Globozoospermia.

Male infertility may be due to low sperm concentration, poor sperm motility, or abnormal morphology. Among the factors involved in male infertility, there is a rare morphology disorder called "Globozoospermia". This condition is primarily characterized by the presence of round-headed spermatozoa, absence of acrosomal cap and cytoskeleton defects around the nucleus. The morphological characteristics of globozoospermia are formed during spermiogenesis. We report here a case of male infertility due to morphological disorder Globozoospermia. Assessment of semen by observing macroscopic and microscopic parameters are not sufficient for sperm analysis. In present case, macroscopic and microscopic assessment was within normal range. Morphological assessment showed 80% of spermatozoa with round head and absence of acrosomal cap. The absence of acrosome makes fertilization impossible since these sperm are unable to bind to the zona pellucida. By using Intracytoplasmic Sperm Injection (ICSI), conception is possible; however, the fertilization rate remains very low.

Hierarchical retinal computations rely on hybrid chemical-electrical signaling.

Bipolar cells (BCs) are integral to the retinal circuits that extract diverse features from the visual environment. They bridge photoreceptors to ganglion cells, the source of retinal output. Understanding how such circuits encode visual features requires an accounting of the mechanisms that control glutamate release from bipolar cell axons. Here, we demonstrate orientation selectivity in a specific genetically identifiable type of mouse bipolar cell-type 5A (BC5A). Their synaptic terminals respond best when stimulated with vertical bars that are far larger than their dendritic fields. We provide evidence that this selectivity involves enhanced excitation for vertical stimuli that requires gap junctional coupling through connexin36. We also show that this orientation selectivity is detectable postsynaptically in direction-selective ganglion cells, which were not previously thought to be selective for orientation. Together, these results demonstrate how multiple features are extracted by a single hierarchical network, engaging distinct electrical and chemical synaptic pathways.

Gain control by sparse, ultra-slow glycinergic synapses.

In the retina, ON starburst amacrine cells (SACs) play a crucial role in the direction-selective circuit, but the sources of inhibition that shape their response properties remain unclear. Previous studies demonstrate that ∼95% of their inhibitory synapses are GABAergic, yet we find that the light-evoked inhibitory currents measured in SACs are predominantly glycinergic. Glycinergic inhibition is extremely slow, relying on non-canonical glycine receptors containing α4 subunits, and is driven by both the ON and OFF retinal pathways. These attributes enable glycine inputs to summate and effectively control the output gain of SACs, expanding the range over which they compute direction. Serial electron microscopic reconstructions reveal three specific types of ON and OFF narrow-field amacrine cells as the presumptive sources of glycinergic inhibition. Together, these results establish an unexpected role for specific glycinergic amacrine cells in the retinal computation of stimulus direction by SACs.

Parallel processing in active dendrites during periods of intense spiking activity.

A neuron's ability to perform parallel computations throughout its dendritic arbor substantially improves its computational capacity. However, during natural patterns of activity, the degree to which computations remain compartmentalized, especially in neurons with active dendritic trees, is not clear. Here, we examine how the direction of moving objects is computed across the bistratified dendritic arbors of ON-OFF direction-selective ganglion cells (DSGCs) in the mouse retina. We find that although local synaptic signals propagate efficiently throughout their dendritic trees, direction-selective computations in one part of the dendritic arbor have little effect on those being made elsewhere. Independent dendritic processing allows DSGCs to compute the direction of moving objects multiple times as they traverse their receptive fields, enabling them to rapidly detect changes in motion direction on a sub-receptive-field basis. These results demonstrate that the parallel processing capacity of neurons can be maintained even during periods of intense synaptic activity.

Thresholds for Spinal Anaesthesia-induced Hypotension During Caesarean Section.

