Atomic view of the HIV-1 matrix lattice; implications on virus assembly and envelope incorporation.

During the late phase of HIV type 1 (HIV-1) infection cycle, the virally encoded Gag polyproteins are targeted to the inner leaflet of the plasma membrane (PM) for assembly, formation of immature particles, and virus release. Gag binding to the PM is mediated by interactions of the N-terminally myristoylated matrix (myrMA) domain with phosphatidylinositol 4,5-bisphosphate. Formation of a myrMA lattice on the PM is an obligatory step for the assembly of immature HIV-1 particles and envelope (Env) incorporation. Atomic details of the myrMA lattice and how it mediates Env incorporation are lacking. Herein, we present the X-ray structure of myrMA at 2.15 Å. The myrMA lattice is arranged as a hexamer of trimers with a central hole, thought to accommodate the C-terminal tail of Env to promote incorporation into virions. The trimer­trimer interactions in the lattice are mediated by the N-terminal loop of one myrMA molecule and α-helices I­II, as well as the 310 helix of a myrMA molecule from an adjacent trimer. We provide evidence that substitution of MA residues Leu13 and Leu31, previously shown to have adverse effects on Env incorporation, induced a conformational change in myrMA, which may destabilize the trimer­trimer interactions within the lattice. We also show that PI(4,5)P2 is capable of binding to alternating sites on MA, consistent with an MA­membrane binding mechanism during assembly of the immature particle and upon maturation. Altogether, these findings advance our understanding of a key mechanism in HIV-1 particle assembly.

Novel pneumococcal capsule type 33E results from the inactivation of glycosyltransferase WciE in vaccine type 33F.

The polysaccharide (PS) capsule is essential for immune evasion and virulence of Streptococcus pneumoniae. Existing pneumococcal vaccines are designed to elicit anticapsule antibodies; however, the effectiveness of these vaccines is being challenged by the emergence of new capsule types or variants. Herein, we characterize a newly discovered capsule type, 33E, that appears to have repeatedly emerged from vaccine type 33F via an inactivation mutation in the capsule glycosyltransferase gene, wciE. Structural analysis demonstrated that 33E and 33F share an identical repeat unit backbone [→5)-ß-D-Galf2Ac-(1→3)-ß-D-Galp-(1→3)-α-D-Galp-(1→3)-ß-D-Galf-(1→3)-ß-D-Glcp-(1→], except that a galactose (α-D-Galp) branch is present in 33F but not in 33E. Though the two capsule types were indistinguishable using conventional typing methods, the monoclonal antibody Hyp33FM1 selectively bound 33F but not 33E pneumococci. Further, we confirmed that wciE encodes a glycosyltransferase that catalyzes the addition of the branching α-D-Galp and that its inactivation in 33F strains results in the expression of the 33E capsule type. Though 33F and 33E share a structural and antigenic similarity, our pilot study suggested that immunization with a 23-valent pneumococcal PS vaccine containing 33F PS did not significantly elicit cross-opsonic antibodies to 33E. New conjugate vaccines that target capsule type 33F may not necessarily protect against 33E. Therefore, studies of new conjugate vaccines require knowledge of the newly identified capsule type 33E and reliable pneumococcal typing methods capable of distinguishing it from 33F.

Increasing Pancreatic Cancer Incidence in Young Women in the United States: A Population-Based Time-Trend Analysis, 2001-2018.

