pregnancy-related cancer; thus, further research is needed in order to confirm the abovementioned findings.In conclusion, further research in the field of prenatal exposure to maternal cancer is highly recommended in order to obtain sufficient evidence and formulate pregnancy-related cancer management guidelines. Even though current guidelines suggest close monitoring of the fetal and the neonatal development, a clearly defined approach to the long-term follow up after prenatal exposure to anti-cancer drugs is not available . The dat


Since their identification as genomic regulatory elements, Transposable Elements (TEs) were considered, at first, molecular parasites and later as an important source of genetic diversity and regulatory innovations. In vertebrates in particular, TEs have been recognized as playing an important role in major evolutionary transitions and biodiversity. Moreover, in the last decade, a significant number of papers has been published highlighting a correlation between TE activity and exposition to environmental stresses and dietary factors. In this review we present an overview of the impact of TEs in vertebrate genomes, report the silencing mechanisms adopted by host genomes to regulate TE activity, and finally we explore the effects of environmental and dietary factor exposures on TE activity in mammals, which is the most studied group among vertebrates. The studies here reported evidence that several factors can induce changes in the epigenetic status of TEs and silencing mechanisms leading to their activation with consequent effects on the host genome. The study of TE can represent a future challenge for research for developing effective markers able to detect precocious epigenetic changes and prevent human diseases. In the 1940s, when the Ac/Ds (activator/dissociation) transposon system was identified as the genetic basis for maize kernel variegation, Barbara McClintock proposed transposable elements (TEs) as genomic regulatory elements . Later, Pseudoviridae), Ty3-gypsy-like (Metaviridae), and Bell/Pao are the three main families of LTR retrotransposons spread among vertebrates. Non-LTR retrotransposons include Long Interspersed Nuclear Elements (LINEs) and Short Interspersed Nuclear Elements (SINEs). As LTR retrotransposons also, LINEs are autonomous elements while SINEs are non-autonomous retrotransposons that use the retrotranscription machinery of other TEs [Sequencing of eukaryotic genomes has revealed that a consistent fraction of repetitive DNA is represented by TEs. The mechanism used by these genetic elements to move and insert into various host genomic positions is called transposition. TEs can be grouped into two major categories based on the way they relocate in the genome: class I retrotransposons and class II DNA transposons. Retrotransposons relocate indirectly via RNA intermediates using a copy and paste mechanism. These elements are divided into Long Terminal Repeat (LTR) retrotransposons and non-LTR retrotransposons on the basis of the presence or absence of flanking sequences ,8 Figura. LTR rether TEs .Class II DNA transposons are wholly DNA-based elements (found in both prokaryotes and eukaryotes) that can directly relocate autonomously from DNA to DNA, via a cut and paste mechanism. However, about a decade ago, analysis of a large amount of eukaryotic genome sequences led to the discovery of a new type of DNA transposons called Polintons  and Helitrons ,11,12,13Arabidopsis genome, while Saccaromyces cerevisiae contains only members of the LTR retrotransposon family. A wide variety, present in limited numbers, of LTR and non-LTR retrotransposon families are present in the genome of Drosophila. Conversely, a very large number of few related retroelements from the IAP  (LTR), LINE1, and SINE B1 (non-LTR) retrotransposon families dominate the mouse genome [The various classes of TEs are differently represented in terms of both quantity and quality across all domains of life. For example, 45% of the repeated elements in the human genome is represented by retrotransposons  while ple genome . The reme genome .Vertebrates are the sister group of urochordates and their common ancestor diverged from cephalochordates about 500 Mya ,52 and tEpigenetic mechanisms such as DNA methylation and histone modifications, as well as small RNAs and sequence-specific repressors such as KRAB zinc-finger proteins, regulate the activity of TEs, generally silencing them. TE reactivation and retro-transposition have been reported in the development of human pathogenesis and environmental stressors seem to play a major role in determining these events. Therefore, TEs are more than junk and have a significant role in maintaining the genome structure and stability, but they are also involved in the onset of diseases and, in this context, an important open question is to what extent diet could affect TEs mediated gene expression. In light of these premises, in this review, we present an overview of the