Suicide is a global public health problem, ranking among the top 20 leading causes of mortality.

Introduction: Our meta-analysis indicated that aging influences the outcomes of acute pancreatitis (AP), however, a potential role for comorbidities was implicated, as well. Here, we aimed to determine how age and comorbidities modify the outcomes in AP in a cohort-analysis of Hungarian AP cases. Materials and Methods: Data of patients diagnosed with AP by the revised Atlanta criteria were extracted from the Hungarian Registry for Pancreatic Patients. Outcomes of interest were mortality, severity, length of hospitalization, local, and systemic complications of AP. Comorbidities were measured by means of Charlson Comorbidity Index (CCI) covering pre-existing chronic conditions. Non-parametric univariate and multivariate statistics were used in statistical analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results: A total of 1203 patients from 18 centers were included. Median age at admission was 58 years (range: 18-95 years), median CCI was 2 (range: 0-10). Only severe comorbidities (CCI ≥ 3) predicted mortality (OR = 4.48; CI: 1.57-12.80). Although severe comorbidities predicted AP severity (OR = 2.10, CI: 1.08-4.09), middle (35-64 years) and old age (≥65 years) were strong predictors with borderline significance, as well (OR = 7.40, CI: 0.99-55.31 and OR = 6.92, CI: 0.91-52.70, respectively). Similarly, middle and old age predicted a length of hospitalization ≥9 days. Interestingly, the middle-aged patients (35-64 years) were three times more likely to develop pancreatic necrosis than young adults (OR = 3.21, CI: 1.26-8.19), whereas the old-aged (≥65 years) were almost nine times more likely to develop systemic complications than young adults (OR = 8.93, CI: 1.20-66.80), though having severe comorbidities (CCI ≥ 3) was a predisposing factor, as well. Conclusion: Our results proved that both aging and comorbidities modify the outcomes of AP. Comorbidities determine mortality whereas both comorbidities and aging predict severity of AP. Regarding complications, middle-aged patients are the most likely to develop local complications; in contrast, those having severe comorbidities are prone to develop systemic complications. Studies validating the implementation of CCI-based predictive scores are awaited.

Background: The distribution and composition of cis-regulatory modules composed of transcription factor (TF) binding site (TFBS) clusters in promoters substantially determine gene expression patterns and TF targets. TF knockdown experiments have revealed that TF binding profiles and gene expression levels are correlated. We use TFBS features within accessible promoter intervals to predict genes with similar tissue-wide expression patterns and TF targets using Machine Learning (ML). Methods: Bray-Curtis Similarity was used to identify genes with correlated expression patterns across 53 tissues. TF targets from knockdown experiments were also analyzed by this approach to set up the ML framework. TFBSs were selected within DNase I-accessible intervals of corresponding promoter sequences using information theory-based position weight matrices (iPWMs) for each TF. Features from information-dense clusters of TFBSs were input to ML classifiers which predict these gene targets along with their accuracy, specificity and sensitivity. Mutations in TFBSs were analyzed in silico to examine their impact on TFBS clustering and predict changes in gene regulation. Results: The glucocorticoid receptor gene ( NR3C1), whose regulation has been extensively studied, was selected to test this approach. SLC25A32 and TANK exhibited the most similar expression patterns to NR3C1. A Decision Tree classifier exhibited the best performance in detecting such genes, based on Area Under the Receiver Operating Characteristic curve (ROC). TF target gene prediction was confirmed using siRNA knockdown, which was more accurate than CRISPR/CAS9 inactivation. TFBS mutation analyses revealed that accurate target gene prediction required  at least 1  information-dense TFBS cluster.  Conclusions: ML based on TFBS information density, organization, and chromatin accessibility accurately identifies gene targets with comparable tissue-wide expression patterns. Multiple information-dense TFBS clusters in promoters appear to protect promoters from effects of deleterious binding site mutations in a single TFBS that would otherwise alter regulation of these genes.

