The Efficacy and Safety of Complementary and Alternative Medicine for Depression: An Umbrella Review.

OBJECTIVE: Depression is a major public health problem. Many complementary and alternative medicine (CAM) interventions have been suggested as potential treatments. METHODS: We comprehensively searched for relevant systematic reviews and meta-analyses in the PubMed, EMBASE, Web of Science, and Cochrane Library databases. We assessed effectiveness based on efficiency and changes in Depression Assessment Scale scores and safety based on adverse events. RESULTS: This umbrella review included twenty-two eligible articles. Yueju antidepressant and Electro-acupuncture (EA) improved depression symptoms better than antidepressants. In addition, omega-3 fatty acids (n-3PUFAs), exercise, manual acupuncture (MA), Hypericum mono-preparations, relaxation, and Vitamin D showed better efficacy than placebo and control. GPD as adjunctive therapies have higher efficacy rates than antidepressant, and MA and Yueju antidepressants have a better safety profile than antidepressants. CONCLUSION: Our study demonstrated that 10 CAMs can effectively improve the condition of patients with clinical depression.

Fifteen years of engine-driven nickel-titanium reciprocating instruments, what do we know so far? An umbrella review.

Numerous systematic reviews (SRs) have produced conflicting findings on engine-driven nickel-titanium reciprocating instruments (reciprocating instruments) since Yared's seminal study 15 years ago. This umbrella review analysed SRs examining the clinical and laboratory evidence regarding reciprocating instruments for root canal treatment. SRs that evaluated qualitatively and/or quantitatively the outcomes postoperative pain, oral health-related quality of life (OHRQoL), shaping ability, debris extrusion, microbial load, endotoxins reduction, cyclic fatigue, file fracture, dentinal cracks and root canal filling removal were included. The AMSTAR 2 tool was used to evaluate SRs quality, while the ROBIS tool to assess risk of bias (RoB). Forty SRs were included. The SRs revealed predominantly 'high' RoB and 'critically low' quality. Most focused on technical outcomes, exhibiting significant methodological and statistical heterogeneity. Findings suggest comparable efficacy between reciprocating and rotary instruments. However, due to the scarcity of high-quality evidence, future well-designed studies and reviews considering core outcome measures are needed.

Efficacy and safety of ozone therapy for knee osteoarthritis: an umbrella review of systematic reviews.

The objective of this study is to evaluate the effectiveness and safety of ozone therapy (OT) in the treatment of knee osteoarthritis (KOA), which is the most common form of the disease. We analysed systematic reviews (SRs) of randomised controlled trials (RCTs) using the "A MeaSurement Tool to Assess systematic Reviews" (AMSTAR2) instrument to evaluate their quality. We developed a narrative synthesis report with eight SRs (15 RCTs/3,685 patients) to summarise the findings. The AMSTAR2 analysis indicated that all reviews had critically low confidence ratings. Statistically significant effects in pain reduction using OT compared to placebo groups were reported in three SRs. OT was shown to be comparable to other therapies in one SR and not superior in the other five. Six SRs highlighted the need for additional RCTs with improved methodological quality to confirm the efficacy of OT for KOA. SRs found fewer consistent effects for improving joint function. Regarding safety, seven SRs reported a low prevalence of minor adverse events linked with OT. Finally, this umbrella review highlights the beneficial effects and safety of OT in the treatment of KOA, particularly in pain control. The low methodological quality of RCTs and SRs limits the possibility of drawing conclusions on the effectiveness of the procedure in comparison to other therapies. Ensure adequate compliance with guidelines such as Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and AMSTAR2 has the ability to improve the quality of SRs in this area.

Modeling the Cellular Uptake of Functionalized Carbon Nanohorns Loaded with Cisplatin through a Breast Cancer Cell Membrane.

The cisplatin encapsulation into carbon nanohorns (CNH) is a promising nanoformulation to circumvent the drug dissipation and to specifically accumulate it in tumor sites. Herein, biased molecular dynamics simulations were used to analyze the transmembrane transport of the CNH loaded with cisplatin through a breast cancer cell membrane prototype. The simulations revealed a four-stage mechanism: approach, insertion, permeation, and internalization. Despite the lowest structural disturbance of the membrane provided by the nanocarrier, the average free energy barrier for the translocation was 55.2 kcal mol-1, suggesting that the passive process is kinetically unfavorable. In contrast, the free energy profiles revealed potential wells of -6.8 kcal mol-1 along the insertion stage in the polar heads region of the membrane, which might enhance the retention of the drug in tumor sites; therefore, the most likely cisplatin delivery mechanism should involve the adsorption and retention of CNH on the surface of cancer cells, allowing the loaded cisplatin be slowly released and passively transported through the cell membrane.

