Study protocol of a randomized controlled trial to assess the efficacy of the "PrEPare for Work" intervention to enhance PrEP uptake and optimize adherence for HIV prevention among male sex workers in the U.S.

BACKGROUND: Male sex workers (MSWs), specifically cisgender men who exchange sex for money, goods, drugs, or other items of value with other cisgender men, are at high risk for HIV infection. Compared to men not engaged in sex work, MSWs are more likely to engage in frequent condomless sex with paying and non-paying sexual partners. While MSWs are often included as a subgroup of gay and bisexual men, data show that a large proportion identify as heterosexual; additionally, most MSWs do not identify as "sex workers." This places MSWs in a unique position where they may not engage with traditional HIV prevention programs, and when they do, they may not feel comfortable, leading to poor retention. Thus, HIV prevention interventions that address MSWs' unique life circumstances and provide support in exploring their sexual health options are needed. METHODS: In this protocol paper, we describe the design and procedures for a National Institute of Health-funded, randomized controlled trial testing the efficacy of "PrEPare for Work,"- a theory-based, manualized PrEP uptake and adherence intervention for MSW - using a 2-stage randomization design. Stage 1: MSWs are equally randomized to receive either the "PrEPare for Work Stage 1 intervention" (strength-based case management and facilitated PrEP linkage) or Standard of Care (SOC) to evaluate successful PrEP uptake (prescription filled) within two months post-randomization. Stage 2: Those who initiate PrEP are then equally re-randomized to receive either the "PrEPare for Work Stage 2 intervention" (1-on-1 skills training, problem-solving, and motivational interviewing adherence counseling and personalized, daily text message reminders) or SOC to assess adherence (Tenofovir concentrations in hair) over 12 months of follow up. Planned analyses will examine intervention efficacy, specific conceptual mediators, and hypothesized moderators. DISCUSSION: Based on our extensive preliminary research, multi-component, theory-informed interventions targeting this subpopulation of MSWs' unique life circumstances are urgently needed. In this study, we are evaluating whether "PrEPare for Work" can improve PrEP uptake and adherence among MSWs. If this intervention is efficacious, it would be readily disseminated to diverse community organizations that serve MSWs and possibly other community or clinic-based settings. TRIAL REGISTRATION: ClinicalTrials.gov number NCT05736614, registered February 8, 2023.

Increased dental comorbidities in patients with psoriasis: a nationwide population-based cohort study in Korea.

BACKGROUND: Limited data are available regarding the association between psoriasis and common dental conditions. OBJECTIVES: To investigate the risk of potential dental comorbidities in patients with psoriasis. METHODS: We conducted a nationwide population-based cohort study to analyse the claims data of patients with psoriasis (n = 15 165) and age- and sex-matched controls (n = 75 825). The incidence risk of the following potential dental conditions was analysed: dental caries, pulp and periapical disease, periodontal disease, gingival changes and tooth loss. RESULTS: After adjusting for potential cofactors, the adjusted hazard ratios (aHRs) of dental caries [1.105; 95% confidence interval (CI) 1.078-1.132], pulp and periapical disease (1.07; 95% CI 1.044-1.096) and periodontal disease (1.108; 95% CI 1.088-1.129) were significantly higher than those in the control cohort (P < 0.001). However, among the subset of patients with psoriasis who received systemic antipsoriatic treatment (n = 4275), the aHR risk of all potential dental comorbidities was not significantly higher from that of the control cohort. CONCLUSIONS: Patients with psoriasis have an increased risk of dental comorbidities, and systemic antipsoriatic treatment may help mitigate this increased risk.

Isavuconazole Is as Effective as and Better Tolerated Than Voriconazole for Antifungal Prophylaxis in Lung Transplant Recipients.

