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Background Drug-induced acute kidney injury (AKI) poses a significant challenge in clinical practice, necessitating a comprehensive understanding of its epidemiology and underlying mechanisms. This prospective study aimed to elucidate the clinico-etiological profile of drug-induced AKI in a tertiary care center in Northeast India and evaluate patient outcomes. Methodology Adults diagnosed with AKI following drug exposure were enrolled in this observational study conducted from August 2022 to January 2024 at Department of Nephrology, Gauhati Medical College and Hospital. Demographic data, clinical characteristics, offending pharmaceutical agents, histopathological patterns, and outcomes were meticulously documented. Results We studied 105 participants (mean age: 45 ± 10 years, 56.2% male) experiencing drug-induced AKI. Antimicrobials (24%), nonsteroidal anti-inflammatory drugs (NSAIDs) (21%), and chemotherapeutic agents (19%) were common causes, leading predominantly to acute interstitial nephritis (58%) and renal tubular epithelial cell injury (30%). Despite challenges, 73% fully recovered, with a 2% mortality rate. Age (odds ratio [OR]: 1.35, 95% confidence interval [CI]: 1.12–1.63, P = 0.002), male gender (OR: 1.84, 95% CI: 1.09–3.11, P = 0.022), diabetes (OR: 2.21, 95% CI: 1.28–3.82, P = 0.005), smoking (OR: 1.92, 95% CI: 1.06–3.48, P = 0.031), antimicrobial use (OR: 3.68, 95% CI: 2.14–6.32, P < 0.001), NSAID use (OR: 2.77, 95% CI: 1.56–4.92, P < 0.001), and chemotherapeutic use (OR: 1.57, 95% CI: 1.10–2.22, P < 0.001) were significant risk factors. Conclusion This study highlights the clinico-etiological profile of drug-induced AKI in Northeast India, emphasizing antimicrobials, NSAIDs, and chemotherapeutics as major contributors. Despite the high prevalence, most patients recovered, stressing early recognition and careful medication management. Age, gender, and comorbidities play critical roles, warranting targeted interventions and vigilant pharmacovigilance to mitigate the AKI burden effectively.

Abstract Anti-HIV-1 broadly neutralizing antibodies (bNAbs) have the dual potential of mediating virus neutralization and antiviral effector functions through their Fab and Fc domains, respectively. So far, bNAbs with enhanced Fc effector functions in vitro have only been tested in NHPs during chronic simian-HIV (SHIV) infection. Here, we investigate the effects of administering in acute SHIVAD8-EO infection either wild-type (WT) bNAbs or bNAbs carrying the S239D/I332E/A330L (DEL) mutation, which increases binding to FcγRs. Emergence of virus in plasma and lymph nodes (LNs) was delayed by bNAb treatment and occurred earlier in monkeys given DEL bNAbs than in those given WT bNAbs, consistent with faster clearance of DEL bNAbs from plasma. DEL bNAb-treated monkeys had higher levels of circulating virus-specific IFNγ single-producing CD8+ CD69+ T cells than the other groups. In LNs, WT bNAbs were evenly distributed between follicular and extrafollicular areas, but DEL bNAbs predominated in the latter. At week 8 post-challenge, LN monocytes and NK cells from DEL bNAb-treated monkeys upregulated proinflammatory signaling pathways and LN T cells downregulated TNF signaling via NF-κB. Overall, bNAbs with increased affinity to FcγRs shape innate and adaptive cellular immunity, which may be important to consider in future strategies of passive bNAb therapy.

Digoxin, a cardiac glycoside, functions by inhibiting the sodium potassium ATPase pump. It’s crucial to note that digoxin has a very narrow therapeutic range. Its serum level vary due to changes in body weight, age, renal function, hepatic impairment and concomitant drug therapy. Chronic toxicity can lead to different types of arrrythmia,which span from heart blocks to ventricular tachycardia.This report present a case of an elderly male, where Digoxin toxicity resulted in syncope and mild traumatic brain injury. Initially upon patient’s presentation ECG indicated myocardial infarction, subsequently bradycardia and complete heart block. The patient had a known history of chronic kidney disease and was prescribed 0.25mg of digoxin regularly without dose adjustment, which might have resulted in reduced digoxin elimination, leading to toxicity. Thus this case demonstrates a classic presentation of digoxin toxicity. Multiple risk factor such as old age, impaired renal function with continued digoxin treatment without dose adjustment was likely the cause of toxicity.

