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Background: High-altitude deacclimatization syndrome (HADAS) is a severe public health issue. The study of the changes in right ventricular function caused by high-altitude deacclimatization (HADA) is of great significance for the prevention and treatment of HADAS. Methods: Six-week-old, male Sprague Dawley (SD) rats were randomly divided into the plain, plateau and the HADA group. Rats in the plateau and plain group were exposed to altitudes of 3,850 and 360 m, respectively, for 12 weeks. Rats in HADA group were exposed to the plateau altitude of 3,850 m for 12 weeks and subsequently transported to the plain altitude of 360 m for 4 weeks. Right ventricular ejection fraction (RVEF), end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and myocardial strain parameters, including the global longitudinal strain (GLS), global radial strain (GRS), and global circumferential strain (GCS), were evaluated by 7.0T cardiac magnetic resonance (CMR). The levels of red blood cell (RBC), hemoglobin (HGB), and hematocrit (HCT) in the blood were measured, and hematoxylin-eosin (HE) staining was used to observe the pathological changes in the myocardium. Results: In rats in the plateau group, the right ventricular fibrous space was slightly widened, and partial focal steatosis were observed. However, in the HADA group, only a few focal steatoses were found. Rats in the plateau group had elevated levels of RBC, HGB and HCT, increased right ventricular end-diastolic volume (RVEDV), right ventricular end-systolic volume (RVESV) and right ventricular stroke volume (RVSV), and decreased right ventricular global longitudinal strain (RVGLS), right ventricular global circumferential strain (RVGCS), and right ventricular global radial strain (RVGRS) compared to rats in the plain group (P<0.001). The RVEDV, RVGCS, and RVGRS in the HADA group basically returned to the plain state. Interestingly, the RVESV in the HADA group was higher, while the RVSV, RVEF, and RVGLS were lower than those in the other two groups. Conclusions: After 12 weeks of exposure to high-altitude environment, there were some pathological changes and the whole contractile strain of the right ventricle was observed. Some pathological changes in the myocardial tissue and stroma recovered after returning to the plain for 4 weeks. However, the right ventricular systolic function and strain did not recover completely.

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AIM: High risk Human Papillomavirus (HPV) is an infectious pathogen implicated in a variety of cancers with poor clinical outcome. The mechanism of HPV induced cellular transformation and its intervention remains to be elucidated. Human ADA3 (hADA3), a cellular target of HPV16 E6, is an essential and conserved component of the ADA transcriptional coactivator complex. High risk HPV-E6 binds and functionally inactivates hADA3 to initiate oncogenesis. The aim of this study was to identify the interaction interface between hADA3 and HPV16E6 for designing inhibitory peptides that can potentially disrupt the hADA3-E6 interaction. MATERIAL METHODS: The present investigation employed structure-based in silico tools supported by biochemical validation, in vivo interaction studies and analysis of posttranslational modifications. KEY FINDINGS: First 3D-model of hADA3 was proposed and domains involved in the oncogenic interaction between hADA3 and HPV16E6 were delineated. Rationally designed peptide disrupted hADA3-E6 interaction and impeded malignant properties of cervical cancer cells. SIGNIFICANCE: Intervention of hADA3-E6 interaction thus promises to be a potential strategy to combat HPV induced oncogenic conditions like cervical cancer. The investigation provides mechanistic insights into HPV pathogenesis and shows promise in developing novel therapeutics to treat HPV induced cancers.

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A novel coumarin-based molecule, designed as a fluorescent surrogate of a thiacetazone-derived antitubercular agent, was quickly and easily synthesized from readily available starting materials. This small molecule, coined Coum-TAC, exhibited a combination of appropriate physicochemical and biological properties, including resistance toward hydrolysis and excellent antitubercular efficiency similar to that of well-known thiacetazone derivatives, as well as efficient covalent labeling of HadA, a relevant therapeutic target to combat Mycobacterium tuberculosis. More remarkably, Coum-TAC was successfully implemented as an imaging probe that is capable of labeling Mycobacterium tuberculosis in a selective manner, with an enrichment at the level of the poles, thus giving for the first time relevant insights about the polar localization of HadA in the mycobacteria.