Background Spinal anaesthesia is the current standard for caesarean section. Hypotension, a common complication, potentially results in adverse foetal and maternal outcomes. However, hypotension-defining criteria are varied. Objective To identify the blood pressure thresholds for spinal anaesthesia-induced hypotension during caesarean section. Method This is a retrospective cohort study of spinal anaesthesia-induced hypotension that occurred till baby-delivery during caesarean section. Reports on intraoperative hypotension, collected previously from January to December 2019, were reviewed to identify the hypotension-defining thresholds. The thresholds were categorized into systolic blood pressure (SBP) of 80, 90 or 100 mmHg, mean arterial pressure (MAP) of 60, 65 or 70 mmHg, combinations, and others. Parturient and anaesthesia characteristics, and associated hypotensive symptoms were also recorded for descriptive analysis. Result Spinal anaesthesia-induced hypotension was identified in 129 (11.5%) cases among 1116 caesarean sections. Altogether, 12 hypotension-defining thresholds were employed. Thresholds of SBP 90, MAP 60, and SBP 80 mmHg were used in 53 (41%), 28 (21.7%), and 21 (16.2%) cases respectively. Mean maternal age was 28 (±4.22) years and 87 (67.4%) cases underwent emergency surgery. Median sensory blockade level was T4. Nausea-vomiting, bradycardia, and tachycardia were associated during five (3.8%), six (4.6%), and 15 (11.6%) hypotensive incidents respectively. Two cases had unrecordable blood pressure but there was no maternal mortality. Conclusion Systolic blood pressure of 90 mmHg and mean arterial pressure of 60 mmHg included the most common thresholds for spinal anaesthesia-induced hypotension during caesarean section. Identifying the safe and clinically relevant hypotension-defining criteria needs further investigation.

Rapid multi-directed cholinergic transmission in the central nervous system.

In many parts of the central nervous system, including the retina, it is unclear whether cholinergic transmission is mediated by rapid, point-to-point synaptic mechanisms, or slower, broad-scale 'non-synaptic' mechanisms. Here, we characterized the ultrastructural features of cholinergic connections between direction-selective starburst amacrine cells and downstream ganglion cells in an existing serial electron microscopy data set, as well as their functional properties using electrophysiology and two-photon acetylcholine (ACh) imaging. Correlative results demonstrate that a 'tripartite' structure facilitates a 'multi-directed' form of transmission, in which ACh released from a single vesicle rapidly (~1 ms) co-activates receptors expressed in multiple neurons located within ~1 µm of the release site. Cholinergic signals are direction-selective at a local, but not global scale, and facilitate the transfer of information from starburst to ganglion cell dendrites. These results suggest a distinct operational framework for cholinergic signaling that bears the hallmarks of synaptic and non-synaptic forms of transmission.

Comparing heart risk scores to identify the most important risk factors for cardiovascular diseases.

OBJECTIVE: Cardiovascular disease (CVD) is the most common non-communicable disease and the leading cause of death worldwide. To reduce the global burden of CVD and related morbidity and mortality, early prediction of CVD risk is essential. Various tools are available to access the risk of cardiovascular disorders. In the present study, we evaluated four risk score calculators associated to CVD for superiority and most reliable CVD prognosis parameters. PATIENTS AND METHODS: In the present prospective study, we investigated the probability of CVD in 150 individuals, including both men and women, using four different cardiovascular risk assessment estimators (Framingham Risk Score [FRS] Calculator, Q-RISK calculator, Reynolds score calculator, and atherosclerotic cardiovascular disease (ASCVD) risk calculator) and evaluated how closely they were related to 16 selected parameters. The four risk estimators shared several common parameters, such as age, smoking status, and blood pressure; however, each of them also used some unique parameters. We used statistical analysis to reduce the number of parameters necessary to predict CVD. RESULTS: Statistical analysis revealed a significant correlation between the main factors responsible for CVD risk. The analysis revealed that out of the four risk calculators tested, the FRS calculator was superior to the others because it showed more significant corroboration with statistical tools and could better predict the most important prognostic factors in CVD. CONCLUSIONS: In all four risk estimators, the parameters that affected risk most significantly and conferred the most reliable CVD prognosis were age, weight, total cholesterol, and hemoglobin levels. With that FRS calculator was superior to the others.

