The link between liver dysfunction and decreased mitochondrial oxidative phosphorylation in sepsis has been clearly established in experimental models. Energy transduction is plastic: the efficiency of mitochondrial coupling collapses in the early stage of sepsis but is expected to increase during the recovery phases of sepsis. Among the mechanisms regulating the coupling efficiency of hepatic mitochondria, the slipping reactions at the cytochrome oxidase and ATP synthase seem to be a determining element, whereas other regulatory mechanisms such as those involving proton leakage across the mitochondrial membrane have not yet been formally proven in the context of sepsis. If the dysfunction of hepatic mitochondria is related to impaired cytochrome c oxidase and ATP synthase functions, we need to consider therapeutic avenues to restore their activities for recovery from sepsis. In this review, we discussed previous findings regarding the regulatory mechanism involved in changes in the oxidative phosphorylation of liver mitochondria in sepsis, and propose therapeutic avenues to improve the functions of cytochrome c oxidase and ATP synthase in sepsis. Sepsis and septic shock remain a main cause of death in intensive care units despite numerous therapeutic trials . Sepsis-Liver failure associated with sepsis is often considered a late-stage feature of critical illness, manifesting as jaundice and hyperbilirubinemia . HoweverIn a previous study, we tested this hypothesis by examining the time course of the functional properties of liver mitochondria in a rodent model of severe sepsis . ContrarMitochondria are double-membrane intra-cytoplasmic organelles found in most eukaryotic cells, with the exception of mammalian erythrocytes. The outer membrane enclosing the organelle forms a semi-permeable barrier separating the mitochondria from the cytosol. The outer mitochondrial membrane is freely permeable to small molecules and contains special channels capable of transporting large molecules. The inner membrane delimits two operating volumes: the matrix and the intermembrane space between the inner and outer membrane . The innMitochondrial oxidative phosphorylation is a major source of hepatocellular ATP production under aerobic conditions. The energy demand of the cell is difficult to quantify during sepsis. Nevertheless, the ability of mitochondria to sense and respond to changes in nutrient availability and energy demand is critical for the maintenance of hepatocellular homeostasis. Within the mitochondria, the coupling between the rate of oxidation and the rate of ATP generation (phosphorylation) is flexible and can be regulated . In a st2) consumption allows the overall efficiency of the reactions (ATP:O) to be determined.In a complex metabolic network such as mitochondrial oxidative phosphorylation, where the coupling between respiration and adenosine diphosphate (ADP) phosphorylation can be regulated at different levels, a rigorous quantitative analysis measuring the rate of ATP synthesis associated with oxygen . This method is commonly used but has the major drawback that the ATP generated from exogenous ADP is only measured at a single level of energy demand: the maximum State 3 phosphorylation rate (State 3), which is far from the physiological state. Another approach is to directly quantify mitochondrial ATP production, either by using a magnesium probe that binds to ATP and ADP [Two methods are generally described in the literature for assessing mitochondrial oxidative phosphorylation efficiency in vitro. An indirect approach is to measure the ADP:O ratio, defined as the amount of O and ADP  or by me and ADP ,12,16,17 and ADP , allowin and ADP ,20,21. U and ADP , Herming and ADP  showed a and ADP  using th and ADP . The que and ADP . The ATP and ADP . Using t and ADP . Note th and ADP ,28 or th and ADP ,30. NeveM) and a chemical  component [2 exhibit a basal oxygen consumption level even if no ADP is provided in the respiratory medium (M) and provided information on membrane conductance to proton [The chemiosmotic theory proposed by Peter Mitchell in 1961 states that substrate oxidation and ATP synthesis are indirectly coupled through the establishment of an electrochemical proton gradient or proton motive force Δp across the inner mitochondrial membrane. This force, which act on protons, comprises an electrical component  of the ETC involves all compounds or mechanisms leading to a decrease in the intrinsic efficiency of proton pumps. The “redox slipping” or “slippage” of proton pumps within the respiratory chain results in reduced proton pumping for the same number of electrons transferred along the respiratory chain . This reM) [This uncoupled proton leakage mechanism occurs at the level of ATP synthase and result in a decrease in the amount of ATP synthesized for a given proton flux. Such an increase in H+/ATP stoichiometry has been demonstrated in vitro . In ATP M) . Further+-dependent nuclear histone deacetylase [20-diterpene alkaloid from the lateral roots of Aconitum carmichaelii [Potential therapeutic strategies targeting the mitochondria, including treatment with antioxidants, ROS scavengers and membrane stabilizers , have already been extensively reviewed ,72,73. Hcetylase , and sonichaelii , have beThe concept of coupling efficiency is essential to explain mitochondrial and liver dysfunction during sepsis and understanding it is necessary for the establishment of new forms of therapy. Depletion and downregulation of cytochrome c oxidase and ATP synthase appear to be consistent and are predominant mechanisms in the occurrence of uncoupling of liver oxidative phosphorylation during sepsis. The mechanism of cytochrome c oxidase depletion could involve phosphorylation of its subunit 1  at an ea


In the future, more new insights are expected to be shed into the brilliant field—regenerative biomaterials.Nowadays, biomaterials have evolved from the inert supports or functional substitutes to the bioactive materials able to trigger or promote the regenerative potential of tissues. The interdisciplinary progress has broadened the definition of ‘biomaterials’, and a typical new insight is the concept of tissue induction biomaterials. The term ‘regenerative biomaterials’ and thus the contents of this article are relevant to yet beyond tissue induction biomaterials. This review summarizes the recent progress of medical materials including metals, ceramics, hydrogels, other polymers and bio-derived materials. As the application aspects are concerned, this article introduces regenerative biomaterials for bone and cartilage regeneration, cardiovascular repair, 3D bioprinting, wound healing and medical cosmetology. Cell-biomaterial interactions are highlighted. Since the global pandemic of coronavirus disease 2019, the review particularly mentions biomaterials for public health emergency. In the last section, perspectives are suggested: (i) creation of new materials is the source of innovation; (ii) modification of existing materials is an effective strategy for performance improvement; (iii) biomaterial degradation and tissue regeneration are required to be harmonious with each other; (iv) host responses can significantly influence the clinical outcomes; (v) the long-term outcomes should be paid more attention to; (vi) the noninvasive approaches for monitoring   With the in-depth understanding of medicine and biomaterials, it is realized that the regeneration process of a damaged cell or a tissue is complex and the interactions between cells and surroundings are crucial for regeneration . T. T450]. Regenerative biomaterials have been developed significantly in recent years , 455–457With the state-of-the-art advances of materials and the in-depth exploration of cell-biomaterial interactions, regenerative biomaterials have achieved exciting outcomes. However, there are still challenges in the field of regenerative biomaterials. In our opinion, there are some critical points that should be carefully considered in the future, as schematically presented in Creation of new materials is the source of innovation in regenerative biomaterials. Molecular engineering allows the precise design of biomaterials. For example, some novel polymeric materials can respond to specific external stimuli via chemical linking of stimulus-generating moieties. The collaboration of chemists and material scientists will be efficient to promote regenerative biomaterials.Modification of existing materials is an effective strategy for improving the material performances. Different types of materials have their own advantages, which can sometimes be unified into one device to improve the entire performance. Advanced techniques of biofabrication of regenerative scaffolds should also be paid attention to . Moreovein vitro and in vivo degradation rates and profiles of a regenerative implant might be different [in vitro [Biomaterial degradation and tissue regeneration are required to be harmonious with each other. Utility of biodegradable raw materials have been the mainstream in the development of many new medical devices and DDSs. Then it is important to regulate the biodegradable profiles , 472. Anifferent , 474, anin vitro , 476. Thin vitro . All of in vivo fate is crucial for a regenerative biomaterial and can be significantly influenced by the host responses [in vivo change of the material itself. Researchers have gradually realized the importance of immunomodulatory effects of regenerative biomaterials [Host responses can significantly influence the clinical outcomes of the biomaterial. Cell-material interactions are particularly important after the concept of ‘materiobiology’ has been put forward . The in esponses . The desaterials . Therebyin vivo examination of the long-term outcome. The translation gap between animals and human seemed to be underestimated previously, and the efficacy of biomaterials between different species might be significantly different in many cases. The authors strongly call for the pertinent R & D centers, and those established large research groups are encouraged to spend more time and money to solve these tough problems and undertake the expensive mission.The long-term outcomes of regenerative biomaterials should be paid more attention to. Since some novel biomaterials just appeared, the long-term outcomes are still inconclusive. More preclinical studies and biosafety evaluation are necessity for R & D of a biomaterial. What is more challenging and expensive is