Characterization of c-di-AMP signaling in the periodontal pathobiont, Treponema denticola.

Pathobionts associated with periodontitis, such as Treponema denticola, must possess numerous sensory transduction systems to adapt to the highly dynamic subgingival environment. To date, the signaling pathways utilized by T. denticola to rapidly sense and respond to environmental stimuli are mainly unknown. Bis-(3'-5') cyclic diadenosine monophosphate (c-di-AMP) is a nucleotide secondary messenger that regulates osmolyte transport, central metabolism, biofilm development, and pathogenicity in many bacteria but is uncharacterized in T. denticola. Here, we studied c-di-AMP signaling in T. denticola to understand how it contributes to T. denticola physiology. We demonstrated that T. denticola produces c-di-AMP and identified enzymes that function in the synthesis (TDE1909) and hydrolysis (TDE0027) of c-di-AMP. To investigate how c-di-AMP may impact T. denticola cellular processes, a screening assay was performed to identify putative c-di-AMP receptor proteins. This approach identified TDE0087, annotated as a potassium uptake protein, as the first T. denticola c-di-AMP binding protein. As potassium homeostasis is critical for maintaining turgor pressure, we demonstrated that T. denticola c-di-AMP concentrations are impacted by osmolarity, suggesting that c-di-AMP negatively regulates potassium uptake in hypoosmotic solutions. Collectively, this study demonstrates T. denticola utilizes c-di-AMP signaling, identifies c-di-AMP metabolism proteins, identifies putative receptor proteins, and correlates c-di-AMP signaling to osmoregulation.

Taming Pseudomonas aeruginosa AM26 the barbarian: Targeting the PQS quorum sensing network using crude mandarin extract.

Pseudomonas aeruginosa, one of the most notorious organisms, causes fatal diseases like-, meningitis, pneumonia as well as worsens the prognosis of cystic fibrosis patients. It is also multi-drug resistant and resists a wide range of antibiotics. Attempts have been made to reduce its virulence/pathogenic potential using a number of organic compounds. For this purpose, the Quorum sensing (QS) system of P. aeruginosa was targeted, which regulates its virulence. Pseudomonas Quinolone System (PQS), one of the four quorum sensing systems, producing pyocyanin pigment was chosen. 2-heptyl-3-hydroxy-4-quinolone (HHQ) is a ligand which binds to PQS protein is responsible for pyocyanin pigment production. Attempts were made to find a compound analogous to HHQ which could bind to PQS active site and inhibit the pigment formation. In-silico analysis was performed to estimate possible interactions and to find/predict the possible PQS inhibitors.

Strategies for enhancing the representation of women in clinical trials: an evidence map.

BACKGROUND: Equitable sex- and gender-based representation in clinical trials is an essential step to ensuring evidence-based care for women. While multi-institutional actions have led to significant improvements in the inclusion of women in trials, inequity persists in areas like sex-neutral cancers and cardiovascular disease. We sought to identify strategies described or evaluated to boost the inclusion of women in clinical trials. METHODS: We used evidence mapping methodology to examine the breadth of relevant literature. We developed an a priori protocol and followed reporting guidance from the Preferred Reporting Items for Systematic Reviews and Meta-Analysis where applicable. We searched MEDLINE® (via PubMed) and EMBASE (via Elsevier) databases from inception through April 4, 2023, and used standardized procedures incorporating duplication and data verification. We included articles that described strategies to improve the recruitment and retention of women in clinical trials. RESULTS: We identified 122 articles describing recruitment and retention strategies for 136 trials (377,595 women). Only one article distinguished between the sex and gender identity of participants, and none defined their use of the terms such as "women" or "female". The majority of articles (95%) described recruitment for only women, and 64% were conducted in the USA. Ninety-two articles (75%) described strategies in the context of sex-specific conditions (e.g., gynecologic diagnosis). The majority of included articles evaluated a behavioral intervention (52%), with 23% evaluating pharmacologic interventions and 4% invasive interventions. The most common trial phase for reported strategies was during outreach to potential participants (116 articles), followed by intervention delivery (76), enrollment (40), outcomes assessment (21), analysis and interpretation (3), and dissemination (4). We describe specific types of strategies within each of these phases. CONCLUSIONS: Most of the existing literature describing strategies to improve the inclusion of women draws from trials for sex-specific conditions and is largely related to outreach to potential participants. There is little information about how and if studies have attempted to proportionally increase the inclusion of women in trials with both men and women or those focused on invasive and pharmacologic interventions. Future work in this area should focus on how to increase the participation of women in mixed-sex studies and on those areas with remaining inequities in trial participation.