BACKGROUND: Invasive fungal infections (IFIs) are common following lung transplantation. Isavuconazole is unstudied as prophylaxis in organ transplant recipients. We compared effectiveness and tolerability of isavuconazole and voriconazole prophylaxis in lung transplant recipients. METHODS: A single-center, retrospective study of patients who received isavuconazole (September 2015-February 2018) or voriconazole (September 2013-September 2015) for antifungal prophylaxis. IFIs were defined by EORTC/MSG criteria. RESULTS: Patients received isavuconazole (n = 144) or voriconazole (n = 156) for median 3.4 and 3.1 months, respectively. Adjunctive inhaled amphotericin B (iAmB) was administered to 100% and 41% of patients in the respective groups. At 1 year, 8% of patients receiving isavuconazole or voriconazole developed IFIs. For both groups, 70% and 30% of IFIs were caused by molds and yeasts, respectively, and breakthrough IFI (bIFI) rate was 3%. Outcomes did not significantly differ for patients receiving or not receiving iAmB. Independent risk factors for bIFI and breakthrough invasive mold infection (bIMI) were mold-positive respiratory culture and red blood cell transfusion >7 units at transplant. Bronchial necrosis >2 cm from anastomosis and basiliximab induction were also independent risk factors for bIMI. Isavuconazole and voriconazole were discontinued prematurely due to adverse events in 11% and 36% of patients, respectively (P = .0001). Most common causes of voriconazole and isavuconazole discontinuation were hepatotoxicity and lack of oral intake, respectively. Patients receiving ≥90 days prophylaxis had fewer IFIs at 1 year (3% vs 9%, P = .02). IFIs were associated with increased mortality (P = .0001) and longer hospitalizations (P = .0005). CONCLUSIONS: Isavuconazole was effective and well tolerated as antifungal prophylaxis following lung transplantation.

Impact of pre-transplant carbapenem-resistant Enterobacterales colonization and/or infection on solid organ transplant outcomes.

The impact of pre-transplant (SOT) carbapenem-resistant Enterobacterales (CRE) colonization or infection on post-SOT outcomes is unclear. We conducted a multi-center, international, cohort study of SOT recipients, with microbiologically diagnosed CRE colonization and/or infection pre-SOT. Sixty adult SOT recipients were included (liver n = 30, hearts n = 17). Klebsiella pneumoniae (n = 47, 78%) was the most common pre-SOT CRE species. Median time from CRE detection to SOT was 2.32 months (IQR 0.33-10.13). Post-SOT CRE infection occurred in 40% (n = 24/60), at a median of 9 days (IQR 7-17), and most commonly due to K pneumoniae (n = 20/24, 83%). Of those infected, 62% had a surgical site infection, and 46% had bloodstream infection. Patients with post-SOT CRE infection more commonly had a liver transplant (16, 67% vs. 14, 39%; p =.0350) or pre-SOT CRE BSI (11, 46% vs. 7, 19%; p =.03). One-year post-SOT survival was 77%, and those with post-SOT CRE infection had a 50% less chance of survival vs. uninfected (0.86, 95% CI, 0.76-0.97 vs. 0.34, 95% CI 0.08-1.0, p =.0204). Pre-SOT CRE infection or colonization is not an absolute contraindication to SOT and is more common among abdominal SOT recipients, those with pre-SOT CRE BSI, and those with early post-SOT medical and surgical complications.

Insulin Induces Microtubule Stabilization and Regulates the Microtubule Plus-end Tracking Protein Network in Adipocytes.

Insulin-stimulated glucose uptake is known to involve microtubules, although the function of microtubules and the microtubule-regulating proteins involved in insulin action are poorly understood. CLASP2, a plus-end tracking microtubule-associated protein (+TIP) that controls microtubule dynamics, was recently implicated as the first +TIP associated with insulin-regulated glucose uptake. Here, using protein-specific targeted quantitative phosphoproteomics within 3T3-L1 adipocytes, we discovered that insulin regulates phosphorylation of the CLASP2 network members G2L1, MARK2, CLIP2, AGAP3, and CKAP5 as well as EB1, revealing the existence of a previously unknown microtubule-associated protein system that responds to insulin. To further investigate, G2L1 interactome studies within 3T3-L1 adipocytes revealed that G2L1 coimmunoprecipitates CLASP2 and CLIP2 as well as the master integrators of +TIP assembly, the end binding (EB) proteins. Live-cell total internal reflection fluorescence microscopy in adipocytes revealed G2L1 and CLASP2 colocalize on microtubule plus-ends. We found that although insulin increases the number of CLASP2-containing plus-ends, insulin treatment simultaneously decreases CLASP2-containing plus-end velocity. In addition, we discovered that insulin stimulates redistribution of CLASP2 and G2L1 from exclusive plus-end tracking to "trailing" behind the growing tip of the microtubule. Insulin treatment increases α-tubulin Lysine 40 acetylation, a mechanism that was observed to be regulated by a counterbalance between GSK3 and mTOR, and led to microtubule stabilization. Our studies introduce insulin-stimulated microtubule stabilization and plus-end trailing of +TIPs as new modes of insulin action and reveal the likelihood that a network of microtubule-associated proteins synergize to coordinate insulin-regulated microtubule dynamics.