impact of TEs on vertebrate genomes, report the silencing mechanisms adopted by host genomes to regulate TE activity, and finally we explore the effects of environmental factor exposures on TE modulation in mammals which is the most studied group among vertebrates.Innovations in cells, tissues, organs, and structures have been responsible for the evolution of new species in vertebrates. Many of these modifications have been linked to TE activity and in particular to exaptation events that contribute to the creation of new genes and regulatory elements . The comEptatretus stouti and the lampreys Lethenteron camtschaticum and Petromyzon marinus. TEs have been investigated only in P. marinus in which these elements constitute the 34.7% of the assembled sequences and are mainly dominated by LINE retroelements followed by DNA transposons [Callorhinchus milii [Lepisosteus oculatus TE content is enriched by retroelements [For Agnatha, genome assemblies are currently available for only three species: the hagfish nsposons ,59,60. Aus milii , in whicelements . Furtherelements . In teleelements ,64,65,66elements .It is interesting that the condition of coelacanths shows some very active TE families despite their slow evolving genome ,69. The Neoceratodus forsteri and the West African lungfish Protopterus annectens allowed the gap in our knowledge about this taxonomic group to be filled. The analysis in N. forsteri revealed that about 90% of the assembly is made up of TEs [P. annectens [P. annectens [The huge size of the lungfish genome has long represented a challenge for assembly procedures. However, the recent genome sequencing of the Australian lungfish p of TEs  while 61nnectens . Both annnectens  and the nnectens .Similarly, Amphibia is a clade characterized by organisms with large genomes as the case of some caecilians with approximately 14 Gb up to extreme values in salamanders with about 120 Gb . These dXenopus tropicalis and Nanorana parkeri, having genomes of 1.5 Gb and 2.3 Gb respectively, differ in their TE content of about 25% for the Western frog and about 50% for the Tibetan frog [X. tropicalis, in particular of Kolobok-T2 elements and of LTR retrotransposons in N. parkeri, in particular of Gypsy elements [Oophaga pumilio [Ichthyophis bannanicus genome evidenced an abundance of Dictyostelium intermediate repeat sequence (DIRS) and LINE/Jockey elements [Indeed, the two tan frog . This inelements . These r pumilio  and have pumilio . Insteadelements . The genelements ,77,78,79elements . This aselements . Howeverelements  demonstrThe complete DNA sequencing of whole mammalian genomes has shown that at least 46% of human DNA, 31% of canine DNA, and 37% of mouse DNA are derived from TEs . In mostChanges of genome size and composition are related to TE mobilization. Although the trigger involved in TE induction is not completely understood, it is clear that the transposition process can cause deleterious effects in the host genome with consequent reduction of fitness and thus also of TE replication and propagation. Therefore, strategies to minimize the negative impact of TE mobilization have been developed. Some TEs have evolved self-regulatory mechanisms controlling their own copy numbers ,86. In tDNA methylation is the most widely adopted mechanism for silencing TEs and consists of the addition of methyl groups to DNA. In particular, a DNA methyltransferase catalyzes the transfer of a methyl group from S-adenyl methionine to the fifth carbon of a cytosine residue to form 5-methylcytosine. This process is connected with the cytosine-guanine dinucleotide (CpG) sites. It is not surprising that about 90% of methylated CpG sites in the mammalian genome are found in repeated elements and above all in TEs such as SINEs and LINEs . BesidesAnother conserved mechanism of silencing of TEs includes the control by regulatory non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), short interspersed RNAs (siRNAs), and PIWI-interacting RNAs (piRNAs). These ncRNAs differ for number of nucleotides, origin, and function. miRNAs and siRNAs have a length of about 21–25 nucleotides and are generated from double-stranded RNA precursors cleaved by Dicer. miRNAs and siRNAs become part of a cytoplasmatic RNA-induced silencing complex (RISC) including Argonaute subfamily proteins, and are able to bind target mRNAs and prevent translation . siRNAs A wealth of data indicates that the evolutionary history of KRAB-ZFPs is strictly linked to that of TEs. Indeed, TEs can evade detection by host KRAB-ZNFs by acquiring mutations and consequently the host repressor mechanisms need to evolve rapidly in order to maintain genome integrity. Two models have been hypothesized to explain the relationship between KRAB-ZFPs and TEs. The first is consistent with an “arms race model” stating that the major role of KRAB-ZFPs is the recognition and transcriptional silencing of TEs as recently demonstrated by large scale ChIP-seq studies and loss-of-function experiments . HoweverTE activation in response to environmental stress was first proposed by Barbara McClintock , who belIn general, environmental stressors, natural or of anthropogenic nature, have been shown to alter epigenetic modifications such as DNA methylation and histone modifications, and the expression of small non-coding RNAs ,103. FaiThe exposition to numerous environmental stresses, such as exposure to pollution, terrestrial and space radiation, temperature changes, endrocrine distruptors, and physiological and psychological stresses, determines most frequently the hypomethylation of L1 retroelements and ERVs and the hypermethylation of Alu elements with consequently cancer and disease development in mammals . Alu retExposure to stressful conditions can cause not only changes in TE transcription but also in transposition rate as in the case of heavy metal exposure. Indeed, arsenic  and mercIn mammals, the L1 element is one of the most abundant retrotransposons whose activity is responsible for a variety of disorders, from hemophilia A , diabeteResponse to heat-shock mediated by TEs is one of the best stress statuses studied in vertebrates. In humans in the presence of heat stress the expression of some genes decreases while that of Alu elements increases. Indeed, it has been demonstrated that mRNAs produced from SINEs act in trans repressing the transcription by directly binding RNA polymerase II forming stable complexes at promoters . In miceIn humans in vitro, in vivo, and epidemiological studies evidence that TEs are sensitive endpoints for detection of the effects caused by environmental stresses suggesting their use as biomarkers and/or targets for therapeutic treatment and prevention of diseases .Overall, a specificity seems to exist between TEs and stress condition  but the agouti gene, as a molecular basis for the observed color shift. Since then, a series of research has led to the rise of nutritional epigenomics as a sub-discipline of environmental epigenomics, focused on the role of dietary factors  on epigenetic modifications and disease risk [Since the pioneering investigations of Wolf et al. , Morgan ase risk . AdditiovyA IAP retrotransposon. More importantly, the authors discovered that maternal nutritional supplementation with methyl donors or genistein counteracts BPA-induced hypomethylation restoring the coat color distribution in BPA-exposed offspring toward the methylated pseudoagouti phenotype. The covalent binding of the vitamin biotin to lysine-12 in histone H4 (H4K12bio), mediated by holocarboxylase synthetase (HCS), has been demonstrated to be responsible for the repression of LTR retrotransposons in human and mouse cell lines [For example, the study of Dolinoy et al.  demonstrll lines . The autll lines  clearly ll lines . By assell lines  demonstrll lines  examinedll lines  additionTransposable elements make genomes dynamic and are responsible for their evolution. It is known that the quantitative impact of total TEs as well as of specific TE types varies in different lineages. Our comparative analysis of TE accumulation in vertebrate genomes revealed that information is mainly focused on mammals, while for many other groups information on TEs is rather scarce or even absent due to the lack of available genome assemblies. Moreover, in the last decade, a significant number of papers have been published highlighting a correlation between TE activity and exposition to environmental stresses and dietary factors. In general, they cause changes in DNA methylation, histone modifications, and in the expression of small non-coding RNAs. These modifications determine the failure of silencing mechanisms with consequent reactivation of TEs. This activity can have an adaptive role generating a higher mutation rate that causes an increase in genetic variability on which natural selection can act to generate advantageous functions for species to survive stressful situations. On the contrary, transposition can have deleterious effects in the host genome and cause the onset of diseases. Certainly, many questions remain to be addressed, such as to unveil the TE diversity and function in a wider range of species than that known today, to detect the wide variety of propagation mechanisms of TEs within genomes, and finally to understand to what extent diet could effect TEs mediated gene expression. The deep knowledge of these aspects will allow the interplay between TE intrinsic characteristics, host biology, and response to the environmental factors  to be co