Metabolic Syndrome Causing Cognitive Impairment in Patients With Schizophrenia: A Systematic Review.

Schizophrenia often exhibits characteristics like cognitive deficits, and individuals with the condition are at a higher risk of developing metabolic syndrome. The effect of metabolic syndrome on schizophrenia-related cognitive impairment is still unknown, though. This systematic review aims to investigate the association between metabolic syndrome and cognitive impairment in patients with schizophrenia, specifically focusing on neurocognitive and social cognitive performance. Schizophrenia significantly strains the public healthcare system since it necessitates tremendous resources and care to support those suffering from the condition. Furthermore, patients with schizophrenia are more susceptible to developing obesity than the general population, leading to a higher possibility of developing metabolic syndrome. The gut microbiota has been recognized as a critical regulator of bidirectional interactions between the central nervous system and the gastrointestinal tract. Emerging evidence suggests that dysbiosis of the gut microbiota is closely linked to the development of both schizophrenia and obesity, sharing common pathophysiological mechanisms, particularly immune inflammation. In this systematic review, we examine the existing literature to explore the relationship between metabolic syndrome and cognitive impairment in individuals with schizophrenia. By synthesizing available evidence on neurocognitive and social cognitive performance, we aim to provide a comprehensive understanding of the association between metabolic syndrome and cognitive deficits in schizophrenia. The findings from this review will contribute to our knowledge of the complex interplay between metabolic abnormalities, gut microbiota dysbiosis, and cognitive impairments in patients with schizophrenia. This understanding may facilitate the development of novel interventions targeting metabolic syndrome as a potential avenue for improving cognitive outcomes in individuals with schizophrenia.

Probiotics and Their Role in the Management of Type 2 Diabetes Mellitus (Short-Term Versus Long-Term Effect): A Systematic Review and Meta-Analysis.

Diabetes is a major economic burden and an illness with a rising incidence worldwide. Type 2 diabetes mellitus (T2DM), the most prevalent kind of diabetes, is characterized by insulin resistance and insufficient insulin production. Recent research has implicated gut microbiota dysbiosis as a contributing factor to T2DM pathogenesis. The present study employed a methodology based on randomized controlled trials (RCTs) to assess the therapeutic efficacy of probiotics in the treatment of T2DM. A thorough search was done in PubMed and Medline for articles written in English and published between 2017 and 2023. Studies were chosen based on predetermined inclusion criteria, and the search technique adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) principles. This study also employed a robust assessment instrument, widely recognized in the medical and health sciences, to evaluate the potential presence of bias within the selected research studies. Out of 96 identified articles, 22 RCTs met the eligibility criteria. Both short-term (8 weeks or less) and long-term (12 weeks or more) probiotic administrations were made. The results of the meta-analysis demonstrated a significant improvement in the homeostatic model assessment of insulin resistance (HOMA-IR) following the probiotic intervention (P=0.02) and considerably decreased glycated hemoglobin HbA1c levels (P=0.004) and fasting blood glucose (FBG) levels (P<0.0001) in T2DM patients compared to placebo. This research offers proof that probiotics are clinically effective in the treatment of T2DM. Probiotic supplementation demonstrated favorable effects on glycemic control markers. However, the findings from RCTs were heterogeneous, and some studies showed inconsistent results. To clarify the processes underlying the probiotics' therapeutic benefits and to determine the best probiotic strains, doses, and therapy durations, more research is required. Nevertheless, probiotics offer a promising therapeutic approach for T2DM management and warrant consideration as a potential adjunct therapy in clinical practice.

What Is Best for Weight Loss? A Comparative Review of the Safety and Efficacy of Bariatric Surgery Versus Glucagon-Like Peptide-1 Analogue.

