HIV1-Nef perturbs the integrity of blood testis barrier in rat model.

The blood-testis barrier is a specialized feature within the mammalian testis, located in close proximity to the basement membrane of seminiferous tubules. This barrier serves to divide the seminiferous epithelium into distinct basal and adluminal (apical) compartments. The selectivity of the BTB to foreign particles makes it a safe haven for the virus, and the high affinity of HIV for testis might lead to the vertical transmission of the virus. In the present study, recombinant HIV1-Nef (rNef) protein was injected intravenously to examine the effect of rNef on BTB. SD male rats received 250 µg and 500 µg of rNef along with 2% Evans blue dye within 1 ml through the tail vein. After 1 hour of perfusion, the animals were sacrificed for analysis. The dye migration assay and ELISA confirmed a significant impairment in the blood-testis barrier (BTB) and the manifestation of rNef in testes tissues, respectively. Moreover, a decline in the expression of tight junction proteins, including ZO1 and Occludin, was observed during rNef-induced BTB disruption. Overall, our findings demonstrated that rNef induces BTB disruption through various signaling events. At the site of ectoplasmic specialization of the seminiferous epithelium, the localization of cadherins was found to be disrupted, making the testis a vulnerable site. In conclusion, rNef perturbs the integrity of the blood-testis barrier in rat models; hence, it can also serve as a suitable model for studying the dynamics of the blood-testis barrier.

Established a rodent model to study the integrity of the blood testis barrier (BTB).Recombinant Nef (rNef) of HIV1 can breach the toughest physiological barrier of BTB.Integrity of BTB gets interrupted by rNef through the 'disengagement' and 'engagement' mechanisms of BTB dynamics.Major constituent proteins of BTB, including Occludin and ZO-1 were found to be highly disrupted by rNef; and seem to be the key aberrant for the compromised BTB.rNef also dislocated the localization of N & E cadherins in the rat testes; which would have affected the cadherin-based epithelial adhesion system of BTB and finally caused the breach.

Evaluation of antiglaucoma drug treatment awareness and patient-reported medication adherence: Determinants of glaucoma management.

Introduction: Primary open angle glaucoma (POAG) treatment is characterized by long-duration therapy, prescription variability, and non-adherence. Patient awareness toward drug treatment is crucial to ensure adherence. The present study was planned to evaluate drug treatment awareness, patient-perceived drug adherence, and prescription patterns in POAG patients. Methodology: This was a cross-sectional, single-center, questionnaire-based study conducted in the ophthalmology out patient department of a tertiary care hospital from April 2020 to November 2021. Patients of either gender, aged 40-70 years, with a confirmed diagnosis of POAG, who had records of POAG medications for at least last 3 months and who provided written informed consent, were included. Prescription details were recorded, and subsequently, patients were administered a pre-validated drug treatment awareness (14 items) questionnaire, a self-reported medication adherence (9-item) questionnaire, and then they performed eye drop instillation in a simulated setting. Results: The total number of patients enrolled was 180, which yielded 200 prescriptions. The mean drug treatment awareness score was 8.18 ± 3.30, and 135 (75%) patients scored more than 50% (≥7/14). Similarly, 159 patients (83.33%) had scored >50% (i.e. >5/9), with a mean score of 6.30 ± 1.70 in the medication treatment adherence questionnaire. The mean eye drop instillation performance score was 7.18 ± 1.20. The 200 POAG prescriptions containing 306 drugs were analyzed, with beta blockers (184/200, 92%) and timolol (168/200, 84% encounters) being the highest prescribed classes/drugs. Conclusion: POAG patients did have adequate treatment awareness with good self-reported medication adherence and performance of eye drop instillation technique. Around 25% patients lacked awareness; hence, reinforcement education programs on medication regimens need to be implemented.

Assessment of prescribing pattern of drugs and completeness of prescriptions as per the World Health Organization prescribing indicators in various Indian tertiary care centers: A multicentric study by Rational Use of Medicines Centers-Indian Council of Medical Research network under National Virtual Centre Clinical Pharmacology activity.

