Genetic Diversity of Mycobacterium tuberculosis Strains Isolated from HIV-Infected Patients in Mexico.

There has been very limited investigation regarding the genetic diversity of Mycobacterium tuberculosis (MTb) strains isolated from human immunodeficiency virus (HIV)-infected patients in Mexico. In this study, we isolated 93 MTb strains from pulmonary and extrapulmonary samples of HIV-infected patients treated in a public hospital in Mexico City to evaluate the genetic diversity using spoligotyping and mycobacterial interspersed repetitive unit-variable-number tandem-repeat (MIRU-VNTR) typing (based on 24 loci). The cohort comprised 80 male and 13 female individuals. There was a positive correlation between a high HIV viral load (>100,000 copies) and extrapulmonary tuberculosis (TB) (r = 0.306, p = 0.008). Lineage 4 was the most frequent lineage (79 strains). In this lineage, we found the H clade (n = 24), including the Haarlem, H3, and H1 families; the T clade (n = 22), including T1 and T2; the X clade (n = 15), including X1 and X3; the LAM clade (n = 14), including LAM1, LAM2, LAM3, LAM6, and LAM9; the S clade (n = 2); Uganda (n = 1); and Ghana (n = 1). We also found 12 strains in the EAI clade belonging to lineage 1, including the EAI2-Manila and EAI5 families. Interestingly, we identified one strain belonging to the Beijing family, which is part of lineage 2. One strain could not be identified. This study reports high genetic diversity among MTb strains, highlighting the need for a molecular epidemiological surveillance system that can help to monitor the spread of these strains, leading to more appropriate measures for TB control in HIV-infected patients.

Nanoscale Dodecahedral and Fullerene-Type Organoboroxine and Borazine Cages from Planar Building Units.

Boroxine- and borazine-cage analogs to C20, C60, and C70 were calculated and compared in terms of structure, strain indicators, and physical properties relevant to nanoscale applications. The results show C60 and C70 type cages are less strained than the smaller congener, primarily due to minimized bending in the B-arylene-B segments. The smallest cage calculated has a diameter of 2.4 nm, which increases up to 4.9 nm by either variation of the polyhedron (C20 < C60 < C70-type cage) or organic spacer elongation between boron centers. All calculated cages are porous (apertures ranging from 0.6 to 1.9 nm). Molecular electrostatic potential and Hirshfeld population analysis revealed both nucleophilic and electrophilic sites in the interior and exterior cage surfaces. HOMO-LUMO gaps range from 3.98 to 4.89 eV and 5.10-5.18 eV for the boroxine- and borazine-cages, respectively. Our findings provide insights into the design and properties of highly porous boroxine and borazine cages for nanoscience.

Chemotherapy-induced tubulopathy: a case report series.

Acquired tubulopathies are frequently underdiagnosed. They can be characterized by the renal loss of specific electrolytes or organic solutes, suggesting the location of dysfunction. These tubulopathies phenotypically can resemble Bartter or Gitelman syndrome). These syndromes are infrequent, they may present salt loss resembling the effect of thiazides (Gitelman) or loop diuretics (Bartter). They are characterized by potentially severe hypokalemia, associated with metabolic alkalosis, secondary hyperaldosteronism, and often hypomagnesemia. Tubular dysfunction has been described as nephrotoxic effects of platinum-based chemotherapy. We present 4 cases with biochemical signs of tubular dysfunction (Bartter-like/Gitelman-like phenotype) related to chemotherapy.

Transgenerational plasticity to drought: contrasting patterns of non-genetic inheritance in two semiarid Mediterranean shrubs.