In the face of the Russia-Ukraine war, Russia’s trade and economic potentials have been limited and restricted mostly due to the imposition of sanctions. Consequently, a bond between Russia and China has developed, putting aside their former disagreements and disputes. This goes together with the fact that both countries face a shared adversary from the US and the West, which has worked in pulling them closer to each other. Amidst the dynamic environment of worldwide trade, the economic collaboration and strategic alignment between China and Russia stand out as a crucial axis. This article investigates the interdependency and asymmetries of their bilateral partnership and how they have shaped their global trade relation. Furthermore, it also analyzes the historical background of Sino-Russian connections, emphasizing significant milestones and policy changes that have influenced their present economic interconnection. It analyses the problem areas of their relation and whether this bonding will withstand future changes in the global order.

Introduction: Spine fixation surgery for traumatic vertebral fractures is associated with severe pain and is often difficult to control. Traditionally systemic opioids have been the mainstay of analgesia for these procedures, which can lead to hyperalgesia, nausea, ileus, sedation, cognitive impairment, dependence, etc., limiting usage of opioids. The Erector spinae plane block (ESPB) is a novel ultrasound-guided procedure with easily identifiable sonoanatomy. We hypothesized that a multimodal approach involving ESPB to a conventional analgesic regimen with local infiltration for patients undergoing major traumatic spine surgeries might provide better perioperative analgesia and reduce the need for postoperative opioid requirements. Material and Methods: A randomized control prospective trial was conducted on 34 ASA grade I –II patients aged 18 to 65 years who were scheduled to undergo elective posterior spine fixation surgery with ASIA B to E after traumatic spine fracture under general anesthesia. Patients were randomized to Group A which included patients who received general anesthesia with ESPB, and Group B, or the control group, included patients who received general anesthesia with systemic analgesics and postoperative local infiltration without ESPB. Intraoperative total fentanyl consumption, VAS score at 0, 3, 6, 12, 18, and 24 hours, time to activate patient-controlled analgesia (PCA) pump, total morphine consumption, and opioid-related side effects were monitored and compared in both groups. Results: Postoperative PCA morphine consumption was significantly lower in group A patients who received ESPB than those in the control group (17.06 ± 9.59 vs 37.82 ± 9.88 P value =

Abstract Broadly neutralizing antibodies are proposed as therapeutic and prophylactic agents against HIV‐1, but their potency and breadth are less than optimal. This study describes the immunization of a llama with the prefusion‐stabilized HIV‐1 envelope (Env) trimer, BG505 DS‐SOSIP, and the identification and improvement of potent neutralizing nanobodies recognizing the CD4‐binding site (CD4bs) of vulnerability. Two of the vaccine‐elicited CD4bs‐targeting nanobodies, G36 and R27, when engineered into a triple tandem format with llama IgG2a‐hinge region and human IgG1‐constant region (G36×3‐IgG2a and R27×3‐IgG2a), neutralized 96% of a multiclade 208‐strain panel at geometric mean IC80s of 0.314 and 0.033 µg mL−1, respectively. Cryo‐EM structures of these nanobodies in complex with Env trimer revealed the two nanobodies to neutralize HIV‐1 by mimicking the recognition of the CD4 receptor. To enhance their neutralizing potency and breadth, nanobodies are linked to the light chain of the V2‐apex‐targeting broadly neutralizing antibody, CAP256V2LS. The resultant human‐llama bispecific antibody CAP256L‐R27×3LS exhibited ultrapotent neutralization and breadth exceeding other published HIV‐1 broadly neutralizing antibodies, with pharmacokinetics determined in FcRn‐Fc mice similar to the parent CAP256V2LS. Vaccine‐elicited llama nanobodies, when combined with V2‐apex broadly neutralizing antibodies, may therefore be able to fulfill anti‐HIV‐1 therapeutic and prophylactic clinical goals.