Obesity is a global health concern, necessitating effective weight-loss interventions. This study aimed to compare the efficacy and safety of semaglutide, a pharmacotherapeutic option, with bariatric surgery, a commonly utilized surgical intervention, for weight reduction. A systematic review of clinical trials, including the STEP (Semaglutide Treatment Effect in People) trials, sustain trials, pioneer trials, and the STAMPEDE (Surgical Treatment and Medications Potentially Eradicate Diabetes Efficiently) trial, was conducted to evaluate the outcomes of these interventions. The analysis of the clinical trials revealed that semaglutide demonstrated significant weight reduction in participants. However, adverse effects such as gastrointestinal (GI) disturbances, increased pulse rate, and rare cases of thyroid cancer were observed. Long-term effects showed partial weight regain and a return of certain cardiometabolic variables to baseline levels after semaglutide withdrawal. Comparatively, bariatric surgery, as demonstrated in the Longitudinal Assessment of Bariatric Surgery (LABS) consortium and supported by the STAMPEDE trial, exhibited higher efficacy in weight reduction and the management of obesity-induced complications such as diabetes. The STAMPEDE trial demonstrated that bariatric surgery, specifically Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), led to a significantly higher percentage of patients achieving desired diabetes treatment targets compared to medical therapy alone. While bariatric surgery showed superior efficacy, it also carried a higher risk of complications. In contrast, semaglutide presented a noninvasive alternative with significant weight reduction and lower incidences of adverse effects. In conclusion, this study highlights that bariatric surgery, such as Roux-en-Y gastric bypass and sleeve gastrectomy, remains a highly effective intervention for weight loss and management of obesity-induced complications. However, semaglutide represents a valuable noninvasive alternative, offering significant weight reduction and lower risks of adverse effects. The choice between these interventions should be based on individual patient characteristics and a comprehensive assessment of the risk-benefit profile.

The Effectiveness of Metformin in Diabetes Prevention: A Systematic Review and Meta-Analysis.

Diabetes mellitus is a growing global health concern, and prevention strategies play a crucial role in reducing its burden. Metformin has been widely studied as a potential intervention for diabetes prevention, but its overall effectiveness and impact on various populations remain unclear. This study aims to provide a comprehensive synthesis of the available evidence on the effectiveness of metformin in diabetes prevention. A systematic search was conducted in PubMed, Scopus, ScienceDirect, and Google Scholar for articles published from inception to June 2023. The reference lists of the included studies were also searched to retrieve possible additional studies. Any quantitative data were analyzed using Review Manager 5.4. A P-value of 0.05 was adopted as the significance threshold. Our analysis included 17 studies with a total sample size of 30,474. Our meta-analysis included two key analyses. First, the meta-analysis evaluating the effects of metformin on prediabetes demonstrated a significant reduction in the risk of progressing to type 2 diabetes mellitus (T2DM). The pooled odds ratio (OR) was 0.65 (95% confidence interval [CI] 0.53-0.80), indicating a 35% lower odds of developing T2DM among individuals with prediabetes who received metformin interventions compared to control groups. Secondly, the meta-analysis assessing the efficacy of metformin interventions in preventing T2DM yielded a significant reduction in the risk of developing the disease. The pooled risk ratio was 0.58 (95% CI 0.44-0.77), indicating a 42% lower risk of developing T2DM in individuals receiving metformin interventions compared to those in non-metformin intervention groups. These findings provide strong evidence for the effectiveness of metformin in preventing the progression of prediabetes to T2DM and reducing the overall incidence of the disease. The review demonstrated that metformin is effective in reducing the risk of developing diabetes mellitus among individuals at risk for the disease. The findings highlight the potential of metformin as a valuable intervention for diabetes prevention, particularly in high-risk populations.

Therapeutic Uses of Rituximab and Clinical Features in Immunoglobulin G4-Related Disease: A Systematic Review.

This research presents a systematic review focusing on rituximab's therapeutic applications in immunoglobulin G4 (IgG4)-related disease (IgG4-RD), a rare condition characterized by immune-mediated systemic inflammation and tissue fibrosis, as well as the clinical features of IgG4-RD. While the disease commonly affects organs such as the bile ducts, lymph nodes, retroperitoneum, pancreas, and salivary glands, it can potentially involve other organs. This intricacy often leads to diagnostic challenges due to clinical overlaps with cancer, infections, and other autoimmune disorders. The diagnosis of IgG4-RD necessitates a comprehensive approach involving laboratory tests, imaging studies, and clinical assessments. Symptoms can vary, ranging from lymphadenopathy to jaundice, affecting multiple organs. Although elevated blood IgG4 levels and findings of tissue involvement and fibrosis on imaging can be suggestive, they lack the specificity for a definitive diagnosis. Early diagnosis is crucial for initiating corticosteroids and immunosuppressive to prevent further damage from IgG4-RD. This study highlights the therapeutic role of rituximab in managing this condition. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, the research identifies and evaluates relevant literature across various electronic databases, including PubMed, ScienceDirect, and Google Scholar. This review includes 14 selected publications, comprising three systematic reviews, three observational studies, four narrative reviews, and four case reports. The study design ensures a comprehensive evaluation of rituximab's potential efficacy in treating IgG4-RD and its associated clinical characteristics. Based on this study, it can be concluded that IgG4-RD can potentially be treated with rituximab, particularly in cases of relapse and maintaining remission.

