This study addressed the hypothesis that dorsomedial hindbrain adenosine 5’-monophosphate-activated protein kinase (AMPK) imposes inherent control over hypothalamic AMPK, neuropeptide, and norepinephrine (NE) activity and governs feeding in an estradiol-dependent manner. Groups of estradiol (E)- or oil (O)-implanted ovariectomized rats were injected with the AMPK inhibitor Compound C (Cc) or vehicle into the caudal fourth ventricle (CV4) prior to micropunch-dissection of individual hypothalamic metabolic loci or assessment of food intake. Cc decreased hindbrain dorsal vagal complex phosphoAMPK (pAMPK) profiles in both E and O; tissue ATP levels were reduced by this treatment in O only. In E/Cc, pAMPK expression was diminished in the lateral hypothalamic area (LHA) and ventromedial (VMH) and paraventricular (PVH) nuclei; only PVH pAMPK was suppressed by this treatment in O/Cc. Cc decreased PVH corticotropin-releasing hormone and arcuate (ARH) proopiomelanocortin (POMC) and neuropeptide Y in O, but suppressed only POMC in E. O/Cc exhibited both augmented (PVH, VMH) and decreased (LHA, ARH) hypothalamic NE content, whereas Cc treatment of E elevated preoptic and dorsomedial hypothalamic nucleus NE. Cc completely or incompletely repressed feeding in E versus O, respectively. Results implicate dorsomedial hindbrain AMPK in physiological stimulus-induced feeding in females. Excepting POMC, hypothalamic neuropeptide targets of input from that sensor may differ in presence vs. absence of estrogen. Estradiol likely determines hypothalamic targets of altered NE signaling due to hindbrain AMPK activation. Divergent changes in NE content of hypothalamic loci in O/Cc uniquely demonstrate sensor-induced bimodal catecholamine signaling to those sites.
Hindbrain adenosine 5'-monophosphate-activated protein kinase (AMPK) activation alters hypothalamic neuronal genomic activity in an estradiol (E)-dependent manner. This study examines the premise that E regulates metabolic effector neuron reactivity to hindbrain AMPK. Paraventricular (PVH), arcuate (ARH), and ventromedial (VMH) nuclei were micropunched from brains of E- or oil (O)-implanted ovariectomized female rats that had been injected, into the fourth ventricle, with the AMPK activator 5-aminoimidazole-4-carboxamide-riboside (AICAR; A) or saline (S) and analyzed by quantitative polymerase chain reaction and Western blotting for neurotransmitter mRNA and protein expression. PVH corticotrophin-releasing hormone gene and protein profiles were decreased in O/A and E/A animals. ARH pro-opiomelanocortin (POMC) mRNA and protein were both elevated in O/A but were diminished or unchanged, respectively, in E/A animals; ARH neuropeptide Y (NPY) transcription was inhibited in O/A and E/A animals, but neuropeptide content was augmented in E/A only. VMH SF-1 mRNA and protein were reduced in O and E animals. AICAR did not alter AMPK protein in any structure but elevated PVH (↑E), did not alter ARH, and decreased VMH (↓O,↓E) pAMPK. Results demonstrate hypothalamic metabolic neurotransmitter and AMPK reactivity to hindbrain AMPK activation, including E-dependent adjustments in POMC and NPY transcription and protein expression. Dissimilar POMC (↑O vs. ↔E) and NPY (↓O vs. ↑E) neuropeptide responses to caudal fourth ventricle AICAR indicate E regulation of hindbrain AMPK signaling and/or target receptivity, implying that ARH-controlled metabolic responses may differ in the presence vs. absence of E. Evidence for variable changes in hypothalamic AMPK activity resulting from hindbrain sensor manipulation suggests that individual (or region-based groups of) AMPK-expressing neuron populations are uniquely impacted by hindbrain AMPK.
Objective: To evaluate the levels of information regarding the current emerging outbreak of coronavirus disease 2019 (COVID-19) among medical and dental students at universities in Saudi Arabia through an online questionnaire. Methods: A detailed structured questionnaire was prepared, containing demographic profiles and questions related to knowledge and awareness of the COVID-19 pandemic, and was emailed to 240 subjects, out of these, 209 responded to all the questions. Results: The majority of the respondents were aware of the current and past epidemics of the coronavirus diseases, and they heard about SARS or MERS (89.5%) and the COVID-19 pandemic (94.7%). Internet was the main source of information (63.1%) followed by professors and physicians (24.2%), print media (6.1%), television (4%), and family or friends (2.5%). The majority of respondents received information about COVID-19 from the Ministry of Health (85.6%) and 44.5% of respondents participated in the COVID-19 symposium or conference. Respondents of the college of Medicine were more aware (96.1%) about COVID-19 than respondents of the college of Dentistry (86.2%; p=0.02). Conclusion: The study finds a high level of COVID-19 awareness among medical and dental students at KSA universities. However, there is a need to study in a community-level assessment regarding knowledge about COVID-19
Dorsal vagal complex (DVC) AMPK regulation of food intake in the estradiol-treated ovariectomized (OVX) female rat is energy state-dependent. Here, RT-PCR array technology was used to identify estradiol-sensitive AMPK-regulated DVC signal transduction pathways that exhibit differential reactivity to sensor activation during energy balance versus imbalance. The AMP mimetic AICAR correspondingly reduced or stimulated cDVC phosphoAMPK (pAMPK) and estrogen receptor-beta (ERβ) proteins in full-fed (F) versus 12 hr food-deprived (D) estradiol-treated ovariectomized (OVX) rats, but elevated ER-alpha (ERα) in F only. Estradiol suppressed DVC ERβ protein and hypoxia, NFκB, STAT3, STAT6, and Hedgehog signaling pathway marker genes against oil-implanted OVX controls. F + (A)ICAR and D + (S)aline groups each exhibited further inhibition of NFκB, STAT3, and Hedgehog pathway genes, and diminished PPAR, Notch, and STAT5 transcripts versus F+S. Conversely, genes in these six pathways were up-regulated by AICAR treatment of D. Results show that in this animal model, acute AMP augmentation or feeding cessation each inhibit both pAMPK and ERβ expression, but in combination increase these protein profiles. pAMPK protein and DVC TNF (NFκB), SOCS3 (JAK/STAT), WNT6 (Hedgehog), and FABP1 (PPAR) mRNAs were down- or upregulated in parallel by AICAR in F versus D states, respectively. Further research is needed to determine the impact of ERβ on opposing directionality of these responses, and to characterize the role of the aforementioned signaling pathways in hyperphagic responses in the female to AICAR-induced DVC AMPK activation during acute interruption of feeding.