Chitinase 3-like 1 drives allergic skin inflammation via Th2 immunity and M2 macrophage activation.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by defective skin barrier and Th2 immune responses. Chitinase 3-like 1 (CHI3L1), also known as breast regression protein 39 (BRP-39) in mice and human homologue YKL-40, plays important roles in Th2 inflammation and allergen sensitization. CHI3L1 has been implicated in a variety of diseases including asthma characterized by inflammation, apoptosis and tissue remodelling, but its role in AD remains elusive. OBJECTIVE: The aim of this study was to investigate the role of CHI3L1 in the development and progression of AD. RESULTS: We investigated YKL-40 levels in the serum and skin of AD patients by ELISA and immunofluorescence, respectively. Using a murine model of AD induced by ovalbumin (OVA), we investigated Th2 immune responses, M2 macrophage activation and skin barrier gene expression using wild-type (WT) and BRP-39 null mutant (BRP-39-/- ) mice. YKL-40 level was significantly increased in serum of AD patients. In addition, both mRNA and protein expression levels of BRP-39 were higher in OVA-sensitized WT mice than in control mice. OVA-sensitized BRP-39-/- mice showed decreased epidermal thickness, lower total serum IgE, Th2 cytokine levels and CD4+ effector T cell populations than OVA-sensitized WT mice. Induction of BRP-39 was dominant in dermal macrophages. BRP-39 deficiency was found to be involved in M2 macrophage activation. Consistently, the YKL-40 level in the skin of AD patients was higher than in normal subjects and it was expressed in dermal macrophages. BRP-39 deficiency attenuated dysregulation of skin barrier and tight junction genes. CONCLUSIONS AND CLINICAL RELEVANCE: These findings demonstrate that CHI3L1 mediates the development of AD induced by OVA, affecting Th2 inflammation, M2 macrophage activation and skin barrier function.

Synergetic roles of TGF-ß signaling in tissue engineering.

Recent advances in tissue engineering highlight biomaterial designs with context-specific growth factors, cytokines and various small molecules to better mimic the natural extracellular matrix (ECM) microenvironments. These efforts have led to direct improvements in cell-cell and cell-ECM interactions while mitigating undesirable cellular and immunogenic responses. In this short review, we focus on the crucial roles and regulation of transforming growth factor ß (TGF-ß) signaling in biomaterial applications during tissue repair and regeneration.

Bleeding related to dental treatment in patients taking novel oral anticoagulants (NOACs): a retrospective study.

OBJECTIVE: Several novel oral anticoagulants (NOACs) are currently prescribed for patients suffering from atrial fibrillation, pulmonary thromboembolism, and venous thrombosis. However, there is no clinical guideline for dental treatment in patients taking NOACs. This study investigated bleeding events related to various dental treatments. MATERIALS AND METHODS: This retrospective study included 120 patients (153 cases) who were prescribed NOACs and received dental procedures in the Department of Advanced General Dentistry at Yonsei University Dental Hospital from January 2014 to June 2017. The indication for NOACs, initiation of NOACs, duration of discontinuance, creatinine clearance, and type of dental treatment were investigated. Bleeding events were assessed at a follow-up visit to the clinic. RESULTS: Postoperative bleeding occurred in only 9 of the 153 included cases; they comprised 2 cases of scaling, 3 cases of simple extraction, 3 cases of the first stage of implant surgery, and 1 case of resin filling. The creatinine clearance (P = .111) and duration of discontinuance (P = .222) did not differ significantly between the groups with and without bleeding events. CONCLUSIONS: Our data indicate that most dental treatments may be performed in patients taking NOACs without an increased likelihood of bleeding events regardless of the discontinuance duration. Moreover, any postoperative bleeding can be stopped by applying compressive pressure or local hemostatic agents. CLINICAL RELEVANCE: Our study suggests that patients taking NOACs who need dental treatments may have a bleeding tendency based on our retrospective data. Preoperative history taking and treatment modification should therefore be considered before performing dental surgery.