BACKGROUND & AIMS: Previous studies have shown an increasing incidence of pancreatic cancer (PC), especially in younger women; however, this has not been externally validated. In addition, there are limited data about contributing factors to this trend. We report age and sex-specific time-trend analysis of PC age-adjusted incidence rates (aIRs) using the National Program of Cancer Registries database without Surveillance Epidemiology and End Results data. METHODS: PC aIR, mortality rates, annual percentage change, and average annual percentage change (AAPC) were calculated and assessed for parallelism and identicalness. Age-specific analyses were conducted in older (≥55 years) and younger (<55 years) adults. PC incidence based on demographics, tumor characteristics, and mortality were evaluated in younger adults. RESULTS: A total of 454,611 patients were diagnosed with PC between 2001 and 2018 with significantly increasing aIR in women (AAPC = 1.27%) and men (AAPC = 1.14%) without a difference (P = .37). Similar results were seen in older adults. However, in younger adults (53,051 cases; 42.9% women), women experienced a greater increase in aIR than men (AAPCs = 2.36%, P < .001 vs 0.62%, P = 0.62) with nonparallel trends (P < .001) and AAPC difference of 1.74% (P < .001). This AAPC difference appears to be due to rising aIR in Blacks (2.23%; P < .001), adenocarcinoma histopathologic subtype (0.89%; P = .003), and location in the head-of-pancreas (1.64%; P < .001). PC mortality was found to be unchanged in women but decreasing in counterpart men (AAPC difference = 0.54%; P = .001). CONCLUSION: Using nationwide data, covering ≈64.5% of the U.S. population, we externally validate a rapidly increasing aIR of PC in younger women. There was a big separation of the incidence trend between women and men aged 15-34 years between 2001 and 2018 (>200% difference), and it did not show slowing down.

Evaluating no fixation, endoscopic suture fixation, and an over-the-scope clip for anchoring fully covered self-expanding metal stents in benign upper gastrointestinal conditions: a comparative multicenter international study (with video).

BACKGROUND AND AIMS: Fully covered self-expandable metal stents (FCSEMSs) are widely used in benign upper gastrointestinal (GI) conditions, but stent migration remains a limitation. An over-the-scope clip (OTSC) device (Ovesco Endoscopy) for stent anchoring has been recently developed. The aim of this study was to evaluate the effect of OTSC fixation on SEMS migration rate. METHODS: A retrospective review of consecutive patients who underwent FCSEMS placement for benign upper GI conditions between 1/2011 and 10/2022 at 16 centers. The primary outcome was rate of stent migration. The secondary outcomes were clinical success and adverse events. RESULTS: A total of 311 (no fixation 122, OTSC 94, endoscopic suturing 95) patients underwent 316 stenting procedures. Compared to the no fixation (NF) group (n=49, 39%), the rate of stent migration was significantly lower in the OTSC (SF) (n=16, 17%, p=0.001) and endoscopic suturing (ES) group (n=23, 24%, p=0.01). The rate of stent migration was not different between the SF and ES groups (p=0.2). On multivariate analysis, SF (OR 0.34, CI 0.17-0.70, p<0.01) and ES (OR 0.46, CI 0.23-0.91, p=0.02) were independently associated with decreased risk of stent migration. Compared to the NF group (n=64, 52%), there was a higher rate of clinical success in the SF (n=64, 68%; p=0.03) and ES group (n=66, 69%; p = 0.02). There was no significant difference in the rate of adverse events between the three groups. CONCLUSION: Stent fixation using OTSC is safe and effective at preventing stent migration and may also result in improved clinical response.

Large language models and bariatric surgery patient education: a comparative readability analysis of GPT-3.5, GPT-4, Bard, and online institutional resources.

BACKGROUND: The readability of online bariatric surgery patient education materials (PEMs) often surpasses the recommended 6th grade level. Large language models (LLMs), like ChatGPT and Bard, have the potential to revolutionize PEM delivery. We aimed to evaluate the readability of PEMs produced by U.S. medical institutions compared to LLMs, as well as the ability of LLMs to simplify their responses. METHODS: Responses to frequently asked questions (FAQs) related to bariatric surgery were gathered from top-ranked health institutions. FAQ responses were also generated from GPT-3.5, GPT-4, and Bard. LLMs were then prompted to improve the readability of their initial responses. The readability of institutional responses, initial LLM responses, and simplified LLM responses were graded using validated readability formulas. Accuracy and comprehensiveness of initial and simplified LLM responses were also compared. RESULTS: Responses to 66 FAQs were included. All institutional and initial LLM responses had poor readability, with average reading levels ranging from 9th grade to college graduate. Simplified responses from LLMs had significantly improved readability, with reading levels ranging from 6th grade to college freshman. When comparing simplified LLM responses, GPT-4 responses demonstrated the highest readability, with reading levels ranging from 6th to 9th grade. Accuracy was similar between initial and simplified responses from all LLMs. Comprehensiveness was similar between initial and simplified responses from GPT-3.5 and GPT-4. However, 34.8% of Bard's simplified responses were graded as less comprehensive compared to initial. CONCLUSION: Our study highlights the efficacy of LLMs in enhancing the readability of bariatric surgery PEMs. GPT-4 outperformed other models, generating simplified PEMs from 6th to 9th grade reading levels. Unlike GPT-3.5 and GPT-4, Bard's simplified responses were graded as less comprehensive. We advocate for future studies examining the potential role of LLMs as dynamic and personalized sources of PEMs for diverse patient populations of all literacy levels.