BACKGROUND AND AIMS: Intra- and transgenerational plasticity may provide substantial phenotypic variation to cope with environmental change. Since assessing the unique contribution of the maternal environment to the offspring phenotype is challenging in perennial, outcrossing plants, little is known about the evolutionary and ecological implications of transgenerational plasticity and its persistence over the life cycle in these species. We evaluated how intra- and transgenerational plasticity interplay to shape the adaptive responses to drought in two perennial Mediterranean shrubs. METHODS: We used a novel common garden approach that reduced within-family genetic variation in both the maternal and offspring generations by growing the same maternal individual in two contrasting watering environments, well-watered and drought, in consecutive years. We then assessed phenotypic differences at the reproductive stage between offspring reciprocally-grown in the same environments. KEY RESULTS: Maternal drought had an effect on offspring performance only in Helianthemum squamatum. Offspring of drought-stressed plants showed more inflorescences, less sclerophyllous leaves and higher growth rates in both watering conditions, and heavier seeds under drought, than offspring of well-watered maternal plants. Maternal drought also induced similar plasticity patterns across maternal families, showing a general increase in seed mass in response to offspring drought, a pattern not observed in the offspring of well-watered plants. In contrast, both species expressed immediate adaptive plasticity, and the magnitude of intragenerational plasticity was larger than the transgenerational plastic responses. CONCLUSIONS: Our results highlight that adaptive effects associated with maternal drought can persist beyond the seedling stage and provide evidence of species-level variation in the expression of transgenerational plasticity. Such differences between co-occurring Mediterranean species in the prevalence of this form of non-genetic inheritance may result in differential vulnerability to climate change.

IL-23/IL-17 axis levels in gingival crevicular fluid of subjects with periodontal disease: a systematic review.

BACKGROUND: The IL-23/IL-17 axis plays an important role in the immunopathogenesis of periodontal disease. A systematic review was conducted to synthesize all research reporting on the levels of the IL-23/IL-17 axis in gingival crevicular fluid (GCF) from subjects with gingivits, and periodontitis, compared to healthy controls. METHODS: The protocol followed the PRISMA, and Cochrane guidelines, and was registered with the Open Science Framework (OSF): https://doi.org/10.17605/OSF.IO/7495V . A search was conducted in the electronic databases PubMed/MEDLINE, Scopus, Google Schoolar, and Cochrane from November 15th, 2005, to May 10th, 2023. The quality of the studies was assessed using the JBI tool for cross-sectional studies. RESULTS: The search strategy provided a total of 2,098 articles, of which 12 investigations met the inclusion criteria. The total number of patients studied was 537, of which 337 represented the case group (subjects with gingivitis, and chronic periodontitis), and 200 represented the control group (periodontally healthy subjects). The ages of the patients ranged from 20 to 50 years, with a mean (SD) of 36,6 ± 4,2, of which 47% were men, and 53% were women. 75% of the investigations collected GCF samples with absorbent paper strips, and analyzed cytokine IL-17 levels individually. In addition, qualitative analysis revealed that there are differences between IL-23/IL-17 axis levels in subjects with chronic periodontitis, gingivitis and healthy controls. CONCLUSIONS: Thus, IL-23/IL-17 axis levels could be used in the future as a diagnostic tool to distinguish between periodontal diseases.

Analysis of subgingival microbiota and IL-1ß, TNF-α and CX3CL1 levels in gingival crevicular fluid of fixed dental prostheses.

Prosthetic biomaterials can affect the composition of the subgingival microbiota and consequently the production of proinflammatory cytokines, causing damage to the periodontium. A total of 40 patients were divided into two groups: 20 with monolithic zirconia (MZ) prostheses and 20 with porcelain fused to metal (PFM) with nickel-chromium (Ni-Cr) alloy prostheses. Subgingival plaque and gingival crevicular fluid samples were taken. The Checkerboard technique for DNA-DNA hybridization and the enzyme-linked immunosorbent assay technique were performed. Teeth with MZ presented a lower percentage of bleeding on probing and tooth mobility compared to teeth with PFM with Ni-Cr alloy. Prosthodontic teeth harbored higher total levels of the 18 bacterial species than non-prosthodontic teeth. There was a higher prevalence of S. gordonii and V. parvula species in PFM with Ni-Cr alloy compared to MZ. There was an increase in IL-1ß, TNF-α and CX3CL1 levels in PFM with Ni-Cr alloy compared to MZ. MZ is a candidate biomaterial with fewer negative effects on the periodontium, allowing for longer prostheses longevity in the mouth.