Oral Papillomatosis in Immunocompromised Patients: A Case Series of Kidney Transplant Recipients and Myelodysplastic Syndrome.

Solitary papilloma is a human papillomavirus (HPV)-induced benign indolent epithelial tumor with limited growth, whereas papillomatosis is an entirely different entity. Papillomatosis requires attention because of its aggressive and recurrent clinical progress with risks of dysplastic and malignant transformation. Recurrent respiratory papillomatosis (RRP) has a high prevalence of dysplasia and reports of transformation to carcinoma-ex-papillomatosis, especially when associated with low-risk HPV type 11. Although papillomatosis seldom occurs in the oral cavity, this report describes 3 cases of oral papillomatosis in immunocompromised patients, with 1 case identified as having HPV type 11. Two cases were kidney transplant recipients and the other case had a history of myelodysplastic syndrome followed by allogeneic bone marrow transplantation and graft-versus-host disease. Oral papillomatosis might be problematic, as in RRP, and periodic oral examination for persistent recurrences and malignant transformation can be beneficial to immunocompromised patients.

Predictors of asthma exacerbation among patients with poorly controlled asthma despite inhaled corticosteroid treatment.

BACKGROUND: Asthma exacerbations are associated with decreased quality of life and increased health care usage. Identification of characteristics that predict increased risk of future exacerbations in patients with suboptimal control of asthma could guide treatment decisions. OBJECTIVE: To examine patient characteristics associated with risk of asthma exacerbations in patients with uncontrolled persistent asthma. METHODS: A retrospective analysis of adults and children with inadequately controlled asthma despite asthma controller therapy and enrolled in 2 randomized trials was conducted. Baseline characteristics of subjects who experienced an asthma exacerbation during the treatment period were compared with those of subjects who did not experience an exacerbation. RESULTS: Of 718 subjects (402 adults and 295 children), 108 adults (27%) and 110 children (37%) experienced an asthma exacerbation during the study period. Unscheduled health care visits for asthma or use of oral corticosteroids in the previous year were significantly associated with asthma exacerbation during the study period (P < .01). Adult subjects who experienced an exacerbation had significantly lower forced expiratory volume in 1 second compared with those who did not (2.3 vs 2.5 L, respectively, P = .02). Children who experienced an exacerbation had lower baseline pre- and post-bronchodilator ratios of forced expiratory volume in 1 second to forced vital capacity (77% vs 81%, P < .01; 82% vs 86%, P < .001, respectively). Symptom scores on validated questionnaires were significantly worse in adults but not in children who developed an exacerbation. CONCLUSION: Spirometric measurements can help identify adults and children at increased risk for asthma exacerbation. Symptom scores could be helpful in identifying adults who are at high risk for exacerbations but could be less helpful in children.

Microfabrication of Custom Collagen Structures Capable of Guiding Cell Morphology and Alignment.

The patterning of biological components into structural analogues of native tissues to simulate an environment for directing cell growth is one important strategy in biomaterials fabrication. It is widely accepted that chemical, mechanical, and topological cues from the extracellular matrix (ECM) provide important signals for guiding cells to exhibit characteristic polarity, orientation, and morphology. To fully understand the delicate relationship between cell behavior and ECM features, biomaterials fabrication requires improved techniques for tailoring nano/microstructured patterns from relevant biological building blocks rather than using nonbiological materials. Here we reveal a unique approach for the nano/microfabrication of custom patterned biomaterials using collagen as the sole building material. With this new fabrication technique, we further revealed that custom collagen patterns could direct the orientation and morphology of fibroblast growth as a function of vertex density and pattern spacing. Our findings suggest that this technique may be readily adopted for the free form fabrication of custom cell scaffolds purely from natural biological molecules including collagen, among other relevant ECM components.