Appropriateness of ChatGPT in Answering Heart Failure Related Questions.

BACKGROUND: Heart failure requires complex management, and increased patient knowledge has been shown to improve outcomes. This study assessed the knowledge of Chat Generative Pre-trained Transformer (ChatGPT) and its appropriateness as a supplemental resource of information for patients with heart failure. METHOD: A total of 107 frequently asked heart failure-related questions were included in 3 categories: "basic knowledge" (49), "management" (41) and "other" (17). Two responses per question were generated using both GPT-3.5 and GPT-4 (i.e., two responses per question per model). The accuracy and reproducibility of responses were graded by two reviewers, board-certified in cardiology, with differences resolved by a third reviewer, board-certified in cardiology and advanced heart failure. Accuracy was graded using a four-point scale: (1) comprehensive, (2) correct but inadequate, (3) some correct and some incorrect, and (4) completely incorrect. RESULTS: GPT-4 provided 107/107 (100%) responses with correct information. Further, GPT-4 displayed a greater proportion of comprehensive knowledge for the categories of "basic knowledge" and "management" (89.8% and 82.9%, respectively). For GPT-3, there were two total responses (1.9%) graded as "some correct and incorrect" for GPT-3.5, while no "completely incorrect" responses were produced. With respect to comprehensive knowledge, GPT-3.5 performed best in the "management" category and "other" category (prognosis, procedures, and support) (78.1%, 94.1%). The models also provided highly reproducible responses, with GPT-3.5 scoring above 94% in every category and GPT-4 with 100% for all answers. CONCLUSIONS: GPT-3.5 and GPT-4 answered the majority of heart failure-related questions accurately and reliably. If validated in future studies, ChatGPT may serve as a useful tool in the future by providing accessible health-related information and education to patients living with heart failure. In its current state, ChatGPT necessitates further rigorous testing and validation to ensure patient safety and equity across all patient demographics.

Discovery and Characterization of Pneumococcal Serogroup 36 Capsule Subtypes, Serotypes 36A and 36B.

Streptococcus pneumoniae can produce a wide breadth of antigenically diverse capsule types, a fact that poses a looming threat to the success of vaccines that target pneumococcal polysaccharide (PS) capsule. Yet, many pneumococcal capsule types remain undiscovered and/or uncharacterized. Prior sequence analysis of pneumococcal capsule synthesis (cps) loci suggested the existence of capsule subtypes among isolates identified as "serotype 36" according to conventional capsule typing methods. We discovered these subtypes represent two antigenically similar but distinguishable pneumococcal capsule serotypes, 36A and 36B. Biochemical analysis of their capsule PS structure reveals that both have the shared repeat unit backbone [→5)-α-d-Galf-(1→1)-d-Rib-ol-(5→P→6)-ß-d-ManpNAc-(1→4)-ß-d-Glcp-(1→] with two branching structures. Both serotypes have a ß-d-Galp branch to Ribitol. Serotypes 36A and 36B differ by the presence of a α-d-Glcp-(1→3)-ß-d-ManpNAc or α-d-Galp-(1→3)-ß-d-ManpNAc branch, respectively. Comparison of the phylogenetically distant serogroup 9 and 36 cps loci, which all encode this distinguishing glycosidic bond, revealed that the incorporation of Glcp (in types 9N and 36A) versus Galp (in types 9A, 9V, 9L, and 36B) is associated with the identity of four amino acids in the cps-encoded glycosyltransferase WcjA. Identifying functional determinants of cps-encoded enzymes and their impact on capsule PS structure is key to improving the resolution and reliability of sequencing-based capsule typing methods and discovering novel capsule variants indistinguishable by conventional serotyping methods.