Abstract Background Existing antidepressants possess various adverse effects and so they are not considered as the first line of drug in mild depression. The lack of proper drugs to treat the mild depression on the other hand alleviates severe depressive cases. To overcome this problem, the nucleus of benzimidazole and cinnamic acid having very less toxicity were fused and a small library of 40 compounds was prepared. The library was then screened for ADMET properties and probable toxicity. Those compounds which had not shown any toxicity as well as possessed better in-silico absorption, distribution and metabolism were selected for the first phase of the study. Synthesized compounds were characterized by FTIR, 1H-NMR and 13C-NMR and were screened for in-vitro antidepressant activity by DNPH spectrophotometry. Result The compounds MS-3 and MS-8 had shown good antidepressant activity with IC50 values of 367.19 μM/mL and 184.56 μM/mL against MAO-A and MAO-B, respectively. Conclusion From this study, it can be concluded that the structural requirements for the inhibition of MAO-A and MAO-B were totally different. MAO-A inhibitors required the presence of nitrogen and oxygen containing ring substitutions whereas MAO-B inhibitors required the presence of 4-halogen containing phenyl ring substitutions. Graphical abstract

Abstract While several COVID-19 vaccines have been in use, more effective and durable vaccines are needed to combat the ongoing COVID-19 pandemic. Here, we report highly immunogenic self-assembling SARS-CoV-2 spike-HBsAg nanoparticles displaying a six-proline-stabilized WA1 (wild type, WT) spike S6P on a HBsAg core. These S6P-HBsAgs bound diverse domain-specific SARS-CoV-2 monoclonal antibodies. In mice with and without a HBV pre-vaccination, DNA immunization with S6P-HBsAgs elicited significantly more potent and durable neutralizing antibody (nAb) responses against diverse SARS-CoV-2 strains than that of soluble S2P or S6P, or full-length S2P with its coding sequence matching mRNA-1273. The nAb responses elicited by S6P-HBsAgs persisted substantially longer than by soluble S2P or S6P and appeared to be enhanced by HBsAg pre-exposure. These data show that genetic delivery of SARS-CoV-2 S6P-HBsAg nanoparticles can elicit greater and more durable nAb responses than non-nanoparticle forms of stabilized spike. Our findings highlight the potential of S6P-HBsAgs as next generation genetic vaccine candidates against SARS-CoV-2.

Abstract Agents that can simultaneously activate latent HIV, increase immune activation and enhance the killing of latently-infected cells represent promising approaches for HIV cure. Here, we develop and evaluate a trispecific antibody (Ab), N6/αCD3-αCD28, that targets three independent proteins: (1) the HIV envelope via the broadly reactive CD4-binding site Ab, N6; (2) the T cell antigen CD3; and (3) the co-stimulatory molecule CD28. We find that the trispecific significantly increases antigen-specific T-cell activation and cytokine release in both CD4+ and CD8+ T cells. Co-culturing CD4+ with autologous CD8+ T cells from ART-suppressed HIV+ donors with N6/αCD3-αCD28, results in activation of latently-infected cells and their elimination by activated CD8+ T cells. This trispecific antibody mediates CD4+ and CD8+ T-cell activation in non-human primates and is well tolerated in vivo. This HIV-directed antibody therefore merits further development as a potential intervention for the eradication of latent HIV infection.