The leptospiral OmpA-like protein (Loa22) is a surface-exposed antigen that elicits bactericidal antibody against heterologous Leptospira.

Leptospirosis is the most widespread zoonosis, affecting over 1 million humans each year, with more than 60,000 deaths worldwide. Leptospirosis poses a significant health threat to dogs, horses, cattle, and wildlife. The disease may be self-limiting or progress to a life-threatening multi-system disorder affecting the kidneys, liver, and lungs. Currently, bacterin vaccine formulations that consist of one or more laboratory-cultivated strains are used for prevention. However, the antibody response elicited by these vaccines is directed primarily at lipopolysaccharide and is generally serovar-specific. The development of broadly protective subunit vaccines for veterinary and human applications would be a significant step forward in efforts to combat this emerging and antigenically variable pathogen. This study assessed the properties and potential utility of the Leptospira Loa22 (Leptospira OmpA-like 22 kDa protein) protein as a vaccine antigen. Loa22 is a virulence factor that is predicted to transverse the outer membrane and present its N-terminal domain on the cell surface. This report demonstrates that diverse Leptospira strains express Loa22 in vitro and that the protein is antigenic during infection in dogs. Immunoblot and size exclusion chromatography revealed that Loa22 exists in monomeric and trimeric forms. Immunization of rats with recombinant Loa22 elicited bactericidal antibodies against diverse Leptospira strains. The immunodominant bactericidal epitopes were localized within the N-terminal domain using protein-blocking bactericidal assays. This study supports the utility of Loa22, or subfragments thereof, in developing a multivalent chimeric subunit vaccine to prevent leptospirosis and sheds new light on the cellular localization of Loa22.

Optimizing the Equitable Deployment of Virtual Care for Women: Protocol for a Qualitative Evidence Synthesis Examining Patient and Provider Perspectives Supplemented with Primary Qualitative Data.

Introduction: Women experience numerous barriers to patient-centered health care (e.g., lack of continuity). Such barriers are amplified for women from marginalized communities. Virtual care may improve equitable access. We are conducting a partner-engaged, qualitative evidence synthesis (QES) of patients' and providers' experiences with virtual health care delivery for women. Methods: We use a best-fit framework approach informed by the Non-adoption, Abandonment, Scale-up, Spread, and Sustainability framework and Public Health Critical Race Praxis. We will supplement published literature with qualitative interviews with women from underrepresented communities and their health care providers. We will engage patients and other contributors through multiple participatory methods. Results: Our search identified 5525 articles published from 2010 to 2022. Sixty were eligible, of which 42 focused on women and 24 on provider experiences. Data abstraction and analysis are ongoing. Discussion: This work offers four key innovations to advance health equity: (1) conceptual foundation rooted in an antiracist action-oriented praxis; (2) worked example of centering QES on marginalized communities; (3) supplementing QES with primary qualitative information with populations historically marginalized in the health care system; and (4) participatory approaches that foster longitudinal partnered engagement. Health Equity Implications: Our approach to exploring virtual health care for women demonstrates an antiracist praxis to inform knowledge generation. In doing so, we aim to generate findings that can guide health care systems in the equitable deployment of comprehensive virtual care for women.

Association Between Vitamin D Deficiency and Testosterone Levels in Adult Males: A Systematic Review.