Patient and the Public's Perceptions of Bariatric Surgery: A Systematic Review.

INTRODUCTION: Bariatric surgery is an effective therapeutic modality for obesity and related comorbidities, yet it remains significantly underutilized. Patient perceptions and expectations may influence the decisions of eligible patients in pursuing surgery. METHODS: PubMed, SCOPUS, and OVID databases were searched in July 2022 to identify published studies discussing patient and the public's perceptions of bariatric surgery. RESULTS: The literature shows participants often reported bariatric surgery to be a life-changing intervention known to induce weight loss, improve obesity-related comorbidities, and improve quality of life. However, a significant proportion of survey respondents perceived bariatric surgery as unsafe or risky. Patients belonging to racial minority groups cited higher concern with mortality risk, lower weight loss expectations, and different motivations to pursue bariatric surgery. Female patients were significantly more likely to have more positive perceptions of, and higher expectations of weight loss from, bariatric surgery. CONCLUSIONS: The literature highlighted discordance between patient perceptions and the demonstrated clinical safety and efficacy profile of bariatric surgery. Overestimations of the risks, unrealistic expectations, and unfamiliarity with bariatric surgery outcomes were common findings. These perceptions of bariatric surgery may contribute to its underutilization among eligible patients. Perceptions and motivations often varied by race, region, sex, and age, which demonstrates the necessity of patient-centered education in the prereferral stage. The literature also demonstrated misconceptions of bariatric surgery among the public. Further research should explore the impact of education on the perceptions of patients and the public.

Structural characterization of HIV-1 matrix mutants implicated in envelope incorporation.

During the late phase of HIV-1 infection, viral Gag polyproteins are targeted to the plasma membrane (PM) for assembly. Gag localization at the PM is a prerequisite for the incorporation of the envelope protein (Env) into budding particles. Gag assembly and Env incorporation are mediated by the N-terminal myristoylated matrix (MA) domain of Gag. Nonconservative mutations in the trimer interface of MA (A45E, T70R, and L75G) were found to impair Env incorporation and infectivity, leading to the hypothesis that MA trimerization is an obligatory step for Env incorporation. Conversely, Env incorporation can be rescued by a compensatory mutation in the MA trimer interface (Q63R). The impact of these MA mutations on the structure and trimerization properties of MA is not known. In this study, we employed NMR spectroscopy, X-ray crystallography, and sedimentation techniques to characterize the structure and trimerization properties of HIV-1 MA A45E, Q63R, T70R, and L75G mutant proteins. NMR data revealed that these point mutations did not alter the overall structure and folding of MA but caused minor structural perturbations in the trimer interface. Analytical ultracentrifugation data indicated that mutations had a minimal effect on the MA monomer-trimer equilibrium. The high-resolution X-ray structure of the unmyristoylated MA Q63R protein revealed hydrogen bonding between the side chains of adjacent Arg-63 and Ser-67 on neighboring MA molecules, providing the first structural evidence for an additional intermolecular interaction in the trimer interface. These findings advance our knowledge of the interplay of MA trimerization and Env incorporation into HIV-1 particles.

Anatomical Site-Specific Carbohydrate Availability Impacts Streptococcus pneumoniae Virulence and Fitness during Colonization and Disease.