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OBJECTIVE: This study was aimed to determine and compare the frequency of the emotional disturbances, anxiety and depression among the medical students on Hospital Anxiety Depression scale (HAD) score among the hostelites and day scholars. METHODS: This cross sectional study was conducted at a private medical college in Faisalabad, Pakistan, from March 2019 to April 2019, comprising of 105 male and female students. Validated Hospital Anxiety depression scale (HAD-A and HAD-D) was used to collect data from 1st year and 2nd year MBBS students in order to evaluate anxiety and depression among them. Data was analyzed on SPSS 21. Pearson's Chi-square was applied to compare the percentages of anxious and depressed subjects among the studied group. Independent sample t-test was applied for comparison of mean HAD scores between hostelites and day scholars. P value ≤ 0.05 was taken as significant. RESULTS: There were 105 students in the study with a mean age of 19.4±0.68 years. Overall, 82.7% students had anxiety, and 52.1% suffered from depression. Average HAD -A and HAD- D scores were 11.2±3.41 and 7.2±3.37 respectively. Greater number of hostelites was suffering from emotional disturbances as compared to day scholars. HAD -A scores was significantly higher in hostelites than day scholars with P value 0.003*(11.85±3.42 Vs 10.92 ±2.56). HAD- D scores were also higher in hostilities but difference was insignificant. (7.57±3.42 Vs 6.85 ±1.58). CONCLUSIONS: Emotional disturbance including anxiety and depression are found to be highly prevalent among medical students of a private medical college in Faisalabad. Hostelites are more prone to anxiety and depression than day scholars.

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ABSTRACT BACKGROUND: Exudative age-related macular degeneration (e-AMD) may cause severe central vision loss. Patients with e-AMD can experience difficulties in daily basic activities and suffer from psychological problems. Our aim was to assess quality of life (QoL) and anxiety and depression status among patients with e-AMD. DESIGN AND SETTING: Cross-sectional study in a state university. METHODS: We included 200 e-AMD patients and 120 age and gender-matched controls. We assessed QoL using the National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) and the Short Form (SF)-36 test; and anxiety and depression status using the Hospital Anxiety Depression Scales A and D (HADS-A and HADS-D). RESULTS: The mean ages in the e-AMD and control groups were 68.40 ± 9.8 and 66.31 ± 8.98, respectively. Visual acuity among e-AMD patients was 0.37 ± 0.31 and 0.39 ± 0.32 in the right and left eyes, respectively. The e-AMD patients performed significantly worse than the controls in NEI-VFQ-25 (P < 0.05 for all items). The proportions of e-AMD patients scoring higher than the cutoffs in HADS-A and HADS-D were significantly higher than among the controls (41.5% versus 12.5% and 63.5% versus 27.5%; P < 0.001). The e-AMD patients had significantly lower mean scores than the controls for each of the SF-36 QoL items (P < 0.001). The NEI-VFQ-25 scores were significantly lower among patients with bilateral e-AMD than among those with unilateral disease (P < 0.05 for all). The HADS scores were positively correlated with duration of e-AMD and patient age, but negatively with vision levels (P < 0.05 for all items). CONCLUSION: The e-AMD patients had higher depression and anxiety scores and lower QoL scores.

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The essential peptidoglycan (PG) layer surrounds the cytoplasmic membrane in nearly all bacteria. It is needed to maintain the shape of the cell and protect it from lysis due to high turgor. Growth of the PG layer is a complex process that involves the activities of PG synthases and hydrolases during elongation and cell division. PG growth sites can be labeled by the recently developed fluorescent D-amino acid (FDAA) probes in a range of different bacteria. FDAAs are incorporated into PG by dd-transpeptidases (Penicillin-binding proteins, PBPs) or, if present, ld-transpeptidase (LDTs). Long-pulse in situ labeling of E. coli cells with the FDAA 7-hydroxycoumarincarbonylamino-D-alanine (HADA) is expected to result in a uniform label at the side wall of cells and enhanced label at cell division sites due to the intense PG synthesis. However, we observed reduced label at mid-cell when labeling E. coli cells with HADA. We reasoned that probe incorporated at cell division sites may be removed by PG hydrolases and modified the labeling protocol to better preserve PG-incorporated HADA for fluorescence microscopy. Here, we report the optimized HADA-labeling protocol by which cells retain an enhanced HADA signal at the division septum.