A 2-year prospective study carried out on ventilator-associated pneumonia (VAP) patients in the intensive care unit at a tertiary care hospital, Hail, Kingdom of Saudi Arabia (KSA), revealed a high prevalence of extremely drug-resistant (XDR) Acinetobacter baumannii. About a 9% increase in the incidence rate of A. baumannii occurred in the VAP patients between 2019 and 2020 (21.4% to 30.7%). In 2019, the isolates were positive for IMP-1 and VIM-2 (31.1% and 25.7%, respectively) as detected by PCR. In comparison, a higher proportion of isolates produced NDM-1 in 2020. Here, we observed a high proportion of resistant ICU isolates towards the most common antibiotics in use. Colistin sensitivity dropped to 91.4% in the year 2020 as compared to 2019 (100%). Thus, the finding of this study has a highly significant clinical implementation in the clinical management strategies for VAP patients. Furthermore, strict implementation of antibiotic stewardship policies, regular surveillance programs for antimicrobial resistance monitoring, and screening for genes encoding drug resistance phenotypes have become imperative.
Catheter-associated urinary tract infections (CAUTIs) are some of the most common hospital-acquired infections (HAIs). Prolonged hospitalization, invasive devices such as catheters, and irrational use of antimicrobial agents are believed to be the major causes of high rates of HAIs. Infections such as pyelonephritis, urethritis, cystitis, and prostatitis are the main concerns in catheterized ICU patients. In these cases, Gram-negative bacteria are the most common bacteria. The present study was undertaken to determine the frequency, antibiograms, disease pattern, and risk factors involved in providing an advocacy recommendation to prevent CAUTI. A total of 1078 patients were admitted to the hospital ICU, out of which healthcare-associated infection was reported in 316 patients. CAUTI was reported only in 70 patients. Klebsiella pneumoniae (20%) was the predominant isolate, with Serratia (3%) and Providencia (3%) species being the least common isolates in this study. The present study provides CAUTI incidence rates in a tertiary care hospital in Hail, Saudi Arabia. Furthermore, information on the risk factors of common associated CAUTI causative organisms and their antibiogram patterns are also presented. This study provides vital information that can be used to formulate an effective antibiotic stewardship program that can be implemented throughout the kingdom.
Estradiol (E) mitigates acute and post-acute adverse effects of 12 hr-food deprivation (FD) on energy balance. Hindbrain 5′-monophosphate-activated protein kinase (AMPK) regulates hyperphagic and hypothalamic metabolic neuropeptide and norepinephrine responses to FD in an E-dependent manner. Energy state information from AMPK-expressing hindbrain A2 noradrenergic neurons shapes neural responses to metabolic imbalance. Here, we investigated the hypothesis that FD causes divergent changes in A2 AMPK activity in E versus oil (O)-implanted ovariectomized female rats, alongside dissimilar adjustments in circulating metabolic fuel [glucose, free fatty acids (FFA)] and energy deficit-sensitive hormone [corticosterone, glucagon, leptin] levels. FD decreased blood glucose in oil (O)-, but not E-implanted ovariectomized female rats, and elevated or reduced glucagon levels in O and E, respectively. FD decreased circulating leptin in O and E, but increased corticosterone and FFA concentrations in E only. Western blot analysis of laser-microdissected A2 neurons showed that glucocorticoid receptor type II and very long-chain acyl-CoA synthetase 3 protein profiles were amplified in FD/E versus FD/O. A2 total AMPK protein was elevated without change in activity in FD/O, while FD/E exhibited increased AMPK activation along with decreased upstream phosphatase expression. The catecholamine biosynthetic enzyme, dopamine-β-hydroxylase (DβH), was increased in FD/O, but not FD/E A2 cells. Data show discordance between A2 AMPK activation and glycemic responses to FD as sensor activity was refractory to glucose decrements in FD/O, but augmented in FD/E despite stabilized glucose and elevated FFA levels. E-dependent amplification of AMPK activity may reflect adaptive conversion to fatty acid oxidation and/or glucocorticoid stimulation. FD augmentation of A2 DβH protein profiles in FD/O but not FD/E animals suggests that FD may correspondingly regulate NE synthesis versus metabolism/release in the absence versus presence of E. Mechanisms underlying translation of E-contingent A2 neuron responses to FD into regulatory signaling remain to be determined.
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