Streptococcus pneumoniae colonizes the nasopharynx asymptomatically but can also cause severe life-threatening disease. Importantly, stark differences in carbohydrate availability exist between the nasopharynx and invasive disease sites, such as the bloodstream, which most likely impact S. pneumoniae's behavior. Herein, using chemically defined medium (CDM) supplemented with physiological levels of carbohydrates, we examined how anatomical site-specific carbohydrate availability impacted S. pneumoniae physiology and virulence. S. pneumoniae cells grown in CDM modeling the nasopharynx (CDM-N) had reduced metabolic activity and a lower growth rate, demonstrated mixed acid fermentation with marked H2O2 production, and were in a carbon-catabolite repression (CCR)-derepressed state versus S. pneumoniae cells grown in CDM modeling blood (CDM-B). Using transcriptome sequencing (RNA-seq), we determined the transcriptome for the S. pneumoniae wild-type (WT) strain and its isogenic CCR-deficient mutant in CDM-N and CDM-B. Genes with altered expression as a result of changes in carbohydrate availability or catabolite control protein deficiency, respectively, were primarily involved in carbohydrate metabolism, but also encoded established virulence determinants, such as polysaccharide capsule and surface adhesins. We confirmed that anatomical site-specific carbohydrate availability directly influenced established S. pneumoniae virulence traits. S. pneumoniae cells grown in CDM-B formed shorter chains, produced more capsule, were less adhesive, and were more resistant to macrophage killing in an opsonophagocytosis assay. Moreover, growth of S. pneumoniae in CDM-N or CDM-B prior to the challenge of mice impacted relative fitness in a colonization model and invasive disease model, respectively. Thus, anatomical site-specific carbohydrate availability alters S. pneumoniae physiology and virulence, in turn promoting anatomical site-specific fitness.

Recombinant guanosine-5'-triphosphate (GTP)-binding protein associated with Poloxamer 407-based polymeric micelles protects against Leishmania infantum infection.

Leishmania virulence proteins should be considered as vaccine candidates against disease, since they are involved in developing infection in mammalian hosts. In a previous study, a Leishmania guanosine-5'-triphosphate (GTP)-binding protein was identified as a potential parasite virulence factor. In the present work, the gene encoding GTP was cloned and the recombinant protein (rGTP) was evaluated as a vaccine candidate against Leishmania infantum infection. The protein was associated with saponin (rGTP/Sap) or Poloxamer 407-based micelles (rGTP/Mic) as adjuvants, and protective efficacy was investigated in BALB/c mice after parasite challenge. Both rGTP/Sap and rGTP/Mic compositions induced a Th1-type immune response in vaccinated animals, with significantly higher levels of IFN-γ, IL-12, IL-2, TNF-α, GM-CSF, nitrite, specific IgG2a isotype antibody and positive lymphoproliferation, when compared to the control groups. This response was accompanied by significantly lower parasite load in the spleens, livers, bone marrows and draining lymph nodes of the animals. Immunological and parasitological evaluations indicated that rGTP/Mic induced a more polarized Th1-type response and higher reduction in the organ parasitism, and with lower hepatotoxicity, when compared to the use of rGTP/Sap. In conclusion, our preliminary data suggest that rGTP could be considered for further development as a vaccine candidate to protect against VL.

Factors Associated With Bariatric Surgery Referral Patterns: A Systematic Review.

INTRODUCTION: Bariatric surgery (BS) has been shown to effectively treat morbid obesity and improve obesity-related comorbidities. Nonetheless, BS remains underutilized among qualified patients. MATERIALS AND METHODS: PubMed, SCOPUS, and OVID databases were searched to identify published comparative studies examining BS referral patterns. Data on barriers to BS referrals were examined and summarized. RESULTS: Barriers to referrals stemmed largely from a lack of familiarity with safety, efficacy, and postoperative care amongst providers. Providers with previous referrals were more likely to report higher knowledge, comfort in referring patients, and ability to provide postoperative care. Provider initiated discussion of BS was positively associated with referrals. Female and younger patients were more likely to receive referrals. Furthermore, access to appropriate peri-operative resources, local bariatric programs, and insurance eligibility were associated with referral rates. Encouragingly, providers across specialties report eagerness to gain exposure and training in BS. CONCLUSIONS: Lack of provider familiarity with BS efficacy, safety and postoperative care likely contributes to low utilization rates of BS. Further potential barriers in access to BS are logistic factors such as insurance coverage, limited local perioperative resources, and clinic time constraints for patient counseling. Promotion of BS amongst providers and both surgical and non-surgical trainees will likely have a significant impact on referral rates and access to this life-saving procedure. Future studies should further investigate the barriers to BS and delineate the effect size of each barrier on referral rates to efficiently increase access.