The role of the CX3CL1/CX3CR1 axis as potential inflammatory biomarkers in subjects with periodontitis and rheumatoid arthritis: A systematic review.

OBJECTIVE: This systematic review aimed to investigate the role of the C-X3-C motif ligand 1/chemokine receptor 1 C-X3-C motif (CX3CL1/CX3CR1) axis in the pathogenesis of periodontitis. Furthermore, as a secondary objective, we determine whether the CX3CL1/CX3CR1 axis could be considered complementary to clinical parameters to distinguish between periodontitis and rheumatoid arthritis (RA) and/or systemically healthy subjects. METHODS: The protocol used for this review was registered in OSF (10.17605/OSF.IO/KU8FJ). This study was designed following Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Records were identified using different search engines (PubMed/MEDLINE, Scopus, Science Direct, and Web of Science) from August 10, 2006, to September 15, 2023. The observational studies on human subjects diagnosed with periodontitis and RA and/or systemically healthy were selected to analyze CX3CL1 and CX3CR1 biomarkers. The methodological validity of the selected articles was assessed using NIH. RESULTS: Six articles were included. Biological samples (gingival crevicular fluid [GCF], saliva, gingival tissue biopsies, serum) from 379 subjects (n = 275 exposure group and n = 104 control group) were analyzed. Higher CX3CL1 and CX3CR1 chemokine levels were found in subjects with periodontitis and RA compared with periodontal and systemically healthy subjects. CONCLUSION: Very few studies highlight the role of the CX3CL1/CX3CR1 axis in the pathogenesis of periodontitis; however, increased levels of these chemokines are observed in different biological samples (GCF, gingival tissue, saliva, and serum) from subjects with periodontitis and RA compared with their healthy controls. Future studies should focus on long-term follow-up of subjects and monitoring changes in cytokine levels before and after periodontal therapy to deduce an appropriate interval in health and disease conditions.

Oral findings and comprehensive dental management of Moebius syndrome: a systematic review.

BACKGROUND: Moebius syndrome (MS) is a rare, non-progressive, neuromuscular, congenic disease involving the oral maxillofacial region. The present study aimed to describe the oral and extraoral findings in MS patients and their comprehensive dental management. METHODS: A digital search was carried out in PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar, restricted to articles in English from Jan 01, 2000, to Apr 02, 2023, following PRISMA guidelines. The methodological quality of the studies was evaluated following the JBI guidelines. Qualitative analysis was carried out on the overall result, extraoral and intraoral manifestations, considering dental management as appropriate. RESULTS: Twenty-three studies were included, and a total of 124 cases of patients with MS were analyzed. The 82% of patients with MS were younger than 15 years of age. The most frequent extraoral manifestations were blinking and visual problems (78,22%), malformations of the upper and lower limbs (58,22%), bilateral facial paralysis (12,90%), lack of facial expression (12.09%), and unilateral facial paralysis (6,45%). On the other hand, the most frequent oral manifestations were tongue deformities (78,22%), micrognathia (37,90%), labial incompetence (36,29%), cleft palate (22,87%), gothic palate (16,12%), microstomia (15,32%), anterior open bite (15,32%), dental caries (8,87%), and periodontal disease (8,06%). The majority of MS patients were treated by pediatric dentistry (60,86%), using a surgical approach (56,52%), and orthodontic and orthopedic maxillary (43,47%) followed by restorative (39,13%), and periodontal treatments (21,73%). CONCLUSIONS: This systematic review demonstrates that patients with MS present a wide variety of oral and extraoral manifestations, for which dental treatments are planned and tailored to each patient in accordance with oral manifestations. These treatments encompass problem resolution and oral health maintenance, incorporating recent techniques in managing and treating patients with MS.

Congenital anomalies and predisposition to severe COVID-19 among pediatric patients in the United States.