the in vivo dynamic evolution of implanted materials and tissue regeneration are required to be developed. The final goal of biomaterial development is clinical translation. While some methods have been developed to observe and evaluate the degradation process in vitro [in vivo and even clinical data. Without suitable and precise noninvasive monitor approaches, the efficacy of biomaterials in human could not be acquired. These facts remind us of the importance of noninvasive evaluation systems, such as MRI [The noninvasive approaches for monitoring in vitro , the finh as MRI , fluoresh as MRI , ultrasoh as MRI , 485, coh as MRI , positroh as MRI  and X-rah as MRI . More noPublic health emergencies call for more R & D of biomaterials. The situation of the COVID-19 pandemic reminds us that modern human being needs high-value flexible solutions to urgent clinical requirement. In this regard, people and government need a solid foundation of biomaterials to offer the tools for the quick and effective responses to global public health emergency in terms of prevention, diagnosis and treatment of various diseases. A biomaterial particularly worthy of attention is lipid nanoparticle, which has been used in the mRNA vaccine of COVID-19 and recently been well reviewed by Langer and Dong groups . NeverthClinical translation needs to be pushed forward in a full-chain way. In the following years, one of critical directions of the development of regenerative biomaterials is the clinical translation. Without a real application for the benefit of mankind, the biomaterials could only be a work of art albeit exquisite design. For example, nanotechnology has held significant promise in the field of regenerative biomaterials, yet only a few nanomedicines have achieved clinical translation partly due to the limited efficacy in human studies compared with the successful outcomes in animal models . SimilarIn summary, regenerative biomaterials have been an interdisciplinary frontier. More new insights will be shed onto this brilliant field. Artificial intelligence (AI) and brain science will revolutionize human life and global economics  and can


Otoliths are biological crystals formed by a layer of calcium carbonate crystal that adhere to the ciliary surface of the utricular and saccular receptors in the vestibule of all vertebrates inner ear, enabling the utricle and saccule to better perceive the changes in linear and gravitational acceleration. However, the molecular etiology of otolith related diseases is still unclear. In this review, we have summarized the recent findings and provided an overview of the proteins that play important roles in otolith formation and maintenance , providing new insight for the prevention and management of benign paroxysmal positional vertigo (BPPV) with basis for otolith-related proteins as potential biomarkers of vestibular disease. The inner ear consists of the cochlea and vestibular organs, where the cochlea is responsible for hearing while the vestibular organs perceive the movement of the head, essential for spatial orientation and body balance . The vesUnlike bones and teeth which are mainly formed from carbonate hydroxyapatite, otoliths are mainly composed of calcium carbonate crystals . Otolith3 can bind. In the absence of OC90, the matrix-bound calcium on the surface of the vestibular maculae is greatly reduced. In both in vivo and in vitro studies, OC90 has shown to promote the nucleation and growth of CaCO3 crystals . Cochlin is involved in clearing bacterial infections in the inner ear, regulating immunity by physically capturing pathogens in the drum stage and recruiting innate immune cells to protect the normal inner ear structure from inflammatory damage . OverexpOtogelin is a non-collagenous component of the cell-free gel structure covering the sensory epithelium of the inner ear, including the covering membrane (TM) in the cochlea, the membranes of the utricule and saccule, and the cell-free material at the apical part of the semicircular canal jugular in the vestibular organ . The senBoth α-tectorin and β-tectorin are non-collagenous glycoprotein components of the cochlear covering membrane (TM). α-tectorin and β-tectorin form a dense matrix within the TM and are used to cross-link type II collagen fibers to adhere the TM to the helical rim . In addi2+ transport and CaCO3 deposition. The PMCA isoform ATP2b1a is an active calcium transporter protein that is essential for normal development and function of the inner ear in zebrafish larvae, and knockout of ATP2b1a in embryos results in larvae exhibiting homeostasis defects, reduced otolith proliferation, ectopic otolith localization and occasional fusion  channel located at the top of the stereocilia and opened to allow cation influx into the cell, where Ca2+ entering through the MET channel is sequestered by the buffer in the stereocilia and then passed PMCA2w/a pump to and from the endolymph. the PMCA2w/a variant is thought to increase calcium ions near the hair bundle and may be related to the complexity of decidual structures on hair cells in the vestibular system, where the pump also contributes to otolith formation and maintenance  is a calmodulin-sensitive plasma membrane calcium ATPase. The lack of otolith formation is more likely due to inhibition of Cal fusion . The PMCntenance . PMCA2w/ntenance .2+-rich vesicles) in an HCO3– rich environment and undergo conformational changes triggered by ROS generated by NOx3 located in the vesicle plasma membrane. This promotes the nucleation of calcite crystals from calcium supplied by the vesicles and bicarbonate ions from endolymph. In conclusion, Nox is a major otolith component and essential for calcium carbonate crystal formation. However, NOX-derived ROS are also implicated in the pathophysiology of sensorineural hearing loss. The absence of functional NOX3 enhances the recovery phase of hearing after noise trauma. This opens an interesting clinical window for pharmacological or molecular interventions aimed at preventing noise-induced hearing loss (Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOx) represent an important family of enzymes that produce reactive oxygen species (ROS) in a regulated manner for host oxidative defense and redox-based signaling . The acting loss .2 to produce bicarbonate and protons, has been proposed to regulate potassium homeostasis and cochlear potential in the mammalian cochlea. There are 16 known mammalian CA isozymes , which catalyzes the hydration of COisozymes . These Cisozymes . Carboniormation . The CA ormation .This review summarizes the inner ear proteins associated with the development and maintenance of otolith and describes the progress in the study of otolith-related proteins and their association with vestibular-related diseases. Little is known about the molecular processes involved in otolith maintenance and human vestibular pathology. Slow and progressive otolith degeneration is part of the normal aging process and can lead to severe balance disorders resulting in falls in the elderly . OtolithBenign paroxysmal positional vertigo is one of the most common otoconia-related balance disorders, and there are no laboratory indicators available to determine the diagnosis of BPPV . In cont3 crystallization, Cochlin mutations in both human and mouse cause vestibular malfunction  . Consistfunction , while sfunction . Notablyfunction . There afunction  and in afunction , which mfunction . While αfunction . Mutatiofunction . Missensfunction . Mutatiofunction . Interesfunction . These fUnderstanding the function of otolith-associated proteins may provide new ideas for the prevention and diagnosis of vestibular disease and provide a basis for otolith-associated proteins as potential biomarkers of vestibular disease and for conducting corresponding genetic testing. Nevertheless, further research is needed to determine the role of many of the newly identified proteins . NeverthIn the future, it is hoped that more otolith-related proteins will be studied and newer diagnostic or therapeutic ideas will be brought to clinic. It is important to be able to determine the use and utility of each otolithic protein in specific vestibular disorders, as well as to combine functional biomarkers and include evoked potentials of hearing and balance-related tests such as vestibular evoked myogenic potentials (VEMPs), posturography, and rotational chair responses which may provide new insights into the diagnosis, treatment or prognosis of vestibular diseases including Meniere’s disease and BPPV. Revisiting the otolith-associated proteins, focusing on the most clinically applicable studies to fill in the knowledge gaps, and linking them to vestibular disorders related diseases, and exploring possible biomarkers and genetic tests, may be the future direction of this research.SH: data curation and writing – original draft, review and editing. SQ: supervision and funding acquisition. Both 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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The impairment of aesthetic function leads to a decreased quality of life. An unaesthetic smile due to excessive gingival exposure demands, most of the time, a complex treatment in which the objective is the vertical reduction of the amount of exposed fixed gingiva by obtaining a complete exposure of the anatomical crown of the teeth and restoring the ideal dimensions of the biological width. This paper presents a case of a 48-year-old female patient who was unsatisfied with her aesthetics and had disturbed masticatory function due to the absence of some posterior teeth. The cone beam computed tomography was performed to evaluate the facial and dental morphology. The treatment plan included diode laser and piezo-surgery utilization for the frontal area of the upper arch and implants to restore the distal area of the lower and upper arch. Zirconia ceramic was used for the final restorations. This complex and multidisciplinary full-mouth rehabilitation lasted for two years, and the patient was pleased with the result. This case showed that a well-established treatment plan is necessary to obtain long-lasting results. The use of adequate procedures and equipment ensures a predictable result. Inadequate facial aesthetics due to an unaesthetic smile, especially in the case of a gummy smile, with a high smile line, can harm patients’ quality of life, even leading to psychical problems in some cases . The AmeThe treatment procedure