Climate change in the Central Amazon and its impacts on frog populations.

Frog population declines have already been observed in the central Amazon even for common species that are considered not to be in danger of extinction. The Amazon is close to its limit of tolerated deforestation, and parts of the forest have already been modified by climate change, which raises questions about how the fauna in these areas would adapt to climate changes by the middle and the end of this century. In this study we used population density data on seven species of Amazonian frogs and analyzed the relationship between the activity of these species and temperature, precipitation, and relative humidity. We also used the least-squares method with logarithmic models to assess whether climate change projected by the Intergovernmental Panel on Climate Change (IPCC) would be an indicator of the population dynamics of these species. Our results suggest that even common species may be may experience population declines and extinction in the next decades due to climate changes.

The complementary and alternative roles of elemene injection in cancer: An umbrella review.

BACKGROUND: In the past, many meta-analyses (MAs) suggested that elemene injection (EI) played a complementary and alternative role in cancer treatment. However, some results were contradictory and a lot of evidences weren't classified. Thus, their clinical guidance effect was very limited. METHODS: Two reviewers independently retrieved 8 databases from their origin to May 19, 2023 and appropriate MAs were taken into consideration. A pooled analysis was conducted to merge results extracted from trials of included MAs. The methodological quality of MAs and the evidence certainty of pooled results were assessed. RESULTS: 31 MAs were taken into analysis with poor methodological quality. The main weaknesses were in the areas of heterogeneity analysis, bias risk, and literature selection. According to the present evidence, on the one hand, compared with conventional treatment (CT) alone, EI combined with CT may significantly enhance short-term or long-term efficacy and reduce adverse reactions caused by CT in multiple cancers. On the other hand, using EI alone also can improve ORR in the malignant (pleural) effusion and lessen the recurrence rate in bladder cancer obviously with fewer adverse reactions compared with CT alone. However, this evidence was rated as moderate to very low certainty mainly due to the risk of bias in clinical trials. CONCLUSION: EI may be a viable medication for the treatment of cancer although more convincing trials are still required to demonstrate its alternative and complementary benefits. Besides, it seems to have a broad potential for further development in immunotherapy, drug delivery technique, and predictive factor.

The negative effect of concomitant medications on immunotherapy in non-small cell lung cancer: An umbrella review.

BACKGROUND: Conflicting results about the effect of concomitant medications on immunotherapy in non-small cell lung cancer (NSCLC) were reported by many meta-analyses (MAs), and the certainty of evidence linking concomitant medications with immunotherapy efficacy has not been quantified, which may cause some evidence to be misinterpreted. METHODS: Four databases including Embase, Cochrane Library, PubMed, and Web of Science were searched from inception to January 2023 in English. Based on prospective or retrospective clinical controlled trials including immunotherapy with concomitant medications or not in NSCLC, quantitative MAs reporting the efficacy of immunotherapy with binary direct comparison and enough extractable data were collected. The methodological quality, reporting quality, and risk of bias of included MAs were evaluated respectively. New meta-analyses were conducted and their evidence certainty was classified as nonsignificant, weak, suggestive, highly suggestive, or convincing. RESULTS: Fifteen MAs with 5 medications were included. After being assessed by AMSTAR-2, PRISMA, and ROBIS, the major shortcomings were focused on the registration of protocol, literature retrieval or data extraction, implementation of sensitivity analysis or evidence certainty assessment, and incomplete reporting in the section of method and result. New pooled analyses indicated that antibiotics (HR = 1.545[1.318-1.811]), steroids (HR = 1.784[1.520-2.093]), proton pump inhibitors (PPIs) (HR = 1.303[1.048-1.621]) and opioids (HR = 1.910[1.213-3.006]) could shorten overall survival (OS) in patients with NSCLC receiving immunotherapy. Besides, antibiotics (HR = 1.285[1.129-1.462]) and steroids (HR = 1.613[1.315-1.979]) were harmful to progression-free survival (PFS) in these patients significantly. No negative effect was found in nonsteroidal anti-inflammatory drugs and the objective response rate of all medications. High-level evidence suggested that using PPIs before or after the initiation of immunotherapy and using steroids during the first-course immunotherapy could weaken the OS of patients with NSCLC. Meanwhile, the negative effects of antibiotics and opioids on OS or PFS were only supported by moderate or low-level evidence. CONCLUSIONS: The concurrent usage of PPIs or steroids adversely affects the survival of patients with NSCLC receiving immunotherapy. Future investigations are required to ascertain whether these adverse effects are primarily attributed to the comorbidities or the concurrent medications.