OBJECTIVE: The rational use of medicines as per the World Health Organization (WHO) should be practiced globally. However, data regarding the completeness of the prescriptions and their rational use is lacking from developing countries like India. Thus, the aim of this study was to assess the prescribing patterns of drugs and completeness of prescriptions as per WHO core drug use and complementary indicators to provide real-life examples for the Indian Council of Medical Research (ICMR) online prescribing skill course for medical graduates. METHODS: Prescriptions of the patients, fulfilling inclusion criteria, attending Outpatient Departments of various specialties of tertiary care hospitals, were collected by thirteen ICMR Rational use of medicines centers located in tertiary care hospitals, throughout India. Prescriptions were evaluated for rational use of medicines according to the WHO guidelines and for appropriateness as per standard treatment guidelines using a common protocol approved by local Ethics committees. RESULTS: Among 4838 prescriptions, an average of about three drugs (3.34) was prescribed to the patients per prescription. Polypharmacy was noted in 83.05% of prescriptions. Generic drugs were prescribed in 47.58% of the prescriptions. Further, antimicrobials were prescribed in 17.63% of the prescriptions and only 4.98% of prescriptions were with injectables. During the prescription evaluation, 38.65% of the prescriptions were incomplete due to multiple omissions such as dose, duration, and formulation. CONCLUSION: Most of the parameters in the present study were out of the range of WHO-recommended prescribing indicators. Therefore, effective intervention program, like training, for the promotion of rational drug use practice was recommended to improve the prescribing pattern of drugs and the quality of prescriptions all over the country.

Association of Interleukin-1ß-31C/T, -511T/C and -3954C/T Single Nucleotide Polymorphism and Their Blood Plasma Level in Acquired Aplastic Anemia.

Aplastic anemia (AA) is an immune-mediated disorder in which hematopoietic stem and progenitor cells are targeted by a number of cellular and molecular pathways. This case control study aims to investigate the association of interleukin-1beta (IL-1ß) gene polymorphisms, (IL-1ß-31, IL-1ß-511 and IL-1ß-3954) and their plasma levels with acquired AA. Genotyping was done by Restricted Fragment Length Polymorphism (PCR-RFLP) method and IL-1ß plasma levels were evaluated in peripheral blood using ELISA. Increased level of IL-1ß was reported to be significant in cases as compared to controls. The susceptibility of developing AA was higher in the cases for IL-1ß-3954 genotype. IL-1ß-511 genotype showed significant association with the severity groups of AA. No significant association was noticed in responder versus non-responder group. Plasma level of IL-1ß gene was found to be significantly higher in severe and very-severe group of AA versus control group. Our findings suggest that IL-1ß gene and its genotypes might be involved in the pathophysiology of AA and play a central role in the etiopathogenesis of AA.

Over-the-counter medicines: Global perspective and Indian scenario.

Patients often approach a pharmacist instead of visiting a doctor for minor ailments such as cough, cold, allergies, pain, fever, acidity, diarrhea, and skin-related conditions. Purchase of specific medicines over the counter is legally recognized in most countries. 'Over-the-Counter (OTC) Medicines' means drugs which are legally allowed to be sold by pharmacists without need for a prescription. The term does not have a legal definition in India. Technically, drugs are OTC unless they are specifically stated as prescription only drugs. OTC drugs allow faster and cheaper access to healthcare; however, their misuse and adverse health effects cause concerns. This article describes concept of OTC medicines and practices in India against the background of globally prevalent regulations and practices. A recognized category of OTC medicines by law, patient awareness programs, and support of pharmacists and pharmaceutical companies are required to optimize the use of OTC medicines in India.

Comparision between bupivacaine and ropivacaine in patients undergoing forearm surgeries under axillary brachial plexus block: a prospective randomized study.

