Limbic network interactions leading to hyperexcitability in a model of temporal lobe epilepsy

In mouse brain slices that contain reciprocally connected hippocampus and entorhinal cortex (EC) networks, CA3 outputs control the EC propensity to generate experimentally induced ictal-like discharges resembling electrographic seizures. Neuronal damage in limbic areas, such as CA3 and dentate hilus, occurs in patients with temporal lobe epilepsy and in animal models (e.g., pilocarpine- or kainate-treated rodents) mimicking this epileptic disorder. Hence, hippocampal damage in epileptic mice may lead to decreased CA3 output function that in turn would allow EC networks to generate ictal-like events. Here we tested this hypothesis and found that CA3-driven interictal discharges induced by 4-aminopyridine (4AP, 50 microM) in hippocampus-EC slices from mice injected with pilocarpine 13-22 days earlier have a lower frequency than in age-matched control slices. Moreover, EC-driven ictal-like discharges in pilocarpine-treated slices occur throughout the experiment (< or = 6 h) and spread to the CA1/subicular area via the temporoammonic path; in contrast, they disappear in control slices within 2 h of 4AP application and propagate via the trisynaptic hippocampal circuit. Thus, different network interactions within the hippocampus-EC loop characterize control and pilocarpine-treated slices maintained in vitro. We propose that these functional changes, which are presumably caused by seizure-induced cell damage, lead to seizures in vivo. This process is facilitated by a decreased control of EC excitability by hippocampal outputs and possibly sustained by the reverberant activity between EC and CA1/subiculum networks that are excited via the temporoammonic path.     

Stress and psychological resilience among general surgery residents during COVID-19 pandemic

Objectives:To evaluate the impact of coronavirus-19 (COVID-19) pandemic and its consequences on general surgery residents.Methods:Cross-sectional, survey based study including surgical residents in Kingdom of Saudi Arabia and Kingdom of Bahrain.Results:Surgical trainees who participated in our survey (n=234) were young (mean age 28), single (53.8%), and males (65.8%). Approximately half (50.4%) have been deployed to cover the staff shortage in intensive care units (ICUs) or emergency departments (EDs). Half of our trainees (117) scored positive in the screening tool of generalized anxiety disorder (GAD). There was a significant association between experiencing anxiety and male gender (p=0.055), level of training (p=0.002), deployment to cover ICUs (p=0.050), testing positive for COVID-19 (p=0.054) and having an infected family member (p=0.004).Conclusion:Coronavirus-19 pandemic has a serious effect on all healthcare workers and surgical residents have experienced a considerable amount of stress. Accordingly, this psychological burden should be appropriately addressed in organizations planning strategies. We suggest formulating guidelines to help surgical trainees to continue their learning process with least psychological burden.     

Risk of adrenal crisis in dental patients: Results of a systematic search of the literature

BackgroundThe authors performed a systematic search of the literature to identify the frequency of, risk of experiencing and factors associated with adrenal crises in dental patients.MethodsThe authors searched PubMed and Ovid MEDLINE (1947-June 20, 2012) and Embase (1974-2012) for English-language articles related to cases of adrenal crisis in dentistry and extracted and analyzed data from the articles. The six authors determined whether the cases identified met a consensus definition of adrenal crisis.ResultsOf 148 articles identified in the initial screening, 34 articles were included in the final review, from which six cases met the criteria of adrenal crisis. The authors categorized four cases as “suggestive of adrenal crisis” and two cases as “consistent with adrenal crisis.” Risk factors were significant adrenal insufficiency, pain, infection, having undergone an invasive procedure, having received a barbiturate general anesthetic, and poor health status and stability at the time of presentation. The authors estimated risk to be less than one in 650,000 in patients with adrenal insufficiency.ConclusionsAdrenal crisis is rare in dental patients, with only six reports of it having been published in the past 66 years. Risk is associated with unrecognized adrenal insufficiency, poor health status and stability at the time of treatment, pain, infection, having undergone an invasive procedure and having received a barbiturate general anesthetic.Clinical ImplicationsRisk of adrenal crisis is reduced through proper evaluation of the patient, identification of risk factors and following appropriate preventive measures.     

Predicting response of severe aplastic anemia to immunosuppression combined with eltrombopag

Pretreatment blood counts, particularly an absolute reticulocyte count ≥25×10⁹/L, correlate with response to immunosuppressive therapy in severe aplastic anemia. In recent trials, eltrombopag combined with standard immunosuppressive therapy yielded superior responses than those to immunosuppressive therapy alone. Our single institution retrospective study aimed to elucidate whether historical predictors of response to immunosuppressive therapy alone were also associated with response to immunosuppressive therapy plus eltrombopag. We sought correlations of blood counts, thrombopoietin levels and the presence of paroxysmal nocturnal hemoglobinuria clones with both overall and complete responses in 416 patients with severe aplastic anemia, aged 2-82 years (median, 30 years), initially treated with immunosuppressive therapy plus eltrombopag between 2012 and 2019 (n=176) or with immunosuppressive therapy alone between 1999 and 2010 (n=240). Compared to non-responders, patients in the group of overall responders to immunosuppressive therapy plus eltrombopag had significantly higher pretreatment absolute reticulocyte counts, higher neutrophil counts and reduced thrombopoietin levels, as also observed for the group treated with immunosuppressive therapy alone. Addition of eltrombopag markedly improved the overall response in subjects with an absolute reticulocyte count between 10-30×10⁹/L from 60% (54 of 90) to 91% (62 of 68). Absolute lymphocyte count correlated with complete response in the groups treated with immunosuppressive therapy with or without eltrombopag, especially in adolescents aged ≥10 years and adults, but the correlation was reversed in younger children. Platelet count and the presence of a paroxysmal nocturnal hemoglobinuria clone did not correlate with responses to immunosuppressive therapy. Blood counts remain the best predictors of response to nontransplant therapies in severe aplastic anemia. Addition of eltrombopag to immunosuppressive therapy shifted patients with a lower absolute reticulocyte count into a better prognostic category.     

Prevalence and Risk Factors of Urinary Incontinence Among Jordanian Women: Impact on Their Life

We estimate the prevalence and type of urinary incontinence (UI), possible associated risk factors, and the impact of UI on women's social and psychological well-being. The sample consisted of women attending a family medicine clinic at Jordan University Hospital (JUH) who answered a self-administered questionnaire. More than one-third of the sample reported the presence of UI. Stress type was the most frequently reported risk factor, followed by mixed incontinence, then urge. Age, diabetes, chronic cough, parity, and hysterectomy were positively associated with the presence of UI. Incontinence caused low self-esteem in more than half of the women who experienced it.     

Unusual florid skeletal manifestations of primary hyperparathyroidism

We report a case of primary hyperparathyroidism (PHPT) with advanced and unusual skeletal manifestations--a rare occurrence in developed countries nowadays. The literature is briefly reviewed.