Up to recent years, several studies have been analyzing damaged parchments from different world’s archives, trying to trace back the culprit of the purple spots. However, standard cultivation and early molecular techniques have been demonstrated to be unsuccessful, leading the parchment damage issue remaining unsolved for many years. Nowadays, some studies have explored the parchment biodeterioration dynamics by adopting a multidisciplinary approach combining standard microbiological methods with high-throughput molecular, chemical and physical techniques. This approach allowed an unprecedented level of knowledge on the complex dynamics of parchment biodeterioration. This mini review discusses the application of the combination of basic and high-throughput techniques to study historical parchments, highlighting the strengths and weaknesses of this approach. In particular, it focuses on how metagenomics has been paramount for the unequivocal identification of the microbial main actors of parchment biodeterioration and their dynamics, but also on how metagenomics may suffer the distortion inflict by the historical perspective on the analysis of ancient specimens. As a whole, this mini review aims to describe the scenario of information on parchment biodeterioration obtained so far by using the integration of metagenomic with recent chemical (Raman spectroscopy) and physical  approaches, which might have key implications in the preservation of many ancient documents.Ancient parchments record an immense part of our cultural heritage, having been used as the main written support material for centuries. Parchment easily undergoes biodeterioration, whose main signs are the so-called  The preservation of cultural heritage is one of the major challenges of today’s society, because of the fundamental right of future generations to inherit it. Writing has always been one of the most effective communicative ways of transmission of the cultural identity and memory; hence, ancient manuscripts represent milestones of cultural uniqueness of a country. For over two millennia, the most used writing material was parchment, a semi-solid collagen matrix, obtained from animal skins . Hence, Biodeterioration has been longish neglected, being physical and chemical processes regarded as dominant factors of decay. In the last decades, this dogma has been countered: it is now generally agreed that microorganisms, besides esthetical damages, cause acid corrosion, enzymatic degradation, and mechanical attack . Biodetepurple spots, often leading to the detachment of the superficial (written) layer, and loss of historical content. Purple spots may affect the entire parchment surface, but a “respect zone” around the inks  proved revolutionary, simultaneously reducing costs, time-consuming, and the scale of genome characterization. NGS allows also to study specific genome regions and to determine community taxonomic analysis. It is therefore utilized in many research fields, including Biocodicology , aimed tThe NGS-based metagenomic analysis has been firstly utilized in Biocodicology by Parallelly, another up-dated physical technique, the light transmission analysis (LTA) was used to evaluate the kind and entity of the damage to native collagen. The LTA of collagen-based materials is a recently developed technique to quantitatively assess the state of collagen integrity, measuring its chemical stability trough the hydrothermal denaturation temperature . Under tThe LTA analysis on purple spotted roll, was performed by comparing the results obtained from the areas showing evident microbiological damage (purple spots) with others from intact parts of the same document. This allowed to highlight the pinpointed nature of the microbial attack, which changes the target collagen populations along the biodegradative process, determining the degradation rate.Halobacterium  to produce the proteolytic and lipolytic enzymes which attack and degrade the parchment collagen matrix n matrix .This allowed to hypothesize that halophilic archaea are the powerful triggering actors, acting as a pioneer species in a two-phases heterotrophic microbial succession able to degrade the parchment : the firThe NGS-based studies of ancient parchments , 2019 alSaccharopolyspora spp.) and fungi (Penicillium and Aspergillus among others) dominate the documents. Their being more recent can be hypothesized not only by the relative DNA abundance, but also by the presence of apparently integer cells and spores  treatment, which make highly toxic the environment within the hides. These treatments have the double effect of killing all the microbes present in the rawhide and stabilizing the collagen matrix  tanned leathers, unequivocally demonstrated that the microbial culprits of present-day hide-products belong to the Halobacteriaceae family, mainly lorubrum . Halophin matrix  producinn matrix , even inConversely, preventive measures of parchment contamination could have been useful in the past to avoid parchment decay: in fact, parchment manufacturing included only “mild” treatments and mechanical removal of skin layers  which ju4) or alkali sulfates, but building materials can be infiltrated by salt from the environment through capillary force, as in the case of caves, or the buildings that receive inputs of salt water from natural sources (as seawater spray), or when salts are used for de-icing.The metagenomic approach allowed to