Vitamin D deficiency and its potential impact on testosterone levels have been subjects of scientific interest. This systematic review aims to evaluate the association between vitamin D deficiency and testosterone levels in adult males and examine the effects of vitamin D supplementation on testosterone. A comprehensive literature search was conducted in accordance with the PRISMA guidelines across PubMed, Google Scholar, and ScienceDirect. The inclusion criteria involved studies published in English between 2013 and 2023, which investigated the correlation between vitamin D and testosterone levels in adult males. The process of data extraction and synthesis encompassed various aspects, including study characteristics, participant demographics, measurement methods, and outcomes pertaining to the association. The initial search resulted in a pool of 354,235 articles. Through the application of relevant filters and the review of titles and abstracts, 48 articles were chosen for further assessment. Out of these, eight studies fulfilled the inclusion criteria and were ultimately incorporated into the final review. The included studies consisted of four cross-sectional studies, three randomized controlled trials (RCTs), and one analysis utilizing Mendelian randomization. The results showed heterogeneity among the studies, as some reported a positive correlation between vitamin D levels and testosterone, while others did not find a significant association. The effects of vitamin D supplementation on testosterone levels were inconclusive, with limited evidence of significant changes in total testosterone. However, potential influences on sex hormone-binding globulin and free testosterone levels were observed. To establish more definitive evidence regarding the impact of vitamin D on testosterone levels, there is a need for further well-designed, long-term RCTs that encompass diverse populations.

Altered color of plasma component - Unnecessary wastage of a precious resource.

BACKGROUND AND OBJECTIVES: The present study was conducted to evaluate the etiology of altered color of plasma component of blood in transfusion practice. MATERIALS AND METHODS: The study was conducted at the blood center of a tertiary care teaching hospital in western India for a period of 6 months. After component separation, all the plasma units with altered color were segregated and samples were taken for further evaluation. Altered colored plasma units were divided into three - green discoloration, yellow discoloration, and lipemic plasma. Donors were called, their detailed history was taken, and necessary investigations were done accordingly. RESULTS: Forty plasma units out of 20,658 (0.19%) donations showed discoloration. Out of which, 3 plasma units showed green discoloration, 9 plasma units showed yellow discoloration, and the remaining 28 plasma units were lipemic. Among three donors whose plasma showed green discoloration, one female donor had a history of oral contraceptive pill usage and had higher values of copper and ceruloplasmin. All donors with yellow plasma had a higher value of unconjugated bilirubin. All the donors with lipemic plasma gave a history of intake of fatty meal prior to donating blood and showed higher values of triglyceride, cholesterol, and very-low-density lipoprotein. CONCLUSION: Plasma component with altered color restricts its issue to the patient and also for use in fractionation. In our study, many of the altered color plasma units were safe to transfuse, but the decision regarding transfusion was debatable on consultation with the treating doctor. Further studies with a large sample size are recommended for the use of these plasma components.

c-di-GMP regulates activity of the PlzA RNA chaperone from the Lyme disease spirochete.

PlzA is a c-di-GMP-binding protein crucial for adaptation of the Lyme disease spirochete Borrelia (Borreliella) burgdorferi during its enzootic life cycle. Unliganded apo-PlzA is important for vertebrate infection, while liganded holo-PlzA is important for survival in the tick; however, the biological function of PlzA has remained enigmatic. Here, we report that PlzA has RNA chaperone activity that is inhibited by c-di-GMP binding. Holo- and apo-PlzA bind RNA and accelerate RNA annealing, while only apo-PlzA can strand displace and unwind double-stranded RNA. Guided by the crystal structure of PlzA, we identified several key aromatic amino acids protruding from the N- and C-terminal domains that are required for RNA-binding and unwinding activity. Our findings illuminate c-di-GMP as a switch controlling the RNA chaperone activity of PlzA, and we propose that complex RNA-mediated modulatory mechanisms allow PlzA to regulate gene expression during both the vector and host phases of the B. burgdorferi life cycle.

A Case Report of Acute Severe Necrotizing Pancreatitis following the Johnson & Johnson Vaccine against the Novel SARS-CoV-2.

Acute pancreatitis is an inflammatory condition, which is a leading gastrointestinal cause of hospitalization in the United States. Several conditions are associated with acute pancreatitis. More recently, there have been a few cases reported of acute pancreatitis following the Pfizer-BioNTech COVID-19 mRNA vaccine. To our knowledge, no cases of acute pancreatitis have been yet reported following the Johnson & Johnson's Janssen COVID-19 vaccine (J& J vaccine). Herein we report a 34-year-old male with no significant past medical history admitted with acute necrotizing pancreatitis, the day following the receipt of the J&J vaccine. Based on the Naranjo and the modified Naranjo scale, the patient met the requirements for probable drug induced pancreatitis. This case report has the objective to raise awareness of a potentially severe side effect of the J&J vaccine. We hope to use this case to support screening all patients for previous history of acute pancreatitis before administration of the J& J vaccine.

