Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) pose increased morbidity and mortality, especially to elderly patients. The effect of anesthesia is debatable. The databases of PubMed, EMBASE, Google Scholar, Cochrane Library and Web of Science were searched from inception until 24 February 2022 to identify randomized-controlled trials (RCTs) studying the effect of depth of anesthesia on POD and POCD primarily. Data on length of hospital stay and mortality were also extracted. Trial sequential analysis was also performed. Seventeen studies were eligible for systematic review and 15 studies of 5392 patients were eligible for meta-analysis. High bispectral index (BIS) favored a reduction in POD and POCD at three months. We found no significant difference between High BIS and Low BIS for mini-mental state exam (MMSE) score and POCD on day 7. However, this did not translate to a significant difference in length of stay and mortality. The data was also underpowered and heterogeneous. Future RCTs should focus on high-risk patients. A standardized methodology of reporting postoperative delirium and cognitive dysfunction is needed to improve comparisons across trials. With developing countries having an increasing burden of elderly patients, the average age of patients undergoing anesthesia and surgery has increased dramatically. Postoperative cognitive dysfunction (POCD) and postoperative delirium (POD) are more common in the elderly, occurring in up to 65% of older patients , 2. PostMultiple risk factors have been identified for POD and POCD. Besides increasing age that we have just mentioned, fewer years of education, depression, and organic brain disease, e.g., lacunar infarct -8 are alMultiple randomized controlled trials (RCTs) have been performed to assess the effects of anesthesia depth on POCD and POD, but the evidence of the influence of anesthesia technique on POCD and POD is still debatable. Recently, Kunst et al.  found biThe present study aimed to assess the relationship between the depth of anesthesia and POD, POCD, mortality, and length of hospital stay. We performed a systematic review of all comparative studies and updated the current literature with a meta-analysis that included the results of the aforementioned study. We evaluated the results with the trial sequential analysis (TSA) method to assess whether the current evidence was conclusive.MethodsSearch StrategyThe meta-analysis and systematic review followed PRISMA guidelines . We searched PubMed, EMBASE, Google Scholar, Cochrane Library and Web of Science from inception until 24 February 2022 for relevant results, using a combination of specific keywords and terms, including “anesthesia depth”, “postoperative delirium” or “POD”, “postoperative cognitive dysfunction” or “POCD”, “BIS” or “bispectral”. We then scanned the reference lists and citations of the studies and any other relevant systematic reviews for further results.Inclusion and Exclusion CriteriaStrict inclusion and exclusion criteria were applied. For the systematic review, we included all RCTs and well-performed prospective studies on the effects of anesthesia depth on POCD and POD. We only included studies of patients aged over 60. From these studies, we only included the studies where patients were divided into statistically significant High and Low BIS values for the meta-analysis. Only traditionally published journal articles in English were included.We excluded studies that did not report the primary outcomes, and non-traditional articles including reports, audits, editorials, commentaries, conference reports, and abstracts. Non-English language articles were excluded due to the lack of manpower and budget for professional translation services.Data Extraction and Quality AssessmentBoth authors (Ling and Yang) assessed all the studies independently and evaluated them using the Cochrane Collaboration risk-of-bias tool to assess for selection bias including random sequence generation and allocation concealment, performance bias such as blinding of participants and personnel, detection bias such as blinding of outcome assessment, attrition bias due to incomplete outcome data and reporting bias. Data extraction was also done independently. We categorized the risk of bias as high risk, low risk, or unclear. Disagreements in the process were referred to another investigator (Lee) for review and discussion.We screened the included studies and extracted the data, and summarized it as a systematic review table. The patient characteristics, study characteristics as well as outcome data were tabulated using standardized forms. The appendices of the studies were checked for any missing data. The authors of the studies were not contacted for missing data due to the risk of introducing bias.The quality of evidence for each outcome was evaluated by Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methods and classified as very low, low, moderate, or high .Primary OutcomesThe primary outcomes were the rate of POCD and POD. As both POCD and POD are difficult to define, and different studies used different tests and assessments to define their outcomes, our definitions were based on the individual trials’ definitions.Secondary OutcomesThe secondary outcomes were mortality and length of hospital stay.Statistical AnalysisThe included studies were screened, and the relevant data were extracted and summarized in a systematic review table. The patient characteristics, study characteristics as well as outcome data were tabulated using standardized forms. The appendices of the studies were checked for any missing data. The authors of the studies were not contacted for missing data due to the potential for introducing bias.2 tests. We took I2 of 0% to 40% to be insignificant heterogeneity, 41% to 60% to represent moderate heterogeneity, and 61% to 100% to represent substantial heterogeneity. We used funnel plots to assess the risk of publication bias as well as Egger’s regression test. We separated the paper by Valentin et al. . Subgroup analysis of TIVA vs VA studies found similar outcomes .Nine studies ,27,28,31Mini-Mental State Examination Score on Postoperative Day Three2 of 96%. The Z-value was insignificant (p = 0.20). Visual examination of the funnel plot ]. Subgroup analysis of only non-cardiac surgeries was performed with a similar outcome .The included studies used different psychological tests to assess POCD, and MMSE was one of the most commonly used tests in all the studies. Seven studies ,26-28,30t Figure  found noPostoperative Cognitive Dysfunction on Postoperative Day Seven2 of 75%. The Z-value was insignificant (p = 0.41). Visual examination of the funnel plot ], and a substantial change in the outcome . Subgroup analysis was not performed as all the included studies were non-cardiac surgery.Seven studies ,19,22-25Postoperative Cognitive Dysfunction at Three Months2 of 0%. The Z-value was significant (p = 0.009). Visual examination of the funnel plot . Visual examination of the funnel plot , but the outcomes remained unchanged . Subgroup analysis was not performed as all the included studies were non-cardiac surgery.Six studies ,22,25,27t Figure  found noLength of Stay2 of 74%. The Z-value was insignificant (p = 0.39). Visual examination of the funnel plot , but outcomes remained the same . Subgroup analysis was not performed as all the included studies were non-cardiac surgery.Eight studies ,25,27,28t Figure  found noTrial Sequential AnalysisTrial sequential analysis is a methodology used in meta-analyses to control random errors and assess the need for further trials, similar to interim analyses performed in single trials used to decide whether a trial should be terminated early because of a sufficiently small P-value. Trial sequential analysis was performed for the significant findings of postoperative delirium and POCD at three months. As seen in Figure DiscussionIn this meta-analysis, we showed that there were protective effects of High BIS value on postoperative delirium and postoperative cognitive dysfunction at three months; however, TSA showed that the result for POD was underpowered, while POCD at three months was statistically significant.Nine meta-analyses -40 were Meta-analyses on observational studies ,16 showeOur study included randomized controlled trials exclusively and also included the subset study of the recent large RCT (Evered 2021) ), which  ), whichThere are several limitations of our study. Our data showed high heterogeneity. For most RCTs, postoperative delirium was assessed by CAM or CAM-ICU score or psychological tests according to DSM-IV criteria; data could be easily analyzed. However, postoperative cognitive dysfunction had various tests for assessment. Some RCTs only reported preoperative and postoperative MMSE scores, while some used a battery of neuropsychological tests and reported absolute change in results without defining POCD through the results. Time intervals for follow-up were also variable. Therefore fewer data could be extracted from the RCTs when assessing POCD. Also, more RCTs are required to perform subgroup studies on different types of surgeries; more stringent protocols are required to minimize confounding factors, e.g., hypotension, intraoperatively.In 2017, the European Society of Anaesthesiology published a guideline on postoperative delirium . It recoOur study only reviewed the effect of the depth of anesthesia on the incidence of POD and POCD. Other modifiable anesthetic factors, including the type of anesthesia, and different anesthetic drugs, may also pose effects on POD and POCD. Some studies were done to compare the incidence of POD and POCD among the use of propofol, benzodiazepines, or dexmedetomidine, but the results were conflicting -48. A loThere is more evidence showing that postoperative delirium and cognitive dysfunction are significant in the elderly after anesthesia, and they pose a detrimental effect on the quality of life of these patients. Depth of anesthesia is one of the potentially modifiable risk factors to minimize the effect of anesthesia on patients’ cognitive function. Our meta-analysis showed that a high BIS value favored less postoperative delirium and postoperative cognitive dysfunction at three months in elderly patients, but this did not translate to a significant difference in length of stay and mortality. Future RCTs should focus on high-risk patients, and a standardized methodology of reporting POD and POCD is needed to improve comparisons across trials.