understand, among other, that ancient parchments are extreme environments, harboring purple spots producing Halobacteria , 2019. Cscenario, metagenomics offers a powerful approach to characterize the complex (mainly not-cultivable) microbial communities that colonized the ancient documents over time. Being able to capture the complexity of biodeterioration, metagenomics conquers a place on the podium among other molecular approaches because it maximizes the understanding of the microbial composition and helps in deciphering the dynamics of biodeteriogen communities. In the case of limited availability of the oldest DNA strands shotgun metagenomics may face the problem, allowing to check for the presence of fragments of different size, including the short damaged ones. On the contrary, proteomics seems less useful in the case of parchments due to the intrinsic protein composition of the matrix, which may overcome all the other signals, and metabolomics could be unable to traces metabolites produced langsyne and subjected to further colonization.Hence, metagenomics may help answer relevant questions and contribute to a better understanding of the history of ancient manufacts, other than ancient parchment manuscripts. In the present-day research Anyway, the concurrent use of other “omics” may help to understand biology at the aggregate level, enabling the analysis of both the whole microbial structure and how microbes might influence each other’s activities affecting collective functions. However, only the integration of many different techniques  allows to produce a comprehensive analysis of the biodeterioration of cultural heritage goods . In any In conclusion, the use of multiple approaches including the omics techniques, will allow an unprecedented level of knowledge on the biological damage and its dynamics, and could be applied to different cultural heritage manufacts. The high-throughput techniques would allow the structural and functional characterization of the biodeteriogen microbial communities, by the sequencing/identification of total pools of biomolecules including DNAs, proteins, or metabolites. As regard the parchments, this information will allow to keep preserved the beauty of these timeless masterpieces of our cultural heritage.NP and LM conceived the manuscript. NP prepared a first draft of the manuscript, with support from FM and SO. LM and MT edited and reviewed the draft to obtain the final manuscript, which has been discussed and approved by all the authors.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Using oil palm trunk (OPT) layered with empty fruit bunch (EFB), so-called hybrid plywood enhanced with palm oil ash nanoparticles, with phenol-formaldehyde (PF) resin as a binder, was produced in this study. The phenol-formaldehyde (PF) resins filled with different loading of oil palm ash (OPA) nanoparticles were prepared and used as glue for layers of the oil palm trunk (OPT) veneer and empty fruit bunch fibre mat. The resulting hybrid plywood produced was characterised. The physical, mechanical, thermal, and morphological properties of the hybrid plywood panels were investigated. The results obtained showed that the presence of OPA nanoparticles significantly affected the physical, mechanical, and thermal properties of the plywood panels. Significant improvements in dimension from water absorption and thickness swelling experiments were obtained for the plywood panels with the highest OPA nanoparticles loading in PF resin. The mechanical properties indicated that plywood composites showed improvement in flexural, shear, and impact properties until a certain loading of OPA nanoparticles in PF resin. Fracture surface morphology also showed the effectiveness of OPA nanoparticles in the reduction of layer breakage due to force and stress distribution. The thermal stability performance showed that PF filled OPA nanoparticles contributed to the thermal stability of the plywood panels. Therefore, the results obtained in this study showed that OPA nanoparticles certainly improved the characteristic of the hybrid plywood. Biocomposites are defined as composites materials that consist of biodegradable matrix and biodegradable lignocellulosic fibre such as oil palm biomass, rice husk, coconut fibre, kenaf, and so on as reinforcement. Furthermore, due to the continuous depletion of bioresources and environmental deterioration, tremendous interest has been drawn to utilize other renewable and sustainable materials . The devA structural biocomposite can be defined as a product that can carry and hold a load in use. For example, wall panels, stairs, roof structures, and flooring systems in a building are applications of structural bio-composites. These applications are the results of the development of bio-based wood structures by combining load-bearing and functional properties. Moreover, their feasible and competitive mechanical properties have made the biodegradable natural fibre a preferred engineering material