Contribution of different mechanisms to aminoglycoside resistance in clinical isolates of Acinetobacter baumannii.

The antibiotics overuse for infection treatment was the sparkle in the spreading of multi-drug resistance Acinetobacter baumannii in hospitals. In our study, we evaluated the contribution of the aminoglycoside resistance mechanisms of A. baumannii to the resistance surge in some selected Egyptian hospitals with a checkerboard assay application to retrieve the aminoglycoside activity. The resistance profile analysis of collected 200 A. baumannii isolates revealed a multidrug-resistant pattern with limited susceptibilities to aminoglycosides. Analysis of the prevalence of aminoglycoside-modifying enzyme (AMEs) genes revealed the presence of the six AMEs genes either singly or in combination in selected isolates and aph (3)-VIa gene was the predominant one. At the same time, four efflux pump genes of AdeABC and AdeKJL family showed significant (P < 0.001) up-regulation levels. Moreover, the implementation of combination strategy showed fourteen synergistic activities against two high-level aminoglycoside-resistance (HLAR) A. baumannii isolates. The findings highlighted the alarming levels of aminoglycoside resistance in A. baumannii isolates, which proved that a common enzymatic modification mechanism acts synergistically with decreased antibiotic accumulation in acquiring aminoglycoside resistance. Additionally, the study provides useful information for the promising synergistic combination therapy that reduces the therapeutic dose of aminoglycosides used and subsequently increases their clinical application.

Characteristics of Asylum Seekers in Collaborative Assessment Program.

The Capital District Asylum Collaborative (CDAC) is an organization that provides psychiatric and medical evaluations to be used as forensic evidence to support asylum applications. Our study assesses the demographics and traumas experienced by CDAC clients. In this retrospective study, 23 completed affidavits for clients evaluated through CDAC between the years 2016 and 2020 were analyzed for demographics, trauma experience, and psychiatric diagnosis given. Most clients experienced at least 4 different forms of trauma. Nearly 78% of clients experienced beating to the body, 43% were raped, 56.5% experienced other forms of sexual abuse or humiliation, 47.8% experienced forced separation from family, and 39.1% experienced illness and poor access to care. Majority of clients were diagnosed with comorbidities most commonly major depressive disorder and post-traumatic stress disorder. This analysis has provided us guidance on how to establish continuing care options for future clients evaluated at CDAC.

Lestaurtinib (CEP-701) modulates the effects of early life hypoxic seizures on cognitive and emotional behaviors in immature rats.

Hypoxic encephalopathy of the newborn is a major cause of long-term neurological sequelae. We have previously shown that CEP-701 (lestaurtinib), a drug with an established safety profile in children, attenuates short-term hyperexcitability and tropomyosin-related kinase B (TrkB) receptor activation in a well-established rat model of early life hypoxic seizures (HS). Here, we investigated the potential long-term neuroprotective effects of a post-HS transient CEP-701 treatment. Following exposure to global hypoxia, 10 day old male Sprague-Dawley pups received CEP-701 or its vehicle and were sequentially subjected to the light-dark box test (LDT), forced swim test (FST), open field test (OFT), Morris water maze (MWM), and the modified active avoidance (MAAV) test between postnatal days 24 and 44 (P24-44). Spontaneous seizure activity was assessed by epidural cortical electroencephalography (EEG) between P50 and 100. Neuronal density and glial fibrillary acidic protein (GFAP) levels were evaluated on histological sections in the hippocampus, amygdala, and prefrontal cortex at P100. Vehicle-treated hypoxic rats exhibited significantly increased immobility in the FST compared with controls, and post-HS CEP-701 administration reversed this HS-induced depressive-like behavior (p < 0.05). In the MAAV test, CEP-701-treated hypoxic rats were slower at learning both context-cued and tone-signaled shock-avoidance behaviors (p < 0.05). All other behavioral outcomes were comparable, and no recurrent seizures, neuronal loss, or increase in GFAP levels were detected in any of the groups. We showed that early life HS predispose to long-lasting depressive-like behaviors, and that these are prevented by CEP-701, likely via TrkB modulation. Future mechanistically more specific studies will further investigate the potential role of TrkB signaling pathway modulation in achieving neuroprotection against neonatal HS, without causing neurodevelopmental adverse effects.

Mechanism of the anticataract effect of liposomal MgT in galactose-fed rats.

