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.

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.

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.

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.

Dynamic tuning of electrical and chemical synaptic transmission in a network of motion coding retinal neurons.

Recently, we demonstrated that gap junction coupling in the population of superior coding ON-OFF directionally selective ganglion cells (DSGCs) genetically labeled in the Hb9::eGFP mouse retina allows the passage of lateral anticipatory signals that help track moving stimuli. Here, we examine the properties of gap junctions in the DSGC network, and address how interactions between electrical and chemical synapses and intrinsic membrane properties contribute to the dynamic tuning of lateral anticipatory signals. When DSGC subtypes coding all four cardinal directions were individually loaded with the gap junction-permeable tracer Neurobiotin, only superior coding DSGCs exhibited homologous coupling. Consistent with these anatomical findings, gap junction-dependent feedback spikelets were only observed in Hb9(+) DSGCs. Recordings from pairs of neighboring Hb9(+) DSGCs revealed that coupling was reciprocal, non-inactivating, and relatively weak, and provided a substrate for an extensive subthreshold excitatory receptive field around each cell. This subthreshold activity appeared to boost coincident light-driven chemical synaptic responses. However, during responses to moving stimuli, gap junction-mediated boosting appeared to be dynamically modulated such that upstream DSGCs primed downstream cells, but not vice versa, giving rise to highly skewed responses in individual cells. We show that the asymmetry in priming arises from a combination of spatially offset GABAergic inhibition and activity-dependent changes in intrinsic membrane properties of DSGCs. Thus, dynamic interactions between electrical and chemical synapses and intrinsic membrane properties allow the network of DSGCs to propagate anticipatory responses most effectively along their preferred direction without leading to runaway excitation.

Serum albumin and creatinine clearance rate among smear positive pulmonary tuberculosis patients in Bangladesh.

This case control study was carried out in the Department of Biochemistry, Mymensingh Medical College in cooperation with the Outpatient Department and Medicine Units of Mymensingh Medical College Hospital, Fulbaria Upazilla Health Complex, Mymensingh and some DOTS centers of BRAC, a non-government organization during the period of July 2006 to June 2007. The aim of the study was to explore the status of serum albumin & creatinine clearance levels in smear positive Bangladeshi pulmonary tuberculosis patients as a means to monitor the possibility of management of these patients as these levels decrease significantly. Serum albumin level was investigated in TB patients for monitoring the nutritional status of TB patients and also for the adjustment of serum calcium level. Creatinine clearance rate was investigated in TB patients for monitoring the impairment of renal function and nutritional depletion in tuberculosis patients. A total of 120 people of different age groups were included in this study. Subjects were divided into two groups- Group I (Control; n=60) - apparently healthy people selected matching by age, sex and socioeconomic status with the cases and Group II (Case; n=60) - people with smear positive pulmonary tuberculosis. Serum albumin was estimated by colorimetric principle. Serum creatinine was also estimated by colorimetric principle & creatinine clearance rate was estimated from serum creatinine by Cockcroft- Gault equation. Statistical analysis was done by using SPSS windows package. Among the groups, mean±SD of serum albumin in Group II (3.74±0.44gm/dl) was significantly lower (p<0.001) than that in Group I (4.85±0.31gm/dl). Mean±SD of creatinine clearance rate in Group II (35.36±8.29ml/min) was also significantly lower than that in Group I (84.16±20.20ml/min). It is evident from the study that serum albumin & creatinine clearance rate levels significantly decrease in smear positive Bangladeshi pulmonary tuberculosis patients.

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.

An intrinsic neural oscillator in the degenerating mouse retina.

The loss of photoreceptors during retinal degeneration (RD) is known to lead to an increase in basal activity in remnant neural networks. To identify the source of activity, we combined two-photon imaging with patch-clamp techniques to examine the physiological properties of morphologically identified retinal neurons in a mouse model of RD (rd1). Analysis of activity in rd1 ganglion cells revealed sustained oscillatory (∼10 Hz) synaptic activity in ∼30% of all classes of cells. Oscillatory activity persisted after putative inputs from residual photoreceptor, rod bipolar cell, and inhibitory amacrine cell synapses were pharmacologically blocked, suggesting that presynaptic cone bipolar cells were intrinsically active. Examination of presynaptic rd1 ON and OFF bipolar cells indicated that they rested at relatively negative potentials (less than -50 mV). However, in approximately half the cone bipolar cells, low-amplitude membrane oscillation (∼5 mV, ∼10 Hz) were apparent. Such oscillations were also observed in AII amacrine cells. Oscillations in ON cone bipolar and AII amacrine cells exhibited a weak apparent voltage dependence and were resistant to blockade of synaptic receptors, suggesting that, as in wild-type retina, they form an electrically coupled network. In addition, oscillations were insensitive to blockers of voltage-gated Ca(2+) channels (0.5 mm Cd(2+) and 0.5 mm Ni(2+)), ruling out known mechanisms that underlie oscillatory behavior in bipolar cells. Together, these results indicate that an electrically coupled network of ON cone bipolar/AII amacrine cells constitutes an intrinsic oscillator in the rd1 retina that is likely to drive synaptic activity in downstream circuits.

Vsx1 regulates terminal differentiation of type 7 ON bipolar cells.

