Angiotensin-(1-12): A Chymase-Mediated Cellular Angiotensin II Substrate

Historically, primary hypertension (HTN) has been prevalent typically in adults. Recent data however, suggests an increasing number of children diagnosed with primary HTN, mainly in the setting of obesity. One of the factors considered in the etiology of HTN is the autonomous nervous system, namely its dysregulation. In the past, the sympathetic nervous system (SNS) was regarded as a system engaged mostly in buffering major acute changes in blood pressure (BP), in response to physical and emotional stressors. Recent evidence suggests that the SNS plays a much broader role in the regulation of BP, including the development and maintenance of sustained HTN by a chronically elevated central sympathetic tone in adults and children with central/visceral obesity. Consequently, attempts have been made to reduce the SNS hyperactivity, in order to intervene early in the course of the disease and prevent HTN-related complications later in life.     

GABAA receptors can initiate the formation of functional inhibitory GABAergic synapses

The mechanisms that underlie the selection of an inhibitory GABAergic axon's postsynaptic targets and the formation of the first contacts are currently unknown. To determine whether expression of GABA_A receptors (GABA_ARs) themselves – the essential functional postsynaptic components of GABAergic synapses – can be sufficient to initiate formation of synaptic contacts, a novel co‐culture system was devised. In this system, the presynaptic GABAergic axons originated from embryonic rat basal ganglia medium spiny neurones, whereas their most prevalent postsynaptic targets, i.e. α1/β2/γ2‐GABA_ARs, were expressed constitutively in a stably transfected human embryonic kidney 293 (HEK293) cell line. The first synapse‐like contacts in these co‐cultures were detected by colocalization of presynaptic and postsynaptic markers within 2 h. The number of contacts reached a plateau at 24 h. These contacts were stable, as assessed by live cell imaging; they were active, as determined by uptake of a fluorescently labelled synaptotagmin vesicle‐luminal domain‐specific antibody; and they supported spontaneous and action potential‐driven postsynaptic GABAergic currents. Ultrastructural analysis confirmed the presence of characteristics typical of active synapses. Synapse formation was not observed with control or N‐methyl‐d ‐aspartate receptor‐expressing HEK293 cells. A prominent increase in synapse formation and strength was observed when neuroligin‐2 was co‐expressed with GABA_ARs, suggesting a cooperative relationship between these proteins. Thus, in addition to fulfilling an essential functional role, postsynaptic GABA_ARs can promote the adhesion of inhibitory axons and the development of functional synapses.     

D-Optimal Design in the Development of Rheologically Improved In Situ Forming Ophthalmic Gel

In situ forming ophthalmic gels need to be fine tuned considering all the biopharmaceutical challenges of the front of the eye in order to increase drug residence time at the application site resulting in its improved bioavailability and efficacy. The aim of this study was to develop in situ forming ophthalmic poloxamer P407/poloxamer P188/chitosan gel fine tuned in terms of polymer content, temperature of gelation, and viscosity. Minimizing the total polymer content while retaining the advantageous rheological properties has been achieved by means of D-optimal statistical design. The optimal in situ forming gel was selected based on minimal polymer content (P407, P188, and chitosan concentration of 14.2%, 1.7%, and 0.25% w/w, respectively), favorable rheological characteristics, and in vitro resistance to tear dilution. The optimal in situ forming gel was proved to be robust against entrapment of active pharmaceutical ingredients making it a suitable platform for ophthalmic delivery of active pharmaceutical ingredients with diverse physicochemical properties.     

Autotransplantation of maxillary canine following removal of compound odontome: a case report

Obstruction remains as an important cause of failure in the eruption of a tooth. In this article, a 15-year-old girl was presented with retained upper left primary canine (63) and first primary molar (64), while the contralateral permanent canine (13) and premolars (14 and 15) have erupted. Upon radiographic examination, a mass which was diagnosed later to be compound odontome was detected. The treatment consisted of surgical removal of the odontome, extraction of the primary canine (63) and left permanent canine (23), and transplantation of the permanent canine (23). The management of this case and the literature related to autotransplantation are discussed.     