PURPOSE: Increased lenticular oxidative stress and altered calcium/magnesium (Ca/Mg) homeostasis underlie cataractogenesis. We developed a liposomal formulation of magnesium taurate (MgT) and studied its effects on Ca/Mg homeostasis and lenticular oxidative and nitrosative stress in galactose-fed rats. METHODS: The galactose-fed rats were topically treated with liposomal MgT (LMgT), liposomal taurine (LTau), or corresponding vehicles twice daily for 28 days with weekly anterior segment imaging. At the end of the experimental period, the lenses were removed and subjected to analysis for oxidative and nitrosative stress, Ca and Mg levels, ATP content, Ca(2+)-ATPase, Na(+),K(+)-ATPase, and calpain II activities. RESULTS: The LTau and LMgT groups showed significantly lower opacity index values at all time points compared to the corresponding vehicle groups (p<0.001). However, the opacity index in the LMgT group was lower than that in the LTau group (p<0.05). Significantly reduced oxidative and nitrosative stress was observed in the LTau and LMgT groups. The lens Ca/Mg ratio in LMgT group was decreased by 1.15 times compared to that in the LVh group. Calpain II activity in the LMgT group was decreased by 13% compared to the LVh group. The ATP level and Na(+),K(+)-ATPase and Ca(2+)-ATPase activities were significantly increased in the LMgT group compared to the LVh group (p<0.05). CONCLUSIONS: Topical liposomal MgT delays cataractogenesis in galactose-fed rats by maintaining the lens mineral homeostasis and reducing lenticular oxidative and nitrosative stress.

Associations of Abdominal Muscle Area with 4-Year Change in Coronary Artery Calcium Differ by Ethnicity Among Post-Menopausal Women.

OBJECTIVE: To examine the association of abdominal muscle area with coronary artery calcium (CAC) presence, extent, and progression in a multi-ethnic cohort of older, community-dwelling post-menopausal women. DESIGN AND SETTING: Cross-sectional and longitudinal population-based cohort. PARTICIPANTS: The sample comprised 179 non-Hispanic White women, 116 Filipina women and 144 African American women, all without known CVD, who underwent chest and abdominal computed tomography (CT) scans twice about four years apart for abdominal muscle and fat, as well as CAC. MAIN OUTCOME MEASURES: CAC presence, extent and progression. RESULTS: There was a significant interaction of ethnicity with baseline oblique muscle area (p-for-interaction .01), and marginally significant interactions with baseline total and paraspinal muscle for change in CAC (p-for-interactions both .09). Among Filipina women, each standard deviation (SD) greater total muscle area was associated with a 26% (95% CI (-43%, -4%), P=.02) reduced rate of change in CAC; higher paraspinal and oblique muscle area were associated with a 24% (-38%, -6%, P=.01) and a 37% (-53%, -16%, P=.0002) reduced rate of change in CAC, respectively. These associations were not significant in African American or non-Hispanic White women. There were no significant associations of abdominal muscle with CAC presence or extent, nor were there significant ethnicity by muscle interactions in these models. CONCLUSIONS: Among Filipina women, greater abdominal muscle mass is associated with a decreased rate of CAC progression. Higher muscle mass may be important for this group in reducing CVD outcomes.

Macular and peripapillary vascular parameters in the fellow eyes of unilateral primary congenital glaucoma: a comparative study.

PURPOSE: To study the fellow eyes of patients with unilateral primary congenital glaucoma (PCG) using optical coherence tomography angiography (OCTA) and compare them to normal age- and refractive error-matched healthy controls. METHODS: Using OCTA, the foveal avascular zone (FAZ) area, cup:disk ratio, vessel density (VD) of the optic nerve head (ONH) and peripapillary area and the macular VD in superficial (SCP) and deep vascular complexes in both 3 mm and 6 mm scans of both groups were compared. Clinical data included best-corrected visual acuity (BCVA), cycloplegic refraction, intraocular pressure (IOP), anterior and posterior segments examination findings, including ONH cup:disk ratio. RESULTS: A total of 48 eyes of 48 children (24 eyes in each group) were included. There was no difference in the mean retinal nerve fiber layer thickness, cup:disk ratio, baseline visual acuity, or spherical equivalent between groups (P > 0.05). In the 3 mm macular scan, the VD of the SCP at the fovea was significantly higher in the PCG group compared to controls (P = 0.04). In the ONH scans, there was a significantly reduced inside the disk VD in the PCG group compared to controls (P = 0.03). There was no significant difference in other macular and ONH vascular parameters between groups (P > 0.05). CONCLUSIONS: In our study cohort, there was no difference in most of the macular and ONH vascular parameters between groups. However, the fellow eyes of PCG patients exhibited higher VD of the SCP at the fovea and reduced inside the disk VD compared with control eyes.