Ganciclovir-resistant cytomegalovirus infections among lung transplant recipients are associated with poor outcomes despite treatment with foscarnet-containing regimens.

Ganciclovir-resistant cytomegalovirus (CMV) infections are reported infrequently among lung transplant recipients receiving extended valganciclovir prophylaxis. We performed a single-center, retrospective review of ganciclovir-resistant CMV infections in a program that employed valganciclovir prophylaxis for ≥6 months after lung transplant. CMV infections were diagnosed in 28% (170/607) of patients. UL97 mutations were detected in 9.4% (16/170) of CMV-infected patients at a median of 8.5 months posttransplant (range, 5 to 21) and despite prophylaxis for a median of 7 months (range, 4 to 21). UL97 mutations were canonical; 25% (4/16) of strains carried concurrent UL54 mutations. Ganciclovir-resistant CMV was more likely with breakthrough infections (75% [12/16] versus 19% [30/154]; P = 0.00001) and donor positive/recipient negative (D+/R-) serostatus (75% versus 45% [69/154]; P = 0.03). The median whole-blood CMV load was 4.13 log10 copies/cm(3) (range, 2.54 to 5.53), and 93% (14/15) of patients had low-moderate immune responses (Cylex Immunoknow). Antiviral therapy was successful, failed, or eradicated viremia followed by relapse in 12% (2/16), 31% (5/16), and 56% (9/16) of patients, respectively. Eighty-seven percent (14/16) of patients were treated with foscarnet-containing regimens; toxicity developed in 78% (11/14) of these. Median viral load half-life and time to viremia eradication among foscarnet-treated patients were 2.6 and 23 days, respectively, and did not correlate with protection from relapse. Sixty-nine percent (11/16) of patients developed CMV pneumonitis, and 25% (4/16) died of it. Serum viral load was independently associated with death among foscarnet-treated patients (P = 0.04). In conclusion, ganciclovir-resistant CMV infections remained a major cause of morbidity and mortality following lung transplantation. Foscarnet-based regimens often eradicated viremia rapidly but were ineffective in the long term and limited by toxicity.

Preclinical pharmacokinetic characterization of 2-(4-(4-(5-(2-phenyl-5-(trifluoromethyl)oxazole-4-carboxamido)-1H-benzo[d]imidazol-2-yl)phenyl)cyclohexyl) acetic acid, a novel DGAT-1 inhibitor.

1. A novel diacylglyceride acyltransferase-1 (DGAT-1) inhibitor, 2-(4-(4-(5-(2-phenyl-5-(trifluoromethyl) oxazole-4-carboxamido)-1H-benzo[d]imidazol-2-yl)phenyl)cyclohexyl) acetic acid (KR-69232), was synthesized for a potential therapeutic use against several metabolic disorders, such as obesity, insulin resistance, and type II diabetes, characterized by excessive triglycerides (TGs) in the blood. 2. The half-lives against phase I metabolism were measured as 75.3 ± 20.9 min and over 120 min in rat and human liver microsomes, respectively. In Caco-2 cell monolayers, extremely low permeability (<0.13 × 10⁻6cm/s) was seen in the absorptive direction, predicting limited intestinal absorption of KR-69232. This compound was highly bound to rat and human plasma proteins (>99.8%). 3. With the intravenous administration of KR-69232 in rats (1, 2, and 5 mg/kg), non-linear kinetics were observed at the highest dose, with significantly higher systemic clearance, higher volume of distribution, and lower dose-normalized AUC. Following oral administration, it exhibited low bioavailability (<10%) and was absorbed slowly (T(max), 3.8-5.2 h) over the dose range. We also confirmed that considerable KR-69232 remained in the intestine at T(max), demonstrating its limited absorption into the systemic circulation.

Determination of a novel diacylglycerol acyltransferase 1 inhibitor, 2-[4-(4-{5-[2-phenyl-5-(trifluoromethyl) oxazole-4-carboxamido]-1H-benzo[d]imidazol-2-yl} phenyl) cyclohexyl] acetic acid (KR-69232) in rat plasma using liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study.