Although retinal bipolar cells represent a morphologically well defined population of retinal interneurons, very little is known about the developmental mechanisms that regulate their processing. Furthermore, the identity of specific bipolar cell types that function in distinct visual circuits remains poorly understood. Here, we show that the homeobox gene Vsx1 is expressed in Type 7 ON bipolar cells. In the absence of Vsx1, Type 7 bipolar cells exhibit proper morphological specification but show defects in terminal gene expression. Vsx1 is required for the repression of bipolar cell-specific markers, including Calcium-binding protein 5 and Chx10. This contrasts its genetic requirement as an activator of gene expression in OFF bipolar cells. To assess possible ON signaling defects in Vsx1-null mice, we recorded specifically from ON-OFF directionally selective ganglion cells (DSGCs), which cofasciculate with Type 7 bipolar cell terminals. Vsx1-null ON-OFF DSGCs received more sustained excitatory synaptic input, possibly due to Type 7 bipolar cell defects. Interestingly, in Vsx1-null mice, the directionally selective circuit is functional but compromised. Together, these findings indicate that Vsx1 regulates terminal gene expression in Type 7 bipolar cells and is necessary for proper ON visual signaling within a directionally selective circuit.

Intrinsic oscillatory activity arising within the electrically coupled AII amacrine-ON cone bipolar cell network is driven by voltage-gated Na+ channels.

In the rd1 mouse model for retinal degeneration, the loss of photoreceptors results in oscillatory activity (∼10­20 Hz) within the remnant electrically coupled network of retinal ON cone bipolar and AII amacrine cells. We tested the role of hyperpolarization-activated currents (I(h)), voltage-gated Na(+) channels and gap junctions in mediating such oscillatory activity. Blocking I(h) (1 mm Cs(+)) hyperpolarized the network and augmented activity, while antagonizing voltage-dependent Na(+) channels (1 µm TTX) abolished oscillatory activity in the AII amacrine-ON cone bipolar cell network. Voltage-gated Na(+) channels were only observed in AII amacrine cells, implicating these cells as major drivers of activity. Pharmacologically uncoupling the network (200 µm meclofenamic acid (MFA)) blocked oscillations in all cells indicating that Na(+) channels exert their influence over multiple cell types within the network. In wt retina, occluding photoreceptor inputs to bipolar cells (10 µm NBQX and 50 µm l-AP4) resulted in a mild (∼10 mV) hyperpolarization and the induction of oscillatory activity within the AII amacrine-ON cone bipolar cell network. These oscillations had similar properties to those observed in rd1 retina, suggesting that no major degeneration-induced network rewiring is required to trigger spontaneous oscillations. Finally, we constructed a simplified computational model that exhibited Na(+) channel-dependent network oscillations. In this model, mild heterogeneities in channel densities between individual neurons reproduced our experimental findings. These results indicate that TTX-sensitive Na(+) channels in AII amacrine cells trigger degeneration-induced network oscillations, which provide a persistent synaptic drive to downstream remnant neurons, thus appearing to replace photoreceptors as the principal drivers of retinal activity.

Genetically timed, activity-sensor and rainbow transsynaptic viral tools.

We developed retrograde, transsynaptic pseudorabies viruses (PRVs) with genetically encoded activity sensors that optically report the activity of connected neurons among spatially intermingled neurons in the brain. Next we engineered PRVs to express two differentially colored fluorescent proteins in a time-shifted manner to define a time period early after infection to investigate neural activity. Finally we used multiple-colored PRVs to differentiate and dissect the complex architecture of brain regions.

Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration.

Genetically encoded optical neuromodulators create an opportunity for circuit-specific intervention in neurological diseases. One of the diseases most amenable to this approach is retinal degeneration, where the loss of photoreceptors leads to complete blindness. To restore photosensitivity, we genetically targeted a light-activated cation channel, channelrhodopsin-2, to second-order neurons, ON bipolar cells, of degenerated retinas in vivo in the Pde6b(rd1) (also known as rd1) mouse model. In the absence of 'classical' photoreceptors, we found that ON bipolar cells that were engineered to be photosensitive induced light-evoked spiking activity in ganglion cells. The rescue of light sensitivity was selective to the ON circuits that would naturally respond to increases in brightness. Despite degeneration of the outer retina, our intervention restored transient responses and center-surround organization of ganglion cells. The resulting signals were relayed to the visual cortex and were sufficient for the animals to successfully perform optomotor behavioral tasks.

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.

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.

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.

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.

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.

Magnetoconductance response in unipolar and bipolar organic diodes at ultrasmall fields.

We measured magnetoconductance (MC) response in a number of unipolar and bipolar organic diodes based on π-conjugated polymers and small molecules at fields |B|<100 mT and various bias voltages and temperatures. Similar to magneto-electroluminescence, the MC(B) response in bipolar diodes shows a sign reversal at ultrasmall |B|<1-2 mT due to interplay of hyperfine and Zeeman interactions in opposite-charge polaron pairs. Surprisingly, similar MC(B) response was also measured in unipolar devices, indicating the existence of like-charge polaron pairs, however, with a clear difference between the hyperfine interaction constants of electron polaron and hole polaron.

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.