Parkinson’s disease (PD) is a neurodegenerative disorder often associated with pre-motor symptoms involving both gastrointestinal and olfactory tissues. PD patients frequently suffer from hyposmia, hyposalivation, dysphagia and gastrointestinal dysfunctions. During the last few years it has been speculated that microbial agents could play a crucial role in PD. In particular, alterations of the microbiota composition (dysbiosis) might contribute to the formation of misfolded α-synuclein, which is believed to be the leading cause of PD. However, while several findings confirmed that there might be an important link between intestinal microbiota alterations and PD onset, little is known about the potential contribution of the nasal microbiota. Here, we describe the latest findings on this topic by considering that more than 80% of patients with PD develop remarkable olfactory deficits in their prodromal disease stage. Therefore, the nasal microbiota might contribute to PD, eventually boosting the gut microbiota in promoting disease onset. Finally, we present the applications of the seed amplification assays to the study of the gut and olfactory mucosa of PD patients, and how they could be exploited to investigate whether pathogenic bacteria present in the gut and the nose might promote α-synuclein misfolding and aggregation. D) in several peripheral tissues  of PD patients or other α-synucleinopathies, including multiple system atrophy (MSA) and dementia with Lewy bodies (DLB) [D generation in the era of the SAAs.The human body hosts and interacts with a huge variety of microorganisms, which are mostly harmless and sometimes essential. They are referred to as microbiota and comprise bacteria, archaea, eukaryotes and viruses and colonize several parts of the body including the skin and different mucosa of the urogenital, gastrointestinal and respiratory tract . The teres (DLB) . In thisLactobacillus spp., Bacillus spp., Clostridium spp., Enterococcus spp. and Ruminicoccus spp. Bacteroidetes consist of predominant genera such as Bacteroides and Prevotella, while the Actinobacteria phylum is proportionally less abundant and mainly represented by the Bifidobacterium genus [Lactobacillus spp., Bifidobacterium spp., Enterococcus spp., Propionibacterium spp. and Peptostreptococcus spp.) and opportunists  is associated with gastrointestinal disorders. In general, the symbiotic relationship between the gut microbiota and the host is regulated and stabilized by a complex network of interactions that encompass metabolic, immune and neuroendocrine crosstalk. This crosstalk is potentially mediated by microbial-synthesized metabolites which exhibit pleiotropic effects, for instance by acting as signalling molecules in regulating host neuro-immune-inflammatory axes that could physiologically link the gut with other organ systems.Most of the microorganisms that constitute the human microbiota resides in the gut and, due to the stability/resilience and the symbiotic interaction with the host, it is possible to consider this huge community of cells a real organ. It has been estimated that the human gastrointestinal (GI) tract contains more than 100 trillion microorganisms, including bacteria, yeast and viruses, and the gut microbiota encodes over 3 million genes producing thousands of metabolites. Each individual is provided with a unique, complex and dynamic microorganism profile that plays many specific functions in host nutrient metabolism, maintenance of the structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens . Gut micum genus . Human gum genus . Indeed,um genus . Moreoveum genus ,21,22,23um genus ,25,26,27Lactobacillus spp. and Bifidobacterium spp. [Bacillus species and E. coli [Lactobacillus spp., Streptococcus spp. and Klebsiella spp. [In recent years, it became evident that intestinal bacteria could alter CNS physiology by promoting pro-inflammatory mechanisms, and that dysbiosis could contribute to pathological processes in complex neurological conditions . The comium spp. ; 2. dopa E. coli ; and 3. lla spp. . Intereslla spp. . Among blla spp. . SCFAs alla spp. . The thrlla spp. . In partlla spp. . Startinlla spp. ,48,49,50Staphylococcus spp., Propionibacterium spp., Corynebacterium spp., Moraxella spp., Dolosigranum spp., and Streptococcus spp. [Moraxella spp., Staphylococcus spp., and Corynebacterium spp. The oropharynx has a more complex microbiota that includes Neisseria spp., Rothia spp., and anaerobic bacteria among which Veillonella spp., Prevotella spp., and Leptotrichia spp. As previously reported, the primary function of any microbial ecosystem is to maintain a state of symbiosis, providing resistance against pathogens. In this context, the URT is considered as a major reservoir of potential pathogens, e.g., Streptococcus pneumoniae and Haemophilus influenzae. The nasal eubiosis is necessary to limit the expansion and subsequently spreading of these microorganisms towards the lungs, potentially leading to symptomatic infection. Thus, establishing and maintaining a balanced microbiota in the URT resilient to pathogenic expansion and invasion is vital for respiratory health [The interconnection between gut and oral/nasal microbiota is still poorly described. However, it is known that nasal microbiota can influence the olfaction, the immune regulation, and the homeostasis of the CNS. The respiratory tract is a complex system in which microbiota acts as a “guardian” that provides resistance to colonization by pathogens, and the nasal region is one of the distinct environments for the survival of specific microorganisms. The upper respiratory tract (URT) is mainly composed of distinct anatomical structures, with different cell populations differently exposed to external factors . Dissimicus spp. . The nasy health ,56. The y health ,58. Somey health . The gut-brain axis is an essential bidirectional communication way that links two important organs and that influence their physiological or pathological conditions. In 2008, Doty and colleagues first proposed the nose-to-brain hypothesis . This hyD). Lewy bodies are also found in other cerebral regions, such as the dorsal motor nuclei of the vagus nerve, the locus coeruleus and the entorhinal cortex, but the exact trigger for the formation of α-synD and the consequent neuronal degeneration is not yet clear [D, in addition to forming intraneuronal protein aggregates which are characteristic of PD, may be directly involved in the onset and progression of the disease. Aggregates of α-synD propagate between neurons, and they can interact with the normal α-syn (which abounds at the level of the synapses) inducing a conformational change that promotes the formation of new α-synD species [D propagates very efficiently within the CNS. Interestingly, in addition to being present in neurons of the CNS, α-synD was also identified in the ENS, especially in the early stages of PD and it could contribute to the onset of gastrointestinal disorders, including constipation and impaired motor function of the colon [D. This pathological protein can finally reach the brain, through the gut-brain axis, causing the clinical and neuropathological changes typical of the disease [D accumulates in peripheral structures such as the enteric plexus of the stomach and in the OB of PD patients. For this reason, it has been proposed that the formation of α-synD may occur in peripheral regions  and that from those organs it could reach the brain  [Parkinson’s disease (PD) is a neurodegenerative disease affecting about 1/100 of people in the sixth decade of life. PD is characterized by motor deficits, including slowness of movement, stiffness and tremor . Howeveret clear . The stuet clear . Growing species ,74 that he colon . These f disease . For thiothesis) . In the D in nigral neurons, thus suggesting that the two mechanisms may be somehow linked [Neuroinflammation plays a crucial role in PD. In particular, it has been shown that inflammation-derived oxidative stress and cytokine-dependent toxicity may contribute to the degeneration of the nigrostriatal pathway and accelerate the progression of the disease . It has w linked . Furtherw linked ,88. In vw linked ,90. Incrw linked . A very w linked . This suD were observed in the biopsies of gastrointestinal tissues of patients with PD [D was also found in salivary glands, esophagus and stomach, organs potentially involved in the common non-motor symptomatology in PD, such as hypersalivation, dysphagia, delayed gastric emptying and gastroparesis [D may originate in the gastrointestinal system, reach the CNS via retrograde transport along the neural projections of the ENS, and from there spread to different neuroanatomical regions in a caudal-rostral manner. Apart from the demonstration of the presence of α-synD aggregates in the vagus nerve [D in the gastrointestinal tract of mice can induce α-synD deposition in the CNS [D in experimental models [D with well-defined pathologic structural properties [D. Indeed, the gut microbiota produces several “amyloid” molecules, including the “curli” protein, expressed in abundance from intestinal strains such as Escherichia coli and the phenol soluble modulins (PSMαs) produced from Staphylococcus aureus. In transgenic mice that overexpress human α-syn, the colonization with E. coli could promote α-synD formation in the gut and its propagation to the brain, while, in vitro studies showed that the presence of PSMαs catalyzes α-syn aggregation [Prevotella spp., Bacteroides spp., Lactobacillus spp., Bifidobacterium spp., Clostridioides spp., Enterococcus spp. and Ruminococcus spp.) contribute to the bioavailability of dopamine, a key neurotransmitter in PD, in the ENS and CNS. Several studies have found that changes in the composition of gut microbiota and dopamine production are linked to the clinical manifestations of PD [α-syn is not only expressed in the CNS, but also by the neurons of the ENS and has a fundamental role in the release/absorption of neurotransmitters . Patholo with PD . Furtheroparesis . Studiesoparesis  and Hawkoparesis  support us nerve , studies the CNS ,99. The  the CNS . In partl models . After toperties . Furtherregation ,104,105.ns of PD . In partns of PD . spp., Oscillibacter, Escherichia/Shigella, LachnospiraceaeAkkermansia