A liquid chromatography-tandem mass spectrometry method was developed and validated for the quantification of KR-69232, a diacyltransferase 1 inhibitor, in rat plasma. KR-69232 in the concentration range of 0.004-4 µg/mL was linear. The intra-and inter-day precision and accuracy were acceptable (<20%). KR-69232 was stable under various storage and handling conditions. The method was applied successfully in a pharmacokinetic study of KR-69232 in rats.

Effects of the COVID-19 pandemic on senior dental students in Korea: Examining stress, burnout, and depression.

Background/purpose: The COVID-19 pandemic has had a profound and enduring impact on various aspects of society, including medical education and the training of dental students. The field of dentistry, given its nature, is particularly susceptible to the challenges posed by a pandemic. Prolonged exposure to the pandemic is believed to have increased stress and burnout among medical and dental students. This study aimed to investigate and analyze the relationship between COVID-19 and stress, burnout, and depression in Korean dental students. Materials and methods: A cross-sectional survey was conducted among 162 third and fourth-grade students from the School of Dentistry at Seoul National University. The survey comprised four main sections: general information, the Maslach Burnout Inventory (MBI), the Patient Health Questionnaire-9 (PHQ-9), and the Impact of Event Scale-Revised (IES-R). Results: The results indicated significant differences in age, study time, career satisfaction, and counseling needs between third and fourth-grade students. The fourth-grade students exhibited higher scores in the IES-R survey, PHQ-9 total score, emotional exhaustion, and depersonalization subscale items of the MBI. Furthermore, the group with abnormal responses to COVID-19 demonstrated lower levels of career satisfaction. Conclusion: Fourth-grade dental students experienced higher levels of depression, vulnerability to the effects of COVID-19, and burnout. These findings highlight the need for addressing the mental health challenges faced by dental students during the COVID-19 pandemic.

Outcomes and complications of heart failure with iron deficiency anemia: a nationwide analysis.

INTRODUCTION: Heart failure is a pressing public health concern, affecting millions in the United States and projected to rise significantly by 2030. Iron deficiency, prevalent in nearly half of ambulatory heart failure patients, contributes to anemia and diminishes patient outcomes. In this study, we aim to evaluate the impact of iron deficiency anemia on acute heart failure hospitalizations outcomes. METHODS: Utilizing the 2019 National Inpatient Sample (NIS) database, a retrospective observational study assessed 112,864 adult patients hospitalized with heart failure and 7,865 cases also had a concomitant diagnosis of iron deficiency anemia (IDA). RESULTS: Among 112,864 heart failure hospitalizations in 2019, approximately 7% had concomitant iron deficiency anemia (IDA). Heart failure patients with IDA exhibited distinct demographic characteristics, with females comprising 51.1% (p < 0.01) and higher rates of complicated hypertension (p < 0.01), complicated diabetes (p < 0.01), and peripheral vascular disease (p < 0.01). Adjusted mean LOS for patients with IDA was significantly longer at 1.31 days (95% CI 0.71-1.47; p < 0.01), persisting in both HFpEF and HFrEF subgroups. While total hospital charges were comparable in HFpEF, HFrEF patients with IDA incurred significantly higher charges ($13427.32, 95% CI: 1463.35-$25391.29, p = 0.03) than those without IDA. Complications such as atrial fibrillation and acute kidney injury were notably more prevalent in HFpEF and HFrEF patients with IDA. CONCLUSION: The study highlighted that iron deficiency in heart failure patients leads to extended hospital stays, increased costs, and heightened risks of specific complications, particularly in HFrEF. Our study emphasized the implications of IDA in patients with heart failure ranging from prolonged hospitalizations and increased costs. Addressing iron deficiency is crucial, given its substantial impact on heart failure hospitalizations and outcomes, emphasizing the need for proactive diagnosis and management.

The efficacy of non-pharmacological and non-pacing therapies in preventing vasovagal syncope: Tilt training, physical counter pressure maneuvers, and yoga - A systematic review and meta-analysis.