BACKGROUND AND OBJECTIVE: Congenital heart defects are known to be associated with increased odds of severe COVID-19. Congenital anomalies affecting other body systems may also be associated with poor outcomes. This study is an exhaustive assessment of congenital anomalies and odds of severe COVID-19 in pediatric patients. METHODS: Data were retrieved from the COVID-19 dataset of Cerner® Real-World Data for encounters from March 2020 to February 2022. Prior to matching, the data consisted of 664,523 patients less than 18 years old and 927,805 corresponding encounters with COVID-19 from 117 health systems across the United States. One-to-one propensity score matching was performed, and a cumulative link mixed-effects model with random intercepts for health system and patients was built to assess corresponding associations. RESULTS: All congenital anomalies were associated with worse COVID-19 outcomes, with the strongest association observed for cardiovascular anomalies (odds ratio [OR], 3.84; 95% CI, 3.63-4.06) and the weakest association observed for anomalies affecting the eye/ear/face/neck (OR, 1.16; 95% CI, 1.03-1.31). CONCLUSIONS AND RELEVANCE: Congenital anomalies are associated with greater odds of experiencing severe symptoms of COVID-19. In addition to congenital heart defects, all other birth defects may increase the odds for more severe COVID-19. IMPACT: All congenital anomalies are associated with increased odds of severe COVID-19. This study is the largest and among the first to investigate birth defects across all body systems. The multicenter large data and analysis demonstrate the increased odds of severe COVID19 in pediatric patients with congenital anomalies affecting any body system. These data demonstrate that all children with birth defects are at increased odds of more severe COVID-19, not only those with heart defects. This should be taken into consideration when optimizing prevention and intervention resources within a hospital.

Optimizing Heart Failure Management: A Review of the Clinical Pharmacist Integration to the Multidisciplinary Health Care Team.

Heart failure (HF) stands as a prevalent chronic ailment, imposing a substantial burden on global healthcare systems due to recurrent hospitalizations, intricate management, persistent symptoms, and polypharmacy challenges. The augmentation of patient safety and treatment efficacy across various care stages, facilitated by a multidisciplinary HF team inclusive of a clinical pharmacist, emerges as paramount. Evidence underscores that the collaborative engagement of a physician and a clinical pharmacist engenders proficient and secure management, forestalling avoidable adversities stemming from drug reactions and prescription inaccuracies. This synergistic approach tailors treatments optimally to individual patients. Post-discharge, the vulnerability of HF patients to re-hospitalization looms large, historically holding sway as the foremost cause of 30-day readmissions. Diverse strategies have been instituted to fortify patient well-being, leading to the formulation of specialized transitional care programs that shepherd patients effectively from hospital to outpatient settings. These initiatives have demonstrably curtailed readmission rates. This review outlines a spectrum of roles assumed by clinical pharmacists within the healthcare cohort, spanning inpatient care, transitional phases, and outpatient services. Moreover, it traverses a compendium of studies spotlighting the affirmative impact instigated by integrating clinical pharmacists into these fields.

Phenotypic and Genotypic Drug Resistance of Mycobacterium tuberculosis Strains Isolated from HIV-Infected Patients from a Third-Level Public Hospital in Mexico.

BACKGROUND: Drug-resistant tuberculosis (TB) is associated with higher mortality rates in patients with human immunodeficiency virus (HIV). In Mexico, the number of deaths due to TB among the HIV-positive population has tripled in recent years. METHODS: Ninety-three Mycobacterium tuberculosis strains isolated from the same number of HIV-infected patients treated in a public hospital in Mexico City were studied to determine the drug resistance to first- and second-line anti-TB drugs and to identify the mutations associated with the resistance. RESULTS: Of the 93 patients, 82.7% were new TB cases, 86% were male, and 73% had extrapulmonary TB. Most patients (94%) with a CD4 T-lymphocyte count <350 cells/mm3 were associated with extrapulmonary TB (p <0.0001), whilst most patients (78%) with a CD4 T-lymphocyte count >350 cells/mm3 were associated with pulmonary TB (p = 0.0011). Eighty-two strains were pan-susceptible, four mono-resistant, four poly-resistant, two multidrug-resistant, and one was extensively drug-resistant. In the rifampicin-resistant strains, rpoB S531L was the mutation most frequently identified, whereas the inhA C15T and katG S315T1 mutations were present in isoniazid-resistant strains. The extensively drug-resistant strain also contained the mutation gyrA D94A. CONCLUSIONS: These data highlight the need to promptly diagnose the drug resistance of M. tuberculosis among all HIV-infected patients by systematically offering access to first- and second-line drug susceptibility testing and to tailor the treatment regimen based on the resistance patterns to reduce the number of deaths in HIV-infected patients.

