Neurons in the Dorsomedial Hypothalamus Promote,Prolong, and Deepen Torpor in the Mouse

Torpor is a naturally occurring, hypometabolic, hypothermic state engaged by a wide range of animals in response to imbalance between the supply and demand for nutrients. Recent work has identified some of the key neuronal populations involved in daily torpor induction in mice, in particular, projections from the preoptic area of the hypothalamus to the dorsomedial hypothalamus (DMH). The DMH plays a role in thermoregulation, control of energy expenditure, and circadian rhythms, making it well positioned to contribute to the expression of torpor. We used activity-dependent genetic TRAPing techniques to target DMH neurons that were active during natural torpor bouts in female mice. Chemogenetic reactivation of torpor-TRAPed DMH neurons in calorie-restricted mice promoted torpor, resulting in longer and deeper torpor bouts. Chemogenetic inhibition of torpor-TRAPed DMH neurons did not block torpor entry, suggesting a modulatory role for the DMH in the control of torpor. This work adds to the evidence that the preoptic area of the hypothalamus and the DMH form part of a circuit within the mouse hypothalamus that controls entry into daily torpor.SIGNIFICANCE STATEMENT Daily heterotherms, such as mice, use torpor to cope with environments in which the supply of metabolic fuel is not sufficient for the maintenance of normothermia. Daily torpor involves reductions in body temperature, as well as active suppression of heart rate and metabolism. How the CNS controls this profound deviation from normal homeostasis is not known, but a projection from the preoptic area to the dorsomedial hypothalamus has recently been implicated. We demonstrate that the dorsomedial hypothalamus contains neurons that are active during torpor. Activity in these neurons promotes torpor entry and maintenance, but their activation alone does not appear to be sufficient for torpor entry.     

Anti-SARS-CoV-2 Titers Predict the Severity of COVID-19

Coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 is associated with a wide spectrum of disease, ranging from asymptomatic infection to acute respiratory distress syndrome. Some biomarkers may predict disease severity. Among them, the anti-SARS-CoV-2 antibody response has been related to severe disease. The aim of this study was to assess the correlation between the anti-SARS-CoV-2 serological response and COVID-19 outcome. Demographic, clinical, and biological data from nasopharyngeal-PCR confirmed COVID-19 hospitalized patients were prospectively collected between April and August 2020 at our institution. All patients had serial weekly serology testing for a maximum of three blood samples or until discharge. Two different serological assays were used: a chemiluminescent assay and an in-house developed Luminex immunoassay. Kinetics of the serological response and correlation between the antibody titers and outcome were assessed. Among the 70 patients enrolled in the study, 22 required invasive ventilation, 29 required non-invasive ventilation or oxygen supplementation, and 19 did not require any oxygen supplementation. Median duration of symptoms upon admission for the three groups were 13, 8, and 9 days, respectively. Antibody titers gradually increased for up to 3 weeks since the onset of symptoms for patients requiring oxygen supplementation with significantly higher antibody titers for patients requiring invasive ventilation. Antibody titers on admission were also significantly higher in severely ill patients and serology performed well in predicting the necessity of invasive ventilation (AUC: 0.79, 95% CI: 0.67–0.9). Serology testing at admission may be a good indicator to identify severe COVID-19 patients who will require invasive mechanical ventilation.     

Vitrectomy for optic disc pit maculopathy: a long-term follow-up study

Graefe's Archive for Clinical and Experimental Ophthalmology - To evaluate the clinical outcomes of vitrectomy with induction of posterior vitreous detachment for the treatment of optic disc...     

Differential distribution of dystrophins in rat retina.