Association between Apical Periodontitis and Chronic Diseases: An Umbrella Review.

Introduction: To assess the methodological quality of systematic reviews (SRs) that evaluated the association between apical periodontitis (AP) and chronic diseases. Materials and Methods: A systematic search was performed in the databases PubMed, Virtual Health Library, Scopus, Cochrane Library, Embase, Web of Science and Open Grey. SRs that evaluated the association between any chronic disease and AP, and that had performed a valid risk of bias assessment were included. The AMSTAR-2 tool was used for quality assessment and each included systematic review received a final categorization as having "high", "moderate", "low", or "critically low" quality. Results: Nine studies that met the eligibility criteria were included. The diseases investigated were cardiovascular diseases, diabetes mellitus, HIV, osteoporosis, chronic liver disease, blood disorders and autoimmune diseases. The systematic reviews included in this umbrella review showed a 'low' to 'high' quality of evidence. Conclusion: There are substantial heterogeneity and several methodological concerns in the included studies. It was observed a positive association between diabetes mellitus and apical periodontitis with limited evidence, no association between HIV and apical periodontitis and a positive association between apical periodontitis and cardiovascular disease, blood disorders, chronic liver disease, osteoporosis and autoimmune diseases with moderate evidence.

Short implants compared to regular dental implants after bone augmentation in the atrophic posterior mandible: umbrella review and meta-analysis of success outcomes.

PURPOSE: To assess the body of evidence of short versus regular implants after bone augmentation (BA) in the atrophic posterior mandible in the context of implant treatment success outcomes. METHODS: Seven databases, two registries, and reference lists were searched for systematic reviews and meta-analysis (SR/MA), randomized controlled trials (RCTs) and longitudinal studies published in English, Spanish or German since 2012. Confidence in the SR/MA methodology was evaluated using AMSTAR-2 and the risk of bias of primary studies using Cochrane's RoB 2.0 and ROBINS-I. A random-effects meta-analysis and a meta-regression were performed for continuous and dichotomous outcomes. GRADE approach was used to assess the certainty of the evidence. RESULTS: Eighteen SRs/MAs, most of them "critically low" and "low" confidence with substantial overlap, included 14 relevant RCTs with a high risk of bias. A cohort study with moderate risk of bias was added. Quantitative synthesis of 595 implants and 281 hemiarches/patients indicates that the use of short implants (< 10 mm) compared to regular implants and BA may reduce implant failure at 1-year follow-up, and marginal bone loss (MBL) at 3-, 5-, and 8-year follow-up; is likely to reduce the risk of biological complications at 1-, 3-, 5-, and 8-year follow-up; and may be the patient's preferred alternative. There is a correlation between bone height, MBL and biological complications. CONCLUSIONS: The available evidence partially suggests that the use of short implants could decrease implant failure, MBL, and biological complications, and increase patient satisfaction. However, given the need for further RCTs and real-world evidence to fully evaluate short- and long-term outcomes, it would be prudent for clinicians to carefully consider the individual needs and circumstances of the patients before deciding whether to use short implants. Trial registration PROSPERO CRD42022333526.

An Umbrella Review With Meta-Analysis of Chest Computed Tomography for Diagnosis of COVID-19: Considerations for Trauma Patient Management.