Wound Infection with Multi-Drug Resistant Clostridium Perfringens: A Case Study.

Wound infections are among public health problems worldwide. However, progress has been made in improving surgical techniques and antibiotic treatments. Misuse/overuse of antibiotics to prevent and treat bacterial infections eventually leads to increased bacterial resistance with rising incidences of multi-drug resistant (MDR) bacterial strains. The wider dissemination of antibiotics may ultimately result in ineffectiveness to antibiotic therapy, thereby complicating/graving the outcome of a patient. In the present study, a 60-year-old male patient having wound infection with MDR bacterium that ultimately required surgical amputation of the toe was investigated. For the confirmation of MDR bacterium, two culture media viz., MacConkeyAgar and Mueller Hinton Agar media were used. The sensitivity of the isolated strain for various antibiotics was tested using the disc diffusion method. The wound sample was found positive for Gram-positive bacterium that was identified as Clostridium Perfringens. The bacterium was screened for 40 antibiotics, and among all the antibiotics, it was found sensitive for only Piperacillin/Tazobactam antibiotic combination. C. perfringens bacterium caused the gas gangrene in the infected wound part of the patient. Amputation of the gangrene -affected foot part was performed by surgery, and with good medical care, the person recovered fast. To the best of our knowledge, this is the first-ever report of MDR C. perfringens single isolate harboring resistance against at least 40 antibiotics tested. More research is needed to develop really new and effective medicines that do not cross-react with antibiotics now in use and have robust activity against MDR organisms.

Multicompartment modeling of protein shedding kinetics during vascularized tumor growth.

Identification of protein biomarkers for cancer diagnosis and prognosis remains a critical unmet clinical need. A major reason is that the dynamic relationship between proliferating and necrotic cell populations during vascularized tumor growth, and the associated extra- and intra-cellular protein outflux from these populations into blood circulation remains poorly understood. Complementary to experimental efforts, mathematical approaches have been employed to effectively simulate the kinetics of detectable surface proteins (e.g., CA-125) shed into the bloodstream. However, existing models can be difficult to tune and may be unable to capture the dynamics of non-extracellular proteins, such as those shed from necrotic and apoptosing cells. The models may also fail to account for intra-tumoral spatial and microenvironmental heterogeneity. We present a new multi-compartment model to simulate heterogeneously vascularized growing tumors and the corresponding protein outflux. Model parameters can be tuned from histology data, including relative vascular volume, mean vessel diameter, and distance from vasculature to necrotic tissue. The model enables evaluating the difference in shedding rates between extra- and non-extracellular proteins from viable and necrosing cells as a function of heterogeneous vascularization. Simulation results indicate that under certain conditions it is possible for non-extracellular proteins to have superior outflux relative to extracellular proteins. This work contributes towards the goal of cancer biomarker identification by enabling simulation of protein shedding kinetics based on tumor tissue-specific characteristics. Ultimately, we anticipate that models like the one introduced herein will enable examining origins and circulating dynamics of candidate biomarkers, thus facilitating marker selection for validation studies.

Study of Dexmedetomidine in Caudal Block for Children Undergoing Inguino-scrotal Surgery.