Use of Novel Homochiral Thioureas Camphor Derived as Asymmetric Organocatalysts in the Stereoselective Formation of Glycosidic Bonds.

We synthesized six new camphor-derived homochiral thioureas 1-6, from commercially available (1R)-(-)-camphorquinone. These new compounds 1-6 were evaluated as asymmetric organocatalysts in the stereoselective formation of glycosidic bonds, with 2,3,4,6-tetra-O-benzyl-D-glucopyranosyl and 2,3,4,6-tetra-O-benzyl-D-galactopyranosyl trichloroacetimidates as donors, and several alcohols as glycosyl acceptors, such as methanol, ethanol, 1-propanol, 1-butanol, 1-octanol, iso-propanol, tert-butanol, cyclohexanol, phenol, 1-naphtol, and 2-naphtol. Optimization of the asymmetric glycosylation reaction was achieved by modifying reaction conditions such as solvent, additive, loading of catalyst, temperature, and time of reaction. The best result was obtained with 2,3,4,6-tetra-O-benzyl-D-galactopyranosyl trichloroacetimidates, using 15 mol% of organocatalyst 1, in the presence of 2 equiv of MeOH in solvent-free conditions at room temperature for 1.5 h, affording the glycosidic compound in a 99% yield and 1:73 α:ß stereoselectivity; under the same reaction conditions, without using a catalyst, the obtained stereoselectivity was 1:35 α:ß. Computational calculations prior to the formation of the products were modeled, using density functional theory, M06-2X/6-31G(d,p) and M06-2X/6-311++G(2d,2p) methods. We observed that the preference for ß glycoside formation, through a stereoselective inverted substitution, relies on steric effects and the formation of hydrogen bonds between thiourea 1 and methanol in the complex formed.

FOXM1 Participates in Trophoblast Migration and Early Trophoblast Invasion: Potential Role in Blastocyst Implantation.

Successful implantation requires coordinated migration and invasion of trophoblast cells into a receptive endometrium. Reduced forkhead box M1 (FOXM1) expression limits trophoblast migration and angiogenesis in choriocarcinoma cell lines, and in a rat model, placental FOXM1 protein expression was significantly upregulated in the early stages of pregnancy compared to term pregnancy. However, the precise role of FOXM1 in implantation events remains unknown. By analyzing mice blastocysts at embryonic day (E3.5), we have demonstrated that FOXM1 is expressed as early as the blastocyst stage, and it is expressed in the trophectoderm of the blastocyst. Since controlled oxygen tension is determinant for achieving normal implantation and placentation and a chronic hypoxic environment leads to shallow trophoblast invasion, we evaluated if FOXM1 expression changes in response to different oxygen tensions in the HTR-8/SVneo first trimester human trophoblast cell line and observed that FOXM1 expression was significantly higher when trophoblast cells were cultured at 3% O2, which coincides with oxygen concentrations in the uteroplacental interface at the time of implantation. Conversely, FOXM1 expression diminished in response to 1% O2 that resembles a hypoxic environment in utero. Migration and angiogenesis were assessed following FOXM1 knockdown and overexpression at 3% O2 and 1% O2, respectively, in HTR-8/SVneo cells. FOXM1 overexpression increased transmigration ability and tubule formation. Using a 3D trophoblast invasion model with trophospheres from HTR-8/SVneo cells cultured on a layer of MATRIGEL and of mesenchymal stem cells isolated from menstrual fluid, we observed that trophospheres obtained from 3D trophoblast invasion displayed higher FOXM1 expression compared with pre-invasion trophospheres. Moreover, we have also observed that FOXM1-overexpressing trophospheres increased trophoblast invasion compared with controls. HTR-8/SVneo-FOXM1-depleted cells led to a downregulation of PLK4, VEGF, and MMP2 mRNA expression. Our current findings suggest that FOXM1 participates in embryo implantation by contributing to trophoblast migration and early trophoblast invasion, by inducing transcription activation of genes involved in these processes. Maternal-fetal communication is crucial for trophoblast invasion, and maternal stromal cells may induce higher levels of FOXM1 in trophoblast cells.