depends on the diagnosis and the etiological factors.Aesthetic crown lengthening is one of the most common surgical treatments for a gummy smile. The objective of this procedure is the vertical reduction of the amount of exposed fixed gingiva by obtaining a complete exposure of the anatomical crown of the teeth and restoring the ideal dimensions of the biological width . FollowiDuring the development of the treatment plan, tridimensional imagistic investigations are necessary. Cone beam computed tomography (CBCT) can provide accurate information about the alveolar bone and the periodontal status of the teeth. Measurements can be performed to define the length of the anatomical crown and root, which is necessary to realize the surgery correctly .The greatest desire during the surgery is good visibility, without bleeding in the working area. The diode laser’s most significant advantages are the non-bleeding operative field, tissue evaporation ability, adequate sterilization of the interventional area and minimal postoperative pain and edema .Piezo-surgery offers a promising alternative to bone resection with significant benefits compared to traditional methods. It reduces the bleeding rate by 25–30% because it does not damage the soft tissues or blood vessels, ensuring a clean operating field during the intervention . Its comThe gingival phenotype and the suture technique influence the evolution of the healing process after the surgery .Dental implants have been considered one of the most important discoveries in dentistry in the past decades. In modern dentistry, the implant-prosthetic approach allows the treatment of partially edentulous spaces with fixed restorations, considerably improving the patient’s quality of life . The impThis case report is a full-mouth rehabilitation of a 48-year-old female patient. She wanted to improve her aesthetics, disturbed by the shape and orientation of the upper frontal teeth and the excessive visibility of the gingiva. The patient also reports difficulties in mastication due to the absence of numerous posterior teeth in the lower arch. To establish the preliminary diagnosis, intraoral examinations a and a pThe clinical examination revealed the presence of inadequate metal-ceramic restorations, teeth with unsatisfactory periodontal status (grade I mobility), aesthetical and functional problems. A full-mouth CBCT scan was performed for the final diagnosis and to establish the treatment plan. The treatment objective was to perform full-mouth rehabilitation and improve the smile’s aesthetics by reducing the excessive gingival displacement.A crown-lengthening surgery was planned before the prosthodontic rehabilitation. The long-term success of future restorations is conditioned by accurately reestablishing the vertical dimension and the occlusal plane. The functional rehabilitation of the jaws needed an implant-prosthodontic approach. The treatment plan was established following the patient’s agreement, considering the principles of the Declaration of Helsinki involving humans as revised in 2013. Informed consent was obtained from the patient regarding the treatment, and written informed consent has been obtained to publish this paper.The full-mouth rehabilitation of this case was performed for two years.Based on the CBCT measurements, the postoperative maxillary crown/root ratio was defined . The rigThe surgical pre-prosthetic treatment protocol combines laser therapy with the piezo-surgery to achieve a minimally invasive intervention with reduced postoperative symptomatology. Intraoral mock-ups were created to simulate and individualize future results and to guide the surgery .The old restorations were removed. The surgical guide was realized after the preliminary preparation of the abutments with the vertical preparation technique. During the surgical interventions, the Optragate  retractor was used, which ensured good visibility and adequate access to the working area. The Lasotronix Smart M Pro diode laser  was used for the guiding incisions at the gingival margin, following the cervical line of the mock-up. No elongation was performed at the right central incisor because this tooth needed to be extracted at the end of the surgery. The alveolar bone margins were removed using the Ultrasurgery US-III LED piezo-surgery device  .To obtain long-lasting results, the placement of the margins of the future restorations must be at a minimum distance of 5 mm from the alveolar bone. Therefore, this desirability was considered during the surgery .After performing the surgery and extracting the right central incisor, socket preservation and bone augmentation were done to maintain the alveolar bone dimensions. Provisional restoration was made to restore the aesthetics and function temporarily. Complete healing was achieved after six months. As expected, the results obtained were stable. The gingival contour was exposed but symmetrical and satisfactory during the smile. The final preparation of the abutments was performed with a heavy chamfer finish line, and zirconia ceramic restorations were used for the prosthodontic rehabilitation . The bitAfter the extraction of teeth 15 and 17, two implants were inserted. The osteointegration of the implants can be seen in the panoramic X-ray after six months .Pre-prosthetic treatments were performed on the lower arch during the upper arch healing period. The endodontic retreatments of the lower premolars were successful. The preparation of the teeth was carried out with a subgingivally placed heavy chamfer finish line. Single crown zirconia ceramic restorations and a bridge were realized, preserving tooth vitality in all abutments .For the restoration of the edentulous space on the lower arch, implant therapy was applied. Two implants were inserted.In the case of the upper arch, a screw-retained titanium-based zirconia ceramic bridge was realized after the osseointegration period. The closed impression tray technique was used .A panoramic X-ray was taken to verify the osseointegration of the lower implants (after six months) .Due to the lack of parallelism of the implant bodies, a cemented zirconia ceramic bridge was realized to re-establish the function on the lower arch. In this case, the open-tray technique was used for the impression .The final aspect of the complex, multidisciplinary full-mouth rehabilitation is presented in Several studies have demonstrated the need for these surgical interventions to obtain an aesthetic smile, predominantly in the case of female patients , as in tThe surgical correction of the upper clinical crown:root ratio and gingival displacement was necessary before the prosthodontic approach.The patient’s systemic health and her expectations;The evaluation of the face and smile line;The lip thickness and size;The size and shape of the teeth;The gingival biotype and the width of keratinized gingiva;The thickness and contour of the alveolar bone .According to Narayan et al., the pretreatment planning included a complex clinical evaluation regarding:CBCT evaluation was performed by measuring the existent and the future crown: root ratio and the crestal bone relation to the cementoenamel junction to decide the surgery type.In the presented case a, mock-up guided crown lengthening procedure was performed based on the diagnostic wax-up, similar to the technique described by Jurado et al.  in theirThe crown-lengthening surgery combined two modern, minimally invasive techniques (laser therapy for soft tissue remodeling and piezo-surgery for bone resection) and the conventional technique to obtain long-lasting results with minor post-interventional symptoms and reduced healing time. The methods reduced surgical chair time and operative trauma, accelerating the healing process and making the patient more comfortable. The flapless surgery was undesirable because it did not allow direct visualization of the operative field and can be challenging regarding soft tissue damage . PerformThe thick gingival phenotype of the patient facilitated the healing process. Three months post-operatively, stabile results were obtained, probably due to minimally invasive techniques and the favorable gingival phenotype. The recovery period, a controversial topic in the literature, can differ individually. After soft tissue remodeling, the final rehabilitation can be done after a healing period of three months ,22. AccoAfter this period, the re-preparation of the teeth was carried out with a subgingivally-placed heavy chamfer finish line at a greater distance from the bone margin than 5 mm. Zirconia ceramic single crown restorations and bridges were used for aesthetic and functional rehabilitation. Several studies have been carried out regarding the marginal adaptation of these restorations, which are superior to conventional metal-ceramics ,26. PropIn the literature, different recommendations can be found for the cementation of zirconia ceramic restorations on teeth and implants. Some studies recommend the adhesive cementation technique in case of poor retention of the abutments ,35. OtheIn the case of implants, the fixation method (screw or cement retained) of the restorations might not directly influence their survival rate. However, it can lead to certain complications (mainly periimplantitis) . Each reThe patient was satisfied with the obtained results, even though she still had a moderate gummy smile. The lip-repositioning surgery represents future possibilities for better aesthetical results , as doesThe patient chose a less invasive way to improve the final aesthetics in the future by using hyaluronic acid filler to make the lips look fuller and more youthful.Lack of periodical CBCT evaluation Lack of periodical periodontal evaluation using periodontal probing.The limitations during the follow-up:Digital planning and using a 3D-printed surgical guide can improve the expected results. A good collaboration between a multidisciplinary dental team and a facial plastic surgeon can result in even better aesthetics.The crown-lengthening surgery is an efficient method to improve aesthetics in the case of a gingival smile. Laser therapy and piezo-surgery are modern methods that allow minimally invasive and efficient interventions with fast postoperative recovery. The zirconia ceramic restorations can be used to restore aesthetics and function with good results. Screw-retained restorations have a better long-term prognosis compared to cemented ones, demonstrated by the one-year follow-up Panoramic X-ray.