Background Caudal block is the most common anaesthetic technique employed in children for managing perioperative pain of inguino-scrotal surgery. However, despite using longacting local anaesthetics, caudal analgesia lasts relatively shorter. Dexmedetomidine, an alpha-2 agonist, augments local anaesthetic action. Objective To assess the analgesic effect of caudal Dexmedetomidine. Method This is a randomized, double-blinded study conducted on otherwise healthy children (one to five years) undergoing elective inguino-scrotal surgery. General anaesthesia was administered and a laryngeal mask airway was inserted for assisting ventilation. The caudal block was applied using 0.8 milliliters/kilogram drug volume comprising either two milligrams/kilogram Bupivacaine in group A (n=42) or two milligrams/ kilogram Bupivacaine mixed with 0.75 micrograms/kilogram Dexmedetomidine in group B (n=42). Intraoperatively, inhaled Halothane, intravenous Fentanyl, fluids, and ventilation were titrated to maintain monitored hemodynamic variables within 15% from baseline values. The primary endpoint comprised the duration of analgesia, defined by a time when postoperative pain score (face, legs, activity, cry, consolability; FLACC scale) reached four out of ten. Perioperative events were studied for 24 hours. Student's t-test and Chi-square test were used for analysis, with p-value less than 0.05 considered as significant. Result Demographic, surgical, and anaesthetic characteristics were similar between the groups. Duration of analgesia was significantly prolonged in group B (group B, 413±101 minutes; group A, 204±40 minutes). The intraoperative requirement for supplement Fentanyl was significantly reduced in group B. Adverse events were comparable between the groups. Conclusion Dexmedetomidine prolongs the duration of analgesia when mixed with caudal Bupivacaine, without increasing adverse events.

'Hiding their troubles': a qualitative exploration of suicide in Bhutanese refugees in the USA.

BACKGROUND: Suicide is a major global health concern. Bhutanese refugees resettled in the USA are disproportionately affected by suicide, yet little research has been conducted to identify factors contributing to this vulnerability. This study aims to investigate the issue of suicide of Bhutanese refugee communities via an in-depth qualitative, social-ecological approach. METHODS: Focus groups were conducted with 83 Bhutanese refugees (adults and children), to explore the perceived causes, and risk and protective factors for suicide, at individual, family, community, and societal levels. Audio recordings were translated and transcribed, and inductive thematic analysis conducted. RESULTS: Themes identified can be situated across all levels of the social-ecological model. Individual thoughts, feelings, and behaviors are only fully understood when considering past experiences, and stressors at other levels of an individual's social ecology. Shifting dynamics and conflict within the family are pervasive and challenging. Within the community, there is a high prevalence of suicide, yet major barriers to communicating with others about distress and suicidality. At the societal level, difficulties relating to acculturation, citizenship, employment and finances, language, and literacy are influential. Two themes cut across several levels of the ecosystem: loss; and isolation, exclusion, and loneliness. CONCLUSIONS: This study extends on existing research and highlights the necessity for future intervention models of suicide to move beyond an individual focus, and consider factors at all levels of refugees' social-ecology. Simply focusing treatment at the individual level is not sufficient. Researchers and practitioners should strive for community-driven, culturally relevant, socio-ecological approaches for prevention and treatment.

Retinal direction selectivity in the absence of asymmetric starburst amacrine cell responses.

In the mammalian retina, direction-selectivity is thought to originate in the dendrites of GABAergic/cholinergic starburst amacrine cells, where it is first observed. However, here we demonstrate that direction selectivity in downstream ganglion cells remains remarkably unaffected when starburst dendrites are rendered non-directional, using a novel strategy combining a conditional GABAA α2 receptor knockout mouse with optogenetics. We show that temporal asymmetries between excitation/inhibition, arising from the differential connectivity patterns of starburst cholinergic and GABAergic synapses to ganglion cells, form the basis for a parallel mechanism generating direction selectivity. We further demonstrate that these distinct mechanisms work in a coordinated way to refine direction selectivity as the stimulus crosses the ganglion cell's receptive field. Thus, precise spatiotemporal patterns of inhibition and excitation that determine directional responses in ganglion cells are shaped by two 'core' mechanisms, both arising from distinct specializations of the starburst network.

Cholinergic excitation complements glutamate in coding visual information in retinal ganglion cells.