muciniphila, Enterobacteriales, Eggerthella  and Streptococcus, and decreased levels of Roseburia, Coprococcus, Faecalibacterium and Eubacterium biforme were described in PD samples [spp., BifidobacteriumEnterococcus  spp. and Ruminococcus spp. and decreased levels of Prevotella, Bacteroides and Clostridium were also described [Lactobacillus spp. are still controversial [D. These latter can spread to the CNS, through the retrograde vagal pathways of innervation, and contribute to the onset of the typical neurodegenerative alterations of PD. The comprehension of the role of the gut microbiota in PD will help to identify new therapies and optimize methods available to prevent, delay or restore dopaminergic deficits of this disorder.Through molecular genotyping studies of the microbial species present in the GI tract of PD patients, it has been shown that the relative composition (at different levels) of all major bacterial phyla are altered if compared to healthy subjects. Therefore, changes in gut microbial species could be considered prodromal biomarkers indicating the early onset of the disease . In this samples . In addiescribed . Of noteoversial . In concCorynebacterium followed by Propionibacterium, Moraxella, Staphylococcus and Burkholderia. Despite the variety of microorganisms found, it was not possible to detect differences in terms of alpha or beta diversity between PD patients and controls [Corynebacterium common to all subjects. However, also in this study, the authors did not find significant differences that could discriminate PD patients from controls. Further statistical analyses, considering 70 anthropometric data, allowed to discover that gender and height of the subjects were able to influence the prokaryotic community. Finally, comparisons between PD patients under treatment with levodopa (L-DOPA) and untreated patients showed a greater relative abundance of Bacillaceae only in treated patients [Moraxella catarrhalis and Ralstonia insidiosa if compared to controls. Interestingly, patients with increased quantities of M. catarrhalis (and other pro-inflammatory bacteria strains) showed more severe PD symptoms and reduced amounts of anti-inflammatory bacteria, including Blautia wexlerae, Lachnospira pectinoschiza and Propionibacterium humerusii . Further analyses performed with machine learning approaches allowed the identification of eight characteristic taxa in PD patients: Escherichia albertii, Peptoniphilus asaccharolyticus, Staphylococcus aureus, Macrococcus brunensis, Ralstonia insidiosa, Staphylococcus epidermidis, Burkholderia xenovorans and Acinetobacter guillouiae. Finally, the severity of motor symptoms  and the olfactory functions were positively correlated with M. catarrhalis and S. epidermidis and with the commensal bacterial species P. asaccharolyticus. The results of this study showed a peculiar pro-inflammatory and dysbiotic environment in the deep nose cavity of PD patients compared to healthy subjects [Stenotrophomonas, u_Corynebacteriaceae and Staphylococcus spp. in both groups of subjects. However, detailed analyses revealed a higher level of g_unidentified_Corynebacteriaceae, f_Corynebacteriaceae, and s_Corynebacterium sp KPL1855 in the PD group compared to healthy controls [D which, settling in the neurons of the olfactory mucosa, can contribute to the olfactory disturbance and later initiate its retrograde transport to the olfactory bulb and finally into the CNS.Dysfunctions of the olfactory system occur in 75–95% of PD patients in the early disease stages. The nasal cavity is considered a secondary site (in addition to the gut) capable to trigger neuroinflammation in PD and, as mentioned before, it has been hypothesized to serve as a route of pathogen invasion/toxin exposure . Similarcontrols . Heintz-patients . Pal et subjects . By sequcontrols . In conccontrols . In addiD in CSF [D in OM samples collected from patients with olfactory impairment might be of utmost importance for identifying patients at higher risk of developing PD or other α-synucleinopathies. Through SAA analyses, different groups have shown that it is possible to detect α-synD in OM of PD, MSA and DLB patients with high sensitivity and specificity [D in samples collected from PD patients at different disease stages [D formation, PD onset and progression. The seed amplification assays (SAAs) are a group of highly sensitive techniques, including the protein misfolding cyclic amplification (PMCA) and the Real-Time Quaking-Induced Conversion (RT-QuIC), that enabled the detection of trace amounts of α-synD in CSF ,122,123,D in CSF ,126,127,D in CSF ,129, skiD in CSF ,131,132,D in CSF  and moreD in CSF  of patieD in CSF ,74. As pcificity ,126,127,cificity . Similarcificity ,136. As e stages . Now, itAlthough there are no therapies capable to halt the neurodegenerative processes of PD , there aSeveral research groups are actively working to find an effective treatment for PD . In thisD formation [D were found in OM and the gut of PD patients, even in the early stages of the disease, and it would be interesting to study whether and to what extent these microbiota alterations might be involved in α-synD formation. A few studies have demonstrated that the formation of α-synD may depend on bacterial products  and considering that these molecules are generated as a result of dysbiosis, it would not be entirely surprising that peripheral organs (connected with the CNS) could serve as sites of origin of the disease. Notably, compared to the gut, the OM can be easily collected and the procedure is not invasive and can be repeated over time. This makes the OM an excellent biological tissue that can be subjected to SAA and microbiota analyses with the aim of improving the diagnosis of PD, especially considering the phenotypic heterogeneity of the disease. This variability seems to be associated with different anomalous conformations of α-synD (strains). It will be therefore important to evaluate whether different alterations of the microbiota can modulate the misfolding process of α-syn and generate different α-synD strains. Finally, it is of utmost importance to clarify whether the nasal dysbiosis really plays some role in PD onset and progression. If this was the case, it would be possible to identify new therapeutic targets and plan personalized treatments aimed at restoring the nasal eubiosis by reducing harmful bacterial strains (for example by administering selective antibiotics) and by introducing alternative bacterial strains (such as probiotics). Finally, as there are several prodromal symptoms of the disease, such as sleep disturbances (iRDB), constipation and loss of smell, we may select patients for OM collection and SAA and NGS analyses with the aim of studying whether α-synD or nasal dysbiosis significantly anticipate the onset of PD. This will help to identify patients at a higher risk of developing the disease. Early PD diagnosis and patient stratification is the key to maximize the effectiveness of treatments and to slow or prevent disease progression. SAA is not only useful to recognize and even stratify PD patients in their early disease stages by analysing easily collectible tissues, but can also be exploited to monitor disease progression  and to study the effect of different bacteria on α-synD generation in vitro. Indeed, since SAA mimics the process of α-synuclein misfolding which occurs in vivo, it represents an important platform to evaluate the influence of harmful bacteria (found in the gut or nose of PD patients) on α-synD generation and strains formation. This will consent to plan innovative therapeutic strategies by looking at PD from a different perspective. In recent years, research on the microbiota field has taken significant steps forward, mainly thanks to the development of new technologies , which allow analysing the composition and the functions of the bacterial flora by deepening certain complex aspects that were previously invaluable ,149. Theormation . Another


Peritonitis is one of the major complications of peritoneal dialysis. The most common cause of peritonitis is infection at the catheter exit site. This study aimed to determine the effect of propolis on the incidence of catheter exit site infection and peritonitis in peritoneal dialysis patients.This study was a double-blind clinical trial (2019–2020) with peritoneal dialysis patients. Ninety peritoneal dialysis patients were allocated to three groups  using block randomization method. Catheter exit site was washed with 0.9% normal saline and dressing was done every other day after the morning peritoneal dialysis exchange by use of normal saline in placebo, mupirocin in control, and propolis in intervention group, for 6 months.P = 0.469). Whereas 6.7% in both the placebo and control groups developed peritonitis, but none patient in the intervention group contracted peritonitis (P = 0.997). No significant differences in the incidence of catheter exit site infection and peritonitis among the three groups were observed. Considering that mupirocin is of chemical origin and may lead to drug resistance whereas propolis is of plant origin and does not produce drug resistance, the use of propolis is recommended.10% of the patients in the placebo and 6.7% in the control group developed catheter Exit Site Infection, but none patient in the intervention group developed this infection (IRCT20110427006318N10] (17/01/2019).Iranian Registry of Clinical Trials [ The loss of renal function due to decreased nephron function is called Chronic Kidney Disease (CKD) . With thPD is highly regarded because of its simplicity, easy access, and reasonable cost . The mosAccording to the recommendations of the International Society for Peritoneal Dialysis (ISPD), the key measure for the prevention and treatment of peritonitis include the use of prophylactic antibiotics before placing the PD catheter, daily use of topical antibiotic cream or ointment at the catheter exit site, and rapid treatment of exit-site infections. Upon the detection of PD-related peritonitis, after taking microbiological samples, antibiotics for gram-positive and gram-negative organisms (including Pseudomonas species) should be initially administered preferably intraperitoneally .Considering