Ma et al.; Zhang et al., Microbes are significant elements of aquatic ecosystem as they play a critical role in the biogeochemical  cycling pathways, transportation of nutrients, and mitigation of pollutants  Relationship between water quality parameters and microbiome assemblage; (b) Functional microbial communities in different water bodies and sediments; (c) Modeling of ecosystems-based water quality data and microbiome function based multi-omic analyses; (d) Functional microbial communities in activated sludges and biofilms; (e) The relationship between microbial communities in drinking water pipelines and reactors.This Research Topic combined the total of 5 articles to emphasis on the new findings and recent advances in various aspects of microbial ecology . The Research Topic in these papers was performed in seawater intrusion of groundwater, eutrophic water, wastewater and surface sediment in different areas of China and Ireland. Therefore, the purpose of this Editorial article is to reveal the fate of microbial communities under complex environmental and effects of microbial on biogeochemical processes are critical for improving water quality and protecting the health of aquatic ecosystems.Ma et al. utilized the high-throughput sequencing to clarify the microbes inhabiting the groundwater and their response to the seawater intrusion. The authors revealed that the composition and distribution of microbe in groundwater were affected by the degree of seawater intrusion and human activities. Meanwhile, the heterotrophic metabolism of microbes increased with the seawater intrusion, whereas the diversity of microbes was decreased. While the salinity of salinized groundwater was remarkably affected by the changes of tidal, the microbial community structure was not significantly affected. The results also indicated that the varying extents of seawater intrusion and the resulting environmental gradients were the primary factors affecting the diversity and structure of microbial communities in the groundwater of Beihai City.In this topic, Criado Monleon et al. investigated the distinguishing feature of the microbial communities in wastewater treatment systems and deteremined the effects on pre-treatment raw-domestic wastewater microbial communities. The authors revealed the comparative analysis of microorganisms in the on-site wastewater treatment system and pre-treatment of domestic sewage for the first time. Under the same environmental, hydrological and subsoil conditions, the analysis has been carried out in soil treatment units that has been achieved in soil clogging. The research effectively analyzed two microbial communities with different developmental states within soil treatment units at two independent study sites. This study showed that the utilization of pretreatment wastewater indicated significant changes in microbial community structure, which in turn had implications for microbial function, potential risks to public health and the environment.Wei et al. employed the potential of Alcanivorax in the autotrophic carbon fixation and Fe(II)-oxidation. In this study, an in situ enrichment experiment was performed using a hydrothermal massive sulfide slab deployed 300 m away from the Wocan hydrothermal vent. The authors hypothesized that the characteristics and composition of microorganisms living in deep-sea hydrothermal sulfides and seawater may have fostered rich chemoautotrophic or chemoheterotrophic iron-oxidizing bacteria. The results indicated that the strain MM125-6 was capable of autotrophic carbon fixation and Fe(II) oxidization chemoautotrophically. The metabolic function of the iron-rich substrate Alcanivorax genus could be favorable for adaptation to various marine environments. This study was the first to perform autotrophic carbon fixation and Fe(II) oxidation from a hydrothermal vent Alcanivorax spp.Wu et al. clarified the biological erosion of Bellamya spp. shells in the aquatic environment via laboratory level infection culture, validation and in situ microbial community structure analysis. The authors found that biocorrosives could be implanted into the CaCO3 layer of the shell, which created small holes in the shell, reduced the shell density, and led the shell to become fragile. The bioeroders were comprised with two phyla, namely, Cyanobacteria and Proteobacteria. Meanwhile, the interaction between Cyanobacteria and other bacteria promoted the biological function of “shell bioerosion”. The research identified the reason of “shell biological erosion” in aquatic environment, and provided one possible theoretical basis for the prevention and control of aquatic industry. The investigation was helpful to elucidate the cause of biological erosion of the aquaculture environment. This issue found that erosion mechanism of CaCO3 shells was triggered by cyanobacteria-cyanobacteria interaction and proposed a new theoretical basis.Hou et al. evaluated organic matter degradation states and estimated bacterial community structures in sediments. The authors explained the affection of crayfish on organic matter degradation, nutrient cycling, sediment characteristics and bacterial communities. According to the functional annotation of procaryotic taxa analysis, four functional groups related to organic matter degradation were identified between the two groups with significant differences. Their findings showed that P. clarkia remarkably enhanced the oxidation-reduction potential values of sediments and provided favorable conditions for organic matter decomposition. In addition, P. clarkia also changed the composition and role of bacterial communities to increase the capacity for organic matter degradation.HZ, DX, YW, RJ, DL, and PD were topic editors for Microbial Ecology and Function of the Aquatic Systems. All authors contributed to the article and approved the submitted version.


COVID19 has brought several psychosocial stressors that are having an impact on global mental health. The impact of the pandemic on the incidence of First Episode of Psychosis (FEP) is not clear.To describe the clinical and sociodemographic characteristics of FEP patients diagnosed since the onset of the COVID19 pandemic and compare them with the equivalent period of the previous year.We included all FEP patients attended at Parc de Salut Mar  from March 14, 2020 (when the state of emergency in Spain began) to December 31, 2020 with the same period of 2019. We assessed sociodemographic variables, duration of untreated psychosis (DUP), cannabis and alcohol use, psychiatric diagnosis, and psychiatric symptom scales. We performed a univariate analysis between the groups using U-Mann Whitney for continuous variables and Chi-Square for qualitative variables.A total of 20 FEP patients were diagnosed in each period. No differences were found in sociodemographic variables, scales scores or DUP. During COVID19 period there was a smaller proportion of cannabis users  and a tendency of lower weekly consumption . There were more cases of BPD  and less of affective psychosis .During the COVID-19 pandemic we did not find an increase of FEP or more severe clinical presentations. However, we identified differences in the type of FEP that could be related to the psychosocial stressors of this time.No significant relationships.


The occurrence of phenotype switch from an epithelial to a mesenchymal cell state during the activation of the epithelial mesenchymal transition (EMT) program in cancer cells has been closely associated with the generation of invasive tumor cells that contribute to metastatic dissemination and treatment failure. Liquid biopsy represents an emergent non-invasive tool that may improve our understanding of the molecular events leading to cancer progression and initiating the metastatic cascade through the dynamic analysis of tumor-derived components isolated from body fluids. The present review will primarily focus on the applications of liquid biopsy in lung cancer patients for identifying EMT signature, elucidating molecular mechanisms underlying the acquisition of an invasive phenotype and detecting new targets for therapy. Cancer metastases are the major cause of treatment failure in oncology and many efforts have been made to elucidate the molecular mechanisms causing cancer spread and tumor relapse. In this context, liquid biopsy (LB) represents an emergent non-invasive tool that may be helpful to better understand the biology of invasive carcinomas by the analysis of tumor-derived factors isolated from body fluids. Blood is the most widely used sample for LB but other fluids such as saliva, pleural effusions, urine, or cerebrospinal fluid (CSF) may represent an useful source of cancer biomarkers and the anatomical localization of tumors and their biological properties may affect the presence and types of circulating factors detected in the corresponding body fluids , 2. The ex vivo culture of CTCs from patients [CTCs are a very heterogeneous population of cancer cells detached from primary tumors and/or metastatic lesions and released into the bloodstream during cancer progression. In different tumors CTCs may undergo several phenotypic changes causing resistance to therapies and tumor relapse , 16. Thepatients , 19 may EML4-ALK and mutant EGFR associated with the presence of mesenchymal markers [During the last decades, the identification of epithelial markers in CTCs have determined the development of clinically approved methods to detect, isolate and enumerate circulating cells in the blood samples . Althoug markers , 31. The markers .Several lines of evidence supported the concept that the activation of an EMT program in CTCs is characterized by a partial and reversible acquisition of a mesenchymal signature , 27, 29.During tumor growth and progression, the activation of EMT program contributes also to modulate the expression of several genes involved in metabolic pathways . Cancer in vitro from normal human bronchial epithelial cells (HBECs) that, upon EVs internalization, showed the acquisition of a metastatic phenotype. These findings were confirmed by the analysis of exosomes contents that showed the presence of both mRNA and proteins associated with mesenchymal properties such as vimentin [FLI1 promoter. FLI1 is aberrantly expressed in TP53 and RB1 deficient SCLC and is associated with late cancer stages and a high proliferation index Ki67. The analysis of exosomes from blood serum samples showed that the levels of circulating exo-FECR1 in patients with advanced metastatic SCLC were higher than in early stage patients and was associated with poor survival and response to chemotherapy. These findings shed light on the potential clinical implications of the isolation and analyse of the circulating exosomes in cancer patients. Although several additional efforts are needed to improve the exosomes identification and extraction from the circulatory system, several techniques are currently available to isolate them from LB such as ultracentrifugation, size exclusion chromatography, density gradients centrifugation and spin column-based methods [EVs are cell-derived membranous bodies that may be secreted in the biofluids by cells of different tissues acting an autocrine, paracrine or endocrine manner and playing an important role in mediating both physiological and pathological conditions , 50. EVsvimentin . Furthervimentin  that tumvimentin . Furthervimentin . Althougvimentin . In anotvimentin  exosomes methods .EGFR mutations has been recently approved by the FDA [ctDNA and ctRNA are two other relevant classes of biomarkers identified by LB. They are cell-free circulating nucleic acids derived from the primary tumor, metastatic lesions or CTCs and released in the body fluid mainly after the execution of apoptotic program and cell lysis , 62. Hig the FDA . Further the FDA .More recently, besides ctDNA several studies have also focused on the analysis of ctRNA. In particular, among the different molecules of ctRNAs isolated by LB, microRNA (miRNAs) has emerged as a new tool to better understand tumor biology. miRNAs are short, non-coding single stranded RNA molecules that modulate gene expression by targeting of mRNAs. Circulating miRNAs represent a stable blood-based markers for cancer detection  that mayThe circulating tumor-derived proteins represent another class of tumor biomarkers widely used in the past years for non-invasive diagnosis, screening and postoperative follow-up of several types of cancer including prostate, colon, breast and lung carcinoma . In partRecent advances in the field of tumor biology highlighted the extremely dynamic nature of cancer leading to multiple phenotypic changes occurring during the different phases of cancer progression. The occurrence of these events may result in the acquisition of highly invasive phenotype characterized by the expression of EMT markers and stem-like properties. Due to its minimally invasive nature, LB emerged as an innovative approach that may contribute to the dynamic monitoring of tumor behaviour by multiple analysis of tumor-derived biological components. This approach may be particularly useful in lung cancer which is generally detected at late stages and not easy to be analysed by multiple traditional biopsies. LB may identify very early in the time the initiation of the metastatic process, the activation of EMT program along with the acquisition of a stem-like state in cancer cell subpopulations. However, although some diagnostic tests based on LB have been approved for patients, several additional efforts are needed to improve the efficiency of isolation from body fluids of tumor-derived factors and to achieve standardized protocols for clinical applications.