The Paris Agreement of 2015 marks a formal shift in global climate change governance from an international legal regime that distributes state commitments to solve a collective action problem to a catalytic mechanism to promote and facilitate transformative pathways to decarbonization. It does so through a system of nationally determined contributions, monitoring and ratcheting up of commitments, and recognition that the practice of climate governance already involved an array of actors and institutions at multiple scales. In this article, we develop a framework that focuses on the politics of decarbonization to explore policy pathways and mechanisms that can disrupt carbon lock-in through these diverse, decentralized responses. It identifies political mechanisms-normalization, capacity building, and coalition building-that contribute to the scaling and entrenchment of discrete decarbonization initiatives within or across jurisdictions, markets, and practices. The role for subnational (municipal, state/provincial) climate governance experiments in this new context is especially profound. Drawing on such cases, we illustrate the framework, demonstrate its utility, and show how its political analysis can provide insight into the relationship between climate governance experiments and the formal global response as well as the broader challenge of decarbonization.

Blood-borne pathogens such as human immunodeficiency virus (HIV), hepatitis B and C (HBV and HCV) viruses and Treponema pallidum remain a major public health problem in sub-Saharan Africa. The purpose of this study was to assess the frequency and clinical implications of HIV, HBV, HCV and Treponema pallidum markers in blood donors in a rural area of Southeast Gabon (Koula-Moutou) from 2012 to 2017.

Chronic illness affects >50% of adults in the United States and accounts for >80% of healthcare spending. The purpose of this study was to determine whether beliefs about one's chronic disease (illness representation) are associated with self-care activation, emergency department (ED) visits, or hospitalizations. Using a cross-sectional design, we recruited older adults with heart failure, chronic obstructive pulmonary disease (COPD), and chronic kidney disease. The Revised Illness Perception Questionnaire (IPQ-R) measured perceptions about disease. The Patient Activation Measure measured self-care activation. ED visits and hospitalizations were measured by self-report. IPQ-R scores were analyzed using latent profile analysis to identify subgroups. Participants included 187 adults (mean age 65 years, 54% female, 74% Black). We found three subgroups (stable, overwhelmed, and confident). Groups did not differ demographically or by disease. The stable group (few consequences, non-fluctuating pattern) had the fewest hospitalizations. The overwhelmed group (many consequences, fluctuating pattern, high negative emotion) had high hospitalizations and low self-care ability. The confident group (high disease control, well-understood) had the highest self-care ability, but also high hospitalizations. ED visits did not differ by group. We found three subgroups that differ in their illness representation and health outcomes. Findings suggest that assessing patients' illness representations may have important implications for subgroup-specific interventions.

Despite obstacles, many rural-dwelling older adults report that positive aspects of rural residence, such as attachment to community, social participation, and familiarity, create a sense of belonging that far outweighs the negative. By being part of a community where they are known and they know people, rural elders continue to find meaning, the key to achieving successful aging in this last stage of life. This scoping review explored factors influencing social participation and, through it, successful aging among rural-dwelling older adults. We sought to answer the question: what factors enhance or detract from the ability of rural-dwelling older adults to engage in social participation in rural communities? The scoping review resulted in 19 articles that highlight the importance of supports to enable older people to spend time with others, including their pets, engage in volunteer and community activities, and help maintain their home and care for their pets. Overall, the lack of services, including local health care facilities, was less important than the attachment to place and social capital associated with aging in place.

Background: Muscle health is recognized for its critical role in the functionality and well-being of older adults. Readily accessible, reliable, and inexpensive methods of measuring muscle health are needed to advance research and clinical care. Methods: In this prospective, blinded study, 27 patients underwent quantitative muscle ultrasound (QMUS), standard electrical impedance myography (sEIM), and handheld electrical impedance myography (hEIM) of the anterior thigh musculature by two independent examiners. Subjects also had dual-energy X-ray absorptiometry (DEXA) scans and standardized tests of physical function and strength. Data were analyzed for intra- and inter-rater reliability, along with correlations with DEXA and physical measures. Results: Measures of intra- and inter-rater reliability were excellent (>0.90) for all QMUS, sEIM, and hEIM parameters except intra-rater reliability of rectus femoris echointensity (0.87-0.89). There were moderate, inverse correlations between QMUS, sEIM, and hEIM parameters and measures of knee extensor strength. Moderate to strong correlations (0.57-0.81) were noted between investigational measures and DEXA-measured fat mass. Conclusions: QMUS, sEIM and hEIM were highly reliable in a controlled, same-day testing protocol. Multiple correlations with measures of strength and body composition were noted for each method. Point-of-care technologies may provide an alternative means of measuring health.