the side effects, inconsistent efficacy, and high cost of chemical treatments, recent years have seen a growing interest in using complementary therapies and traditional methods whenever possible . ComplemHoney, is a promising preventive and therapeutic agent, especially against resistant organisms, thanks to its broad-spectrum antibacterial coating . The safPropolis is a beehive by-product consisting of different substances, the most important of which are phenolic compounds. The main constituents of propolis are polyphenols such as phenolic acids and flavonoids, which are beneficial to human health and have medicinal and biological effects. Flavonoids are derivatives of phenylpropanoids characterized by their 15-carbon structure, which play a role in the processing of waste substances. Flavonoids also inhibit cancer cells, increase immunity (antioxidants), have antiviral, antibacterial, anti-inflammatory, and anti-allergic effects, and reduce the permeability and fragility of capillaries , 18. ProThis study aimed to determine the effect of propolis on the incidence of ESI and peritonitis in PD patients.n = 90) were randomly divided into three groups: placebo , control (mupirocin), and intervention (propolis).This study was a double-blind clinical trial (2019). Propolis ointment was given to dialysis patients, without specifications and labels and they did not know the type of treatment. Also, in this study, the participant, did not know they were in which group, the diagnosis of ESI and peritonitis in PD was based on ISPD findings, the clinician, laboratory specialist, and data analyzer  were unaware of the arrangement of the groups. They didn’t know whether group received the intervention, the placebo group, or the control group. After completing the study and interpreting the results, the arrangement of the groups was determined to which group belonged. Participation in this study was completely voluntary. After agreeing to participate in the research, the patients were participated in a study group. They could withdraw from the research whenever they wanted, after notifying the moderator, and in case of non-participation, they would not be deprived of the usual diagnostic and therapeutic care. There was no cost for them to participate in this study. It was also explained to them that this study will continue for 6 months and once every 2 weeks, they will go to the PD unit for a free visit to check the symptoms of ESI and peritonitis, and they will be examined by a doctor, and a monthly culture will be taken from the dialysis effluent. The results of the tests will be made known to them and these results will be used completely confidentially and only for the purposes of this research, and their identities will remain confidential and will not be revealed within the framework of the law. After obtaining permission from the relevant officials, eligible subjects were selected from among PD patients who were receiving treatment in the dialysis wards. Using the block randomization method, a total of 90 patients .Staphylococcus aureus, history of mental disease, impaired perception, unwillingness to continue participation, receiving kidney transplant, shift to hemodialysis, and death.Exclusion criteria were as follows: having other infections, having peritonitis or catheter ESI in the past month, receiving antibiotic treatment during the last 4 weeks, nasal carrying Staphylococcus aureus are more likely to develop peritonitis  (17/01/2019) and (IR.SEMUMS.REC.1397.200). The ethical approval was obtained from Semnan University’s Ethics Committee. Informed consent was obtained from all the participants. All methods were carried out in accordance with relevant guidelines and regulations. Obtaining a letter of introduction from the university’s vice-chancellor of research, obtaining permit from the officials in charge of hospitals and PD wards, explaining the purpose of the study to patients and their guardians, reassuring patients of the confidentiality of their information, and informing patients about their right to withdraw from the study at any time were respected. The intervention did not have any side-effect and was not endangering the health of subjects, and patients were reassured of this by their physicians. Also, participation in the study was free of charge and imposed no extra cost on patients.The statistical analysis of demographic and background information and catheter ESI and peritonitis incidence in the three groups was carried out by the Shapiro-Wilk test, chi-square test, and one-way analysis of variance . The effect of each method on the incidence of catheter ESI and peritonitis was evaluated by logistic regression. The analyses were performed using the software SPSS24.P = 0.464). The gender ratio  in both placebo and control groups was 50%, and in the intervention group was 63.3%. The three groups were not significantly different in terms of gender distribution (P = 0.954). The mean ± standard deviation of body mass index in the placebo group, the control group, and the intervention group was 25.8 ± 5.8 kg/m2, 25.4 ± 4.2 kg/m2, and 25.4 ± 4.2 kg/m2, respectively, which were not significantly different (p = 0.932). There was also no significant difference between the three groups in terms of education level (p = 0.461) or the number of PD frequency per a day (p = 0.194). All patients had at least one underlying disease. In placebo and control groups, 60%, and in the intervention group 76.7% of patients had hypertension. The groups were not significantly different in terms of the distribution of underlying diseases (p = 0.060) .During the first and second months, none of the patients showed catheter ESI whereas in the third month one patient (3.3%) in the placebo group showed catheter ESI with Methicillin-Resistant During the fourth month, one patient (3.3%) in the placebo group with Acinetobacter and one patient (3.3%) in the control group with erythema and negative culture showed catheter ESI whereas in the fifth month, only one patient (3.3%) in the placebo group presented with catheter ESI by Diphtheroids and in the sixth month one patient (3.3%) in the control group with erythema and negative culture presented with catheter ESI.n = 3) of patients in the placebo group and 6.7% (n = 2) of patients in the control group developed catheter ESI. No patient in the intervention group developed catheter ESI. The results of logistic regression did not show any significant effect on the catheter ESI rate (p = 0.469) .ESI Free Survival Curve the three groups are shown in Fig. p = 1.00) showed a significant effect on peritonitis).During the first 3 months, none of the patients in the three groups developed peritonitis. However, during the fourth month, one patient (3.3%) in the MRSE control group developed peritonitis (none of the variables including interventions (p = 0.94) had a significant effect on the incidence of peritonitis.During the fifth month, none of the patients in the three groups developed peritonitis. Meanwhile, during the sixth month, two patients (6.7%) in the MRSE placebo group and one patient (3.3%) in the MRSE control group developed peritonitis. The results of logistic regression showed that none of the variables including interventions .Peritonitis Free Survival Curve the three groups are shown in Fig. This study aimed to determine the effect of propolis on catheter ESI and peritonitis in PD patients. In this study, 10% of patients (three patients) in the placebo group and 6.7% of patients (two patients) in the control group developed catheter ESI, but none of the patients in the intervention group contracted this infection. However, the results of logistic regression showed that propolis had no statistically significant impact on the incidence of catheter ESI. In a study by Nochaiwong, using mupirocin and chlorhexidine gluconate ointments rather than normal saline the risk of catheter ESI was reduced .P = 0.035) and for peritonitis alone (P = 0.172). These results suggest that honey is more effective than povidone-iodine and could be a safe, broad-spectrum, low-cost alternative ointment for catheter exit site [The results of logistic regression again showed that propolis had no statistically significant effect on the incidence of peritonitis. In a study by Ceri et al. ESI and peritonitis rates tended to be lower in polyhexanide group compared with the povidone-iodine group, but were not statistical significantly . In a stxit site . AlthougSimilar to the present study, which found no statistically significant difference between the incidences of peritonitis and catheter ESI in placebo, control and intervention groups, a study by Zhang et al. in Australia also reported no significant difference between the groups that used mupirocin and those that used a honey-based agent in terms of incidence of gram-positive, gram-negative, and multi-organism peritonitis in PD patients . ConsideThe most important limitation of this study was difficulty in recruiting patients because of their doubts about the intervention, but this issue was largely resolved by educating the patients both directly and through their physicians. Another limitation was small sample size. Nevertheless, it is recommended to conduct a similar study with a larger sample and a longer follow up period.Staphylococcus aureus peritonitis by only 40% [Considering that peritonitis is one of the major complications of peritoneal dialysis, ISPD has recommended the daily use of antibacterial ointments, including mupirocin, to prevent catheter ESI and peritonitis. However, there are reports of resistance to mupirocin after regular use , 27. Whionly 40% . In viewIn general, the findings did not show a significant difference among the three groups in terms of incidence of catheter ESI and peritonitis. Considering that mupirocin is of chemical origin and may lead to drug resistance whereas propolis is effective against infections, instead of mupirocin or other agents to prevents ESI and peritonitis, propolis is more convenient, patient-friendly, cost-effective and easily available for PD patients. More studies with larger number of patients enrolled in future studies, being defined by a power calculation execution, as well as longer interventional time is needed.