Comparison of control and transmission of COVID-19 across epidemic waves in Hong Kong: an observational study.

Background: Hong Kong contained COVID-19 for two years but experienced a large epidemic of Omicron BA.2 in early 2022 and endemic transmission of Omicron subvariants thereafter. We reflected on pandemic preparedness and responses by assessing COVID-19 transmission and associated disease burden in the context of implementation of various public health and social measures (PHSMs). Methods: We examined the use and impact of pandemic controls in Hong Kong by analysing data on more than 1.7 million confirmed COVID-19 cases and characterizing the temporal changes non-pharmaceutical and pharmaceutical interventions implemented from January 2020 through to 30 December 2022. We estimated the daily effective reproductive number (Rt) to track changes in transmissibility and effectiveness of community-based measures against infection over time. We examined the temporal changes of pharmaceutical interventions, mortality rate and case-fatality risks (CFRs), particularly among older adults. Findings: Hong Kong experienced four local epidemic waves predominated by the ancestral strain in 2020 and early 2021 and prevented multiple SARS-CoV-2 variants from spreading in the community before 2022. Strict travel-related, case-based, and community-based measures were increasingly tightened in Hong Kong over the first two years of the pandemic. However, even very stringent measures were unable to contain the spread of Omicron BA.2 in Hong Kong. Despite high overall vaccination uptake (>70% with at least two doses), high mortality was observed during the Omicron BA.2 wave due to lower vaccine coverage (42%) among adults ≥65 years of age. Increases in antiviral usage and vaccination uptake over time through 2022 was associated with decreased case fatality risks. Interpretation: Integrated strict measures were able to reduce importation risks and interrupt local transmission to contain COVID-19 transmission and disease burden while awaiting vaccine development and rollout. Increasing coverage of pharmaceutical interventions among high-risk groups reduced infection-related mortality and mitigated the adverse health impact of the pandemic. Funding: Health and Medical Research Fund.

Dosing Challenges and Benefits of Vericiguat in a Patient With Decompensated Heart Failure: A Case Report.

Vericiguat has emerged as a promising add-on therapy for decompensated heart failure with reduced ejection fraction (HFrEF) patients requiring hospitalization or IV diuretic administration. In the VICTORIA trial (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction), vericiguat was demonstrated to significantly reduce mortality and hospitalization rates. However, the effect of vericiguat on patients receiving SGLT2 inhibitors remains uncertain. In this report, we present a complicated case of dilated heart failure receiving low doses of foundational therapy due to a patient's intolerance but still experiencing recurrent hospital readmissions. Following six months of low-dose vericiguat as an add-on therapy, the patient exhibited important improvements in various clinical parameters, including cardiac and renal function. Nonetheless, further investigation is crucial to substantiate the additional benefits of combination therapy. These findings provide further evidence for the potential benefits of vericiguat when treating HFrEF.

Implant-supported prosthetic rehabilitation after Ameloblastomas treatment: a systematic review.