CONTEXT: Brachial plexus block is a suitable alternative to general anaesthesia for patient undergoing upper extremity surgery. Ropivacaine the S-enantiomer emerged as a possible replacement of Bupivacaine without undesirable toxic effects. It provides similar duration of sensory analgesia with early recovery of motor block. AIMS: Comparision of onset, duration of sensory- motor block and any adverse effects between 0.5% Bupivacaine and 0.5% Ropivacaine in axillary brachial plexus block. SETTINGS AND DESIGN: Prospective randomized study. MATERIALS AND METHODS: This study was carried out in 50 patients between 18-55 y, comparable in demographic variables was randomly allocated to two groups of 25 each. Group I received 30ml 0.5% Bupivacaine, Group II received 30 ml 0.5% Ropivacaine in axillary brachial plexus block for forearm surgeries. Onset, Duration of sensory-motor block, Heart rate, Blood pressure, Oxygen saturation and Respiratory rate were recorded. STATISTICAL ANALYSIS: Statistical analysis used was Statistical Package for Social Sciences version 15.0, Chi-square test was used to evaluate the proportional data. Odds ratio/risk ratios have been calculated wherever necessary. Parametric data has been evaluated using Student t-test while non-parametric data has been evaluated using Mann-Whitney U-test. RESULTS: Onset of motor blockade was earlier in ropivacaine group (5 min) as compared to bupivacaine group (20 min), Higher levels of motor blockade, Mean onset time for motor block was significantly shorter in ropivacaine group (14.88±3.35 min) as compared to bupivacaine group (22.92±3.79 min), Mean duration of block was significantly longer in bupivacaine group (408.40±50.39 min) as compared to ropivacaine group (365.60±34.29 min) (p=0.001), Onset of sensory block was observed from 5 min itself in ropivacaine group as compared to bupivacaine group (10 min), Duration of sensory block was significantly longer in bupivacaine group (450.40±54.50 min) as compared to ropivacaine group (421.20±38.33 min) . CONCLUSION: On the basis of present study, conclusions were drawn that onset of action of sensory, motor block was early in Ropivacaine group with faster recovery of motor functions as compared to Bupivacaine group. No adverse effects were noted in either groups. This study suggests that Ropivacaine is a suitable alternative to Bupivacaine for forearm surgeries under Brachial Plexus Block.

Surgical and endovascular interventions for chronic mesenteric ischemia.

The aim of this manuscript was to describe and discuss the rationale and conduct of currently available endovascular and open surgical techniques to treat chronic mesenteric ischemia (CMI) and thus support the process of decision-making in mesenteric revascularization.

Structural, nanomechanical, field emission and ammonia gas sensing properties of nitrogenated amorphous carbon films deposited by filtered anodic jet carbon arc technique.

This paper reports the effect of substrate bias on the structural, nanomechanical, field emission and ammonia gas sensing properties of nitrogenated amorphous carbon films embedded with nanocrystallites (a-C: N: nc) deposited by a filtered anodic jet carbon arc (FAJCA) technique. The films are characterized by X-ray diffraction, high resolution transmission electron microscopy, energy dispersive X-ray spectroscopic analysis, Raman spectroscopy, nanoindentation, field emission and ammonia gas sensing measurements. The properties of the films obtained are found to depend on the substrate bias. The maximum hardness (H)=42.7 GPa, elastic modulus (E)=330.4 GPa, plastic index parameter (H/E)=0.129 and elastic recovery (% ER)=74.4% have been obtained in a-C: N: nc films deposited at -60 V substrate bias which show the lowest ID/IG=0.43, emission threshold (ET)=4.9 V/µm accompanied with the largest emission current density (Jmax)=1 mA/cm(2) and field enhancement factor (ß)=1805.6. The gas sensing behavior of the a-C: N: nc film has been tested by measuring the change in electrical resistance of the sample in ammonia environment at room temperature with the fast response and recovery time as 29 and 66.9s, respectively.

Role of Clonidine as adjuvant to intrathecal bupivacaine in patients undergoing lower abdominal surgery: A randomized control study.

BACKGROUND: Neuraxial anesthesia greatly expands the anesthesiologist armamentarium, providing alternatives to general anesthesia, especially in the lower abdominal surgeries. Clonidine, an alpha-2 adrenergic agonist, has a variety of actions, including potentiation of effects of local anesthetics. This study was undertaken to assess the degree of sensory and motor block and postoperative analgesia provided by low dose (50 mcg) intrathecal clonidine admixed with bupivacaine. AIMS: The aim of this study is to establish efficacy and safety of intrathecal clonidine as adjuvant to bupivacaine. SETTINGS AND DESIGN: The type of the study was double-blind randomized trial. MATERIALS AND METHODS: Hundred patients were randomly allocated in two groups, A and B. Group A received bupivacaine 0.5%, 3 ml with placebo (normal saline 0.33 ml) and Group B, bupivacaine 0.5%, 3 ml with clonidine 50 µg (0.33 ml). STATISTICAL ANALYSIS USED: Statistical Package for Social Sciences version 15.0 statistical analysis software. RESULTS: Mean duration of motor block was significantly higher in Group B (280.80 ± 66.88 min) as compared with Group A (183.60 ± 77.06 min). Significant difference in duration of sensory block was noted between Group B (295.20 ± 81.17 min) and Group A (190.80 ± 86.94 min). Duration of postoperative analgesia was significantly higher in Group B as compared to Group A (551.06 ± 133.64 min and 254.80 ± 84.19 min respectively). Mean visual analog scale scores at different time intervals were significantly lower in the study group (except for 4-h time interval), but the control group had better hemodynamic stability as compared with study group. CONCLUSION: The findings in this study suggested that use of clonidine 50 µg added to bupivacaine for spinal anesthesia effectively increased the duration of sensory block, duration of motor block, and duration of analgesia.