Background: RT-PCR testing is the standard for diagnosis of COVID-19, although it has its suboptimal sensitivity. Chest computed tomography (CT) has been proposed as an additional tool with diagnostic value, and several reports from primary and secondary studies that assessed its diagnostic accuracy are already available. To inform recommendations and practice regarding the use of chest CT in the in the trauma setting, we sought to identify, appraise, and summarize the available evidence on the diagnostic accuracy of chest CT for diagnosis of COVID-19, and its application in emergency trauma surgery patients; overcoming limitations of previous reports regarding chest CT accuracy and discussing important considerations regarding its role in this setting. Methods: We conducted an umbrella review using Living Overview of Evidence platform for COVID-19, which performs regular automated searches in MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and more than 30 other sources. The review was conducted following the JBI methodology for systematic reviews. The Grading of Recommendations, Assessment, Development, and Evaluation approach for grading the certainty of the evidence is reported (registered in International Prospective Register of Systematic Reviews, CRD42020198267). Results: Thirty studies that fulfilled selection criteria were included; 19 primary studies provided estimates of sensitivity (0.91, 95%CI = [0.88-0.93]) and specificity (0.73, 95%CI = [0.61; 0.82]) of chest CT for COVID-19. No correlation was found between sensitivities and specificities (ρ = 0.22, IC95% [-0.33; 0.66]). Diagnostic odds ratio was estimated at: DOR = 27.5, 95%CI (14.7; 48.5). Evidence for sensitivity estimates was graded as MODERATE, and for specificity estimates it was graded as LOW. Conclusion: The value of chest CT appears to be that of an additional screening tool that can easily detect PCR false negatives, which are reportedly highly frequent. Upon the absence of PCR testing and impossibility to perform RT-PCR in trauma patients, chest CT can serve as a substitute with increased value and easy implementation. Systematic Review Registration: [www.crd.york.ac.uk/prospero], identifier [CRD42020198267].

A Computational-Experimental Investigation of the Molecular Mechanism of Interleukin-6-Piperine Interaction.

Herein, we elucidate the biophysical aspects of the interaction of an important protein, Interleukin-6 (IL6), which is involved in cytokine storm syndrome, with a natural product with anti-inflammatory activity, piperine. Despite the role of piperine in the inhibition of the transcriptional protein NF-κB pathway responsible for activation of IL6 gene expression, there are no studies to the best of our knowledge regarding the characterisation of the molecular interaction of the IL6-piperine complex. In this context, the characterisation was performed with spectroscopic experiments aided by molecular modelling. Fluorescence spectroscopy alongside van't Hoff analyses showed that the complexation event is a spontaneous process driven by non-specific interactions. Circular dichroism aided by molecular dynamics revealed that piperine caused local α-helix reduction. Molecular docking and molecular dynamics disclosed the microenvironment of interaction as non-polar amino acid residues. Although piperine has three available hydrogen bond acceptors, only one hydrogen-bond was formed during our simulation experiments, reinforcing the major role of non-specific interactions that we observed experimentally. Root mean square deviation (RMSD) and hydrodynamic radii revealed that the IL6-piperine complex was stable during 800 ns of simulation. Taken together, these results can support ongoing IL6 drug discovery efforts.

Photodynamic therapy for root canal disinfection in endodontics: an umbrella review.

To evaluate and synthesize the evidence from the individual reviews that evaluated the efficacy of PDT therapy in root canal disinfection by undertaking an umbrella review. The protocol of the review was registered in the PROSPERO database under number CRD42021214056. The literature search was conducted using the following electronic databases: PubMed, Scopus, Web of Science, BVS, Cochrane Database of Systematic Reviews, Embase, and Epistemonikos, from inception to July 2021. Systematic reviews that evaluated the efficacy of PDT for root canal disinfection were included. Two authors independently performed a literature search, data extraction, and quality assessment of the included studies. Any disagreements were resolved by a third reviewer. The quality of the reviews was assessed using the AMSTAR 2 tool and the final categorization of each systematic reviews was classified as of "high," "moderate," "low," or "critically low" quality. Six systematic reviews were included in the current umbrella review and all of them were graded as critically low quality. From the critically low-quality evidence available, this umbrella review showed that the efficacy of PDT in root canal disinfection remains yet undetermined.

Regenerative Endodontics Success Factors and their Overall Effectiveness: An Umbrella Review.