Preterm birth (PTB) was one of the leading causes of neonatal death. Predicting PTB in the first trimester and second trimester will help improve pregnancy outcomes. The aim of this study is to propose a prediction model based on machine learning algorithms for PTB.  Data for this study were reviewed from 2008 to 2018, and all the participants included were selected from a hospital in China. Six algorisms, including Naive Bayesian (NBM), support vector machine (SVM), random forest tree (RF), artificial neural networks (ANN), K-means, and logistic regression, were used to predict PTB. The receiver operating characteristic curve (ROC), accuracy, sensitivity, and specificity were used to assess the performance of the model.  A total of 9550 pregnant women were included in the study, of which 4775 women had PTB. A total of 4775 people were randomly selected as controls. Based on 27 weeks of gestation, the area under the curve (AUC) and the accuracy of the RF model were the highest compared with other algorithms : 0.873–0.897). Meanwhile, there was positive association between the accuracy and AUC of the RF model and gestational age. Age, magnesium, fundal height, serum inorganic phosphorus, mean platelet volume, waist size, total cholesterol, triglycerides, globulins, and total bilirubin were the main influence factors of PTB.  The results indicated that the prediction model based on the RF algorithm had a potential value to predict preterm birth in the early stage of pregnancy. The important analysis of the RF model suggested that intervention for main factors of PTB in the early stages of pregnancy would reduce the risk of PTB. Preterm birth (PTB) is defined as births before 37 completed weeks of gestation . The PTBCurrently, numerous studies have attempted to predict preterm birth in pregnant women. Several studies supported that sonographic measurement of cervical length (CL) could be used for the prediction of PTB in the first trimester of pregnancy , 15, butInconsistent predictive power of machine learning in preterm birth. In this study, we try to use a new method to preprocess predictors. At the same time, we compared the predictive power of 6 machine learning algorithms in PTB.Data for this study were reviewed from 2008 to 2018. All the participants included in this study were collected from Haidian Maternal & Child Health Hospital. The inclusion criteria of the PTB group were as follows: (1) signed informed consent; (2) gestational age between 28 and 37 weeks; and (3) maternal age older than 18 years. The exclusion criteria of the PTB group are as follows: (1) missing maternal age; (2) missing gestational age; and (3) chronic diseases such as diabetes, hypertension, and heart disease. Controls were selected from hospitals in the same period in a 1 : 1 ratio. The inclusion criteria of controls were as follows: (1) signed informed consent; (2) gestational age ≥37 weeks; and (3) maternal age ≥18 years. Exclusion criteria are as follows: (1) missing maternal age; (2) missing gestational age; (3) and chronic diseases such as diabetes, hypertension, and heart disease. The flowchart of the study is shown in Demographic factors , physical examination, blood test (red blood cells (RBC), white blood cell count (WBC), and plateletcrit (PCT)), urine test strip , and gynecological examination , cleaning degree of vagina (CDV), and vaginal yeast infection (VYI)) were collected in our study. All participants had at least five antenatal check-ups before 27 weeks of gestation. For avoiding the overfitting of the model, variables that were measured multiple times were represented using the mean and mode, depending on the type of variable. With the increase in the gestational age, variables were more influence on the outcome. Therefore, we gave more weight to the later data. The equation is defined asAs shown in In this study, six algorisms, including Naive Bayesian (NBM), support vector machine (SVM), random forest tree (RF), artificial neural networks (ANN), K-means, and logistic regression, were used to predict PTB .In this study, 4 metrics were used to measure the predictive performance of the model: accuracy, area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. The accuracy is the proportion of correct predictions among the total number of cases examined . Sensitit-test or Wilcoxon test for continuous variables.The Kolmogorov–Smirnov test was used to test the normality of continuous variable. If the variable satisfies normal distribution, the mean ± standard deviation was used to describe the continuous variable. Categorical variables were shown as numbers and percentages. Because our data were collected from electronic medical records, there were missing values in the dataset. Therefore, we excluded cases and variables that were missing more than 10%. For categorical variables, mode was used to fill, and for continuous variables, mean was used to fill. Comparison between the outcome groups was made by the chi-square test or Fisher's exact test for categorical variables and by the P value <0.05, the result was considered statistically significant.The dataset was randomly divided into a training set (70%) and a test set (30%). The training set was used to train the model, and the test set was used to evaluate the model. Four indicators, the area under the curve (AUC), accuracy, sensitivity, and specificity, were used to measure the performance of the model. The importance of a variable was assessed by the decreased accuracy of the model after removing the variable. The higher the decreased accuracy of the model, the more important the variable. All statistical analyses were performed in R software (version 3.5.1) using the “e1071” , “randomForest” (random forest tree), and “kknn” (K-means) packages. For all analyses, if the two-tailed Ethics approval of this research was approved by the Institutional Research Review Board at National Research Institute for Family Planning and performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.P < 0.001). The gestation of pregnant women was 251.19 ± 11.51 days in the case group and 274.66 ± 7.15 days in the control group (P < 0.001). The gravidity and parity of pregnant women in the PTB group were lower than those in the control group . The weight and height of newborns in the control group were higher than those in the PTB group . The Apgar scores  of newborns in the control group were higher than those in the case group . The characteristics of pregnant women and newborns were summarized in A total 9550 of pregnant women  were included in our study. The mean ages of the PTB group were lower than those of the control group (PTB: 29.94 ± 5.39), control: 30.72 ± 4.00, P < 0.05). Meanwhile, the plasma glucose (fasting) is lower in the PTB group than that in the control group . Total biliary acid (TBA) and urea levels were higher in the PTB group than those in the control group . Platelet, intermediate cell, lymphocyte (LY), monocytes (MO), neutrophil granulocytes (NE), red blood cell distribution width-SD (RDW-SD), and WBC levels were higher in the PTB group than those in the control group. Mean cell hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and platelet distribution width (PDW) were lower in the PTB group than those in the control group. Waist size, fundal height, SBP, and DBP were higher in the PTB group than those in the control group. Fetal heart rate (FHR) in the PTB group was slower than that in the control group. Urine PH was higher in the PTB group than those in the control group. Pregnant women with blood type B were found to be more common in the case group than in the control group , total serum iron (TSI), magnesium (Mg), and triglycerides (TG) levels were higher in the PTB group than those in the control group  were used to build the model based on five datasets .The importance analysis of the RF model found that the top 10 most important variables were age, magnesium, fundal height, serum inorganic phosphorus, mean platelet volume, waist size, total cholesterol (TC), TG, globulins, and total bilirubin (TB) . AccordiIn this study, six algorithms were used to establish the prediction model of premature birth in the early stage of gestation. The overall prediction effect of the RF model was better than that of other models. We also found that the predictive power of the RF model increased with the increase of gestational age. Age, magnesium, fundal height, serum inorganic phosphorus, mean platelet volume, waist size, TC, TG, globulins, and TB were found to be the main influencing factors of preterm birth.α, angiopoietin 2, TNFRI, IL-5, MIP1α, IL-1β, and TGF-α), resulting in a high AUC  [In our study, we used the data from the production inspection to build the model based on the machine learning algorithm. The prediction performance of the model was relatively good, and the cost of the model was low. Ramkumar et al. using multivariate adaptive regression splines established a prediction model based on biomarkers  . Teresa 66–0.86) . Thuy et66–0.86) . In thes66–0.86) . Liu et 66–0.86) . The aboIn this study, the results of the numerical experiments show that the AUC of SVM, RF, and ANN models were higher than logistic, NBM, and k-means. The possible reason for the low AUC of the NBM model is that the NBM model assumes that features are independent of each other, which is often not true in practice. For logistic regression and k-means algorithms, they were susceptible to outliers and noise that reduce prediction accuracy. For the other 3 machine algorithms, the AUC value of the RF model was the highest. The RF model is an ensemble learning method, which constructs a multitude of decision trees at training time and then sets up the trees to give the classification . This enIn the importance analysis of the RF model, we found that age was the greatest effect on preterm birth. A case-control study showed that premature delivery was associated with greater maternal age . We alsoThere were some limitations in our study. First, our dataset, collection from electronic medical records, and lack of some data such as smoking, drinking, family income, method of conception, medication, and fetal fibronectin. The absence of these factors may underperform our model. Second, previous studies found that the conception method has an important effect on preterm birth , 37, butOur results indicated that the prediction model based on the RF algorithm had a potential value to predict preterm birth early stage of pregnancy. The RF model also found the main influence factors of PTB, suggesting that intervention in the early stages of pregnancy could decrease the risk of preterm birth.