Comparison of effects of intravenous clonidine and dexmedetomidine for blunting pressor response during laryngoscopy and tracheal intubation: A randomized control study.

CONTEXT: Laryngoscopy and endotracheal intubation activates the sympathetic nervous system, causing tachycardia and hypertension. Dexmedetomidine has an affinity for alpha2 receptors 8 times greater than that of clonidine. It diminishes norepinephrine release and inhibits sympathetic activity leading to decreased heart rate (HR) and blood pressure. AIMS: The aim was to compare the effect of intravenous (IV) infusion of dexmedetomidine and clonidine on the pressor response among patients undergoing tracheal intubation in elective surgeries under general anesthesia. SETTINGS AND DESIGN: A prospective, randomized control study. SUBJECTS AND METHODS: Seventy-five adult patients of age 18-55 years in American Society of Anesthesiologists physical status I and II were included in this study. Patients were allocated randomly into Group P, Group D and Group C of 25 patients each. In the operation theatre, clonidine (3 µg/kg) or dexmedetomidine (0.5 µg/kg) or placebo (0.9% normal saline) diluted in 100 ml NaCl 0.9% were infused over a period of 10 min. STATISTICAL ANALYSIS USED: Statistical analysis was done using Statistical Package for Social Sciences version 15.0. Chi-square test, ANOVA, Student's t-test, and Paired t-test were used. RESULTS: As compared to Group P, the mean systolic blood pressure in Group D and Group C were significantly lower (<0.01) after intubation and all the subsequent intervals. After infusion and after the induction interval, the maximum value was observed in Group D while minimum mean value was observed in Group C. As compared to Group P, the mean arterial pressure in Group D was significantly higher at after infusion and after induction intervals but significantly lower after intubation and subsequent intervals. However, in Group C, the mean value was significantly lower as compared to Group P at all-time intervals except after infusion and after induction intervals. As compared to Group P, the mean HR in Group D was significantly higher at after infusion and after induction intervals. However at all the subsequent intervals, Group D was significantly lower as compared to Group P. CONCLUSION: It was found that attenuating response to hemodynamic changes were observed with dexmedetomidine and clonidine IV infusion. The early onset of dexmedetomidine makes it a promising choice. Hence premedication with IV infusion of dexmedetomidine can safely be recommended for attenuation of hemodynamic response to endotracheal intubation.

Influence of silver incorporation on the structural and electrical properties of diamond-like carbon thin films.

A simple approach is proposed for obtaining low threshold field electron emission from large area diamond-like carbon (DLC) thin films by sandwiching either Ag dots or a thin Ag layer between DLC and nitrogen-containing DLC films. The introduction of silver and nitrogen is found to reduce the threshold field for emission to under 6 V/µm representing a near 46% reduction when compared with unmodified films. The reduction in the threshold field is correlated with the morphology, microstructure, interface, and bonding environment of the films. We find modifications to the structure of the DLC films through promotion of metal-induced sp2 bonding and the introduction of surface asperities, which significantly reduce the value of the threshold field. This can lead to the next-generation, large-area simple and inexpensive field emission devices.

Surgical and endovascular treatment of occlusive aortic syndromes.

Aortic occlusive syndromes encompass a wide variety of aortic and aortoiliac conditions that present with devastating clinical sequale of hypertension coupled with visceral and lower limb ischemia. Clinical presentations, natural history, etio-pathology, diagnosis, management and outcomes of each of these disorders is unique. Risk factor management, endovascular intervention, and/or surgical revascularization compete and complement each other in an exciting manner to give best long-term outcomes. Common causes of aortic occlusion include: 1) atherosclerotic occlusive disease, including aortoiliac occlusive diseases (AIOD); acute aortic occlusion (embolic/thrombotic/dissection; 2) mid aortic syndrome: Takayasu arteritis; congenital aortic hypoplasia; fibromuscular dysplasia; neurofibromatosis; 3) coral reef aorta.