Introduction: Regenerative endodontics is a developing field of dentistry and aims to recover the physiological and anatomical functions of the tooth for cases of severe dental caries, pulpal pathologies and dental trauma. Materials and Methods: This umbrella review seeks to discover the scientific evidence on the effectiveness and the factors result in successful regenerative endodontic therapies in teeth with necrotic pulps and with incomplete root development. The study was conducted following the PRISMA Guidelines. There were no restrictions regarding search period. A comprehensive literature search was carried out in EMBASE, LILACS, PubMed, Cochrane, Scopus, and Google Scholar. A quality evaluation was conducted by using AMSTAR-2. A descriptive analysis of the included systematic reviews and meta-analysis were conducted. Results: Thirteen descriptive systematic reviews and 7 meta-analyses were included. Three articles evidenced low methodological quality according to AMSTAR-2 tool. Overall success rates for the endodontic regeneration procedures ranged from 50% to 98% and the survival rates were between 94% and 100%. Pulp regeneration had a high success rate, evidenced by factors such as the resolution of symptoms, healing, increased root length, dentin thickening and recovery of sensitivity. Follow-up varied from 1 to 48 months for the original studies included in the systematic reviews and meta-analyses. Conclusions: Endodontic practice offers the clinician a good treatment option in case of necrotic pulp with immature roots such as the endodontic regeneration, that is supported by high and moderate quality scientific literature.

Bibliometric study of 'overviews of systematic reviews' of health interventions: Evaluation of prevalence, citation and journal impact factor.

Overviews synthesising the results of multiple systematic reviews help inform evidence-based clinical practice. In this first of two companion papers, we evaluate the bibliometrics of overviews, including their prevalence and factors affecting citation rates and journal impact factor (JIF). We searched MEDLINE, Epistemonikos and Cochrane Database of Systematic Reviews (CDSR). We included overviews that: (a) synthesised reviews, (b) conducted a systematic search, (c) had a methods section and (d) examined a healthcare intervention. Multivariable regression was conducted to determine the association between citation density, JIF and six predictor variables. We found 1218 overviews published from 2000 to 2020; the majority (73%) were published in the most recent 5-year period. We extracted a selection of these overviews (n = 541; 44%) dated from 2000 to 2018. The 541 overviews were published in 307 journals; CDSR (8%), PLOS ONE (3%) and Sao Paulo Medical Journal (2%) were the most prevalent. The majority (70%) were published in journals with impact factors between 0.05 and 3.97. We found a mean citation count of 10 overviews per year, published in journals with a mean JIF of 4.4. In multivariable analysis, overviews with a high number of citations and JIFs had more authors, larger sample sizes, were open access and reported the funding source. An eightfold increase in the number of overviews was found between 2009 and 2020. We identified 332 overviews published in 2020, which is equivalent to one overview published per day. Overviews perform above average for the journals in which they publish.

Evidence-based umbrella review of cognitive effects of prefrontal tDCS.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique, which has been increasingly used as an investigational tool in neuroscience. In social and affective neuroscience research, the prefrontal cortex has been primarily targeted, since this brain region is critically involved in complex psychobiological processes subserving both Șhotș and Școldș domains. Although several studies have suggested that prefrontal tDCS can enhance neuropsychological outcomes, meta-analyses have reported conflicting results. Therefore, we aimed to assess the available evidence by performing an umbrella review of meta-analyses. We evaluated the effects of prefrontal active vs sham tDCS on different domains of cognition among healthy and neuropsychiatric individuals. A MeaSurement Tool to Assess Systematic Reviews 2 was employed to evaluate the quality of meta-analyses, and the GRADE system was employed to grade the quality of evidence of every comparison from each meta-analysis. PubMed/MEDLINE, PsycINFO and the Cochrane Database of Systematic Reviews were searched, and 11 meta-analyses were included resulting in 55 comparisons. Only 16 comparisons reported significant effects favoring tDCS, but 13 of them had either very low or low quality of evidence. Of the remaining 39 comparisons which reported non-significant effects, 38 had either very low or low quality of evidence. Meta-analyses were rated as having critically low and low quality. Among several reasons to explain these findings, the lack of consensus and reproducibility in tDCS research is discussed.