Cirrospilus pictus, parasitoid of the citrus leafminer Phyllocnistis citrella were observed. Adults were obtained from field sampling carried out during four consecutive years and grouped in different classes depending on sex and color. Results highlighted a phenotypic pigmentation variation in head, thorax, gaster and legs of the adults. Individuals were yellow–green in summer months while having dark pigmentation in autumn and winter months. In both sexes a correlation between color patterns and seasonal temperatures was evident. These observations can contribute to the description of the intraspecific variability of this species, improving its identification.Many studies highlighted that the body color variation in insects is an adaptation factor that preserves them from possible population reductions due to adverse conditions such as low temperatures. In this study, the coloration seasonal changes of Cirrospilus pictus (Nees) (Hymenoptera: Eulophidae: Eulophinae) parasitoid of leafminers is reported. Observations were made from January 2000 to December 2003 in north-western Sicily , in relation to sex, body regions of adults and seasonal periods. Wasps parasitizing Phyllocnistis citrella Stainton (Lepidoptera: Gracillariidae) were collected from organic citrus orchards . Adults were grouped in classes: yellow males, black males, yellow females, yellow–black females and black females. The results highlighted a phenotypic pigmentation variation in the head, thorax, gaster and legs of individuals influenced by the season of sampling. Adults were yellow–green in summer months, whereas individuals with dark pigmentation were found in autumn and winter months. A correlation between color patterns and seasonal temperatures was found for both females and males. This work provides a contribution to the description of the intraspecific variability of this species, improving its identification.As part of the studies on the morphological color variation of insects, a case study on the seasonal body color variation of  Perreya tropica Norton) have some males showing the mesoscutum orange while others the entire thorax and abdomen, and females with both the thorax and abdomen orange, but the dark wings [Cirrospilus vittatus Walker shows an extensive color variation, with individuals ranging from almost completely dark metallic green or blue to completely yellow with no metallic markings [Insects show a great variety of colors  that canrk wings . In addimarkings .The morphological diversity in the Chalcidoidea, as a function of the host, seasonal dimorphism and dichroism , complicCirrospilus pictus (Nees) (Hymenoptera: Eulophidae: Eulophinae) is a species that shows a phenotypic variability in relation to pigments of the body. Normally its body is yellow–green, but sometimes it is darker in some parts. It shows considerable variation in size and body coloration in relation to dark spots and stripes. Indeed, it has been re-described by some authors and synonymies were published by Zhu and coworkers [Among chalcidoid parasitoids, oworkers . Here, wCirrospilus pictus is one of the indigenous larval parasitoids found on Phyllocnistis citrella Stainton (Lepidoptera: Gracillariidae) in Sicily  since the summer of 1995 [P. citrella, being, in some periods of the year, the only species present on the leafminer [Cirrospilus pictus, also, can develop as primary or secondary parasitoids of other lepidopterous, hymenopterous and coleopterous leafminers [C. pictus can exhibit a variation of body colors depending on climatic factors, especially temperature. of 1995 ,19,20, t of 1995 . This pe of 1995 . From Jueafminer . Cirrospafminers . Since safminers , we hypoC. pictus obtained from P. citrella collected in different period of the year in order to detect the chromatic variation of the body, in relation to sex and body regions. The main objective of our research was to provide a tabulation of the color pattern in C. pictus developing on the citrus leafminer during the year to improve its identification. In addition, we investigated the correlation between color patterns and seasonal temperatures.In this study, we focused on adults of This study was carried out during four consecutive years, from January 2000 to December 2003, in six distinct locations belonging to organic citrus orchards, situated in areas of north-western Sicily  . C. pictus were obtained from plants of Citrus limon L., var. “Femminello zagara bianca” and “Femminello comune”, infested by Phyllocnistis citrella Stainton (Lepidoptera: Gracillariidae). No insecticides were applied to the organic citrus orchards. In each location, 200 young citrus shoots (length 20 cm) were randomly collected every 7 days, placed in plastic bags, and brought to the laboratory of the SAAF Department of the University of Palermo . In the laboratory , leaves were observed under a stereomicroscope, in order to detect parasitized hosts. Pre-imaginal individuals with their hosts were put singly into glass tubes (l = 7.5 cm Ø = 1 cm) sealed with wet cotton and containing a small amount of honey as food. All the test tubes, appropriately marked, were kept in a climatic chamber under the same environmental conditions previously mentioned and observed daily until emergence of parasitoid adults. Once emerged, parasitoid adults were counted, isolated and sexed. Adults were examined under the microscope, noting the pigmented parts of the body, such as head, thorax, gaster and legs, and grouped into chromatic classes. Color patterns were recorded in dorsal view and the diversity of yellow–black patterns of all the observed wasps was documented. The individuals were assigned to 5 chromatic classes: I = yellow females, II = yellow–black females, III = black females, IV = yellow males, V = black males, grouped according to the different colors of the parts of their body. An aliquot of adults of each class was sent for their identification to Dr. John LaSalle of the International Institute of Entomology, CAB International of London.Wasps of A regression analysis between the number of yellow wasps and mean temperature  in the four years of observations was performed. A one-way ANOVA was used to evaluate the mean number of wasps belonging to the five chromatic classes detected in the different months. Finally, the chromatic variation between females and males was evaluated by a Student’s t-test. Statistical analyses were performed using Statistica 7.1 for Windows Package .Cirrospilus pictus adults, either males or females, showed a chromatic variability depending on the month of the year in which they developed. In addition, the sexes differed in the color patterns. During the four years of study, the adults were obtained from June to February (period of main activity of the host P. citrella) and the color patterns observed always appeared similar in each year. The rainfall and temperature reported during the period of the study are reported in P. citrella were active, is reported in Assuming that, generally, the body of adults is yellow–green, a partial or total darkening of some parts of the body was observed. In total, five color patterns were observed in this species, three patterns in females and two in males. Specifically, the parts subject to change in color were the occiput, pronotum, mesoscutum, axilles, tergites and tibiae of middle legs, with differences between males and females . The perC. pictus varies greatly in coloration. Results highlighted that yellow individuals (classes I and IV) were the only phenotype present in the summer months and their percentage decreased to a minimum of 50% in the autumn and winter months. Black males (class V) began to appear from October up to February, whereas females showed yellow–black individuals (class II) from September to December and black individuals (class III) from November to February. In November and December, the three classes  of females coexisted. The infestation of host P. citrella was not detected in the areas of observation from March to May; therefore, no parasitoids were recorded in this period. The percentage of yellow wasps ranged between 50% (winter months) and 100% (summer months) for both females and males. In the period of appearance, the percentage of yellow–black females ranged from a minimum of 7.2% (September) to a maximum of 32.8% (October). The percentage of black wasps ranged between 14.3% (November) and 50% (December) for females, and between 9.75% (October) and 50% (December) for males. Generally, the dark color of black wasps on the thorax has some metallic shine. Males show a dark patch on the pronotum and a large transverse brown stripe on the gaster, and often a black spot on the yellow middle tibiae. This spot may also be present in females, but not dark. Statistical analysis showed significant differences among the number of wasps belonging to the five classes detected in the different months for both females  and males . Significant differences in the chromatic variation were also found between females and males . This phenotypic variability dependent on season was confirmed by the regression analysis that showed a significant correlation between the number of yellow wasps and temperature (SIAS data) for both females   (Our observations confirmed that < 0.001)  and male< 0.001) .C. pictus observed in both female and male individuals. Seasonal dichroism is known in Eulophidae [Eulophus larvarum L. [Atoposomoidea unipunctata (Nees) [Cirrospilus, Sympiesis, Eulophus and Olynx exhibit seasonal dichromism [C. pictus found in this study is also reported in other areas of the Mediterranean basin, such as in Spain [Variation in body coloration is well documented in insects and generally has a large genetic component ,26,27. Tlophidae ,28, and lophidae ,30,31,32varum L.  and Atopa (Nees)  show colchromism . The seain Spain .The chromatic variation can be affected by several factors, such as temperature, humidity ,37, hostC. pictus, only some parts of body were subjected to chromatic variation and these differed between sexes. In agreement, Zhu and colleagues [C. pictus females from different regions show some varieties in the coloration of the ocellar triangle, occiput, pronotum, axilla, hind coxae, and gaster. The coloration of some parts of the body due to temperature is also reported in other parasitoid species, for example in Pnigalio soemius  in which this parameter determines a strong influence on the pigmentation of the gastral tergites and other body parts, with both the tergites and tarsi tending appearing darker at lower temperatures [Bracon hebetor (Say), the body color of adults observed appears black at 15–18 °C, yellowish-black at 25 °C, and a yellow color at temperatures over 30 °C [Trioxys utilis Van de Bosh (Hymenoptera: Braconidae) that presents white-colored cocoons during warm-weather conditions and dark brown cocoons during cold-weather conditions [Our results showed that, in the case of lleagues  reportederatures . Similarer 30 °C . Anothernditions . It is lnditions .C. pictus obtained from Phyllocnistis labyrintella Bierk showed a variation based on a darker pigmentation of thorax, not detected in males, but in our observations the darkening can affect almost the entire body of females.In our results, the dark pigmentation was sharper in females than in males, likely in dependence on the temperature. A lesser effect of temperature on the chromatic variation of males has been also reported for other insects ,16,66,67In terms of seasonal distribution, the most widespread patterns were yellow wasps (classes I and IV), followed by black (classes III and V) and then yellow–black (class II) wasps.The detected chromatic classes of wasps have been similar for each year of the studied period and strongly dependent on climatic conditions. In particular, the increase in the temperature caused an increase in individuals belonging to classes I and IV (yellow wasps).C. pictus depending on the seasonal temperature. In particular, light individuals are more frequent in spring–summer and dark ones in autumn–winter, showing a correlation between color patterns and seasonal temperature. These results suggest an ecological adaptation to climatic conditions and could help in the identification of the species. In addition, the application of this knowledge could be useful to improve the suitability of natural enemies and their effectiveness in pest control.The observations conducted in this study confirm the hypothesis of a color variation of the body of


