Hickmanvedel4053

San Andrés and Providencia are Colombian islands in the Caribbean Sea. San Andrés has 68,283 inhabitants and has registered cases of leprosy in immigrants from continental Colombia. Providencia has 5,037 inhabitants and historically health programs did not have records of the disease, but in 2009 two cases of multibacillary histoid leprosy were confirmed and, subsequently, another two, which represents a prevalence of 8 cases per 10,000 inhabitants and places the island as a hyperendemic site for leprosy. Initially, a 14-year-old girl with histoid leprosy was diagnosed and, exploring this case, her father was diagnosed with the same clinical form of leprosy. Recently, a new intrafamilial patient with multibacillary leprosy and an extrafamilial case of a girl with undetermined leprosy were detected. The objective of this study was to present to the scientific community and the public health officers these clinical cases and to draw the attention of the sanitary authorities on the necessity of establishing continuous programs of leprosy epidemiological surveillance on the island using the new tools available in the Programa de Control de la Lepra (Leprosy Control Program).Primary adrenal insufficiency is a defect in glucocorticoid, mineralocorticoid and sexual androgens production. Patients with this disorder have low cortisol levels and aldosterone deficiency with concomitant hyponatremia and hyperkalemia. The most common etiology of this disease is the production of antibodies against the enzyme 21 hydroxylase. Another common cause, particularly in low income countries, are infectious diseases. Several micro-organisms have been reported as a causal agent in adrenal insufficiency including Mycobacterium tuberculosis, Mycobacterium avium complex, Neisseria meningitidis, Pseudomonas aeruginosa, Haemophilus influenzae, cytomegalovirus, Pneumocystis jirovecii, Histoplasma capsulatum, Blastomyces dermatiditis, Cryptococcus neoformans, Cocciodiodes immitis, Nocardia spp. and Paracoccidioides brasiliensis. In this article, we present the computerized tomography and the adrenal biopsy of a patient with adrenal insufficiency. The final diagnosis was paracoccidioidomycosis.Introduction The social history of written culture reflects the reading and writing habits and practices that allow us to appropriate the texts to build our sense of community. Hence, the library of individuals reflects their reading habits, their way of imagining nature, their relationship with political and religious power, and their involvement with society. Objective To interpret Antonio Nariño’s reading practices by means of the medical books in his library to approach the way he developed a presumably effective vaccine against smallpox. Materials and methods We made a bibliographic description of the documents “Confiscación y embargo de bienes de Nariño” and “Papeles, libros y bienes de Sebastián López Ruiz en poder de Nariño” from the Nariño Archive of the Universidad Nacional de Colombia. Results Out of the 39 books about Medicine (seven treatises on surgery, 12 compendia of practical exercise, 11 disease manuals, seven compendia of medical topics, and two books on childbirth) three were smallpox treatises. Conclusion Antonio Nariño’s medical and scientific practice reflects his reading and writing habits, his skills and competences, and his cultural attitudes, which promoted the notion of public health. The study of Nariño as a self-taught physician allowed for relating the scientific production techniques (development of the vaccine) and the cultural materiality (state of the art) based on the medical texts in his library.Background Bisphosphonates (BPs) are widely used as anti-bone-resorptive agents. Despite the great benefits of BPs, they may cause local and systemic adverse side effects. Objectives The aim of this study was to evaluate the histopathological effect zoledronic acid (ZA), which belongs to BPs, has on the intrinsic tongue muscles in a rat model. Material and methods A total of 30 adult male albino rats were divided into 3 groups (10 rats each) group I served as a control; group II was given an intraperitoneal (i.p.) injection of 0.2 mg/kg of ZA once per week for 3 weeks; and group III received the same dosage of ZA, but for 8 weeks. After the animals were euthanized, the tongue tissue was dissected and examined histologically, histochemically and immunohistochemically. Results Histologically, a normal architecture of the muscle fascicles was observed in the control group. Group II showed degenerated muscle fibers with an indistinct sarcolemma. In group III, the muscle fibers were degenerated with severe sarcoplasmic dissolution. The histochemical examination using Masson's trichrome (MT) demonstrated a significant increase in collagen fibers in groups II and III as compared to the control group. The immunohistochemical results revealed a statistically significantly higher expression of nuclear factor kappa B (NF‑κB) in the ZA-treated groups (II and III) as compared to the control group, with the highest mean value recorded in group III. Conclusions Zoledronic acid induced histopathological changes to the intrinsic tongue muscles, and this effect was exaggerated with a longer duration of administration.A comparison of the immunogenicity, safety, and pharmacokinetic properties of HS016 and its originator, adalimumab, was conducted in Chinese healthy male subjects. This was a phase 1 single-center, randomized, parallel-group double-blind clinical trial. Chinese healthy male subjects (11) allocated to HS016 and adalimumab groups were treated with single subcutaneous injections (40 mg/0.8 mL). The pharmacokinetic equivalence of HS016 and adalimumab was assessed by (1) the area under the plasma concentration-time curve (AUC) from time 0 to the last detectable drug concentration (AUC0-t ), (2) the AUC from time 0 extrapolated to infinity (AUC0-∞ ), and (3) the maximum plasma concentration (Cmax ). Other pharmacokinetic parameters (time to Cmax , apparent clearance, and half-life), safety, and immunogenicity were also evaluated. A total of 136 subjects were randomly divided into HS016 (n = 68) or adalimumab (n = 68) groups. The geometric means of AUC0-t , AUC0-∞ , and Cmax were similar for HS016 and adalimumab. The 90%CIs of AUC0-t (87.2% to 106.1%), AUC0-∞ (87.4% to 108.4%), and Cmax (98.6% to 113.6%) were all within the prespecified bioequivalence criteria (80% to 125%). The incidence of treatment-emergent adverse events (TEAEs) was similar in both groups, with most TEAEs being mild; only 3 (4.4%) subjects in the HS016 group experienced moderate TEAEs. No significant differences in the time to Cmax , apparent clearance, half-life, and immunogenicity were detected. The pharmacokinetic profile of HS016 was equivalent to that of the originator, adalimumab, with similar safety and immunogenicity profiles. HS016 may be considered for assessment in the treatment of patients with ankylosing spondylitis.Comprehensive molecular-level models of human metabolism have been generated on a cellular level. However, models of whole-body metabolism have not been established as they require new methodological approaches to integrate molecular and physiological data. We developed a new metabolic network reconstruction approach that used organ-specific information from literature and omics data to generate two sex-specific whole-body metabolic (WBM) reconstructions. These reconstructions capture the metabolism of 26 organs and six blood cell types. Each WBM reconstruction represents whole-body organ-resolved metabolism with over 80,000 biochemical reactions in an anatomically and physiologically consistent manner. We parameterized the WBM reconstructions with physiological, dietary, and metabolomic data. The resulting WBM models could recapitulate known inter-organ metabolic cycles and energy use. We also illustrate that the WBM models can predict known biomarkers of inherited metabolic diseases in different biofluids. Predictions of basal metabolic rates, by WBM models personalized with physiological data, outperformed current phenomenological models. EGFR inhibitor Finally, integrating microbiome data allowed the exploration of host-microbiome co-metabolism. Overall, the WBM reconstructions, and their derived computational models, represent an important step toward virtual physiological humans.Background KIT proto-oncogene ligand (KITLG) is a pleiotropic factor which is found in diverse cancers and is involved in cell proliferation, differentiation, and survival. However, the value of KITLG in thymoma remains unclear. Methods A total of 121 thymoma samples from The Cancer Genome Atlas Thymoma (TCGA-THYM) dataset were used to analyze KITLG related genome-wide expression profiles, and microRNA profiles and methylation alterations and a GEO dataset-GSE29695, including 37 samples was used as verification. For cell-based studies, specific small interfering RNA targeting KITLG or a KITLG overexpression vector were used to clarify the changes of the MAPK pathway in an AB thymoma cell line Thy0517. Results Both datasets showed that high expression of KITLG was significantly associated with type A and AB thymoma. Through multiomic analysis of the TCGA-THYM, it was found that with the high expression of KITLG, there were 220 upregulated and 72 downregulated genes at the mRNA level, 79 positive and 78 negativdiagnostic biomarker or target.Plasma functionalization can increase the efficiency of MoSe2 in the hydrogen evolution reaction (HER) by providing multiple species but the interactions between the plasma and catalyst are not well understood. In this work, the effects of the ion energy and plasma density on the catalytic properties of MoSe2 nanosheets are studied. The through-holes resulting from plasma etching and multi-vacancies induced by plasma-induced damage enhance the HER efficiency as exemplified by a small overpotential of 148 mV at 10 mA cm-2 and Tafel slope of 51.6 mV dec-1 after the plasma treatment using a power of 20 W. The interactions between the plasma and catalyst during etching and vacancies generation are evaluated by plasma simulation. Finite element and first-principles density functional theory calculations are also conducted and the results are consistent with the experimental results, indicating that the improved HER catalytic activity stems from the enhanced electric field and more active sites on the catalyst, and reduced bandgap and adsorption energy arising from the etched through-holes and vacancies, respectively. The results convey new fundamental knowledge about the plasma effects and means to enhance the efficiency of catalysts in water splitting as well insights into the design of high-performance HER catalysts.Sildenafil citrate is approved to treat erectile dysfunction. link2 An orally disintegrating tablet (ODT) of sildenafil citrate that does not require swallowing or administration with fluids has been developed. The bioequivalence and bioavailability of sildenafil citrate ODT (50 mg) without and with water were compared with conventional sildenafil citrate tablets (50 mg) in an open-label, randomized crossover study. Healthy Chinese male subjects (n = 36) were allocated to 1 of 6 sildenafil citrate treatment sequences under fasted conditions, and plasma samples for determination of sildenafil concentrations were collected predose through 14 hours postdose. link3 Bioequivalence was demonstrated for sildenafil citrate ODT administered without water relative to the sildenafil citrate tablet administered with water; 90%CIs for the ratios of adjusted geometric means for sildenafil AUClast , Cmax , and AUCinf (ratio, 101.41%; 90%CI, 95.49%-107.70%; ratio, 93.55%; 90%CI, 84.15%-104.00%; and ratio, 101.03%; 90%CI, 94.80%-107.66%; respectively) were wholly contained within the bioequivalence acceptance range of 80% to 125%, indicating bioequivalence criteria were met.