Increased rate of ptosis following glaucoma drainage device placement and other anterior segment surgery: a prospective analysis

Graefe's Archive for Clinical and Experimental Ophthalmology - To determine the degree and rate of ptosis in patients undergoing glaucoma and cataract surgery. Patients undergoing...     

Clinical characteristics and functional outcome of patients with West Nile neuroinvasive disease in Serbia

Neurologic manifestations are prominent characteristic of West Nile virus (WNV) infection. The aim of this article was to describe neurological manifestations in patients with WNV neuroinvasive disease and their functional outcome at discharge in the first human outbreak of WNV infection in Serbia. The study enrolled patients treated in the Clinic for Infectious and Tropical Diseases, Clinical Center Serbia in Belgrade, with serological evidence of acute WNV infection who presented with meningitis, encephalitis and/or acute flaccid paralyses (AFP). Functional outcome at discharge was assessed using modified Rankin Scale (mRS) and Barthel index. Fifty-two patients were analysed. Forty-four (84.6 %) patients had encephalitis, eight (15.4 %) had meningitis, and 13 (25 %) had AFP. Among patients with AFP, 12 resembled poliomyelitis and one had clinical and electrodiagnostic findings consistent with polyradiculoneuritis. Among patients with encephalitis, 17 (32.7 %) had clinical signs of rhombencephalitis, and eight (15.4 %) presented with cerebellitis. Respiratory failure with subsequent mechanical ventilation developed in 13 patients with WNE (29.5 %). Nine (17.3 %) patients died, five (9.6 %) were functionally dependent (mRS 3–5), and 38 (73.1 %) were functionally independent at discharge (mRS 0–2). In univariate analysis, the presence of AFP, respiratory failure and consciousness impairment were found to be predictors of fatal outcome in patients with WNV neuroinvasive disease (p < 0.001, p < 0.001, p = 0.018, respectively). The outbreak of human WNV infection in Serbia caused a notable case fatality ratio, especially in patients with AFP, respiratory failure and consciousness impairment. Rhombencephalitis and cerebellitis could be underestimated presentations of WNV neuroinvasive disease.     

Gender-based measurement invariance of the Substance Use Risk Profile Scale

Gender may influence the psychometric properties of psychological and affect-related measures. The American Psychological Association has made recommendations to conduct tests of group-level measurement invariance (MI) before comparing scores between groups. Gender-based measurement invariance has been examined in many well-known psycho-social scales such as the CES-D and the Big Five Inventory. The Substance Use Risk Profile is a 23-item scale measuring affective- and personality-related traits known to increase risk for substance use, with 4 dimensions: anxiety sensitivity, hopelessness, sensation seeking and impulsivity. Despite similarities in the constructs assessed by the SURPS, the CES-D and the Big Five Inventory, gender-based measurement invariance of the SURPS has not yet been published. Multi-group confirmatory factor analysis was used to assess the measurement invariance of the four dimensions of the SURPS across gender. MI was conducted with M-Plus 6.2 using a 2-step analysis for ordinal variables suggested by Muthén and Muthén, and model fit was assessed using the comparative fit index (CFI) criteria recommended by Cheung and Rensvold. A single group confirmatory factor analysis (CFA) was also conducted. The sample was composed of 1352 adolescents (56% female, mean age of 14 years) participating in the BC Adolescent Substance Use Survey, an online survey capturing substance use and psychosocial trends in secondary students across British Columbia, Canada. Measurement invariance across gender was demonstrated for the SURPS (ΔCFI = 0.003), and the single group CFA supported a four-dimensional structure for the SURPS items (CFI = 0.92, RMSEA = 061, 95% CI = 0.058–0.065).