P=0.02), and a decreasing trend was significant across baseline, 12 weeks, and 24 weeks between groups (P < 0.05). The 12-week Tai Chi training significantly reduced the BP level and moderately improved stress level, fatigue status, and sleep quality among Chinese women with episodic migraine. Therefore, Tai Chi could be considered a promising mind-body exercise with good feasibility for migraineurs in the future. This trial is registered with registration number NCT03015753.The beneficial effects of Tai Chi on the cardiovascular risk profile and the migraine trigger factors among female migraineurs remain unknown. This study aimed to evaluate the effectiveness of a 12-week Tai Chi training on blood pressure (BP) and migraine-related trigger factors, including stress, fatigue, and sleep quality among Chinese women with episodic migraine. In this study, eligible Hong Kong Chinese women aged 18–65 years were randomly assigned to the Tai Chi group adopting a modified 33-short form of Yang style Tai Chi training for 12 weeks, followed by additional 12 weeks of self-practice or the waiting list control group that maintained the usual lifestyle for 24 weeks. The primary outcome was the changes in BP from the baseline to 12 and 24 weeks. The secondary outcomes included the stress level, fatigue, and sleep quality measured by the perceived stress scale (PSS), the numeric rating scale-fatigue (NRS-fatigue), and the Pittsburgh sleep quality index (PSQI), respectively. Significant between-group differences were found in systolic BP (−6.8 mmHg at 24 weeks,  Migraine is one of the most common headache disorders worldwide; it is characterised by attacks of headache and associated symptoms such as photophobia, phonophobia, somatosensory stimuli, nausea, and vomiting. According to the global burden of disease report, migraine imposed the second highest nonfatal burden in both 1990 and 2019 . MigrainVarious trigger factors may stimulate migraine attacks. Stress and sleep disturbance have been considered the most frequent trigger factors of migraine , 8. In aqi  throughout the body, thereby integrating both physical and spiritual elements. The significant beneficial effects of Tai Chi in reducing the severity of headaches and improving energy expenditure, emotional well-being, and mental health have already been reported in previous literature [The standard treatment for migraine includes acute and prophylactic treatment. Acute treatment is used to rapidly and consistently alleviate the pain and associated symptoms. The first-line treatment for acute migraine includes nonsteroidal anti-inflammatory drugs, nonopioid analgesics, acetaminophen, or caffeinated analgesic combinations . Meanwhiterature . We beliterature –22. Howeterature . We furtThe study was a two-arm, individual-level, parallel-group, randomised controlled trial (RCT), comprising one intervention group that received a 12-week Tai Chi training with an additional 12-weekfollow-up and one waiting list control group. The waiting list setting aimed to encourage subjects in the control group to keep in the study by providing them with delayed Tai Chi training at the end of the study (24 weeks).This study was approved by the Human Subjects Ethics Subcommittee, the Hong Kong Polytechnic University (reference no: HSEARS20160329002). Participation was voluntary and written informed consent was collected from all participants. All collected personal information and data remained confidential. Should there be any adverse events associated with the intervention, the participants would be asked to immediately stop the intervention and seek medical attention if necessary. All adverse events would be recorded and reported to the ethics committee. All procedures were implemented based on the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.The sample population of this study was Hong Kong Chinese women with clinical diagnoses of episodic migraine. Subjects were eligible if they were 18–65 years old with a diagnosis of episodic migraine (≤15 migraine days per month) based on the third edition of the International Classification of Headache Disorders (ICHD-III) . They shα = 0.050. Taking a 10% dropout rate into consideration, additional five subjects were recruited in each group to ensure that the statistical power was higher than 80%.Referring to other complementary treatments , Tai ChiParticipants were recruited via e-mail, the school's alumni system, and WhatsApp, as well as fliers and posters disseminated in the communities. Prospective participants who met the basic criteria after the initial screening were asked to record their migraine attacks in the next 4 weeks by using a migraine diary, including the frequency, intensity, duration, and medication usage of migraine attacks. The diaries were collected for further consultation with the collaborative neurological physician at the University Health Service (UHS) to make the final diagnosis of migraine based on the ICHD-III criteria .Eligible participants were randomly assigned to a Tai Chi training group (TC) or waiting list control group (control) in a 1 : 1 ratio by using the permuted block algorithm with a block size of four generated by a computer random number generator, blinded to the participant's identity. The allocation was concealed from the investigators until the assignments had been made. The outcome measurements were performed by research assistants who were blinded to the treatment group assignment.A modified 33-short form of Yang style Tai Chi Chuan was adopted. The classical Yang-style Tai Chi Chuan consisted of 108 postures and thus needed a relatively long learning period . This moParticipants assigned to the waiting list control group just maintained their usual lifestyles for 24 weeks. Afterwards, they took Tai Chi training similar to the TC group. Both TC and control group participants received a HK$100 supermarket coupon at the baseline as a participation incentive for this study. Another HK$100 coupon was delivered to participants in the control group at 12 weeks to encourage them to complete the study to maintain a good retention rate.The primary outcome was BP, including systolic and diastolic BP, which were measured by using a corrected electronic sphygmomanometer with appropriate cuffs after the participants took at least 10 minutes of seated rest. The measurements were taken twice, and the average value was used as the final measurement.Meanwhile, the secondary outcomes were stress level, fatigue, and sleep quality. The stress level was evaluated by the 14-item perceived stress scale (PSS-14), a tool with seven positive items and seven negative items rated on a 5-point Likert scale ranging from “never” (0) to “very often” (4) to measure how often participants experience general stressfulness within a given period . The PSSData on demographics including age, marital status, education, employment, housing, living district, and family income, as well as anthropometrics (weight and height), medical history, lifestyle factors , reproductive information, and family history of migraine were collected in a structured interview. Weight was measured by a weighing machine to the nearest 0.1 kilograms; meanwhile, height was measured by the height measurer to the nearest 0.1 meter. Body mass index (BMI) was then calculated as weight in kilograms divided by height in meters squared. Physical activity was then measured by using the Chinese version of the International Physical Activity Questionnaire (IPAQ), which has been reported to be reliable and valid for the measurement of total physical activity in the Chinese population . The rest-test was used within the group comparison of normally distributed variables, and a Wilcoxon signed-rank test was used for skewed variables. An independent t-test was used for between-group comparison. In addition, repeated measure analysis of covariance (ANCOVA) was used to test the difference of mean changes and the interaction effect between time and group across baseline, 12 weeks, and 24 weeks, respectively. The variables which were significantly different between groups at baseline were inputted as covariates in the ANCOVA. Both per-protocol and intention-to-treat (ITT) analyses were performed. Statistical significance was defined as a p value <0.05 by using two-tailed tests.Statistical analyses were performed by using statistic software, and SPSS 23.0 (SPSS Institute) was used for data analysis. Descriptive statistics including mean (SD) or median  for continuous variables, and numbers and proportions (%) for categorical variables were calculated. The paired n = 42) and control group (n = 40). After randomisation, a total of 40 participants in the TC group started the Tai Chi training, whereas the 33 participants in the control group remained in the study, and 10 of them withdrew for several reasons. A participant in the TC group also withdrew. Therefore, there were a total of 39 and 23 participants in the TC group and control group, respectively, kept in the study until the end of the 24 weeks. However, five participants in the TC group were excluded from the per-protocol analysis because they only attended less than 10 Tai Chi sessions and thus were considered invalid. The retention rates in the TC and control groups were 98% (39/40) and 70% (23/33), respectively. There were no significant differences in the baseline characteristics between the participants who completed the whole study and those who withdrew . The flow diagram of the study is shown in Supplementary Materials . Moreover, it showed that diastolic BP in the control group was significantly higher than those in the TC group (P < 0.05). No significant differences were found in other variables.The baseline characteristics of the two groups are presented in P > 0.05). In addition, both TC and control groups had a significant decrease in systolic and diastolic BP at 24 weeks as compared with the baseline, and the reduction of systolic BP in the TC group was significantly greater than that in the control group (P < 0.05). In the per-protocol analysis, similar results were found in BP, except a 3.0 mmHg  reduction in diastolic BP was found in the TC group at 12 weeks. By the repeated ANCOVA analysis, systolic BP in the TC group was significantly lower at 24 weeks and across the whole study period (both P < 0.05) than in the control group (ol group .P < 0.01) at 12 weeks. The improvement of sleep quality in the TC group was greater (P < 0.01), and significant alleviations in stress and fatigue were also found among participants in the TC group at 24 weeks. The PSS score and NRS-fatigue score in the TC group were reduced by −2.0 (95% CI: −3.7 to −0.2) and −1.2 (95% CI: −1.9 to −0.4), respectively. There were no significant changes found in stress level, fatigue, and sleep quality in the control group , and the per-protocol analysis suggested similar results  or low-effect exercise  , 43. SimAlthough other common nonpharmacologic treatments, such as biofeedback, cognitive-behavioural therapy, and acupuncture, have been reported to be effective for the prophylaxis of migraine –51, Tai However, this study has some limitations. First, it is impossible to implement blinding to participants, given that Tai Chi is a behaviour-based intervention. In addition, the waiting list control group was utilised in this study to maintain a high retention rate. Therefore, the placebo effects might not be fully examined or the effect could be slightly overestimated. Nevertheless, we believe that the evidence from this pilot study is still acceptable and reliable because the intervention design was rigorously scientific, and the effect detected existed. An active control group is suggested for further studies. The findings from this study can be used as a foundation for further investigations. Second, measurements used in this study for stress level, fatigue, and sleep quality were subjective, which may have recall bias. However, the measurement scales used in this study were all widely used tools with acceptable reliability and validity, and it is unlikely to cause a significant effect on the resulting outcomes. Third, the relatively small sample size might reduce the strength of the study. Therefore, future study with larger sample size and longer intervention period is needed to further evaluate the clinical efficacy of Tai Chi training on certain outcomes.The 12-week Tai Chi training could be recommended as a promising mind-body exercise for Chinese female migraineurs because Tai Chi has beneficial effects on lowering BP, alleviating stress, reducing fatigue, and improving sleep quality. The finding provided new insight regarding the role of mind-body exercise in improving health conditions among migraineurs. The modified short-form Tai Chi is easy to learn, and its practice is cost-effective and convenient. It would be helpful for healthcare and medical practitioners to make an evidence-based suggestion, which has the potential to be promoted and widely implemented in community settings.