Optimal Use of Tumor-Based Molecular Assays for Localized Prostate Cancer.

PURPOSEOF REVIEW: The use of genomic testing for prostate cancer continues to grow; however, utilization remains institutionally dependent. Herein, we review current tissue-based markers and comment on current use with active surveillance and prostate MRI. RECENT FINDINGS: While data continues to emerge, several studies have shown a role for genomic testing for treatment selection. Novel testing options include ConfirmMDx, ProMark, Prolaris, and Decipher, which have shown utility in select patients. The current body of literature on this specific topic remains very limited; prospective trials with long-term follow-up are needed to improve our understanding on how these genomic tests fit when combined with our current clinical tools. As the literature matures, it is likely that newer risk calculators that combine our classic clinical variables with genomic and imaging data will be developed to bring about standard protocols for prostate cancer decision-making.

History of abuse and bariatric surgery outcomes: a systematic review.

BACKGROUND: Although there is evidence to support the relationship between abuse history and obesity, the association between abuse history and outcomes after bariatric surgery is not well-established. We aimed to summarize the current literature examining this relationship, as well as provide clinical recommendations to optimize postoperative outcomes. METHODS: PubMed and SCOPUS databases were queried to identify relevant published studies. RESULTS: Overall, 20 studies were included. Rates of the various types of abuse reported in the bariatric surgery population varied widely across studies, as did the methodology used to assess it. The majority of studies found no significant associations between abuse history and postoperative weight loss outcomes. The literature examining the relationship between abuse history and postoperative psychiatric outcomes was less conclusive. CONCLUSIONS: Most current evidence demonstrates that abuse history is not associated with weight loss outcomes after bariatric surgery. Literature on postoperative psychiatric outcomes is mixed, and more robust studies are needed to further investigate the relationship between abuse history and postoperative psychiatric outcomes. Importantly, abuse history should not preclude patients from undergoing bariatric surgery. Of note, patients may benefit from careful monitoring for emotional distress and worsening of psychiatric comorbidities after surgery and psychiatric counseling and treatment when indicated.

Gastric electric stimulator versus gastrectomy for the treatment of medically refractory gastroparesis.

BACKGROUND: Gastric electrical stimulation (GES) and laparoscopic gastrectomy (LG) are known therapeutic options for medically refractory gastroparesis (MRG) although there are limited data comparing their outcomes. We aim to compare clinical outcomes between patients undergoing GES vs upfront LG for the treatment of MRG while examining factors associated with GES failure and conversion to LG. METHODS: We retrospectively analyzed 181 consecutive patients who underwent GES or LG for MRG at our institution from January 2003 to December 2017. Data collection consisted of chart review and follow-up telephone survey. Statistical analysis utilized Chi-squared, ANOVA, and multivariable logistic regression. RESULTS: Overall, 130 (72%) patients underwent GES and 51 (28%) LG as primary intervention. GES patients were more likely to have diabetic gastroparesis (GES 67% vs LG 39%, p < 0.001), while primary LG patients were more likely to have post-surgical gastroparesis (GES 5% vs LG 43%, p < 0.001). Postoperatively, primary LG patients had higher rates of major in-hospital morbidity events (GES 5% vs LG 18%, p = 0.017) and longer hospital stays (GES 3 vs LG 9 days, p < 0.001). However, over a mean 35-month follow-up period, there were no differences in the rates of major morbidity, readmissions, or mortality. Multivariable regression analysis revealed patients undergoing GES as a primary intervention were less likely to report improvement in symptoms on follow-up compared to primary LG patients OR 0.160 (95% CI 0.048-0.532). Additionally, patients who converted to LG from GES were more likely to have post-surgical gastroparesis as the primary etiology. CONCLUSION: GES as a first-line surgical treatment of MRG was associated with worse outcomes compared to LG. Post-surgical etiology was associated with an increased likelihood of GES failure, and in such patients, upfront gastrectomy may be a superior alternative to GES. Further studies are needed to determine patient selection for operative treatment of MRG.