The ecological balance of an ecosystem has a relation to its biodiversity. Although it has been established that biodiversity and ecological stability are related, generalization about the exact nature of this relation remains elusive and more so in microbial diversity. A growing volume of studies has indicated that anthropogenic activities impact biodiversity, but it is difficult to generalize the impact of anthropogenic activities on microbial diversity. Landfilling by municipal solid waste is one such activity where microbes play a major role, and leachates are released from the landfill, altering the soil’s physical and chemical nature. Change in factors like carbon source, pH, and toxicity of the soil is most likely to affect the indigenous microflora of the soil. The present study was undertaken to compare the microbial diversity of soil receiving landfill leachate with that of the soil not receiving any landfill leachate to assess the impact of the landfilling activity on microbial diversity. The landfill site selected for the study was that of Kamrup Metro District of Assam, located at Boragaon, near the Ramsar wetland called Deeporbeel. By using the Denaturing Gradient Gel Electrophoresis (DGGE) method, it has been found that the microbial diversity of the soil receiving leachate was higher than that of the soil not receiving any leachate from the landfill.

Conventional thermally processed apple juices are nutritionally depleted because the heat sensitivity degrades the bioactive compounds that comprise them. This study proposed a non-thermal technique, hydrodynamic cavitation (HC), to preserve the nutritional content and prevent the loss of bioactive components in apple juice. In addition, the effect of hydrodynamic cavitation on the physicochemical, nutrition, and enzyme inactivation of freshly expressed apple juice has been studied. The design expert software has been used for process optimization, while fuzzy logic was applied for sensory. Hydrodynamic cavitation has been used on freshly extracted apple juice with inlet pressure in the range of (34.47–103.421 kPa) for a treatment time of (0–30 min). The apple juice was treated thermally at 90 °C for 2.5 min to compare the cavitation results. The settling of particles in the cavitation sample was 7%, which was lower than the heat-treated sample (10%) and untreated control sample (39%) and had a noticeable effect on the cloud value and stability of the apple juice. The HC treatment reduces the particle size of fresh apple juice from 8934.09 nm to 1112 nm, resulting in a homogenizing effect, a decrease in viscosity, and improved juice stability. Hydrodynamic cavitation reduced the antioxidant activity from 0.4987 mg GAE mL−1 (control) to 0.3951 mg GAE mL−1 yet retained better activity than the heat-treated apple juice (0.3489 ± 0.34 mg GAE mL−1) with microbial log reduction of 0.9 at 103.42 kPa treated for 30 min. After 15 days of storage at 4 °C, HC-treated juice had higher quality features and nutrient retention than heat-treated apple juice.

The conventional thermal treatment causes chemical modifications to milk constituents such as protein denaturation, loss of vitamins and flavoring compounds, depression at freezing point, and nonenzymatic browning, which may result in adverse changes to the flavor, color, and nutritional value of milk. This review looks into the emerging non-thermal processing techniques such as high-pressure processing (HPP), pulsed electric field (PEF), ultrasonication and hydrodynamic, UV-irradiation and plasma technology, cavitation, and their effects on milk components and bioactive compounds. For consumer acceptability and safety, simultaneous and crucial needs exist: microbial safety, fresh like quality and preservation of bioactive compounds. Technologies like HPP and PEF have been capable of achieving microbial reduction with moderate thermal inputs. Ultrasonication and hydrodynamic cavitation have the dual functions of deactivating microorganisms and homogenizing, and plasma and UV-C radiation could ensure minimal loss of heat-sensitive components. These processing techniques could be an alternative to pasteurization and sterilization of milk with assured microbial inactivation and maximal retention of nutrients in dairy.

ABSTRACTThe amino-acid composition of the immunoglobulin variable region has been observed to impact antibody pharmacokinetics (PK). Here, we sought to improve the PK of the broad HIV−1-neutralizing VRC01-class antibodies, VRC07-523LS and N6LS, by reducing the net positive charge in their variable domains. We used a structure-guided approach to generate a panel of antibody variants incorporating select Arg or Lys substituted to Asp, Gln, Glu, or Ser. The engineered variants exhibited reduced affinity to heparin, reduced polyreactivity, and improved PK in human FcRn-transgenic mice. One variant, VRC07-523LS.v34, with three charge substitutions, had an observed in vivo half-life and an estimated human half-life of 10.8 and 60 days, respectively (versus 5.4 and 38 days for VRC07-523LS) and retained functionality, neutralizing 92% of a 208-strain panel at a geometric mean IC80