Sampling techniques and environmental variables influence the distribution of pseudoscorpions in urban forest fragments in the central Amazon / Métodos de amostragem e variáveis ambientais influenciam a distribuição de pseudoescorpiões em fragmentos florestais urbanos na Amazônia central

The growth of urban landscapes has genarally reduced biodiversity worldwide. Invertebrates have explored different environments, and it usually takes different sampling techniques to get a representative sample of the species assemblage in a given location. Some studies have sought to determine the minimum necessary number of sampling techniques, including ecological relationships or costs to guide the sampling protocol. In the Amazon, the effect of soil characteristics on invertebrate distribution is well known. We evaluated if sampling techniques have a complementary effect on the detection of pseudoscorpion assemblages and tested whether environmental variables affect the distribution of pseudoscorpion species. The study sites were two urban forest fragments in the city of Manaus, in the central Amazon. In each fragment, we sampled 20 palm trees using the beating technique, and installed transects with 12 sampling points for collection of soil and litter samples for extraction of arthropods in a Berlese funnel and a Winkler extractor, respectively. We collected 267 individuals of 11 species of pseudoscorpions. Most records were obtained through the Winkler extraction in both fragments. The assemblage from the palm trees was different from that in the edaphic samples. Pseudoscorpion species composition also differed significantly between soil and litter, and was influenced by potassium concentration. The number of species in the fragments and the environmental effect on the distribution of pseudoscorpions was similar to that recorded in environmental protection areas, evidencing that urban forest fragments can serve as an efficient repository of Amazonian pseudoscorpion biodiversity.(AU)

O crescimento das paisagens urbanas geralmente reduziu a biodiversidade em todo o mundo. Os invertebrados exploram diferentes ambientes, e geralmente são necessárias diferentes técnicas de amostragem para obter uma amostra representativa da assembleia de espécies em um determinado local. Alguns estudos têm buscado determinar o número mínimo necessário de técnicas de amostragem, incluindo relações ecológicas ou custos para orientar o protocolo de amostragem. Na Amazônia, o efeito das características do solo na distribuição dos invertebrados é bem conhecido. Nós avaliamos se as técnicas de amostragem têm um efeito complementar na detecção de assembleias de pseudoescorpiões e testamos se as variáveis ambientais afetam a distribuição das espécies de pseudoescorpiões. Os locais de estudo foram dois fragmentos florestais urbanos na cidade de Manaus, Amazônia central. Em cada fragmento, amostramos 20 palmeiras com guarda-chuva entomológico e instalamos transectos com 12 pontos amostrais para coleta de solo e serrapilheira para extração de artrópodes em funil de Berlese e extrator de Winkler, respectivamente. Coletamos 267 indivíduos de 11 espécies de pseudoescorpiões. A maioria dos registros foi obtida com Winkler em ambos fragmentos. A assembleia em palmeiras foi diferente das amostras edáficas. A composição de espécies de pseudoescorpiões também diferiu significativamente entre solo e serapilheira, e foi influenciada pela concentração de potássio. O número de espécies nos fragmentos e o efeito ambiental na distribuição de pseudoescorpiões foram semelhantes aos registrados em áreas de proteção ambiental, evidenciando que fragmentos florestais urbanos podem servir como um eficiente repositório da biodiversidade de pseudoescorpiões amazônicos.(AU)

Appraising the effectiveness of electrical and magnetic brain stimulation techniques in acute major depressive episodes: an umbrella review of meta-analyses of randomized controlled trials

Electrical and magnetic brain stimulation techniques present distinct mechanisms and efficacy in the acute treatment of depression. This was an umbrella review of meta-analyses of randomized controlled trials of brain stimulation techniques for managing acute major depressive episodes. A systematic review was performed in the PubMed/MEDLINE databases from inception until March 2020. We included the English language meta-analysis with the most randomized controlled trials on the effects of any brain stimulation technique vs. control in adults with an acute depressive episode. Continuous and dichotomous outcomes were assessed. A Measurement Tool to Assess Systematic Reviews-2 was applied and the credibility of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework. Seven meta-analyses were included (5,615 patients), providing evidence for different modalities of brain stimulation techniques. Three meta-analyses were evaluated as having high methodological quality, three as moderate, and one as low. The highest quality of evidence was found for high frequency-repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation, and bilateral rTMS. There is strong clinical research evidence to guide future clinical use of some techniques. Our results confirm the heterogeneity of the effects across these techniques, indicating that different mechanisms of action lead to different efficacy profiles.

Finite-temperature effect in the O-acylation of (R,S)-propranolol catalyzed by Candida antarctica lipase B.