Structural and electronic characterization of nanocrystalline diamondlike carbon thin films.

The origin of low threshold field-emission (threshold field 1.25 V/µm) in nanocrystalline diamond-like carbon (nc-DLC) thin films is examined. The introduction of nitrogen and thermal annealing are both observed to change the threshold field and these changes are correlated with changes to the film microstructure. A range of different techniques including micro-Raman and infrared spectroscopy, X-ray diffraction, electron microscopy, energy-dispersive X-ray analysis and time-of-flight-secondary ion mass spectroscopy are used to examine the properties of the films. A comparison of the field emission properties of nc-DLC films with atomically smooth amorphous DLC (a-DLC) films reveals that nc-DLC films have lower threshold fields. Our results show that nc-DLC can be a good candidate for large area field emission display panels and cold cathode emission devices.

Computational methods for the HZETRN code.

Asymptotic expansion has been used to simplify the transport of high charge and energy ions for broad beam applications in the laboratory and space. The solution of the lowest order asymptotic term is then related to a Green's function for energy loss and straggling coupled to nuclear attenuation providing the lowest order term in a rapidly converging Neumann series for which higher order collisions terms are related to the fragmentation events including energy dispersion and downshift. The first and second Neumann corrections were evaluated numerically as a standard for further analytic approximation. The first Neumann correction is accurately evaluated over the saddle point whose width is determined by the energy dispersion and located at the downshifted ion collision energy. Introduction of the first Neumann correction leads to significant simplification of the second correction term allowing application of the mean value theorem and a second saddle point approximation. The regular dependence of the second correction spectral dependence lends hope to simple approximation to higher corrections. At sufficiently high energy nuclear cross-section variations are small allowing non-perturbative methods to all orders and renormalization of the second corrections allow accurate evaluation of the full Neumann series.

Validation of the HZETRN code for laboratory exposures with 1A GeV iron ions in several targets.

A new version of the HZETRN code capable of validation with HZE ions in either the laboratory or the space environment is under development. The computational model consists of the lowest order asymptotic approximation followed by a Neumann series expansion with non-perturbative corrections. The physical description includes energy loss with straggling, nuclear attenuation, nuclear fragmentation with energy dispersion and downshift. Measurements to test the model were performed at the Alternating Gradient Synchrotron and the NASA Space Radiation Laboratory at Brookhaven National Laboratory with iron ions. Surviving beam particles and produced fragments were measured with solid-state detectors. Beam analysis software has been written to relate the computational results to the measured energy loss spectra of the incident ions for rapid validation of modeled target transmission functions.

Deep space environments for human exploration.

Mission scenarios outside the Earth's protective magnetic shield are being studied. Included are high usage assets in the near-Earth environment for casual trips, for research, and for commercial/operational platforms, in which career exposures will be multi-mission determined over the astronaut's lifetime. The operational platforms will serve as launching points for deep space exploration missions, characterized by a single long-duration mission during the astronaut's career. The exploration beyond these operational platforms will include missions to planets, asteroids, and planetary satellites. The interplanetary environment is evaluated using convective diffusion theory. Local environments for each celestial body are modeled by using results from the most recent targeted spacecraft, and integrated into the design environments. Design scenarios are then evaluated for these missions. The underlying assumptions in arriving at the model environments and their impact on mission exposures within various shield materials will be discussed.

An improved Green's function for ion beam transport.

Ion beam transport theory allows testing of material transmission properties in the laboratory environment generated by particle accelerators. This is a necessary step in materials development and evaluation for space use. The approximations used in solving the Boltzmann transport equation for the space setting are often not sufficient for laboratory work and those issues are the main emphasis of the present work. In consequence, an analytic solution of the linear Boltzmann equation is pursued in the form of a Green's function allowing flexibility in application to a broad range of boundary value problems. It has been established that simple solutions can be found for high charge and energy (HZE) ions by ignoring nuclear energy downshifts and dispersion. Such solutions were found to be supported by experimental evidence with HZE ion beams when multiple scattering was added. Lacking from the prior solutions were range and energy straggling and energy downshift with dispersion associated with nuclear events. Recently, we have found global solutions including these effects providing a broader class of HZE ion solutions.