The circadian system is an inbuilt timekeeping mechanism that tracks the 24-h day through the generation of circadian rhythms. Circadian rhythms enable animals to forecast and anticipate regular changes in their environment, and orchestrate biochemical, physiological and behavioral events so that the right process occurs at the right time. The 24 h rhythms generated by circadian clocks are integrated into homeostatic feedback loops and repair pathways. Metabolic and reproductive systems are highly integrated with the circadian timing system and demonstrate reciprocal regulation. Circadian clocks set the timing of circadian rhythms by gathering temporal information from external and internal signals to include light and nutrients. Exogenous and endogenous factors that function as inputs to the circadian clocks can disrupt their timing when applied at unusual and inappropriate times, and are referred to as chronodisruptors. Changes in the natural light-dark cycle perturb the circadian system. Other chronodisrupters include inappropriately timed food intake and physical activity and biological stress. Knowledge of the biology underlying circadian clock timing is critical to understanding how to maximize health and production efficiency of cattle. Here we review circadian clocks and their function in the regulation of metabolic and reproductive systems as well as the consequence of circadian disruption on mammary development and lactation with a particular focus on recent research findings from studies of dairy cows. Knowledge of the biology underlying circadian clock timing is critical to understanding how to maximize cow health and production efficiency. Many modern dairy production systems expose cows to 24 h of light, activity and feed availability. These management factors can impact the temporal organization of an animal’s physiology and affect their welfare and production efficiency. Timing of behavior and physiology underlies health and homeostasis . CentralHere we review circadian clocks and their function in the regulation of metabolic and reproductive systems as well as the consequence of circadian disruption on mammary development and lactation with a particular focus on recent research findings from studies of dairy cows. Cows like all mammals show seasonal and daily variations in the timing of physiology and behavior. Metabolic and reproductive status interact and affect these variations, and are realized in the daily and seasonal rhythms of milk yield and composition. Knowledge of the biology underlying circadian clock timing is critical to understanding how to maximize cow health and production efficiency.input (zeitgebers) and a way to receive temporal information , (2) the core molecular clock that generates circadian rhythms of gene expression, and (3) output or clock controlled genes  ed genes .BMAL1 (aka ARNTL) and CLOCK are the positive elements of the feedback loop. The BMAL1:CLOCK heterodimer functions as a transcription factor that drives the expression of clock controlled genes, including their own negative regulators Period (PER) and Cryptochrome (CRY) genes. Upon translation PER and CRY proteins heterodimerize and prevent the binding activity of the BMAL1:CLOCK transcription factor to the enhancer box sequence  in the promoter region of clock controlled genes, shutting down their own transcription and decreasing transcription of other genes. Molecular redundancy exists for all core clock genes with three PER  and two CRY  genes, and paralogues of BMAL1 and CLOCK being BMAL2 and NPAS2. The redundancy likely reflects the importance of circadian clocks to fitness and survival of the animal (REV-ERBA and RORA. RORA and REV-ERBA encode proteins that compete to bind the retinoid acid receptor response element (RORE) in the promoter region of the BMAL1 gene. RORA activates while REV-ERBA represses BMAL1 expression. The periodicity of the core clock transcription-translation feedback loop is about 24 h  is the primary input to the SCN. Activity, stress, fasting-feeding and nutrients also serve as inputs to the SCN. Moreover, information on metabolic state arrives to the SCN from sympathetic and parasympathetic branches of the autonomic nervous system and hormones and nutrients, such as glucose, that cross the blood-brain barrier . Non-phopression . In addipression .Seasonal changes in light drive changes in phase relationship among the core clock genes in the SCN . By detePER1 and PER2  are highly predictable and provide the primary environmental cue of seasonal changes in food availability and climate . Dairy cSeasonal changes in physiology are regulated at the cellular level by changes in core clocks across the entire animal, with studies showing that changes in photoperiod alter core clock genes expression rhythms in the SCN, pituitary and liver , as wellMultiple investigations have aimed to determine if changes in hormonal milieu reflective of seasonal changes can mimic the photoperiod responses in cattle. Melatonin administration by feeding or implants failed to mimic or only partially mimicked photoperiod responses in production output variables e.g., . Thus, aSimilar to circadian rhythms, circannual rhythms persist even in constant conditions. Thus, the annual rhythms of production are innate to animals. A better understanding of mechanisms that generate seasonal rhythms and responses of tissues to these changes will help in developing novel feeding and reproductive management practices that synchronize with physiological systems of production animals. Current knowledge also needs to be applied to analyzing the effects of changes in feed management on milk production performance within the context of annual rhythms. As an example given by the Harvatine group, 3.6% milk fat may indicate suboptimal milk fat in January but normal milk fat in July. Whereas feeding a dietary supplement in July may appear to improve milk fat percent in the following months. However, the increase in fat may actually be due to the annual rhythm of milk production .The circadian system coordinates daily patterns of feeding, energy utilization and energy storage across the 24 h day . MetabolAt the cellular level circadian clocks interact with nutrient-sensing pathways and nuclear receptors to respond to fasting and feeding states of the animal. Oral administration of short chain fatty acids to mice caused phase changes in the peripheral clocks located in the liver, kidney, and submandibular gland . This shEpidemiological studies of humans have linked circadian disruption with development of diabetes, obesity, and cardiac disease . ExperimEating, rumination, and rumen pH of dairy cattle show exhibit daily rhythms . MultiplRestricted feeding induces food anticipatory activity which is characterized by an increase of locomotor activity, a rise in core body temperature, and elevated serum corticosterone in rodents. Ruminants also show food anticipatory activity, as circadian rhythms of activity and temperature similarly shifted in response to timed meal feeding in sheep and goats . Our stufatty acid synthase (FASN) and acetyl CoA-carboxylase (ACACA) in the mammary gland . Analysis of genes related to changes in carbon flux ratios indicated that propionate was preferentially used for energy generation rather than gluconeogenesis in cows with disrupted circadian rhythms. Rodents exposed to circadian disrupting environments also exhibited a decreased capacity for gluconeogenesis , there is no detectable luteinizing hormone (LH) surge  surge . In wildH) surge . When miIn humans, circadian disruption has been linked to reproductive dysfunction and subfertility . Women rStudies of the impact of circadian disruption on ruminant reproduction are limited, but existing data suggest that exposure to chronodisruptors decrease reproductive competence. The endocrine milieu of late pregnant ewes and their fetuses was significantly altered when transitioned to constant light for 48 h compared to control groups that remained on 12 h light-12 h dark cycles. The constant light increased levels of follicle-stimulating hormone and estradiol and decreased progesterone levels in both maternal and fetal circulation . Low levCircadian clocks are also important to timing parturition. In mammals, labor preferentially occurs during the rest phase of the day, which translates into labor at night in diurnal species . The mecMajor changes occur in the physiology and behavior of females at the onset of pregnancy and lactation . Among tCircadian rhythms of hormones also become attenuated during lactation. Basal prolactin levels are elevated in rats during peak lactation, and the circadian rhythm of prolactin observed during estrous cycles is lost in lactating animals. Diurnal variations in ACTH and corticosterone remain in lactating rats, however relative to virgin animals, rhythms are attenuated with elevation in trough levels . LactatiARNTL (a.k.a. BMAL1) and NPAS2 —are core clock genes , SREBF1 (sterol regulatory-element-binding protein 1), and FASN (fatty acid synthase) genes all showed circadian rhythms during lactation (BMAL1 and PER2 showed circadian patterns of expression in RNA isolated from milk fat globules in ewe’s milk which correlated with circadian changes in expression of acetyl-CoA carboxylase (ACACA) as well as percent milk fat . Deletion of BMAL1 in mammary epithelial cells led to decreased ability to form acini in 3D cultures. Together indicating multiple ways in which circadian clock disruption has the potential to impair mammary development and the signaling needed to initiate the timing of the onset of lactogenesis, milk synthesis, and maintenance of tissue homeostasis, which is important to lactation persistence.Studies of circadian regulation of reproduction in the ostnatal . Death wer bouts , which iestation . Studiesestation . Milk yiestation . Our stuestation . ChIP-seestation . MoreoveThe circadian system enables animals to follow time. This ability is important for the temporal separation of incompatible processes and the maximal efficiency of others. There is a growing understanding of factors that affect circadian clock function. These factors include light, season, nutrition, and stress as well as reproductive status of the animal. Although more work needs to be done, current dairy systems should consider these factors in determining how they impact production efficiency and welfare of cattle. More knowledge and application of this knowledge may lead to better scheduling of daily management practices that are consistent with the cows’ physiology and behavior, as well as interpretation of production data in relation to the time of year. Knowledge of daily patterns of cow behavior and physiology can help in the identification of disturbances in the system that may be related to reproductive events or indicative of disease. Limiting exposure to factors that disrupt circadian clocks, especially when cows are metabolically challenged may be particularly important to minimizing the risk for disease, it may also potentially increase reproductive efficiency.