for reinforcement . MeanwhiIn wood-based industries, plywood composites are one of the most important types of conventional composites that still relevant today. The plywood name was originated from the wood product where three or more plies of thin sheets of wood and well known wood veneers were bonded together with the application of adhesives. Most of the applications of plywood composites that are relevant until today are due to some of the plywood characteristics that are superior and comparable to solid wood properties. Many applications of plywood, such as in furniture products, structural and non-structural panels, interior and exterior design, have some advantages in terms of cost, processing, design, and so forth. In plywood manufacturing, there are two classes of plywood, which (1) are for construction and industrial, and (2) are for hardwood and decorative plywood . In consIn the past, solid wood has been chosen to produce structural materials due to the excellent properties, but the escalated demand for solid wood has caused the reduction of forest resources. Hence, a plywood product which originated from veneer that was manufactured from good quality timber has been developed in straight, large diameter, and cylindrical forms, as an alternative to solid wood products . As the In the past few decades, oil palm trunk has been partially utilized to be an alternative supply for wood-based industries and the most viable alternative in plywood production. Even though oil palm trunk is available in a great amount, the successful utilization of oil palm trunk is still limited due to the weaknesses such as being very hygroscopic, a higher rate of shrinking and swelling compared to solid wood. Furthermore, lower strength, poor durability, dimensional stability, and machining properties are the reason for the limited utilization of oil palm trunk ,11. HoweThe utilisation of oil palm trunk veneer to produce plywood has been successfully reported by Mokhtar et al. . HardwooSince oil palm trunk is a potential raw material for value-added products, particularly in plywood industries, it is possible to utilize it with other lignocellulosic materials to produce better products to meet market demand . Moreove2 into the urea-formaldehyde (UF) matrix 2 nanopar● Impact PropertiesThe Izod impact test was applied in this study. The value of impact strength was calculated by the loss energy of the pendulum, the energy absorbed in breakage, and the difference of initial and final height of pendulum’s swing ,70. The It is observed that the PWV showed greater impact resistance compared to PWH at 4% loading of PF resin-filled OPA nanoparticles, though, at the initial improvement of impact strength, the PWH obtained greater improvement compared to PWV. At the lower loading of PF resin-filled OPA nanoparticles (1–3%) in PWH, OPA nanoparticles uniformly dispersed in the matrix and constantly spread between fibre spaces. During this process, any cavities or void between EFB mat fibre and EFB fibre/OPT veneer could be filled with or fully covered by PF resin-filled OPA nanoparticles. Then, due to vast interfacial interaction between fibre, panel surface, PF resin, and OPA nanoparticles, this reaction certainly enhanced the impact resistance of plywood panels. The energy that absorbed from the pendulum during impact test was converted into stress; then, the interaction that occurred previously acted as a bridge to propagate the stress evenly between EFB fibres and OPT veneer, resulting in increases of impact strength.In this experiment, the impact strength of PWH slightly decreased once the PF resin-filled OPA nanoparticles exceeded 4% loading. The reduction of PWH impact resistance is probably due to the matric fracture that occurred from poor bonding between PF resin and EFB fibre/OPT veneer. At a high concentration of OPA nanoparticles in the PF resin, the agglomeration of OPA nanoparticles was highly anticipated due to their surface energy. According to Zahedi et al. , increasAs for the impact properties of the PWV, it is obvious that the impact strength slightly increased as the PF resin-filled OPA nanoparticles loading increased from 1% to 4%. The higher results in the impact strength were obtained at 4% of OPA nanoparticles loading with the maximum strength of 431 J/m. These results indicate that the PWV panels reinforced with OPA nanoparticles enhanced the impact properties until optimum OPA nanoparticle content was reached. The presence of OPA nanoparticles at 4% loading in the PF resin influenced the rigidity of the polymer. Furthermore, with the improvement of the PF resin, the OPA nanoparticles acted as obstacles to obstruct the crack propagation while absorbing impact energy. This means that the optimum level of PF resin-filled OPA nanoparticles at 4% loading needed more energy to past the obstacles resulting in increasing the impact strength. Moreover, introducing the OPA nanoparticles into plywood panels from the lower to