PURPOSE: Duchenne muscular dystrophy is frequently associated with a reduced amplitude of b-wave under scotopic conditions in the electroretinogram. This suggests that the dystrophin gene-encoded proteins play a role in retinal neurotransmission. The abnormal neurotransmission has been attributed to altered expressions of C-terminal products of the dystrophin gene in the outer plexiform layer, where photoreceptor cells form synapses with secondary neurons. The present study was undertaken to determine the cellular distribution of each member of the dystrophin superfamily in rat retina. METHODS: Examined in the study were the developmental pattern of dystrophins in rat retinae that exhibit inherited progressive photoreceptor degeneration; dystrophins messengers expression in the outer and the inner retina of normal rats, prepared by mechanical fractionation through the outer plexiform layer; and immunolocalization of dystrophin proteins and utrophin in normal and degenerated adult rat retinae, with several antibodies prepared against specific regions of the dystrophin superfamily. RESULTS: The results showed that Dp260 is exclusively localized in photoreceptor cells; Dp140 seems to be present in perivascular astrocytes; the exon 78 spliced isoform of Dp71 and the unspliced form are located in Müller glial cells and in perivascular astrocytes, respectively. Müller glial cells also contain utrophin. CONCLUSIONS: Although the role of these membrane cytoskeletal proteins remains to be elucidated in retina, the results support the hypothesis that b-wave reduction may be caused by molecular anomalies of C-terminal products of the dystrophin gene expressed in both neuron and glial cells.     

Management of uterine giant myoma

BACKGROUND: Giant myomas of the uterus are uncommon, particularly in developed countries. CASE: This report illustrates a case of a woman with a bilobated giant myoma of the uterus weighed in total 27.7 kg. The patient had an abdominal distension first noted 18 months before and the personal history evidenced difficulties in walking and tiredness. Abdominal hysterectomy and bilateral salpingo-oophorectomy were carried out. CONCLUSIONS: The knowledge of the different clinical manifestation of these myomas may allow to face that with adequate perioperative care, in order to assure a carefully and successfully surgery, although sometimes a benign pathology may be not easy to suspect in a first time.     

High-affinity autoreactive plasma cells disseminate through multiple organs in patients with immune thrombocytopenic purpura

The major therapeutic goal for immune thrombocytopenic purpura (ITP) is to restore normal platelet counts using drugs to promote platelet production or by interfering with mechanisms responsible for platelet destruction. Eighty percent of patients with ITP possess anti–integrin αIIbβ3 IgG autoantibodies that cause platelet opsonization and phagocytosis. The spleen is considered the primary site of autoantibody production by autoreactive B cells and platelet destruction. The immediate failure in approximately 50% of patients to recover a normal platelet count after anti-CD20 rituximab-mediated B cell depletion and splenectomy suggests that autoreactive, rituximab-resistant, IgG-secreting B cells (IgG-SCs) reside in other anatomical compartments. We analyzed more than 3,300 single IgG-SCs from spleen, bone marrow, and/or blood of 27 patients with ITP, revealing high interindividual variability in affinity for αIIbβ3, with variations over 3 logs. IgG-SC dissemination and range of affinities were, however, similar for each patient. Longitudinal analysis of autoreactive IgG-SCs upon treatment with the anti-CD38 mAb daratumumab demonstrated variable outcomes, from complete remission to failure with persistence of high-affinity anti–αIIbβ3 IgG-SCs in the bone marrow. This study demonstrates the existence and dissemination of high-affinity autoreactive plasma cells in multiple anatomical compartments of patients with ITP that may cause the failure of current therapies.     

A Low-Cost Wireless Bite Force Measurement Device

Assessing maximum voluntary bite force is important to characterize the functional state of the masticatory system. Due to several factors affecting the estimation of the maximum bite force, a unique solution combining desirable features such as reliability, accuracy, precision, usability, and comfort is not available. The aim of the present study was to develop a low-cost bite force measurement device allowing for subject-specific customization, comfortable bite force expression, and reliable force estimation over time. The device was realized using an inexpensive load cell, two 3D printed ergonomic forks hosting reusable subject-specific silicone molds, a read-out system based on a low-cost microcontroller, and a wireless link to a personal computer. A simple model was used to estimate bite force taking into account individual morphology and device placement in the mouth. Measurement reliability, accuracy, and precision were assessed on a calibration dataset. A validation procedure on healthy participants was performed to assess the repeatability of the measurements over multiple repetitions and sessions. A 2% precision and 2% accuracy were achieved on measurements of forces in the physiological range of adult bite forces. Multiple recordings on healthy participants demonstrated good repeatability (coefficient of variation 11%) with no significant effect of repetition and session. The novel device provides an affordable and reliable solution for assessing maximum bite force that can be easily used to perform clinical evaluations in single sessions or in longitudinal studies.