BACKGROUND: Ameloblastoma (AM), the benign counterpart of ameloblastic carcinoma, is a benign odontogenic tumor of epithelial origin, naturally aggressive, with unlimited growth potential and a high tendency to relapse if not adequately removed. Patients with AM treated surgically can benefit from dental implant therapy, promoting oral rehabilitation and improving their quality of life. The present study aimed to determine the survival rate of dental implants placed after surgical treatment of patients affected by AM. In addition, there were two secondary objectives: 1) To evaluate which dental implant loading protocols are most frequently used and 2) To determine the type of prosthetic restoration most commonly used in these patients. METHODS: The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were followed during the study. Searches were performed in three databases (PubMed/MEDLINE, Scopus, and Google Scholar) until November 2023. Additionally, the electronic search was enriched by an iterative hand search of journals related to oral pathology and medicine, maxillofacial surgery, and oral prosthodontics and implantology. Only reports and case series in English from January 2003 to date were included. The Joanna Briggs Institute tool (JBI-Case Reports/Case Series) was used for the study quality assessment. RESULTS: The total number of patients and implants studied were 64 and 271, respectively, all with surgically treated AM. The patient's ages ranged from 8 to 79 years, with a mean (SD) age of 37.3 ± 16.4. Fifty-three percent were male and 47% were female. The range of follow-up duration was 1 to 22 years. An implant survival/success rate of 98.1% was reported. In addition, most of them were conventionally loaded (38.3%). Hybrid implant-supported fixed dentures were the most commonly used by prosthodontists (53%). CONCLUSIONS: Oral rehabilitation with dental implants inserted in free flaps for orofacial reconstruction in surgically treated patients with AM can be considered a safe and successful treatment modality.

Treatment variability and its relationships to outcomes among patients with Wernicke's encephalopathy: A multicenter retrospective study.

BACKGROUND: Despite guidelines and recommendations, Wernicke's encephalopathy (WE) treatment lacks evidence, leading to clinical practice variability. AIMS: Given the overall lack of information on thiamine use for WE treatment, we analyzed data from a large, well-characterized multicenter sample of patients with WE, examining thiamine dosages; factors associated with the use of different doses, frequencies, and routes; and the influence of differences in thiamine treatment on the outcome. METHODS: This retrospective study was conducted with data from 443 patients from 21 centers obtained from a nationwide registry of the Spanish Society of Internal Medicine (from 2000 to 2012). Discharge codes and Caine criteria were applied for WE diagnosis, and treatment-related (thiamine dosage, frequency, and route of administration) demographic, clinical, and outcome variables were analyzed. RESULTS: We found marked variability in WE treatment and a low rate of high-dose intravenous thiamine administration. Seventy-eight patients out of 373 (20.9%) received > 300mg/day of thiamine as initial dose. Patients fulfilling the Caine criteria or presenting with the classic WE triad more frequently received parenteral treatment. Delayed diagnosis (after 24h hospitalization), the fulfillment of more than two Caine criteria at diagnosis, mental status alterations, and folic acid deficiency were associated significantly with the lack of complete recovery. Malnutrition, reduced consciousness, folic acid deficiency, and the lack of timely thiamine treatment were risk factors for mortality. CONCLUSIONS: Our results clearly show extreme variability in thiamine dosages and routes used in the management of WE. Measures should be implemented to ensure adherence to current guidelines and to correct potential nutritional deficits in patients with alcohol use disorders or other risk factors for WE.

Online transdiagnostic intervention for emotional, trauma- and stressor-related disorders in the Mexican population: A randomized pilot and feasibility trial.

•Mexican individuals received via telehealth the unified protocol for anxiety, depression, and trauma related disorders.•Online unified protocol reduced depression, anxiety, emotional issues, uncertainty intolerance, and psychological distress.•The transdiagnostic unified protocol is well-suited to train therapists for emotional, trauma, and stressor-related disorders.

Comparative antibody and cell-mediated immune responses, reactogenicity, and efficacy of homologous and heterologous boosting with CoronaVac and BNT162b2 (Cobovax): an open-label, randomised trial.