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Cyanobacteria were the first oxygenic photosynthetic organisms during evolution and were ancestors of plastids. Cyanobacterial cells exhibit an extraordinary diversity in their size and shape, and bacterial cell morphology largely depends on the synthesis and the dynamics of the peptidoglycan (PG) layer. Here, we used a fluorescence analog of the PG synthesis precursor D-Ala, 7-Hydroxycoumarin-amino-D-alanine (HADA), to probe the PG synthesis pattern in live cells of cyanobacteria with different morphology. They displayed diverse synthesis patterns, with some strains showing an intensive HADA incorporation at the septal region, whereas others gave an HADA signal distributed around the cells. Growth zones covering several cells at the tips of the filament were present in some filamentous strains such as in Arthrospira. In Anabaena PCC 7120, which is capable of differentiating heterocysts for N2 fixation, PG synthesis followed the cell division cycle. In addition, an HADA incorporation was strongly activated from 12 to 15 h following the initiation of heterocyst development, indicating a thickening of the PG layer in heterocysts. The PG synthesis pattern is diverse in cyanobacteria and responds to developmental regulation. The use of fluorescent analogs may serve as a useful tool for understanding the mechanisms of cell growth and morphogenesis operating in these organisms.

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The effect on Salmonella hadar growth was investigated using fresh sterile liquid medium (Pronadisa, Hispanlab) containing aqueous garlic extract (AGE) at different concentration (0, 11, 12, and 13 mg/ml). The garlic extract added at these final concentrations had a bacteriostatic effect on Salmonella hadar. The effect of these bacteriostatic concentration of AGE on the growth of the tested serovar, revealed a pattern of inhibition characterized by: (i) a transitory inhibition phase whose duration was proportional to AGE concentration (ii) a resumed growth phase which showed a lower rate of growth than in uninhibited controls, and (iii) an entry into stationary phase at a lower culture density. The minimal inhibitory concentration and minimum bactericidal concentrations were very close, garlic MIC was 12 mg/ml and the MBC was 14 mg/ml. Among enzymatic activities followed with the API-ZYM system, significant changes during the inhibition phase were detected. These biochemical changes represent an adaptative response towards the garlic stress. Some cellular enzymatic activities disappeared, whereas others were induced or maintained after AGE addition. TEM images of the samples treated with the bacteriostatic concentration of AGE (12 mg/ml) revealed the rupture of cell walls and nonhomogeneous disposition of cytoplasmic materials within treated bacteria.

El efecto sobre el crecimiento de Salmonella hadar fue investigado utilizando un medio líquido estéril fresco (Pronadisa, Hispanlab) conteniendo el extracto acuoso de ajo (EAA) en diferentes concentraciones (0, 11, 12 y 13 mg/ml). El extracto de ajo añadido con estas concentraciones tuvo un efecto bacteriostático sobre Salmonella hadar. La prueba serovar reveló un patrón de inhibición caracterizado por: (i) una fase de inhibición transitoria cuya duración fue proporcional a la concentración de EAA, (ii) una reanudación de la fase de crecimiento, la cual mostró una tasa más baja de crecimiento que controles sin inhibición, y (iii) una ingreso en fase estacionaria con una menor densidad de cultivo. La concentración mínima inhibitoria (CMI) y la concentración mínima bactericida (CMB) fueron muy cercanas, la CMI de ajo fue de 12 mg/ml y la CMB fue de 14 mg/ml. Las actividades enzimáticas seguidas con el sistema API-ZYM, mostraron cambios significativos durante la fase de inhibición. Estos cambios bioquímicos representan una respuesta adaptativa al estrés del ajo. Algunas actividades enzimáticas celulares desaparecieron, mientras que otras fueron inducidas o mantenidas después de la adición de EAA. Las imágenes de MET de las muestras tratadas con la concentración del bacteriostático EAA (12 mg/ml) revelaron la ruptura de las paredes celulares y la disposición no homogénea de materiales citoplasmáticos dentro de las bacterias tratadas.

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