Comparative effects of estradiol, methyl-piperidino-pyrazole, raloxifene, and ICI 182 780 on gene expression in the murine uterus

Selective estrogen receptor modulators (SERMs) are potentially useful in treating various endometrial disorders, including endometrial cancer, as they block some of the detrimental effects of estrogen. It remains unclear whether each SERM regulates a unique subset of genes and, if so, whether the combination of a SERM and 17beta-estradiol has an additive or synergistic effect on gene expression. We performed microarray analysis with Affymetrix Mouse Genome 430 2.0 short oligomer arrays to determine gene expression changes in uteri of ovariectomized mice treated with estradiol (low and high dose), methyl-piperidino-pyrazole (MPP), ICI 182 780, raloxifene, and combinations of high dose of estradiol with one of the SERM and dimethyl sulfoxide (DMSO) vehicle control. The nine treatments clustered into two groups, with MPP, raloxifene, and high dose of estradiol in one, and low dose of estradiol, ICI + estradiol, ICI, MPP + estradiol, and raloxifene + estradiol in the second group. Surprisingly, combining a high dose of estradiol with a SERM markedly increased (P<0.02) the number of regulated genes compared with each individual treatment. Analysis of expression for selected genes in uteri of estradiol and SERM-treated mice by quantitative (Q)RT-PCR generally supported the microarray results. For some cancer-associated genes, including Klk1, Ihh, Cdc45l, and Cdca8, administration of MPP or raloxifene with estradiol resulted in greater expression than estradiol alone (P<0.05). By contrast, ICI 182 780 suppressed more genes governing DNA replication compared with MPP and raloxifene treatments. Therefore, ICI 182 780 might be superior to MPP and raloxifene to treat estrogen-induced endometrial cancer in women.     

Bordetella bronchiseptica infections in patients with HIV/AIDS: A case report and review of the literature

Rationale:Bordetella bronchiseptica is a common cause of upper respiratory tract infections in domesticated dogs and cats and a rare zoonotic pathogen in immunocompromised humans. With increasing numbers of people acquiring pets and spending time with them in confined spaces due to COVID-19 lockdowns, it is important to be aware of adverse health consequences brought about by this interaction. We present a case of B bronchiseptica pneumonia in a patient with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and review key characteristics of an additional 30 cases of B bronchiseptica infections in 29 patients with HIV/AIDS that were identified by literature review.Patient concerns:A 61-year-old male with HIV/AIDS who was not on antiretroviral therapy and had advanced immunosuppression with a CD4+ T-lymphocyte count of 3 cells/μL sought medical attention for multiple somatic issues including subjective fevers, shortness of breath, and intermittent chest pain.Diagnosis:Computed tomography of the chest identified bilateral nodular opacities in the lower lobes with scattered areas of ground glass opacities. B bronchiseptica was identified in sputum culture by mass spectrometry followed by supplementary biochemical testing.Interventions:Empiric broad-spectrum antibiotics were initiated and changed to levofloxacin after susceptibility testing was completed.Outcomes:The patient was discharged after symptomatic improvement with levofloxacin.Lessons:Pneumonia with interstitial infiltrates in the setting of advanced CD4 lymphocyte depletion is the most common clinical syndrome caused by B bronchiseptica in patients with HIV/AIDS, and may be accompanied by sepsis. Advanced immune suppression, as well as chronic medical conditions, for example, alcoholism, diabetes, and renal failure that compromise host defenses are also commonly found in cases of B bronchiseptica infection in patients who do not have HIV infection. Reported animal contact among patients was not universal. Isolates were susceptible to aminoglycosides, carbapenems, fluoroquinolones, but typically resistant to most cephalosporins.     

Neural gain control measured through cortical gamma oscillations is associated with sensory sensitivity

Gamma oscillations facilitate information processing by shaping the excitatory input/output of neuronal populations. Recent studies in humans and nonhuman primates have shown that strong excitatory drive to the visual cortex leads to suppression of induced gamma oscillations, which may reflect inhibitory‐based gain control of network excitation. The efficiency of the gain control measured through gamma oscillations may in turn affect sensory sensitivity in everyday life. To test this prediction, we assessed the link between self‐reported sensitivity and changes in magneto‐encephalographic gamma oscillations as a function of motion velocity of high‐contrast visual gratings. The induced gamma oscillations increased in frequency and decreased in power with increasing stimulation intensity. As expected, weaker suppression of the gamma response correlated with sensory hypersensitivity. Robustness of this result was confirmed by its replication in the two samples: neurotypical subjects and people with autism, who had generally elevated sensory sensitivity. We conclude that intensity‐related suppression of gamma response is a promising biomarker of homeostatic control of the excitation–inhibition balance in the visual cortex.     

Ramadan and diabetes: As-Saum (The fasting)

Ramadan, the ninth month of Islamic lunar calendar, is marked by religious ritual of fasting from early dawn till sunset by Muslims. Islam has allowed many categories of people to be exempt totally or temporarily from fasting. Patients with uncontrolled diabetes face possible major metabolic risks including hypoglycemia, hyperglycemia with or without the risk of impending ketosis, dehydration, and thrombosis. Diabetics can be stratified into four categories based on their level of risk associated with fasting. The recommended ruling for persons in categories 1 and 2 is that they are prohibited from fasting to prevent harming themselves based on the certainty or the preponderance of probability that harm will occur, whereas the recommended ruling for those in categories 3 and 4 is that they should fast. The strategies to ensure safety of diabetics who are planning to fast include Ramadan-focused patient education, pre-Ramadan medical assessment, following a healthy diet and physical activity pattern, physician-recommended modifications in medication protocol and therapeutic recommendations and checking blood glucose as and when required.