Human papillomavirus (HPV) cause common warts, laryngeal papilloma, and genital condylomata and might lead to development of cervical cancer. Lactoferrin (LF) is a member of the transferrin family, which has antiviral activity against HPV-16.  LF is an important player in the defense against pathogenic microorganisms and has also been shown to have activity against several viruses including herpesvirus, adenovirus, rotavirus, and poliovirus. Bovine LF (BLF) has been reported to be a more potent inhibitor of HPV entry in comparison to human LF. The goal of the present study is to formulate, evaluate and optimize transfersomal vesicles as a non-invasive transdermal delivery system which assumed to be a suitable for treatment of genital warts. Transfersomes have been prepared by two methods including reverse phase evaporation and thin film hydration with different ratios of cholesterol: lecithin: DOTAP in the presence of SDS or Tween 80. The transferosomes were then evaluated regarding size, polydispersity, and LF loading. In-vitro release studies in pH 5.3 and 7.4, stability evaluation in 4 °C and 25 °C, and TEM imaging hve been performed on optimized transferosomal lactoferrin. The optimized transferosomes were found to have 100 nm sizes with good polydispersity index and encapsulation efficiency of 91% for lactoferrin as well as sustained release of lactoferrin during 24 h. Transferosomal lactoferrin efficacy was evaluated by MTT assay. It was seen that the viral inhibitory concentration (IC50) of transfersomal lactoferrin has been significantly improved to nearly one tenth in comparison to free lactoferrin.

Terpenes are active constituents of many pharmaceutical dosage forms with natural products origin. One of the challenges in developing dosage forms with herbal origin is their standardization as pharmaceutical products. GC-Mass is the most decisive and reliable technique to fulfill the requirements in this regard. In the present study, a reliable, rapid, and accurate method was developed for determination of 7 monoterpenoids in two selected pharmaceutical dosage forms (rowatinex and rowachol soft gelatin capsules) by gas chromatography-mass spectrometry triple quadrupole selected ion monitoring GC/MS-TQ-SIM. The method was validated for various parameters such as precision, linearity, accuracy, solution stability, limit of detection, and quantification. The average recovery of terpens was in the range of 91.6-105.7%. The method was proved to be repeatable with RSD in the range of 0.28-11.18 for all of the concentration levels. The developed method is simple, rapid, and sensitive and was applied for determination of alpha pinene, camphene, beta pinene, cineol, fenchone, borneol, trans-anethol and menthol in a few batches of rowachol and rowatinex capsules purchased from local drug stores.

Some new diazo incorporated coumarin compounds were designed and synthesized to evaluate their anti-HIV activity. Overall, compounds were active against HIV at 100 μM. Additionally, no cytotoxic effect was observed at this concentration. The compound with 4-chlorobenzyl group indicated the best anti-HIV activity (52%). Docking studies using the later crystallographic data available for PFV integrase showed similar binding modes to HIV-1 integrase inhibitors. On the basis of these data, nitrogen atoms of 1,3,4-oxadiazole ring have been involved in the Mg2+ chelation and 4-chlorobenzyl group occupies the same position as 4-flourobenzyl group of raltegravir in the active site. In addition, in silico ADME assay demonstrated favorable physicochemical properties for the new designed compounds. Thus, synthesized structures could be introduced as a novel template for designing safe anti-HIV compounds with integrase inhibitory potential.

Emerging line research showed that silk nanoparticles (NPs) have toxicity on the fibroblast and Huvec cells without any toxicity recognized mechanisms. Recently, it suggested peripheral arterial disease confounds almost eight million Americans. Also, due to the main effect of fibroblast in a production of extracellular matrix (ECM), adhesive molecules, glycoproteins and various cytokines, it decided to define the toxicity mechanistic of silk NPs in fibroblast and Huvec cells based on oxidative stress markers. Therefore, it investigated whether silk NPs is able to induce any abnormality in the fibroblast and Huvec cells based on reliable and documented oxidative stress methods. Our results indicated that silk NPs (0.5, 1 and 2 mg/mL) induces cellular and mitochondrial dysfunction including an increase in ROS production, lipid peroxidation, mitochondria membrane potential (MMP) collapse, and oxidation of thiol groups which caused to cytochrome c release. Besides, lysosomal integrity damage and decreased in ATP/ADP ratio proposed disruptive effect of silk NPs on the mitochondrial respiratory chain and cell death signaling induction.