The knowledge of anatomy is essential for surgical safety and impacts positively on patients' outcomes. Surgeons operating on the liver and bile ducts should keep in mind the normal anatomy and its variations as the latter are common.We conducted a structured surgical dissection course of the supra-colic compartment of the abdominal cavity on 2nd and 3rd October 2020. While dissecting a 46years-old male cadaver, we encountered unusual anatomical variations of the hepatic arterial branching, the biliary tree, and arterial supply to the common bile duct. The common hepatic artery was dividing into two branches: a common short trunk for the left hepatic artery and the right gastric artery (hepato-gastric trunk) and a common trunk for the right hepatic artery and gastroduodenal artery . The right hepatic duct was duplicated with a main right hepatic duct and an additional smaller duct. The bile duct was supplied by an artery coming from the abdominal aorta.We described three unusual anatomical variations: a variation of the hepatic arteries branching pattern, an aberrant right hepatic duct, and blood supply to the bile duct from the abdominal aorta. Surgeons should be aware of these rare variations. Sound knowledge of normal anatomy and its variations is fundamental to hepatic and biliary surgery Hepatic arterial anatomy also has many variations, and these are highly relevant for radiological and surgical interventions. Michel's classification Additionally, the extrahepatic biliary tract frequently presents with varied anatomy, and the classical configuration of hepatic ducts is described in 60% of the population We report a case of unusual hepatic artery and bile duct anatomical variations encountered during a cadaver anatomy dissection course. This course was delivered to surgery residents at the University of Rwanda, Clinical Anatomy Laboratory on October 2nd and 3rd, 2020 in Huye Campus, Rwanda. The surgical dissection course was designed by the Clinical Anatomy Unit in collaboration with the Department of Surgery. Trainers included consultant surgeons and anatomy experts. The dissection course received approval and accreditation from the Rwanda Medical and Dental Council.Dissection was performed on a 46-year-old male deceased a year back from an unknown cause. The cadaver was embalmed through the femoral artery by injecting five liters of Dr Dankemeyer solution (a formula available at the laboratory) and conserved in the freezer up to its use. The dissection was about the supra-colic compartment of the abdominal cavity, which was accessed using three conventional incisions of the abdomen: a supra-umbilical median incision and two oblique incisions from the umbilicus to the anterior superior iliac spines. While dissecting the celiac trunk and its branches, we found the celiac giving, as commonly observed, the left gastric artery, the common hepatic artery, and the splenic artery.Contrary to what is commonly seen, the common hepatic artery was dividing into two branches: a common short trunk for the left hepatic artery and the right gastric artery (hepatogastric trunk) and a common trunk for the right hepatic artery and gastroduodenal artery  . The rigThe bile duct was supplied by an artery, the biliary artery, coming from the abdominal aorta passing between the inferior vena cava and the portal vein. This biliary artery was dividing into two branches, the superior biliary branch that supplied the proximal part of the bile duct and the inferior biliary branch that supplied the distal part of the bile duct .In addition, the bile ducts branching presented an unusual pattern. The right hepatic duct was duplicated, a main right hepatic duct, and an additional much smaller duct. The main right hepatic duct was fusing with the left hepatic duct to form the common hepatic duct. The additional (aberrant) right hepatic duct fused with the cystic duct to form a short hepatocystic bile duct which joined the common hepatic duct to form the common bile duct . The calFailure to recognize anatomic variations while performing procedures in the hepatobiliary region can result in major complications. Therefore, clinicians should master the relevant surgical anatomy before engaging in procedures involving the liver and biliary tree in order to minimize adverse outcomes. We are reporting three uncommon variations: variation of the hepatic arteries, variation of bile ducts branching pattern, and the blood supply to the common bile duct from the abdominal aorta. Radiologists and surgeons need to be acquainted with these rare variations.In the present case, we observed a common hepatic artery that divided into two trunks: the hepato-gastric trunk (for the left hepatic artery and the right gastric artery), and the hepato-gastroduodenal trunk . The proper hepatic artery was absent. As the right and left hepatic arteries are branches of the common hepatic artery, which in turn rises from the CT, our case can be classified in the Michel's and Hiatt's type I categories Another variation we found in the current case is an aberrant right hepatic duct which joined the cystic duct to form a short duct that drained into the common hepatic duct.As a result, the content of the Calot's triangle included this aberrant right hepatic duct. Previous reports show that anomalous ducts are quite common, occurring in 12% of cases on average The third variation we observed was blood supply to the common bile duct from an artery originating directly from the abdominal aorta. Usually, blood supply to the bile duct comes from branches of the gastroduodenal artery, right hepatic artery, and cystic artery Our findings carry numerous surgical implications. Firstly, surgeons performing procedures on the liver, biliary tree, and upper gastrointestinal tract need to look out for anatomic variations as they are common in this region. Meticulous dissection and proper identification of structures before any clamping and division are always warranted. Furthermore, pre-operative imaging studies such as computed tomography (CT) angiography and magnetic resonance (MR) cholangiopancreatography should be done as indicated to guide operative planning Lastly, Calot's triangle is a very important landmark during both open and laparoscopic cholecystectomy. The presence of variant anatomy increases the risk of biliary and vascular injuries, more so during laparoscopic procedures


Ghana adopted the 2012 World Health Organization (WHO) policy on intermittent preventive treatment of malaria in pregnancy (IPTp) and implemented it in 2014 in all regions of Ghana. Despite the implementation of this policy, there has been an unacceptably low percentage of eligible women receiving the optimal dose of IPTp in Ghana which leaves millions of pregnant women unprotected from malaria. The study, therefore, assessed the predictors of three or more doses  of sulfadoxine-pyrimethamine (SP) in Northern Ghana.A cross-sectional study was conducted among 1188 women in four selected health facilities in Northern Ghana from September 2016 to August 2017. Information on socio-demographic and obstetric characteristics reported SP use, and maternal and neonatal outcomes were collected which was double-checked from the maternal health book as well as the antenatal care register. Pearson chi-Square and ordered logistic regression were used to determine the predictors of reported optimal SP use.Out of the 1146 women, 42.4% received 3 or more doses of IPTp-SP as recommended by the national malaria control strategy. SP uptake was significantly associated with antenatal care (ANC) attendance , primary education , four or more antenatal care visits , ANC care visit in second trimester  and third trimester  and malaria infection during late gestation .The percentage of pregnant women who received three or more doses is below the target of the National Malaria Control Programme (NMCP). The push factors for the optimal use of SP are higher educational attainment, four or more ANC visits, and early initiation of ANC. The study also confirmed earlier findings that IPTp-SP uptake of three or more doses prevents malaria in pregnancy and improves birth weight. The uptake of IPTp-SP among expectant women will be informed and increased by encouraging formal general education beyond the primary level and encouraging early initiation of ANC visits. Pregnant women and their unborn babies are exposed to several harmful diseases including malaria which remains a global public health problem . The mos-endemic areas of the world suffer yearly from malaria-related infant mortalities in the region of 75,000 and 200,000  and gave birth to low-birth-weight babies  were less likely to have taken the optimal dose than those who had no malaria in pregnancy and gave birth to normal weight babies. These findings support the argument that using an optimal dose of SP is still effective in preventing malaria in pregnancy , 27 and The study used a cross-sectional study design, which has the disadvantage of making it impossible to infer causation. Again, there was the possibility of the women reporting the usage of IPTp inaccurately. However, these women were interviewed while they were still on admission and the information given was double-checked from their maternal health care records as well as the ANC register book at the various facilities.According to the findings of the study, early initiation of ANC and four or more ANC visits during pregnancy increased the uptake of the optimal dose of SP. Postpartum women who had late gestational malaria and had low birth weight babies reported low SP uptake. Women with a primary education who were enrolled in ANC during the second and third trimesters reported less use of SP as an intermittent malaria preventive treatment in Northern Ghana. This study emphasizes the importance of expanding general education beyond primary school and encouraging early ANC visits to increase coverage of the recommended IPTp-SP uptake among pregnant women, thereby preventing gestational malaria infection and improving birth weight.


