Leptin receptor neurons in the dorsomedial hypothalamus input to the circadian feeding network.

Salient cues, such as the rising sun or availability of food, entrain biological clocks for behavioral adaptation. The mechanisms underlying entrainment to food availability remain elusive. Using single-nucleus RNA sequencing during scheduled feeding, we identified a dorsomedial hypothalamus leptin receptor-expressing (DMHLepR) neuron population that up-regulates circadian entrainment genes and exhibits calcium activity before an anticipated meal. Exogenous leptin, silencing, or chemogenetic stimulation of DMHLepR neurons disrupts the development of molecular and behavioral food entrainment. Repetitive DMHLepR neuron activation leads to the partitioning of a secondary bout of circadian locomotor activity that is in phase with the stimulation and dependent on an intact suprachiasmatic nucleus (SCN). Last, we found a DMHLepR neuron subpopulation that projects to the SCN with the capacity to influence the phase of the circadian clock. This direct DMHLepR-SCN connection is well situated to integrate the metabolic and circadian systems, facilitating mealtime anticipation.

A leptin-responsive hypothalamic circuit inputs to the circadian feeding network.

Salient cues, such as the rising sun or the availability of food, play a crucial role in entraining biological clocks, allowing for effective behavioral adaptation and ultimately, survival. While the light-dependent entrainment of the central circadian pacemaker (suprachiasmatic nucleus, SCN) is relatively well defined, the molecular and neural mechanisms underlying entrainment associated with food availability remains elusive. Using single nucleus RNA sequencing during scheduled feeding (SF), we identified a leptin receptor (LepR) expressing neuron population in the dorsomedial hypothalamus (DMH) that upregulates circadian entrainment genes and exhibits rhythmic calcium activity prior to an anticipated meal. We found that disrupting DMHLepR neuron activity had a profound impact on both molecular and behavioral food entrainment. Specifically, silencing DMHLepR neurons, mis-timed exogenous leptin administration, or mis-timed chemogenetic stimulation of these neurons all interfered with the development of food entrainment. In a state of energy abundance, repetitive activation of DMHLepR neurons led to the partitioning of a secondary bout of circadian locomotor activity that was in phase with the stimulation and dependent on an intact SCN. Lastly, we discovered that a subpopulation of DMHLepR neurons project to the SCN with the capacity to influence the phase of the circadian clock. This leptin regulated circuit serves as a point of integration between the metabolic and circadian systems, facilitating the anticipation of meal times.

Moraxella Keratitis: A Case Series.

OBJECTIVE: To report the ocular and systemic risk factors, clinical manifestations, and management outcomes of Moraxella keratitis. METHODS: This retrospective study included patients with culture-proven Moraxella keratitis in South Texas between 2012 and 2018. Clinical data including demographics, ocular and systemic risk factors, clinical presentation, speciation, and treatment course were collected. RESULTS: Fourteen eyes of 14 patients had culture-proven Moraxella keratitis which made up 8.1% of cases of culture-proven bacterial keratitis in the period studied. These included 10 men and 4 women with a mean age of 52.7±11.3 years. Ten patients (71.4%) had different ocular risk factors such as ocular trauma, corneal foreign body, contact lens use, preceding viral keratitis, neurotrophic cornea, and recent corneal transplant on topical steroids. Systemic risk factors included diabetes mellitus, systemic immunosuppressive therapy, cancer chemotherapy, and AIDS. There was no specific clinical manifestation. The size of stromal infiltration on initial presentation varied among the cases, with 71.4% stromal infiltrations of 4 mm or less. The patients were managed with fortified tobramycin, fortified vancomycin, and moxifloxacin eye drops. No eyes required surgical intervention during treatment for the active infection, except for one eye with pre-existing no light perception that was enucleated because of chronic pain. CONCLUSIONS: Moraxella keratitis is a less frequent form of bacterial keratitis that appears more prevalent in patients with previous ocular conditions. Early diagnosis of this infection and medical treatment with a conventional corneal ulcer regimen can result in good clinical outcomes without the need for a surgical intervention.

Etiology and Risk Factors for Infectious Keratitis in South Texas.