BACKGROUND: Vasovagal syncope (VVS) is a prevalent condition characterized by a sudden drop in blood pressure and heart rate, leading to a brief loss of consciousness and postural control. Recurrent episodes of VVS significantly impact the quality of life and are a common reason for emergency department visits. Non-pharmacological interventions, such as tilt training, physical counter pressure maneuvers, and yoga, have been proposed as potential treatments for VVS. However, their efficacy in preventing VVS remains uncertain. METHODS: A systematic review and meta-analysis were conducted following PRISMA guidelines. PubMed, Web of Science, and Embase were searched up to March 2023 for randomized controlled trials comparing non-pharmacological interventions with control in preventing VVS recurrence. The primary outcome was the recurrence rate of VVS episodes. RESULTS: A total of 1130 participants from 18 studies were included in the meta-analysis. The overall mean effect size for non-pharmacological interventions versus control was 0.245 (95 % CI: 0.128-0.471, p-value <0.001). Subgroup analysis showed that yoga had the largest effect size (odds ratio 0.068, 95 % CI: 0.018-0.250), while tilt training had the lowest effect size (odds ratio 0.402, 95 % CI: 0.171-0.946) compared to control. Physical counter pressure maneuvers demonstrated an odds ratio of 0.294 (95 % CI: 0.165-0.524) compared to control. CONCLUSION: Non-pharmacological interventions show promise in preventing recurrent VVS episodes. Yoga, physical counter pressure maneuvers, and tilt training can be considered as viable treatment options. Further research, including randomized studies comparing pharmacological and non-pharmacological approaches, is needed to evaluate the safety and efficacy of these interventions for VVS treatment.

Pharmacokinetic characterization of the novel TAZ modulator TM-25659 using a multicompartment kinetic model in rats and a possibility of its drug-drug interactions in humans.

This study evaluated the pharmacokinetics of the novel TAZ modulator TM-25659 in rats following intravenous and oral administration at dose ranges of 0.5-5 mg/kg and 2-10 mg/kg, respectively. Plasma protein binding, plasma stability, liver microsomal stability, CYP inhibition, and transport in Caco-2 cells were also evaluated. After intravenous injection, systemic clearance, steady-state volumes of distribution, and half-life were dose-independent, with values ranging from 0.434-0.890 mL · h(-1) · kg(-1), 2.02-4.22 mL/kg, and 4.60-7.40 h, respectively. Mean absolute oral bioavailability was 50.9% and was not dose dependent. Recovery of TM-25659 was 43.6% in bile and <1% in urine. In pharmacokinetic modeling studies, the three-compartment (3C) model was appropriate for understanding these parameters in rats. TM-25659 was stable in plasma. Plasma protein binding was approximately 99.2%, and was concentration-independent. TM-25659 showed high permeation of Caco-2 cells and did not appear to inhibit CYP450. TM-25659 was metabolized in phase I and II steps in rat liver microsomes. In conclusion, the pharmacokinetics of TM-25659 was characterized for intravenous and oral administration at doses of 0.5-5 and 2-10 mg/kg, respectively. TM-25659 was eliminated primarily by hepatic metabolism and urinary excretion.

Periodontal disease does not increase the risk of subsequent psoriasis.

Previous studies suggested that chronic periodontitis may be a risk factor for psoriasis. However, no study has confirmed this relationship for all stages of periodontal disease (gingivitis and periodontitis). This nationwide population-based retrospective cohort study aimed to investigate whether periodontal disease is an independent risk factor for the development of subsequent psoriasis. Patients aged ≥ 20 years who underwent both medical and oral checkups from the National Health Screening Program between 2002 and 2007 were selected from a customized database provided by the National Health Insurance Service (NHIS). Then, patients with periodontal disease (n = 3,682,468) and without periodontal disease (control, n = 3,637,128) according to oral examination results were identified. We tracked each patient for subsequent psoriasis diagnosis until the end of 2018 using NHIS database. The incidence rates of psoriasis per 1000 person-years were 0.36 and 0.34 in the periodontal disease group and control groups, respectively. After adjusting for potential cofactors, no significant increase in risk (adjusted hazard ratio, 0.994; 95% confidence interval, 0.974-1.015) was observed. Similar results were observed when analyzing the risk of psoriasis in patients who required scaling or periodontal surgery. In conclusion, periodontal disease is not an independent risk factor of psoriasis.