Aim: This study was conducted to assess patient satisfaction with the e-prescription service implemented by the Ministry of Health hospitals and primary healthcare centres in Saudi Arabia. Methods: The study used a cross-sectional approach. Data were collected using a random sampling technique, and an online questionnaire was distributed among the study population. A five-point Likert scale, ranging from 1  to 5 (very satisfied), was used to assess patient satisfaction. Results and Conclusions: A total of 400 patients participated in the study. More than half (57.5%) of them were males, and approximately one-third were between the ages of 30 and 39. Aspects related to the pharmacy, i.e., accessibility of pharmacies in terms of numbers, location, and opening hours, as well as pharmacy facilities, including waiting area, counselling area, dispensing area and parking lots, were skewed towards 5 (very satisfied). Aspects related to pharmacy personnel, i.e., knowledge, skills, and competencies, as well as friendliness and approachability, were also skewed towards 5 (very satisfied). Factors related to patient experience with Wasfaty, the new service, as compared with old primary healthcare centres’ pharmaceutical services, such as the availability of pharmacists, procedures for refills, waiting time, privacy, and confidentiality, were also skewed towards 5 (very satisfied). The healthcare system in Saudi Arabia has changed drastically in the last few years . The govE-prescribing is defined as “the direct computer-to-computer transmission of electronic prescriptions (e-prescriptions) from the prescriber office to community pharmacies” . The e-pCommunity pharmacy is the largest private sector in the pharmacy field and employs the largest proportion of the pharmacy workforce in the country. In 2021, community pharmacies numbered 9026 around the country, employing 17,815 pharmacists [Community pharmacies are required to fulfil the criteria that enable them to join the Wasfaty system. This includes a valid license for the premises, registration at Nupco , the use of approved suppliers from the Wasfaty list, a valid pharmacist license from the Saudi Commission for Healthcare Specialties for all employees, a computer with Internet connection to access the online system, and a label printer. Currently, 3100 community pharmacies are registered and are serving 228 hospitals and 2069 primary healthcare centres in 174 cities around the country [Similar information technology systems that facilitate the electronic transfer of prescriptions have been used in several countries around the world, including Sweden, Italy, the United States, and England . For exaSeveral benefits were identified with the use of EPS, including the fact that electronic prescriptions are accurate, complete, and readable, which reduces the chance of dispensing errors and omissions. It provides higher levels of security, regulates the repeat dispensing workload enabling patients to collect their medication on time, is a convenience to the patients since they do not have to wait for the paper prescription to be dispensed, and opens two-way communication between the prescriber and the pharmacist, allowing pharmacists to be more involved in patient-centred care. On the other hand, EPS is also associated with delays in receiving prescriptions and inaccurate prescriptions from physicians. An overwhelming number of prescriptions with unclear information may lead to delays in dispensing. A lack of formal training also affects the speed of dispensing . A nationwide patient satisfaction survey assessing the newly implemented e-prescriptions system in Finland reported high satisfaction levels. The study concluded that no difficulties were encountered in purchasing medications, renewing prescriptions, or acting on behalf of someone in the pharmacy . SimilarNational studies have concluded that replacing handwritten prescriptions with e-prescribing would have several benefits . Hence, The study used a cross-sectional anonymous self-administered online questionnaire. The study was conducted between January and March 2022. http://www.raosoft.com/samplesize.html (accessed on 15 March 2022)) with a predetermined margin of error of 5% and a confidence level of 95%. In order to minimise erroneous findings and increase study reliability, the target sample size was set at 370 patients. A non-probability convenience sampling method was used. Data were initially collected by two family medicine residents who interviewed patients at the end their visits and invited them to complete and submit the questionnaire electronically. Recruiting more participants was achieved by distributing the questionnaire through social media applications, including WhatsApp and Instagram community groups around Saudi Arabia. The sample size was determined based on the total population of Saudi Arabia  and determined by using a Raosoft sample size calculator  version 26.0 for Mac. Demographic and background information were described in terms of frequencies. Community pharmacy premises features (two items), pharmacy personnel (two items) and e-prescription-related features (eight items) used a Likert scale ranging from 1  to 5 (very satisfied). The distribution of the scale was presented in percentages, as well as mean and SD. A mean value of ≥3 was considered skewed towards high satisfaction, while a mean value of <3 is considered skewed towards low satisfaction. The internal consistency and reliability of the scales was assessed using Cronbach’s alpha coefficient, with the minimum recommended level being 0.70 [An ethical clearance was given by the Ethical Committee of Scientific Research, King Khalid University (ECM #2022-503).A total of 400 patients participated in the study. More than half (57.5%) of them were males, and around one-third were between the ages of 30 to 39. Slightly less than three-quarters (72%) were educated to university level and above. The vast majority were Saudi nationals (94.3%) who utilised Wasfaty services for an acute condition .The distribution of scale scores for all questions related to pharmacy personnel and services is presented in This research was conducted to assess patient satisfaction with the e-prescribing system, Wasfaty, that connects Ministry of Health hospitals and primary healthcare centres to community pharmacies. The findings of the study indicated moderate satisfaction levels, with highest satisfaction given to pharmacy personnel in terms of their knowledge, communication skills, counselling skills, and therapy management, as well as openness and approachability (3.5/5). This national study on the Saudi population’s perceptions and attitudes towards community pharmacy services found high satisfaction levels with pharmacists’ commitment and communication skills.Moderate satisfaction levels were also reported for the pharmacy premises-related features in terms of the facilities and accessibility, with a mean of (3.3/5). Similar findings were reported in a local study where patients had the same satisfaction levels regarding the counselling area and its privacy, but higher satisfaction levels were reported with waiting time (4.3/5) and waiting area (4.3/5) . This coPatient experience with Wasfaty scored the same mean, i.e., (3.3/5), as the pharmacy related aspects. Patients were satisfied with pharmacists’ availability with a mean of (3.6/5), with the given instructions (3.4/5) and with privacy and confidentially (3.5/5), but were less satisfied with medication availability (2.9/5) and communication between pharmacists and prescribers (3.07/5).The transition to e-prescribing services has helped to engage the private sector in providing pharmaceutical services to the public through community pharmacies. Hence, it overcomes the issue of insufficient numbers of pharmacy personnel in primary healthcare centres . As was Medication availability was the criterion that patients found least satisfactory. This issue was previously reported in a local study , and in Communication between physicians and pharmacists was also seen to have room for improvement. This issue has been previously identified, particularly communication regarding suspected medication errors . CommuniThis study has some limitations. The majority of participants were younger adults with higher education. Hence, the findings might not be generalizable to the entire population, especially the elderly, who are likely to have multiple chronic conditions and polypharmacy, yet comprise only 13% of the study population. Additionally, 70% of the sample visited community pharmacies for acute conditions, so they are not regular users of the service and probably reflect a one-time experience that might not be an accurate representation of the service pattern. The random distribution of the online questionnaire might have limited the variety of the sample, excluding older illiterate people from participation in the study. In addition, this study did not evaluate the Wasfaty e-prescribing system medication errors. Therefore, further study will be conducted to evaluate the effect of medication errors and extend the research. The current study was conducted to assess the digitalization of medication prescriptions and the shifting of the receipt of medications from pharmacies located within primary healthcare centres to community pharmacies. The study suggested moderate satisfaction levels overall, with highest satisfaction given to pharmacy personnel in terms of their knowledge, communication skills, counselling skills, and therapy management, as well as openness and approachability. Pharmacy premises-related features in terms of the facilities’ availability and accessibility also scored high. Patient experience with Wasfaty was equally rated with their experience with the pharmacy-related aspects. Patients were satisfied with pharmacists’ availability, the given instructions, privacy, and confidentially, but were less satisfied with medication availability and communication between pharmacists and prescribers.


L. monocytogenes) [Mycotoxin contamination is an important issue that has plagued the world. Mycotoxins not only contaminate food and feed but, more importantly, can further cause poisoning in humans and animals through food and feed. Moreover, children seem to be more sensitive to mycotoxins . The ristogenes)  and virutogenes) . On the togenes) ,9.Currently, studies have focused on the potential mechanisms of mycotoxin immunotoxicity and found that oxidative stress, apoptosis, and autophagy are important toxic effects and mechanisms. Researchers have tried to reveal the upstream regulatory mechanisms from signaling pathways such as hemopoietic cell kinase (HCK) and RNA-activated protein kinase R (PKR) ,11. In a2/M transition by increasing the expression of cyclin B and SA-β-gal activity [CXCL8 expression and causes cell cycle arrest [0G1 cell cycle arrest by downregulating cyclin D1 expression [Indeed, hypoxia is involved in the toxic mechanisms of mycotoxins ,18. In aactivity ,32. Aflae arrest . In addipression . We belipression , we suspToxins . The aim of this Special Issue is to assemble reviews and original research articles on mycotoxins and toxins, including their new toxic mechanisms and signaling and especially on hypoxia, cell senescence, and immunosuppressive effects. We welcome researchers to submit their relevant research articles and excellent work on mycotoxins and toxins to this Special Issue with the aim of sharing the latest ideas and progresses in this field with the readers of Toxins.Therefore, under these circumstances, we are pleased to have this opportunity to compile a Special Issue entitled “Hypoxia, Cellular Senescence, and Immunosuppression: Emerging Toxic Mechanisms of Mycotoxins and Toxins” for