In vitro, in vivo, and in silico analysis of synbiotics as preventive interventions for lipid metabolism in ethanol-induced adipose tissue injury.

The risk of alcoholic liver disease (ALD) is increased by excessive ethanol drinking. For the prevention of ALD, the effects of ethanol on the liver, adipose tissue, and gut are crucial. Interestingly, garlic and a few probiotic strains can protect against ethanol-induced hepatotoxicity. However, the relationship between adipose tissue inflammation, Kyolic aged garlic extract (AGE), and Lactobacillus rhamnosus MTCC1423 in developing ALD is unknown. Therefore, the present study explored the effect of synbiotics (a combination of prebiotics and probiotics) on adipose tissue to prevent ALD. To investigate the efficacy of synbiotics administration on adipose tissue in preventing ALD, in vitro (3T3-L1 cells, N = 3) groups: control, control + LPS (lipopolysaccharide), ethanol, ethanol + LPS, ethanol + synbiotics, ethanol + synbiotics + LPS; in vivo (Wistar male rats, N = 6) groups: control, ethanol, pairfed, ethanol + synbiotics and in silico experiments were conducted. Lactobacillus multiplies in accordance with the growth curve when exposed to AGE. Additionally, Oil red O staining and scanning electron microscopy (SEM) demonstrated that synbiotics therapy maintained the morphology of adipocytes in the alcoholic model. In support of the morphological changes, quantitative real-time PCR demonstrated overexpression of adiponectin and downregulation of leptin, resistin, PPARγ, CYP2E1, iNOS, IL-6, and TNF-α after administration of synbiotics compared to the ethanol group. In addition, MDA estimation by high-performance liquid chromatography (HPLC) indicated that the synbiotics treatment reduced oxidative stress in rat adipose tissue. Consequently, the in-silico analysis revealed that AGE inhibited the C-D-T networks as PPARγ acting as the main target protein. The current study demonstrates that using synbiotics improves adipose tissue metabolism in ALD.

Synbiotic Intervention Ameliorates Oxidative Stress and Gut Permeability in an In Vitro and In Vivo Model of Ethanol-Induced Intestinal Dysbiosis.

Alcoholic liver disease (ALD) alters gut microbiota and tight junctions, causing bacterial components to enter the portal vein and induce oxidative stress-induced inflammation in the liver. Only corticosteroids and liver transplants are treatment options for severe alcoholic hepatitis. ALD's pathophysiology is unknown. However, acetaldehyde's toxic effects cause oxidative stress and intestinal permeability. This study investigates the influence of a synbiotic (a combination of aged garlic extract (AGE) and Lactobacillus rhamnosus MTCC1423) on colonic oxidative stress and inflammation in ALD male Wistar rats and Caco2 cells. MDA measurement by HPLC in CaCo2 cells, blood serum, and colon tissue demonstrated that synbiotic treatment in the ALD model reduces oxidative stress. Further, fecal high-throughput 16S rRNA gene sequencing revealed the microbiome's shift towards Firmicutes in the synbiotic group compared to ethanol. In addition, DCFDA labeling and H/E staining demonstrate that the synbiotic is beneficial in inhibiting the development of ALD. In the colon, the synbiotic reduces the activation of CYP2E1 and the inflammatory markers TNF-a and IL-6 while elevating the mRNA expression of ZO-1, occludin, and IL-10. Synbiotics colonize Lactobacillus to restore barrier function and microbiota and reduce colon oxidative stress. Thus, a synbiotic combination can be used in ALD treatment.

FtlA and FtlB Are Candidates for Inclusion in a Next-Generation Multiantigen Subunit Vaccine for Lyme Disease.