This paper contributes to the literature on marine conservation and its implication for coastal governance and sustainability. The study investigates factors influencing fisherfolk compliance with the temporal fishing bans in Ghana. The purpose is to understand the factors influencing compliance behaviour to help design an improved conservation strategy to achieve management objectives. A mixed-method approach was employed, consisting of 200 household surveys and 17 in-depth interviews with stakeholders at the local, district, regional, and national levels. The results reveal that a combination of instrumental and normative factors influences fisherfolk’s compliance behaviour concerning the closed fishing season. Participation of fisherfolk and coastal communities in the fisheries management decision-making processes positively influenced compliance. The key drivers of non-compliance with the closed season emanate from a perceived lack of ecological effectiveness, lack of enforcement of sanctions, and lack of compensation for loss of income during the ban. The study suggests co-management that includes fisheries agencies and traditional authorities as a viable option for fisheries management and marine conservation initiatives. In addition, the paper recommends the introduction of conservation payment schemes alongside strict monitoring of the temporal ban on fishing. Small-scale fisheries (SSF) are vital in providing food security in Africa. An estimate shows that approximately 200 million Africans rely on fish as their primary source of animal protein, with another 90 million depending on fisheries as part of a diversified livelihood strategy Motta, . In receIn Ghana, the SSF classification is based on the type of gear the canoes operate; the most common are: purse seine, hook and line, drift gillnet, beach seine, and lobster set net. SSF target both pelagic and demersal species. The ones targeting high-value large aquatic and demersal species  use hook and line and, drift gillnets. In contrast, others target mackerel, cassava fish, herrings, barracuda, and lobsters using pursing and lobster nets. Canoes with 25–40 horsepower outboard motors and electronic devices such as Global Positioning Systems (GPS) and echo sounders can travel further offshore to exploit high-value species. Fishers who travel further distances offshore use ice to preserve the fish caught whilst staying at sea for 2–4 days  of Ghana’s coast.In response to the reduced marine fish stock, the Ministry of Fisheries and Aquaculture Development (MoFAD) implemented the closed fishing season policy in 2019 in consultation with diverse stakeholders, including the coastal fishing communities, NGOs (e.g. Friends of the Nation and Hen Mpoano), and civil organizations . MoFAD is responsible for managing fish and other related fisheries products in Ghana. The Fisheries Act 2002 (ACT 625) and the Fisheries Management Plan (2014–2019) are two significant elements of the fishery management framework with specific policies that promote the sustainable harvest of marine resources. Since 2019, three closed fishing seasons have been enforced for the SSF sector. The first closed season was implemented between May 15 and June 15, 2019. The other two closed seasons were implemented in July 2021 and 2022. The closed season was not implemented by the authorities in 2020 due to COVID -19 pandemic  and burrito (Brachydeuterus auritus)  MoFAD, .Sarinellas) dominate the area, but occasionally the billfishes are also landed by the drift gill operators  were conducted with community leaders (n = 12), government officials (n = 4), and NGO officials (n = 1) to gain insights into the level of compliance.The study used a mixed-methods approach to investigate fisherfolks’ compliance with the closed-season policy. The empirical data consist of a questionnaire survey of 200 SSF-dependent households and 17 interviews with stakeholders in the fisheries sector. The surveys and interviews were conducted between September and October 2021. The surveys were conducted in the communities of Apam in the Gomoa West District and Winneba in the Effutu District. The individual in-depth interviews  and sustained engagement after the enforcement of the closed season. Fisherfolk mentioned that they interacted with the local fisheries leaders and municipalities. According to survey respondents, the regional fisheries leaders and municipal fishery officers cautioned them to desist from fishing during the ban and abstain from using unapproved gear for fishing. They reported that this interaction occurred during the distribution of compensation packages.Five main factors were identified regarding compliance with the temporal ban on fishing. These include; awareness and knowledge of the closed season, participation in the decision-making process before the implementation of the ban on fishing, involvement in the decision-making process during the ban on fishing, awareness of sanctions for breaching the ban on fishing, and acceptance of the closed season by traditional authorities. The results from Table A council, including the chief Fisher, chief fish trader, and selected canoe owners, represents all fishermen at various stakeholder engagements, where they convey the views of the local people to authorities .No fisherman from here ever dared to go to sea during the ban on fishing. The government placed the ban, and whether you like it or not, we have to obey, so everyone here complied with the closed season during the implementation .The first statement below illustrates the representation of fisherfolk in the decision-making process, and the second statement shows that community leaders expect fishers’ to comply with government policies:These findings are consistent with results from previous studies . The presence of laws is a deterrent to people who think of committing a crime. Sanctions are a deterrent only when perceived as more costly than the potential gains of breaking the law. Guirkinger et al. .The acceptance of the closed season by community leaders  positively influences the compliance of fisherfolk . However, fisherfolk disagree  with the assertion that temporal bans on fishing would contribute towards rebuilding the declining fish stock. This could negatively affect the effectiveness of the regulation because knowledge of relevance influences the effectiveness of policies  of the factors listed stimulating compliance with the fishing ban. The chi-squared test shows a positive relationship between closed-season compliance and compensation for not fishing . The significant association between closed-season compliance and payment for not fishing suggests that the closed-season policy would be successful when compensation packages and schemes are in place to support fisherfolks. Table Survey respondents complained about the lack of compensation schemes during the fishing ban. Most fisherfolks said they did not receive compensation from the government during the prohibition of fishing. The availability of compensation schemes received one of the lowest mean scores . Various studies have found that Ghana’s fisheries regulations are not efficiently enforced . The enforcement of fisheries regulations and fairness in applying the law are principal factors influencing fishers’ compliance with conservation initiatives (Al-Subhi et al., Respondents disagreed with the statement indicating that sanctions for breaching the closed season are enforced (Even though the findings from this study cannot be assumed to represent the situation in other coastal communities in Africa, the results provide two vital implications for marine conservation and coastal livelihood development. These are the co-management of conservation initiatives and the introduction of conservation payment schemes.A co-management -made up of fisheries agencies and traditional authority committee members is a viable option to govern resources such as the ocean. The conventional conservation values and norms held in the community could result in high social acceptance of marine conservation-leading to the sustainable harvest of marine resources. It is worth mentioning that national fisheries agencies must demonstrate the political will to enforce sanctions on illegal fishing activities. Conservation measures are ineffective if they are not aligned with local development needs and complemented by a continuous drive toward reducing illegal fishing (Macusi et al., The study suggests the introduction of conservation payment schemes alongside strict monitoring of the temporal ban on fishing. The conservation payment schemes could be in the form of cash payments or food items such as rice, sugar, cooking oil, etc., to cushion fishing households during the temporal ban on fishing. The Fishery officers must target the most vulnerable fishing households to achieve the objective of fisheries management (Bladon et al., This paper investigated the factors influencing fisherfolk behaviour concerning compliance with fisheries regulations. The results reveal that a combination of instrumental and normative factors affects fisherfolk’s compliance behaviour concerning the closed fishing season. Participation of fisherfolk and coastal communities in the fisheries management decision-making processes positively influenced compliance.The key drivers of non-compliance with the prohibition on fishing emanate from a perceived lack of ecological effectiveness, the lack of enforcement of sanctions, and the lack of compensation during the ban on fishing.This study focused mainly on two fishing communities in the Central Region of Ghana. Thus, future studies can consider multiple case study sites of coastal areas across the country using qualitative and quantitative approaches. Future studies should consider a comparative analysis of compliance behaviours between the SSF and industrial trawlers.