The Interplay Between Hyperthyroidism and Ovarian Cytoarchitecture in Albino Rats.

Background Hyperthyroid females often complain of menstrual disturbances and impaired fertility. This study was designed to observe the effect of hyperthyroidism on ovarian folliculogenesis and the hypophyseal-gonadal axis. Methodology Adult female Wistar albino rats (n= 12), six to eight weeks of age, and weighing 70-162 g, were divided randomly into control (Group A) and experimental (Group B) groups. Group A received daily intraperitoneal injections of 250 µL normal saline (10 µL 5 µM NaOH dissolved in it) for 14 days. Group B received a daily intraperitoneal injection of levothyroxine (600 µg/kg body weight) to induce hyperthyroidism. Rats were weighed at the start and the end of the experimental period on the day of sacrifice. Results Statistical analysis of the data revealed successful induction of hyperthyroidism in Group B as their thyroid-stimulating hormone (TSH) levels decreased significantly. The ovarian size was significantly reduced in the hyperthyroid group (p < 0.029). There was a significant decrease in thickness of the ovarian capsule (p < 0.000), an increase in the number of primordial, primary, and secondary follicles (p < 0.001, 0.000, and 0.001, respectively), and a decrease in size of primary and secondary follicles (p < 0.041 and 0.020) in the hyperthyroid group. Conclusion Hyperthyroidism can affect ovarian cytoarchitecture, probably by acting directly on its receptors and thus affects female fertility.

Overview on Emotional Behavioral Testing in Rodent Models of Pediatric Epilepsy.

Psychiatric and cognitive disturbances are the most common comorbidities of epileptic disorders in children. The successful treatment of these comorbidities faces many challenges including their etiologically heterogonous nature. Translational neurobehavioral research in age-tailored and clinically relevant rodent seizure models offers a controlled setting to investigate emotional and cognitive behavioral disturbances, their causative factors, and potentially novel treatment interventions. In this review, we propose a conceptual framework that provides a nonsubjective approach to rodent emotional behavioral testing with a focus on the clinically relevant outcome of behavioral response adaptability. We also describe the battery of neurobehavioral tests that we tailored to seizure models with prominent amygdalo-hippocampal involvement, including testing panels for anxiety-like, exploratory, and hyperactive behaviors (the open-field and light-dark box tests), depressive-like behaviors (the forced swim test), and visuospatial navigation (Morris water maze). The review also discusses the modifications we introduced to active avoidance testing in order to simultaneously test auditory and hippocampal-dependent emotionally relevant learning and memory. When interpreting the significance and clinical relevance of the behavioral responses obtained from a given testing panel, it is important to avoid a holistic disease-based approach as a specific panel may not necessarily mirror a disease entity. The analysis of measurable behavioral responses has to be performed in the context of outcomes obtained from multiple related and complementary neurobehavioral testing panels. Behavioral testing is also complemented by mechanistic electrophysiological and molecular investigations.

Pericardial fat is associated with all-cause mortality but not incident CVD: the Rancho Bernardo Study.

OBJECTIVE: Pericardial and intra-thoracic fat are associated with prevalent cardiovascular disease (CVD) and CVD risk factors. However, it is unclear if these fat depots predict incident CVD events and/or all-cause mortality. We examined prospective associations between areas of pericardial and intra-thoracic fat and incident CVD and mortality over a 12-year follow-up in a subset of participants without baseline clinical CVD from the Rancho Bernardo Study (RBS). METHODS: Participants were 343 community-dwelling older adults (mean baseline age = 67) who completed a clinic visit in 2001-02, including a computed tomography scan of the chest. Incident CVD and mortality were recorded through January 2013. RESULTS: Over a 12.6-year median follow-up, there were 60 incident CVD events and 49 deaths. Pericardial fat was associated with all-cause mortality, such that each standard deviation increment predicted a 34% higher chance of death after adjusting for demographics, lifestyle factors, comorbidities, and visceral fat (95% CI = 1.01-1.78). When categorized by tertile, those in the middle tertile of pericardial fat showed no increased risk of mortality, while those in the highest tertile had 2.6 times the risk (95% CI = 1.10-5.97) compared to the lowest tertile. There was a marginal association between intra-thoracic fat and mortality (p = 0.06). Neither pericardial nor intra-thoracic fat was significantly associated with incident CVD. There were no significant interactions by sex. CONCLUSIONS: Higher pericardial, but not intra-thoracic, fat was associated with earlier all-cause mortality in older adults over a 12-year follow-up. This association was primarily driven by a higher mortality rate in those in the highest tertile of pericardial fat.