A group of 4-month-old beef calves were examined for clinical respiratory disease with labored breathing, coughing, and fevers of over 104°F. Necropsy of one of the calves revealed lungs that were not collapsed but had red mottled appearance on cut surface. Assessment of lung tissue by bacterial culture and PCR did not reveal bovine bacterial or viral respiratory pathogens. Histopathology of affected tissues and lymph nodes revealed larval ascarid nematodes. In combination with phylogenetic analysis, amplification and sequencing of ITS1 was used to identify the larvae as Ascaris.

The aim of the present study was to evaluate the relationship between social deprivation indexes and anti-influenza vaccination coverage in the elderly population (over 65 years old) in Sardinia. This relationship was first observed in a regional context. An already-known deprivation index was used, and its trivial relationship with anti-influenza vaccination coverage was evaluated. Secondly, the same relationship was assessed in the homogeneous area of the Municipality of Sassari. This required the adoption of an ad hoc deprivation index, which allowed us to stratify the population into deprivation groups and to correlate vaccination coverage with socio-economic variables. The results showed that regional anti-influenza vaccination coverage increased linearly as deprivation decreased. This trend was confirmed in the Municipality of Sassari. Pearson's analysis highlighted factors that significantly correlate with vaccination coverage. In Sardinia, the relationship between anti-influenza vaccination coverage and socio-economic status is consistent with the international panorama, and highlights the necessity to implement interventions to promote vaccination coverage among the elderly.

Background: Kenya introduced the monovalent Rotarix® rotavirus group A (RVA) vaccine nationally in mid-2014.  Long-term surveillance data is important prior to wide-scale vaccine use to assess the impact on disease and to investigate the occurrence of heterotypic strains arising through immune selection. This report presents baseline data on RVA genotype circulation patterns and intra-genotype genetic diversity over a 7-year period in the pre-vaccine era in Kilifi, Kenya, from 2002 to 2004 and from 2010 to 2013. Methods: A total of 745 RVA strains identified in children admitted with acute gastroenteritis to a referral hospital in Coastal Kenya, were sequenced using the di-deoxy sequencing method in the VP4 and VP7 genomic segments (encoding P and G proteins, respectively). Sequencing successfully generated 569 (76%) and 572 (77%) consensus sequences for the VP4 and VP7 genes respectively. G and P genotypes were determined by use of BLAST and the online RotaC v2 RVA classification tool. Results: The most common GP combination was G1P[8] (51%), similar to the Rotarix® strain, followed by G9P[8] (15%) , G8P[4] (14%) and G2P[4] (5%).  Unusual GP combinations-G1P[4], G2P[8], G3P[4,6], G8P[8,14], and G12P[4,6,8]-were observed at frequencies of <5%. Phylogenetic analysis showed that the infections were caused by both locally persistent strains as evidenced by divergence of local strains occurring over multiple seasons from the global ones, and newly introduced strains, which were closely related to global strains. The circulating RVA diversity showed temporal fluctuations both season by season and over the longer-term. None of the unusual strains increased in frequency over the observation period.   Conclusions: The circulating RVA diversity showed temporal fluctuations with several unusual strains recorded, which rarely caused major outbreaks.  These data will be useful in interpreting genotype patterns observed in the region during the vaccine era.

The RNA-guided endonuclease CRISPR-Cas system from Streptococcus pyogenes (SpCas9) is widely used for generating genetically modified mice via zygotic microinjection. Although SpCas9 is a potent mutagen, it requires an NGG proto-spacer adjacent motif (PAM) at the target site, restricting sequence targetability. Here, we show that RNA-guided endonucleases that utilize a range of alternative PAM sequences can edit the mouse genome at the neurog3 (Ngn3) locus: SpCas9 VQR (NGAN PAM), SpCas9 VRER (NGCG), AsCas12a (TTTN), SaCas9 (NNGRRT), and SaCas9 KKH (NNNRRT). Additional experiments targeting tyrosinase and frizzled3 with SaCas9 KKH and its parent protein demonstrated that these endonucleases generated mutations in up to 100% of embryos across three loci. Remarkably, in contrast to wild-type SpCas9, these endonucleases frequently generated mutant embryos that retain unmodified alleles in both template-free and HDR-repair experiments. Our findings broaden PAM recognition options for mouse genome editing and identify SaCas9/SaCas9 KKH as useful alternatives when targeting genes with null lethal phenotypes.