KEY POINTS: Starburst amacrine cells release GABA and ACh. This study explores the coordinated function of starburst-mediated cholinergic excitation and GABAergic inhibition to bistratified retinal ganglion cells, predominantly direction-selective ganglion cells (DSGCs). In rat retina, under our recording conditions, starbursts were found to provide the major excitatory drive to a sub-population of ganglion cells whose dendrites co-stratify with starburst dendrites (putative DSGCs). In mouse retina, recordings from genetically identified DSGCs at physiological temperatures reveal that ACh inputs dominate the response to small spot-high contrast light stimuli, with preferential addition of bipolar cell input shifting the balance towards glutamate for larger spot stimuli In addition, starbursts also appear to gate glutamatergic excitation to DSGCs by postsynaptic and possibly presynaptic inhibitory processes ABSTRACT: Starburst amacrine cells release both GABA and ACh, allowing them to simultaneously mediate inhibition and excitation. However, the precise pre- and postsynaptic targets for ACh and GABA remain under intense investigation. Most previous studies have focused on starburst-mediated postsynaptic GABAergic inhibition and its role in the formation of directional selectivity in ganglion cells. However, the significance of postsynaptic cholinergic excitation is only beginning to be appreciated. Here, we found that light-evoked responses measured in bi-stratified rat ganglion cells with dendrites that co-fasciculate with ON and OFF starburst dendrites (putative direction-selective ganglion cells, DSGCs) were abolished by the application of nicotinic receptor antagonists, suggesting ACh could act as the primary source of excitation. Recording from genetically labelled DSGCs in mouse retina at physiological temperatures revealed that cholinergic synaptic inputs dominated the excitation for high contrast stimuli only when the size of the stimulus was small. Canonical glutamatergic inputs mediated by bipolar cells were prominent when GABA/glycine receptors were blocked or when larger spot stimuli were utilized. In mouse DSGCs, bipolar cell excitation could also be unmasked through the activation of mGluR2,3 receptors, which we show suppresses starburst output, suggesting that GABA from starbursts serves to inhibit bipolar cell signals in DSGCs. Taken together, these results suggest that starbursts amplify excitatory signals traversing the retina, endowing DSGCs with the ability to encode fine spatial information without compromising their ability to encode direction.

Computational Convolution of SELDI Data for the Diagnosis of Alzheimer's Disease.

Alzheimer's disease is rapidly becoming an endemic for people over the age of 65. A vital path towards reversing this ominous trend is the building of reliable diagnostic devices for definite and early diagnoses in lieu of the longitudinal, usually inconclusive and non-generalize-able methods currently in use. In this article, we present a survey of methods for mining pools of mass spectrometer saliva data in relation to diagnosing Alzheimer's disease. The computational methods provides new approaches for appropriately gleaning latent information from mass spectra data. They improve traditional machine learning algorithms and are most fit for handling matrix data points including solving problems beyond protein identifications and biomarker discovery.

An Old Neuron Learns New Tricks: Redefining Motion Processing in the Primate Retina.

Motion sensitivity requires the comparison of neural responses activated by nearby points in visual space. In this issue of Neuron, Manookin et al. (2018) find that in the primate retina, such comparisons are already manifest in second-order retinal bipolar cells, relying on lateral excitation mediated by gap junctions.

"Silent" NMDA Synapses Enhance Motion Sensitivity in a Mature Retinal Circuit.

Retinal direction-selective ganglion cells (DSGCs) have the remarkable ability to encode motion over a wide range of contrasts, relying on well-coordinated excitation and inhibition (E/I). E/I is orchestrated by a diverse set of glutamatergic bipolar cells that drive DSGCs directly, as well as indirectly through feedforward GABAergic/cholinergic signals mediated by starburst amacrine cells. Determining how direction-selective responses are generated across varied stimulus conditions requires understanding how glutamate, acetylcholine, and GABA signals are precisely coordinated. Here, we use a combination of paired patch-clamp recordings, serial EM, and large-scale multi-electrode array recordings to show that a single high-sensitivity source of glutamate is processed differentially by starbursts via AMPA receptors and DSGCs via NMDA receptors. We further demonstrate how this novel synaptic arrangement enables DSGCs to encode direction robustly near threshold contrasts. Together, these results reveal a space-efficient synaptic circuit model for direction computations, in which "silent" NMDA receptors play critical roles.