PURPOSE: To determine the causative organisms and associated risk factors for infectious keratitis in South Texas. METHODS: This retrospective study was performed at a tertiary teaching hospital system in South Texas. Medical records of all patients who presented with infectious keratitis from 2012 to 2018 were reviewed. Only patients with culture-proven bacterial, fungal, and Acanthamoeba keratitis were included. RESULTS: In total, 182 eyes of 181 patients had culture-proven bacterial, fungal, or Acanthamoeba keratitis. The age of patients ranged from 3 to 93 years, with a mean of 48.3 ± 20.8 years. The most common etiologic agent was bacteria, with 173 bacterial cultures (95.1%) recovered, followed by 13 fungal cultures (7.1%), and 3 Acanthamoeba cultures (1.6%). Of the 218 bacterial isolates, coagulase-negative Staphylococcus was the most common (25.7%), followed by Pseudomonas aeruginosa (23.4%), Staphylococcus aureus (11.0%), and Moraxella (7.8%). Fusarium was the most common fungal isolate (46.2%). The most common risk factors for infectious keratitis included contact lens wear (32.4%), underlying corneal disease (17.6%), trauma (14.3%), and ocular surface disease (13.7%). CONCLUSIONS: Bacteria are the most common cause of infectious keratitis in this patient population, with coagulase-negative Staphylococcus and Pseudomonas as the most common isolates. The prevalence of culture-positive fungal keratitis is significantly lower than that of bacterial keratitis. Contact lens wear is the most common risk factor associated with infectious keratitis in South Texas.

Floppy eyelid syndrome: A comprehensive review.

Floppy eyelid syndrome (FES) is defined as eyelid hyperlaxity with reactive palpebral conjunctivitis. It is a common condition that can be associated with significant ocular irritation. FES presents with easily everted eyelids and chronic papillary conjunctivitis in the upper eyelids. It is frequently associated with ocular and systemic diseases, notably keratoconus and obstructive sleep apnea, respectively. This comprehensive review describes the epidemiology, pathological changes, proposed pathogenesis, clinical manifestations, and a variety of treatment options for this condition. Conservative treatment of FES includes aggressive lubrication, nighttime eye shield, and avoiding sleeping on the affected eye. Patients with FES and obstructive sleep apnea may have an improvement in their ocular signs and symptoms after long-term therapy with continuous positive airway pressure. In refractory cases, a corrective surgery that addresses the eyelid laxity can result in significant improvement. All patients with ocular irritation should be evaluated for the presence of FES.

Controlled antifungal behavior on Ti6Al4V nanostructured by chemical nanopatterning.

Infections associated with bone implant prostheses are mainly related to bacterial contaminations. Recent investigations have suggested an important role of opportunistic fungal cells associated with non-responding antibacterial treatments. Thus, in order to evaluate the early Candida albicans (C. albicans) behavior; we built on Ti6Al4V surfaces nanopores (NPs) with controlled diameters applying oxidative nanopatterning for 30 (NP30) and 60 min (NP60). As a result of nanopatterning NPs with diameters of 12 and 24 nm were synthesized. Physicochemical differences were observed between both types of NPs, the most highlighting of which are anatase phase formation and improved hydrophilicity of NP60. C. albicans adhesion and colonization was assessed using scanning electron microscopy and by yeast counting for viability evaluation. The fungal behavior on the substrates was significantly different, showing an initial exopolysaccharide secretion stimulated by the nanopatterned surfaces. Larger NPs led to an important reduction in viability with decreased cell-surface contact bonds. The obtained results demonstrate that special control in the fabrication of nanostructured TiO2 materials can improve the early fungal resistance, especially for dental implants.

Model of End-Stage Liver Disease Score and Derived Variants Lack Prognostic Ability after Liver Transplantation.

BACKGROUND The model of end-stage liver disease (MELD) score is currently used for donor liver allocation in many regions. The objective of this retrospective study was to assess the MELD score and its diverse variants as prognostic models for mortality after liver transplantation. MATERIAL AND METHODS An analysis of 454 consecutive adult liver transplants since the introduction of MELD-based donor liver allocation was conducted. Eight different MELD score variants were investigated. Receiver operating characteristic (ROC) curve analysis was performed to calculate the sensitivity, specificity, and overall model correctness of the investigated scores as a predictive model. The Brier score was used for the prediction of model accuracy and calculated as described before. Study endpoints were 90-day mortality and long-term patient mortality. RESULTS A 90-day mortality of 15.4% (n=69) and long-term mortality of 25% (n=112) were observed. All investigated models fail to reach relevant areas under the ROC curve greater than 0.700 for the prediction of mortality after liver transplantation. All calculated Brier scores were greater than 0.25, indicating a significant lack of model discrimination and calibration of the investigated scores. CONCLUSIONS A prognostic model for the prediction of outcome after transplantation still needs to be identified and should allow weighing urgency against utility in liver transplantation.

Risk factors for short- and long-term mortality in liver transplant recipients with MELD score ≥30.