optimum loading showed the existence of PF resin-OPT veneer interaction and enhancement of impact performance.It was also observed that increasing the loading of OPA nanoparticles beyond 4%, decreased the impact strength of PWV. The resin spreading and homogenous distribution of OPA nanoparticles are the most important factors that affect the mechanical properties of the plywood panels. At the optimum loading of OPA nanoparticles, the plywood panels produced greater bonding with the cured resin and surface panels then developed rigid structural integrity. As reported by El-Bashir , at the The details of the fracture surface of PWH and PWV due to shear stress are presented in The SEM micrograph also shows that the force did not completely break the layers, but rather separated the plies due to weak interlaminate adhesion gap. This behaviour showed that the PWH with PF resin-filled OPA nanoparticles was strong enough to tolerate the force from the shear test and prevent EFB fibre from breakage. As reported by Kumar et al.  who usedAs for PWV with neat PF resin presented in The effect on the impact properties of plywood panels due to the presence of OPA nanoparticles was described by the Field Emission Scanning Electron Microscope (FESEM) micrograph, as shown in In the meantime, the PWH with PF filled 4% OPA nanoparticles improved the crack propagation when force was applied at high speed, as shown in the SEM micrograph displayed in PWV with neat PF resin and with 4% OPA nanoparticle loading are shown in Meanwhile, the PWH with 4% OPA nanoparticles loading in TGA thermograms and derivative thermogravimetric curves of plywood veneer (PWV) are shown in From the TGA and DTG curves illustrated in TGA thermograms of PWC and PWH with different loading of PF resin-filled OPA nanoparticles are illustrated in This second stage of mass loss mainly involved decomposition of the three main constituents in PWH, which are lignocellulosic materials, polymers, and nanoparticles, respectively. The major weight loss of PWH illustrated in At the end of the degradation process that was recorded at 800 °C, the fraction of non-volatile matters denoted as residue remained below 30 % from the overall weight of the PWH specimens. The details of the TGA/DTG curve behaviour are presented in Correspondingly, at a given datum, the PWH with PF filled OPA nanoparticles was more thermally stable than the PWH with neat PF and PWC. According to Peng and Kong , the anaThe improvement of the thermostability may be attributed to the performance of the OPA nanoparticles that could disseminate the heat from polymer onto nanoparticles. From the thermogravimetry curve illustrated in The results obtained from this study showed there was an improvement of plywood veneer and hybrid plywood properties such as physical, mechanical, and thermal properties compared to commercial plywood. The FT-IR analysis of PF nanocomposite filled OPA nanoparticles showed changes in the FT-IR spectrum in terms of peak intensity, peak broadening, and new absorption peak. Thermogravimetric analysis (TGA) for PF nanocomposite filled OPA nanoparticles; the PF nanocomposite exhibited better thermal stability in terms of higher initial temperature degradation, maximum temperature degradation, and percentage of ash residue. The X-ray Diffraction (XRD) results of PF nanocomposite filled OPA nanoparticles illustrated a significant presence of a peak in PF nanocomposite samples compared to neat PF. The absence of a peak in the neat PF XRD spectrum indicates that the neat PF resin consists of amorphous structures. The occurrence of a peak indicated the crystallinity material that has been incorporated with neat PF resin. The intensity of the peak in XRD spectroscopy showed the loading of OPA nanoparticles that was introduced into PF resin. Meanwhile, the micrograph of PF nanocomposite (1–5%) showed less void and porosity that was due to the incorporation of PF resin with OPA nanoparticles. This behaviour increases the viscosity and solids content of the PF resin, then leads to curing stability due to the energy of OPA nanoparticles that can disseminate heat uniformly. In density profile analysis for plywood veneer (PWV) and hybrid plywood (PWH) with PF resin-filled OPA nanoparticles, there was a significant improvement of the density profile throughout sample thickness as compared to PWV and PWH with neat PF resin and commercial plywood (PWC). The application of PF resin-filled OPA nanoparticles in plywood panel (PWV and PWH) production showed dimensional stability improvement, particularly in water absorption and thickness swelling. From the overall experimental results, the introduction of OPA nanoparticles into PF resin then applied on plywood panels showed a great improvement in terms of physical, mechanical, thermal, and fracture morphology properties. Therefore, to achieve durable and superior properties performance, proper addition of OPA nanoparticles can be introduced into plywood panels.