Several therapeutic products based on mesenchymal stem cells (MSCs) have been translated into clinical applications. MSCs should undergo in vitro culture before a sufficient quantity can be achieved. Hence, both expansion kinetics and the biological characteristics of derived cells from primary culture are pertinent to their applications. In the present study, MSCs were isolated from rat bone marrow and adipose tissue (designated as bMSCs and aMSCs, respectively) and cells were comparatively analyzed regarding cell morphology, proliferation, colony formation, differentiation potential, and immunophenotype following the long-term subculture. No apparent differences could be noticed concerning the morphology between bMSCs and aMSCs. The long-term subculture made both types of cells smaller, weakened their colony-forming ability, and stimulated the proliferation rate. However, bMSCs demonstrated better proliferation and colony-forming ability than aMSCs. No significant difference was observed about the expression of some immunophenotypes (i.e. CD29+/CD90+/CD34-/CD45-) regardless of cell types or population doublings. Notably, bMSCs, but not aMSCs, maintained the differentiation potential well after the long-term subculture. The present study demonstrates that MSCs derived from different tissues can be well expanded for the long term, although cells display gradually declined self-renewal and differentiation potentials to different extents depending on the tissue origins.

Decellularization is a process that involves the removal of cellular material from the tissues and organs while maintaining the structural, functional, and mechanical properties of extracellular matrix. The purpose of this study was to carry out decellularization of rat adipose tissue, diaphragm, and heart by using two different methods in order to compare their efficiency and investigate proliferation profiles of rat adipose-tissue-derived mesenchymal stem cells (AdMSCs) on these scaffolds. Tissues were treated with an optimized detergent-based decellularization (Method A) and a freeze-and-thaw-based decellularization (Method B). AdMSCs were then seeded on scaffolds having a density of 2 × 105 cells/scaffold and AO/PI double-staining and MTT assays were performed in order to determine cell viability. In this study, which is the first research comparing two methods of decellularization of an adipose tissue, diaphragm, and heart scaffolds with AdMSCs, Method A provided efficient decellularization in these three tissues and it was shown that these porous scaffolds were cyto-compatible for the cells. Method B caused severe tissue damage in diaphragm and insufficient decellularization in heart whereas it also resulted in cyto-compatible adipose tissue scaffolds.

Toxoplasma gondii has a complex life cycle involving different hosts and is dependent on fast responses, as the parasite reacts to changing environmental conditions. T. gondii causes disease by lysing the host cells that it infects and it does this by reiterating its lytic cycle, which consists of host cell invasion, replication inside the host cell, and egress causing host cell lysis. Calcium ion (Ca2+) signaling triggers activation of molecules involved in the stimulation and enhancement of each step of the parasite lytic cycle. Ca2+ signaling is essential for the cellular and developmental changes that support T. gondii parasitism. The characterization of the molecular players and pathways directly activated by Ca2+ signaling in Toxoplasma is sketchy and incomplete. The evolutionary distance between Toxoplasma and other eukaryotic model systems makes the comparison sometimes not informative. The advent of new genomic information and new genetic tools applicable for studying Toxoplasma biology is rapidly changing this scenario. The Toxoplasma genome reveals the presence of many genes potentially involved in Ca2+ signaling, even though the role of most of them is not known. The use of Genetically Encoded Calcium Indicators (GECIs) has allowed studies on the role of novel calcium-related proteins on egress, an essential step for the virulence and dissemination of Toxoplasma. In addition, the discovery of new Ca2+ players is generating novel targets for drugs, vaccines, and diagnostic tools and a better understanding of the biology of these parasites.

Bacterial Non-Specific Acid Phosphatase (NSAP) enzymes are capable of dephosphorylating diverse organic phosphoesters but are rarely studied: their distribution in natural and managed environments is poorly understood. The aim of this study was to generate new insight into the environmental distribution of NSAPs and establish their potential global relevance to cycling of organic phosphorus.