BACKGROUND: After introduction of MELD-based allocation in Germany, decreased waiting list mortality and increased mortality after transplantation have been reported. MATERIAL AND METHODS: This study compares relevant outcome parameters in patients with high MELD ≥30 versus lower MELD scores in a retrospective analysis including 454 consecutively performed liver transplantations in adults (age >16 years) at Hannover Medical School between 01/01/2007 and 31/12/2012 and a follow-up until 31/12/2013. Multivariable risk-adjusted models were applied to identify independent risk factors for 90-day and long-term mortality. RESULTS: MELD score ≥30 (n=117; 26.1%) was an independent risk factor for 90-day mortality (p=0.004, odds ratio: 3.045, 95% CI 1.439-6.498) and long-term mortality (p=0.016, hazard ratio: 1.620, 95% CI 1.095-2.396) and was associated with significantly longer hospital and intensive care unit stays (p<0.001), and death occurred in more cases earlier after transplantation (90-day mortality 21.6% vs. 13.0%; p=0.029). Portal vein thrombosis at transplantation was significantly associated with 90-day mortality after transplantation in patients with MELD scores ≥30 (p=0.041), but this was not the case for patients with MELD scores <30, although portal vein thrombosis was equally frequent in individuals of both groups (3.0% vs. 3.4%, p=0.824). CONCLUSIONS: Results of this study suggest that liver transplant recipients with portal vein thrombosis at transplantation should be transplanted before reaching a MELD score ≥30.

Nonequilibrium molecular dynamics of the rheological and structural properties of linear and branched molecules. Simple shear and poiseuille flows; instabilities and slip.

Nonequilibrium molecular-dynamics simulations are performed for linear and branched chain molecules to study their rheological and structural properties under simple shear and Poiseuille flows. Molecules are described by a spring-monomer model with a given intermolecular potential. The equations of motion are solved for shear and Poiseuille flows with Lees and Edward's [A. W. Lees and S. F. Edwards, J. Phys. C 5, 1921 (1972)] periodic boundary conditions. A multiple time-scale algorithm extended to nonequilibrium situations is used as the integration method, and the simulations are performed at constant temperature using Nose-Hoover [S. Nose, J. Chem. Phys. 81, 511 (1984)] dynamics. In simple shear, molecules with flow-induced ellipsoidal shape, having significant segment concentrations along the gradient and neutral directions, exhibit substantial flow resistance. Linear molecules have larger zero-shear-rate viscosity than that of branched molecules, however, this behavior reverses as the shear rate is increased. The relaxation time of the molecules is associated with segment concentrations directed along the gradient and neutral directions, and hence it depends on structure and molecular weight. The results of this study are in qualitative agreement with other simulation studies and with experimental data. The pressure (Poiseuille) flow is induced by an external force F(e) simulated by confining the molecules in the region between surfaces which have attractive forces. Conditions at the boundary strongly influence the type of the slip flow predicted. A parabolic velocity profile with apparent slip on the wall is predicted under weakly attractive wall conditions, independent of molecular structure. In the case of strongly attractive walls, a layer of adhered molecules to the wall produces an abrupt distortion of the velocity profile which leads to slip between fluid layers with magnitude that depends on the molecular structure. Finally, the molecular deformation under flow depends on the attractive force of the wall, in such a way that molecules are highly deformed in the case of strong attracting walls.

Impacto del apoyo emocional durante el parto en la disminución de cesáreas y gratificación del proceso / Emotional support impact during labor in cesarian decreasing and gratefulling the process

Se evaluó el efecto del apoyo durante el parto, mediante una acompañante elegida antes del parto, por la propia embarazada, sobre la incidencia de cesáreas, proceso de parto y satisfacción del mismo. La investigación clínica se ralizó en la maternidad del Hospital J.J. Aguirre (1997-1999). El estudio aleatorizado incluyó un grupo de intervención con acompañante (217 gestantes) y otro control (218). La muestra consideró 40 por ciento incidencia de cesáreas, 30 por ciento reducción, alfa, 0,05 beta 80 por ciento. El análisis calculó riesgo relativo con intervalo de confianza 95 por ciento. Los grupos fueron semejantes. Las embarazadas sintieron menos el temor al parto cuando hubo acompañante (RR 0,79 IC 0,63-0,99). No hubo diferencias en incidencia de cesáreas ni otros resultados maternos y neonatales. Los beneficios restringidos podrían explicarse por: capacitación simplificada de acompañante, o profesionales asumiendo ese papel y limitaciones impuestas por rutinas médicas independientes