BACKGROUND: Few trials have compared homologous and heterologous third doses of COVID-19 vaccination with inactivated vaccines and mRNA vaccines. The aim of this study was to assess immune responses, safety, and efficacy against SARS-CoV-2 infection following homologous or heterologous third-dose COVID-19 vaccination with either one dose of CoronaVac (Sinovac Biotech; inactivated vaccine) or BNT162b2 (Fosun Pharma-BioNTech; mRNA vaccine). METHODS: This is an ongoing, randomised, allocation-concealed, open-label, comparator-controlled trial in adults aged 18 years or older enrolled from the community in Hong Kong, who had received two doses of CoronaVac or BNT162b2 at least 6 months earlier. Participants were randomly assigned, using a computer-generated sequence, in a 1:1 ratio with allocation concealment to receive a (third) dose of CoronaVac or BNT162b2 (ancestral virus strain), stratified by types of previous COVID-19 vaccination (homologous two doses of CoronaVac or BNT162b2). Participants were unmasked to group allocation after vaccination. The primary endpoint was serum neutralising antibodies against the ancestral virus at day 28 after vaccination in each group, measured as plaque reduction neutralisation test (PRNT50) geometric mean titre (GMT). Surrogate virus neutralisation test (sVNT) mean inhibition percentage and PRNT50 titres against omicron BA.1 and BA.2 subvariants were also measured. Secondary endpoints included geometric mean fold rise (GMFR) in antibody titres; incidence of solicited local and systemic adverse events; IFNγ+ CD4+ and IFNγ+ CD8+ T-cell responses at days 7 and 28; and incidence of COVID-19. Within-group comparisons of boost in immunogenicity from baseline and between-group comparisons were done according to intervention received (ie, per protocol) by paired and unpaired t test, respectively, and cumulative incidence of infection was compared using Kaplan-Meier curves and a proportional hazards model to estimate hazard ratio. The trial is registered with ClinicalTrials.gov, NCT05057169. FINDINGS: We enrolled participants from Nov 12, 2021, to Jan 27, 2022. We vaccinated 219 participants who previously received two doses of CoronaVac, including 101 randomly assigned to receive CoronaVac (CC-C) and 118 randomly assigned to receive BNT162b2 (CC-B) as their third dose; and 232 participants who previously received two doses of BNT162b2, including 118 randomly assigned to receive CoronaVac (BB-C) and 114 randomly assigned to receive BNT162b2 (BB-B) as their third dose. The PRNT50 GMTs on day 28 against ancestral virus were 109, 905, 92, and 816; against omicron BA.1 were 9, 75, 8, and 86; and against omicron BA.2 were 6, 80, 6, and 67 in the CC-C, CC-B, BB-C, and BB-B groups, respectively. Mean sVNT inhibition percentages on day 28 against ancestral virus were 83%, 96%, 87%, and 96%; against omicron BA.1 were 15%, 58%, 19%, and 69%; and against omicron BA.2 were 43%, 85%, 50%, and 90%, in the CC-C, CC-B, BB-C, and BB-B groups, respectively. Participants who had previously received two doses of CoronaVac and a BNT162b2 third dose had a GMFR of 12 (p<0·0001) compared with those who received a CoronaVac third dose; similarly, those who had received two doses of BNT162b2 and a BNT162b2 third dose had a GMFR of 8 (p<0·0001). No differences in CD4+ and CD8+ T-cell responses were observed between groups. We did not identify any vaccination-related hospitalisation within 1 month after vaccination. We identified 58 infections when omicron BA.2 was predominantly circulating, with cumulative incidence of 15·3% and 15·4% in the CC-C and CC-B groups, respectively (p=0·93), and 16·7% and 14·0% in the BB-C and BB-B groups, respectively (p=0·56). INTERPRETATION: Similar levels of incidence of, presumably, omicron BA.2 infections were observed in each group despite very weak antibody responses to BA.2 in the recipients of a CoronaVac third dose. Further research is warranted to identify appropriate correlates of protection for inactivated COVID-19 vaccines. FUNDING: Health and Medical Research Fund, Hong Kong. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.