The association between abdominal muscle and type II diabetes across weight categories in diverse post-menopausal women.

CONTEXT: Despite the key role of muscle in glucose regulation, little is known about the association between muscle area and prevalence of metabolic disorders, or the role low muscle may play in normal weight metabolic obesity. OBJECTIVE: The objective was to assess the independent associations between both abdominal muscle and fat depositions (measured by computed tomography) and the prevalence of type II diabetes, and to explore the modifying role of weight category. DESIGN: We conducted a cross-sectional analysis of the 2001-2002 visit for the Rancho Bernardo Study, Filipino Women's Health Study, and Health Assessment Study of African American Women. SETTING AND PARTICIPANTS: Participants were 392 community-dwelling older women (mean age = 64) free of clinical cardiovascular disease. MAIN OUTCOME MEASURE: The main outcome was prevalence of type II diabetes, defined as use of anti-diabetes medication, fasting plasma glucose ≥ 126 mg/dL, and/or OGTT ≥ 200 mg/dL. RESULTS: Adjusting for demographics, hypertension, estrogen use, lipids, smoking, physical activity, visceral fat area, and height, a greater muscle-to-total abdominal area ratio (MAR) was associated with lower odds of diabetes [OR = 0.63 per standard deviation, 95% CI (0.43-0.92), p = .02]. Higher visceral fat was associated with greater odds of diabetes in fully adjusted models including total muscle area [OR = 1.48, 95% CI (1.09, 2.01), p = .01]. Associations between MAR and diabetes were stronger for normal weight (BMI 18.5-24.9; OR = 0.32) than overweight/obese women (BMI ≥ 25, OR = 0.71, p-for-interaction = 0.046). Associations with visceral fat did not differ by BMI (p-for-interaction = 0.71). CONCLUSIONS: In older women, abdominal muscle area is inversely associated with type II diabetes independent of visceral adiposity, particularly for normal weight women.

Associations of physical activity and sedentary behavior with regional fat deposition.

INTRODUCTION: Increased sedentary behavior predicts greater cardiovascular morbidity and mortality and does so independently of physical activity (PA). This association is only partially explained by body mass index (BMI) and overall body fat, suggesting mechanisms besides general increased adiposity. The purpose of this study was to explore associations of self-reported leisure PA and sitting time with regional fat depositions and abdominal muscle among community-dwelling older adults. METHODS: Participants were 539 diverse adults (mean age = 65 yr) who completed a study visit in 2001-2002. Areas of pericardial, intrathoracic, subcutaneous, visceral, and intermuscular fat, as well as abdominal muscle, were measured using computed tomography. Leisure PA and sitting hours were entered simultaneously into multivariate regression models to determine associations with muscle and fat areas. RESULTS: After adjusting for demographics, smoking, diabetes, hypertension, triglycerides, and cholesterol, greater PA was associated with less intrathoracic, visceral, subcutaneous, and intermuscular fat (for all P < 0.05), while greater sedentary time was associated with greater pericardial and intrathoracic fat (for both P < 0.05). After further adjusting for BMI, each hour of weekly PA was associated with 1.85 cm less visceral fat (P < 0.01) but was not associated with other fat depositions. Conversely, each hour of daily sitting was associated with 2.39 cm more pericardial fat (P < 0.05) but was not associated with any other fat depositions. There were no associations with abdominal muscle area. Adjusting for common inflammatory markers had little effect. Associations between fat and PA were stronger for men. CONCLUSIONS: Sitting and PA have distinct associations with regional fat deposition in older adults. The association between sitting and pericardial fat could partially explain the link between sitting and coronary heart disease.