Ventricular pre-excitation in primary care patients: Evaluation of the risk of mortality.

BACKGROUND: Ventricular pre-excitation is characterized by the presence of atrioventricular accessory pathways, predisposing to arrhythmias. Although it is well established that risk stratification in symptomatic patients should be invasive, there is a lack of evidence of the benefit in asymptomatic. OBJECTIVE: Evaluate ventricular pre-excitation in the electrocardiogram (ECG) as a risk factor for overall mortality in patients of Telehealth Network of Minas Gerais (TNMG), Brazil. METHODS: This observational study was developed with the database of digital ECGs (2010-2017) from TNMG. The electronic cohort was obtained by linking data from ECG exams and those from the national mortality information system. Only the first ECG was considered. Clinical data were self-reported, and ECGs were interpreted manually by cardiologists and automatically by the Glasgow University Interpreter software. Hazard ratio (HR) for mortality was estimated using weighted Cox regression. RESULTS: Nearly 1 665 667 patients were included (median age: 50 [Q1: 34; Q3: 63] years; 41.4% were male). In a mean follow-up of 3.7 years, the overall mortality rate was 3.1%. The prevalence of ventricular pre-excitation was 0.07%. In multivariate analysis, adjusting for sex and age, ventricular pre-excitation was not associated with an increased risk of mortality (HR: 1.41; 95% confidence interval [CI]: 0.56-3.57; p = .47) when compared to the whole sample or to patients with normal ECG (HR: 1.41; 95% CI: 0.53-4.36; p = .43). In a subanalysis on accessory pathway location, there was no evidence of a higher risk of death related to any location. CONCLUSION: Ventricular pre-excitation was not associated with an increased risk of mortality in a primary care cohort.

Leishmania eukaryotic elongation Factor-1 beta protein is immunogenic and induces parasitological protection in mice against Leishmania infantum infection.

Treatment for visceral leishmaniasis (VL) is hampered mainly by the toxicity and/or high cost of antileishmanial drugs. What is more, variability on sensitivity and/or specificity of diagnostic tests hinders effective disease management. In this context, prophylactic vaccination should be considered as a strategy to prevent disease. In the present study, immunogenicity of the Leishmania eukaryotic Elongation Factor-1 beta (EF1b) protein, classified as a Leishmania virulence factor, was evaluated in vitro and in vivo and tested, for the first time, as a vaccine candidate against Leishmania infantum infection. The antigen was administered as DNA vaccine or as recombinant protein (rEF1b) delivered in saponin. BALB/c mice immunization with a DNA plasmid and recombinant protein plus saponin induced development of specific Th1-type immunity, characterized by high levels of IFN-γ, IL-12, GM-CSF, both T cell subtypes and antileishmanial IgG2a isotype antibodies, before and after infection. This immunological response to the vaccines was corroborated further by parasitological analysis of the vaccinated and then challenged mice, which showed significant reductions in the parasite load in their liver, spleen, bone marrow and draining lymph nodes, when compared to the controls. Vaccination using rEF1b/saponin induced a more robust Th1 response and parasitological protection when compared to the DNA vaccine. Furthermore, in vitro analysis of lymphoproliferation, IFN-γ and IL-10 levels in human PBMC cultures showed as well development of a specific Th1-type response. In conclusion, data suggest that EF1b could be a promising vaccine candidate to protect against L. infantum infection.

Impact of smoking on weight loss outcomes after bariatric surgery: a literature review.