Lyme disease (LD) is a tick-transmitted bacterial infection caused by Borreliella burgdorferi and other closely related species collectively referred to as the LD spirochetes. The LD spirochetes encode an uncharacterized family of proteins originally designated protein family twelve (PF12). In B. burgdorferi strain B31, PF12 consists of four plasmid-carried genes, encoding BBK01, BBG01, BBH37, and BBJ08. Henceforth, we designate the PF12 proteins family twelve lipoprotein (Ftl) A (FtlA) (BBK01), FtlB (BBG01), FtlC (BBH37), and FtlD (BBJ08). The goal of this study was to assess the potential utility of the Ftl proteins in subunit vaccine development. Immunoblot analyses of LD spirochete cell lysates demonstrated that one or more of the Ftl proteins are produced by most LD isolates during cultivation. The Ftl proteins were verified to be membrane associated, and nondenaturing PAGE revealed that FtlA, FtlB, and FtlD formed dimers, while FtlC formed hexamers. Analysis of serum samples from B. burgdorferi antibody (Ab)-positive client-owned dogs (n = 50) and horses (n = 90) revealed that a majority were anti-Ftl Ab positive. Abs to the Ftl proteins were detected in serum samples from laboratory-infected dogs out to 497 days postinfection. Anti-FtlA and FtlB antisera displayed potent complement-dependent Ab-mediated killing activity, and epitope localization revealed that the bactericidal epitopes reside within the N-terminal domain of the Ftl proteins. This study suggests that FtlA and FtlB are potential candidates for inclusion in a multivalent vaccine for LD.

Alterations in bone metabolites with age in C57BL/6 mice model.

Understanding the pathophysiology behind age-related diseases is an urgent need as the elderly population continues to grow. With age, there is a high risk of musculoskeletal deterioration and associated morbidity and mortality. Although the exact mechanism behind age-related degeneration is unknown, it is well established that alteration in cellular metabolism is one of the important contributing factors. Alteration in signaling pathways with age leads to the accumulation or depletion of several metabolites that play a vital role in musculoskeletal pathophysiology. This study aimed to identify age-related changes in bone tissue metabolites in C57BL/6 mice. We then correlated the differentially expressed metabolites with their functions in bone biology. In both aged males and females, hydroxyproline, glutamine, and alpha-linolenic acid levels were decreased. In aged females, Ornithine (p value = 0.001), L-Proline (p value = 0.008), Uridine (p value = 0.001), Aspartic Acid (p value = 0.004) levels were significantly decreased, and glutamate (p value = 0.002) was elevated. In aged males, N-acetyl-D-glucosamine (pvalue = 0.010), Adrenic acid (pvalue = 0.0099), Arachidonic acid (p value = 0.029) and Allantoin (p value = 0.004) levels were decreased. Metabolic pathway analysis revealed that purine and D-glutamine and D-glutamate metabolism were significantly altered in both sexes, while arginine biosynthesis in females and lipid metabolism in males were highly affected. These differences in metabolic signaling might be one of the reasons for the discrepancy in musculoskeletal disease manifestation between the two sexes. Understanding the role of these metabolites play in the aging bone will allow for new sex-specific targeted therapies against the progression of musculoskeletal diseases.

Antibiotic cement-coated intramedullary nail is cost-effective for the initial treatment of GAâ ¢ open tibia fractures.

OBJECTIVE: To evaluate the cost-effectiveness of antibiotic cement-coated intramedullary nails (IMN) in the initial management of Gustilo-Anderson type Ⅲ (GAIII) open tibia fractures. METHODS: A break-even equation was used to analyze the costs associated with antibiotic cement-coated IMN and postoperative infection following GAⅢ open tibia fractures. This equation produced a new infection rate, which defines what percentage the antibiotic coated IMN needs to decrease the initial infection rate for its prophylactic use to be cost-effective. The postoperative infection rate used for calculations was 30%, a value established in current literature for these fracture types (6-33%). The institutional costs associated with a single operative debridement and resultant inpatient stay and treatment were determined. A sensitivity analysis was conducted to demonstrate how various total costs of infection and different infection rates affected the break-even rate, the absolute risk reduction (ARR), and the number needed to treat (NNT). RESULTS: Financial review yielded an average institutional cost of treating a postoperative infection to be $13,282.85. This number was inclusive of all procedures during an inpatient stay. The added cost of the antibiotic coated implant to the hospital is $743.42. Utilizing the break-even formula with these costs and a 30% initial infection rate, antibiotic coated IMN was economically viable if it decreased infection rate by 0.056% (NNT = 1,785.714). CONCLUSION: This break-even analysis model suggests the initial use of an antibiotic coated IMN in the setting of GAⅢ open tibia fractures is cost-effective.