CalB is a triacylglycerol hydrolase (E.C.3.1.1.3) used in the O-acylation of the beta-adrenergic blocking agent (R,S)-propranolol. The catalytic mechanism involves two steps: enzyme acylation and enzyme deacylation. The enantioselectivity of the O-acylation of (R,S)-propranolol originates from the second step, where the acyl-enzyme transfers the acyl group to the racemic substrate. This step occurs via an initial Michaelis complex (MCC) and a tetrahedral intermediate (TI-2). To gain more insight into the molecular basis of this reaction, we performed an exhaustive conformational sampling along the reaction coordinate of the enantioselective step of the reaction (MCC→TI-2→EPC) applying a QM/MM MD protocol (SCC-DFTB/CHARMM) in combination with umbrella sampling and the weighted histogram analysis method. To identify finite temperature effects we compare the PMF and the potential energy pathway. It is found that the effect of the finite temperature in this reaction is a destabilization of the tetrahedral intermediate and an increase of the barrier height of its formation. This increase is higher for the S-enantiomer.

Risk factors for eating disorders: an umbrella review of published meta-analyses

Objective: To grade the evidence about risk factors for eating disorders (anorexia nervosa, bulimia nervosa, and binge eating disorder) with an umbrella review approach. Methods: This was a systematic review of observational studies on risk factors for eating disorders published in PubMed/PsycInfo/Embase until December 11th, 2019. We recalculated random-effect meta-analyses, heterogeneity, small-study effect, excess significance bias and 95% prediction intervals, grading significant evidence (p < 0.05) from convincing to weak according to established criteria. Quality was assessed with the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool. Results: Of 2,197 meta-analyses, nine were included, providing evidence on 50 risk factors, 29,272 subjects with eating disorders, and 1,679,385 controls. Although no association was supported by convincing evidence, highly suggestive evidence supported the association between childhood sexual abuse and bulimia nervosa (k = 29, 1,103 cases with eating disorders, 8,496 controls, OR, 2.73, 95%CI 1.96-3.79, p = 2.1 x 10-9, AMSTAR-2 moderate quality) and between appearance-related teasing victimization and any eating disorder (k = 10, 1,341 cases with eating disorders, 3,295 controls, OR 2.91, 95%CI 2.05-4.12, p = 1.8x10-9, AMSTAR-2 moderate quality). Suggestive, weak, or no evidence supported 11, 29, and 8 associations, respectively. Conclusions: The most credible evidence indicates that early traumatic and stressful events are risk factors for eating disorders. Larger collaborative prospective cohort studies are needed to identify risk factors for eating disorders, particularly anorexia nervosa.

In-silico drug repurposing study: Amprenavir, enalaprilat, and plerixafor, potential drugs for destabilizing the SARS-CoV-2 S-protein-angiotensin-converting enzyme 2 complex.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that leads to coronavirus disease (COVID-19) has put public health at risk in 2020. The spike protein (SP) in SARS-CoV-2 is primarily responsible for the attachment and entry of the virus into the cell, which binds to the angiotensin-converting enzyme 2 (ACE2). Owing to the lack of an effective therapy, drug repositioning is an opportunity to search for molecules with pharmacological potential for the treatment of COVID-19. In this study, three candidates with the potential to destabilize the SP-ACE2 complex are reported. Through molecular docking, 147 drugs were evaluated and their possible binding sites in the interface region of the SP-ACE2 complex and the SP of SARS-CoV-2 were identified. The five best candidate molecules were selected for molecular dynamics studies to observe changes in interactions between SP-ACE2 and ligands with the SP-ACE2 complex. Using umbrella sampling molecular dynamics simulations, the binding energy of SP with ACE2 (-29.58 kcal/mol) without ligands, and in complex with amprenavir (-20.13 kcal/mol), enalaprilat (-23.84 kcal/mol), and plerixafor (-19.72 kcal/mol) were calculated. These drugs are potential candidates for the treatment of COVID-19 as they destabilize the SP-ACE2 complex; the binding energy of SP is decreased in the presence of these drugs and may prevent the virus from entering the cell. Plerixafor is the drug with the greatest potential to destabilize the SP-ACE2 complex, followed by amprenavir and enalaprilat; thus, these three drugs are proposed for future in vitro and in vivo evaluations.