Attachment theory provides a conceptual framework to understand the impact of early child–caregiver experiences, such as loss or separation, on adult functioning and psychopathology. In the current study, scenes from the Adult Attachment Projective Picture System (AAP), a validated, commonly used standardized diagnostic instrument to assess adult attachment representations, were used to develop a short fMRI assay eliciting the neural correlates of encoding of potentially hurtful and threatening social situations such as social losses, rejections or loneliness. Data from healthy participants (N = 19) showed activations in brain areas associated with social cognition and semantic knowledge during exposure to attachment-related scenes compared to control scenes. Extensive activation of the temporal poles was observed, suggesting the use of semantic knowledge for generating social concepts and scripts. This knowledge may underlie our ability to explain and predict social interactions, a specific aspect of theory of mind or mentalization. In this replication study, we verified the effectiveness of a modified fMRI assay to assess the external validity of a previously used imaging paradigm to investigate the processing of emotionally negatively valenced and painful social interactions. Our data confirm the recruitment of brain areas associated with social cognition with our very short neuroimaging assay. Research on human attachment has provided evidence on the importance of the child–caregiver relationship in the development of personality functioning and in psychopathology  in concAn evolving research area has focused on the identification of cortical substrates of adult attachment representations using functional imaging . The resAn issue raised in previous imaging studies concerns the cortical substrates associated to exposure to the drawings of the Adult Attachment Projective Picture System (AAP) , a validAn issue emerging from these neuroimaging studies is the relationship with studies explicitly investigating the neural correlates of loss or mourning ,13, whicwww.neurosynth.org; [The present study had three aims. First, as noted, we were interested in verifying the replicability of our previous study (AAP here). Second, we were interested in identifying the neural substrates that may be shared with those activated in studies of negative emotion and the substrates specific to the attachment-related scenes, as well as with studies of social cognition more generally. To this end, we applied a quantitative decoding approach by comparing our fMRI results with the data of the Neurosynth database  using tnth.org; ,18. Thirnth.org; . BesidesThe initial sample consisted of 21 healthy participants recruited through local announcements. Two participants interrupted the experiment while in the scanner. The final sample comprised n = 19 , and participants’ mean age was 24.16 years (std. dev. = 4.66). Depression severity was assessed using the computerized German Version of the Centre for Epidemiologic Studies Depression Scale . The prThe stimulus set was taken from the Adult Attachment Projective Picture System (AAP), a semi-standard interview to assess adult attachment representations . The oriThe control condition included eight drawings of non-attachment-related scenes carefully matched with the attachment-related AAP drawings of the original set of pictures. The first seven control scenes were obtained by manually redrawing aspects of the original AAP scenes to replace the elements that would have activated the attachment system with neutral elements while preserving the spatial arrangement and the shape of the objects as closely as possible. For example, reaching out hands to be embraced in the AAP scene was replaced by outstretched hands manipulating an object . All data were acquired in a single run consisting of 4 blocks of scenes . In each block, four scenes were shown consecutively for 3 s for a total duration of 12 s for each block. These blocks were separated by 4 blocks presenting scrambled scenes of the same duration. The whole experiment required 1 min 39 s, including a trail-off interval of 3 s, resulting in 50 scans per experiment.MR images were acquired using a 3 T Prisma system  located on the premises of the Department of Psychiatry and Psychotherapy at the University of Ulm. Functional data were acquired using T2*-weighted echo-planar imaging sequence (EPI) sensitive to the blood oxygen level-dependent (BOLD) signal .www.fil.ion.ucl.ac.uk/spm, accessed on 1 March 2012) in MATLAB . For each participant, data were realigned to the first image of the series and re-sampled to a voxel size of 2 × 2 × 2 mm and normalized to standard MNI space. They were subsequently spatially smoothed with an 8 mm full width at half-maximum (FWHM) Gaussian kernel.Functional images were processed with SPM8  and six regressors obtained from realignment to model head motion confounds. Estimates of the contrast image attachment-related vs. neutral from all participants were entered into a second-level analysis, where full brain activations were thresholded voxel-wise at http://people.cas.sc.edu/rorden/mricron/index.html, accessed on 11 September 2019).From the technical point of view of the study design, the effectiveness of a short paradigm is made plausible by the fact that in a repeated measurements setting, variance ensues at two different levels: between scans and between subjects. Here, notwithstanding the brevity of the paradigm, there were fifty scans at the first level, which are multiplied by the number of subjects at the second level for estimates of the precision of between scans effects , suggestt-map of our main contrast from 19 participants. Neurosynth is a valuable open-source web-based database for human neuroimaging research that aggregates activation coordinates from tens of thousands of published fMRI studies and published papers and compiles thematic maps based on their spatial distribution [https://neurosynth.org) uses text mining and meta-analysis techniques to create accurate mappings between the brain activation patterns and peak signal coordinates in the database with associated topics.After the fMRI data analysis, we used the Neurosynth decoding tool to extract relevant topics generated from the resulting ribution . The Neut-statistics map (after removing negative coefficients) to NeuroVault [t-map and the term-based statistic maps extracted from Neurosynth database. This correlation was used by Neurosynth to create a ranked list of terms arising from previous studies activating the same regions. In the next step, all anatomical and methodological terms were excluded from this list . Two raters evaluated the resulting list and selected by consensus the most relevant hits from the Neurosynth terms, revealing the following domains: social cognition, the default mode network, memory, semantic and language/music.Taking a reverse inference approach, we first uploaded our main contrast uroVault ,18. NeurThe contrast attachment vs. neutral revealed significant activations in associative areas such as the right superior temporal gyrus .The right medial portion of the same contrast showed a significantly greater activation in the middle/posterior cingulus (cluster #5) and in the adjacent cuneus/precuneus (cluster #6).In the contrast control vs. attachment, there was a significant effect on the right hemisphere in the primary visual cortex .To provide valid reverse inference into the mental and psychological processes, we performed functional decoding of the results of the main contrast of our fMRI data from the entire sample. We used the Neurosynth decoder function to assess the similarity of the activation of the non-thresholded result map of our main contrast without negative values generated for the entire set of terms included in that database .Decoding analysis revealed that the regions identified by the map of the main contrast, attachment vs. control, had two main areas of association . One refExposure to attachment-related images was associated in our study with a cluster of bilateral activations in temporoparietal areas . More anteriorly, the temporal poles were also active. A second group of activations was detected in the medial portion of the brain (posterior cingulate and precuneus). These areas are predominantly described in the literature as being of associative nature, and include neural substrates of social cognition as reported in previous studies of encoding of human actions, feelings or postures from exposure to attachment-related scenes ,14,27,28When considering previous studies concerned with representations of attachment more specifically, we found correspondence between the areas detected here and those reported in the literature. A recently published fMRI study by  examinedThe parietal operculum has been shown in FMRI studies and in studies using electrical stimulation to host the secondary somatosensory cortex, SII ,36,37,38The middle and superior temporal gyri have been shown to be involved in encoding visual features of bodies and bodily motion  and neurRelative to a study of exposure to explicit mourning scenes , which uSchurz and colleagues (2021) recently published a meta-analysis of neuroimaging studies of social cognition and empathy, in which they provide evidence for a model of social cognition in a multilevel approach with a hierarchical structure. Their data suggest the existence of three groups of processes involved in social cognition: cognitive, affective and a combination of both cognitive and affective processes. The cognitive cluster from their meta-analysis  revealedThese findings suggest that attachment-related material prevalently recruited cortical areas associated with cognitive components of social cognition. Similar activations  described as a mentalization network were also prevalent in the findings of a study in a sample of children exposed to the AAP scenes, where areas associated with emotional processing were detected only as individual differences among attachment classifications . In receThe present study also addresses the issue of reproducibility and replicability of our paradigm and provides information on the effectiveness of a short fMRI assay. The importance of verifying replicability of neuroimaging effects is being increasingly recognized, especially in the context of prospective clinical applications . The potSeveral limitations of the present study should also be considered. Notwithstanding replication of group effects in these studies, it is important to stress that in clinical applications, replication of individual differences would be important. We could not assess this aspect of replication here since the participants differed between the present and previous studies. Furthermore, estimates of sample sizes to achieve reliable results in such individual effects would also be required.In summary, exposure to the AAP scenes with this study design elicited the activation of neural substrates of the cognitive component of social cognition, including those concerned with the encoding of mental states of others, and of the Rolandic/parietal operculum and precuneus, which may relate to encoding painful experiences such as those related to loss. This novel paradigm may be of use in composite fMRI batteries for the assessment of intermediate phenotypes referring to the neural processing of social interactions with negative emotional valence.