BACKGROUND: The association between smoking and surgical complications after bariatric surgery has been well-established. However, given that this patient population is inherently weight-concerned, understanding the effects of tobacco use on postoperative weight loss is essential to guiding clinicians in counseling patients. We aimed to summarize the current literature examining the effects of preoperative and postoperative smoking, as well as changes in smoking status, on bariatric surgery weight loss outcomes. METHODS: Ovid MEDLINE, PubMed, and SCOPUS databases were queried to identify relevant published studies. RESULTS: Overall, 20 studies were included. Preoperative and postoperative smoking rates varied widely across studies, as did requirements for smoking cessation prior to bariatric surgery. Reported preoperative smoking prevalence ranged from 1 to 62%, and postoperative smoking prevalence ranged from 6 to 43%. The majority of studies which examined preoperative and/or postoperative smoking habits found no association between smoking habits and postoperative weight loss outcomes. A minority of studies found relatively small differences in postoperative weight loss between smokers and nonsmokers; these often became nonsignificant with longer follow-up. No studies found significant associations between changes in smoking status and weight loss outcomes. CONCLUSION: While smoking has been associated with weight loss in the general population, most current evidence demonstrates that smoking habits are not associated with weight loss outcomes after bariatric surgery. However, due to the heterogeneity in study design and analysis, no definitive conclusions can be made, and more robust studies are needed to investigate any relationship between smoking and long-term weight loss outcomes. Given the established increased risk of surgical complications and mortality in smokers, smoking cessation should be encouraged.

Effects of smoking on bariatric surgery postoperative weight loss and patient satisfaction.

BACKGROUND: While general population studies have demonstrated a relationship between cigarette smoking and weight loss, this association is not well established among the bariatric patient population. Given that bariatric patients are inherently weight-concerned, understanding the effects of smoking on postoperative weight loss is essential. We examined the association of preoperative smoking, postoperative smoking and changes in smoking status with weight loss after bariatric surgery. In addition, we examined the association of changes in smoking status with subjective indices of patient satisfaction while controlling for weight loss. METHODS: Retrospective chart review of patients who underwent Sleeve Gastrectomy or Roux-en-Y Gastric Bypass for weight loss at a single institution between August 2000 and November 2017. Additional follow up was obtained by telephone survey. Statistical analysis utilized multivariate logistical regressions. RESULTS: Our study included 512 patients. Majority were female (n = 390, 76.2%) and underwent laparoscopic Roux-en-Y gastric bypass (n = 362, 70.7%). Average age was 46.8 years and average follow up was 6.99 years. Preoperative, postoperative and changes in smoking status were not significantly associated with weight loss. Former smokers were significantly more likely to report postoperative satisfaction with self-overall OR 10.62 (p < 0.01), satisfaction with postoperative outcomes OR 4.18 (p = 0.02), and improvement in quality of life OR 4.05 (p = 0.04) compared to continued smokers independent of weight loss. No difference in rates of satisfaction were found between former smokers and never smokers. Smoking cessation and weight loss were independently predictive of positive responses to these satisfaction indices. CONCLUSIONS: We found no association between preoperative smoking, postoperative smoking or changes in smoking status with postoperative weight loss. Smoking cessation was associated with patient satisfaction and improvement in quality of life compared to continued smokers. Smoking cessation and postoperative weight loss were independently predictive of increased patient satisfaction.

Sequestration of p-nitrophenol from liquid phase by poly(acrylonitrile-co-acrylic acid) containing thioamide group.

In this paper, the adsorptive performance of synthesized thiourea (TU) modified poly(acrylonitrile-co-acrylic acid) (TU-P(AN-co-AA)) polymeric adsorbent for capturing p-nitrophenol (PNP) from aqueous solution was investigated. TU-P(AN-co-AA) was synthesized via the redox polymerization method with acrylonitrile (AN) and acrylic acid (AA) as the monomers, then modified chemically with thiourea (TU). Characterization analysis with Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), elemental microanalysis for CHNS, zeta potential measurement, Brunauer-Emmett-Teller (BET) surface analysis and thermal analyses were carried out to determine the morphology and physico-chemical properties of the synthesized polymer. The characterization results indicated successful surface modification of polymer with TU. The performance of TU-P(AN-co-AA) for the removal of PNP was investigated under various experimental parameters (adsorbent dosage, initial adsorbate concentration, contact time and temperature). The results demonstrated that the Freundlich isotherm model and pseudo-second-order kinetic model best described the equilibrium and kinetic data, respectively. Thermodynamic studies showed that the uptake of PNP by TU-P(AN-co-AA) was spontaneous and exothermic in nature. The results of the regeneration studies suggested that the TU-P(AN-co-AA) polymer is a reusable adsorbent with great potential for removing PNP from wastewater.