Influence of C-4 Axial/Equatorial Configuration and Neighboring Group/Remote Group Participation (NGP/RGP) Driven Conformational Evidence in Chemoselective Activation of Glycals.

We herein reveal the possibility of the C-4 neighboring group/remote group participation (NGP/RGP) facilitating the stabilization of the anomeric center via dioxolenium intermediates in the chemoselective activation of glycal donors. We further realized that the axial/equatorial configuration of the C-4 group in the galacto- and gluco-glycal series enables diverse pathways to give direct 1,2-addition or Ferrier rearrangement, respectively. A proof-of-principle for stereoselective glycosylation was amply illustrated by employing carbohydrates, amino acids, natural products, and bioactive molecules to develop 2-deoxy-glycan analogs.

The potential of MXene-based materials in fluorescence-based sensing/biosensing of ionic and organic contaminants in environment and food samples: Recent advancements and challenges.

MXenes belong to one of the recently developed advanced materials with tremendous potential for diverse sensing applications. To date, various types of MXene-based materials have been developed to generate direct/indirect ultrasensitive sensing signals against various forms of analytes via fluorescence quenching or enhancement. In this work, the fluorescence sensing/biosensing capabilities of the MXene-based materials have been explored and evaluated against a list of ionic/emerging pollutants in environment and food matrices. The suitability of an MXene-based sensing approach is also validated through the assessment of the performance based on the basic quality assurance parameters, e.g., limit of detection (LOD), sensing range, and response time. Accordingly, the best performing MXene-based materials are selected and recommended for the given target(s) to help facilitate their scalable applications under real-world conditions.

Neuronal toxicity of monoclonal antibodies (mAbs): an analysis of post-marketing reports from FDA Adverse Event Reporting System (FAERS) safety database.

BACKGROUND: Monoclonal antibodies (mAbs) are pivotal in treating various diseases, including cancers and autoimmune disorders. Despite their therapeutic benefits, mAb therapy has been associated with neurological toxicity. OBJECTIVES: This study aimed to assess the occurrence of neuronal toxicity associated with mAbs, utilizing data from the FDA Adverse Event Reporting System (FAERS) safety database. The study also sought to delineate the medical characteristics of the reported cases. METHODS: A comprehensive analysis of neurological adverse events reported in the FAERS database was conducted, employing computational methodologies such as proportional relative risk (PRR), information component (IC025), and chi-square (χ2). Individual case safety reports (ICSRs) pertaining to neurological disorders linked to mAbs from the date of first global marketing authorization until June 30, 2023, were meticulously examined. RESULTS: The FAERS safety database contains 79,022 ICSRs linking mAbs to nervous system disorders. Rituximab, bevacizumab, denosumab, nivolumab, and trastuzumab were frequently cited. Reported adverse events include headache, peripheral neuropathy, dizziness, and cerebrovascular accident. Most ICSRs (85.81%) were serious, mainly affecting females (57.04%) with a 14.09% fatality rate. Panitumumab, atezolizumab, bevacizumab, and trastuzumab showed strong drug-event associations. Signal disproportionate reporting (SDR) analysis flagged myasthenia gravis, peripheral neuropathy, and neurotoxicity across multiple mAbs, suggesting potential signals. CONCLUSIONS: Interdisciplinary collaboration between oncologists and neurologists is crucial for safe mAb use. Our study enhances understanding of mAb neurological safety. Disproportionality signal analysis provides valuable evidence for risk mitigation.

Efficacy of Intravenous 20% Mannitol vs 3% Hypertonic Saline in Reducing Intracranial Pressure in Nontraumatic Brain Injury: A Systematic Review and Meta-analysis.

Background: Nontraumatic brain injury encompasses various pathological processes and medical conditions that result in brain dysfunction and neurological impairment without direct physical trauma. The study aimed to assess the efficacy of intravenous administration of 20% mannitol and 3% hypertonic saline to reduce intracranial pressure in nontraumatic brain injury. Materials and methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed for study selection and data extraction. The search was conducted in the PubMed, Embase, and Scopus databases, including articles published in English from January 2003 to December 2023. Our study included randomized controlled trials, comparative studies, prospective analyses, and retrospective cohort studies. We extracted data on baseline characteristics of patients, intervention details, major outcomes, and complications. Quality assessment was performed using the Jadad scale and the Robvis assessment tool for risk of bias. Results: A total of 14 studies involving 1,536 patients were included in the analysis. Seven studies reported hypertonic saline as more effective in reducing intracranial pressure, while three studies found similar effectiveness for both interventions. Adverse events were reported in only three studies. The studies that reported complication rates ranged from 21 to 79%. A meta-analysis was conducted on five studies, showing varying rates of adverse events associated with mannitol and hypertonic saline. Conclusion: Both hypertonic saline solution and mannitol have been explored as treatment options for decreasing intracranial pressure in nontraumatic brain injuries. While some studies indicate the superiority of hypertonic saline, others report similar effectiveness between the two interventions. How to cite this article: Choudhury A, Ravikant, Bairwa M, Jithesh G, Kumar S, Kumar N. Efficacy of Intravenous 20% Mannitol vs 3% Hypertonic Saline in Reducing Intracranial Pressure in Nontraumatic Brain Injury: A Systematic Review and Meta-analysis. Indian J Crit Care Med 2024;28(7):686-695.

Formulation of Phytosomes Containing Rubia cordifolia Extract for Neuropathic Pain: In Vitro and In Vivo Evaluation.

This study aimed to develop a delivery system for the dried aqueous extract of Rubia cordifolia leaves (RCE) that could improve the neuroprotective potential of RCE by improving the bioavailability of the chief chemical constituent rubiadin. Rubiadin, an anthraquinone chemically, is a biomarker phytoconstituent of RCE. Rubiadin is reported to have strong antioxidant and neuroprotective activity but demonstrates poor bioavailability. In order to resolve the problem related to bioavailability, RCE and phospholipids were reacted in disparate ratios of 1:1, 1:2, and 1:3 to prepare phytosome formulations PC1, PC2, and PC3, respectively. The formulation PC2 showed particle size of 289.1 ± 0.21 nm, ζ potential of -6.92 ± 0.10 mV, entrapment efficiency of 72.12%, and in vitro release of rubiadin of 89.42% at pH 7.4 for a period up to 48 h. The oral bioavailability and neuroprotective potential of PC2 and RCE were assessed to evaluate the benefit of PC2 formulation over the crude extract RCE. Formulation PC2 showed a relative bioavailability of 134.14% with a higher neuroprotective potential and significantly (p < 0.05) augmented the nociceptive threshold against neuropathic pain induced by partial sciatic nerve ligation method. Antioxidant enzyme levels and histopathological studies of the sciatic nerves in various treatment groups significantly divulged that PC2 has enough potential to reverse the damaged nerves into a normal state. Finally, it was concluded that encapsulated RCE as a phytosome is a potential carrier system for enhancing the delivery of RCE for the efficient treatment of neuropathic pain.

Assessment for Diabetic Neuropathy: Treatment and Neurobiological Perspective.

Diabetic neuropathy, also known as diabetic peripheral sensorimotor neuropathy (DPN), is a consequential complexity of diabetes, alongside diabetic nephropathy, diabetic cardiomyopathy, and diabetic retinopathy. It is characterized by signs and symptoms of peripheral nerve damage in diabetes patients after ruling out other causes. Approximately 20% of people with diabetes are affected by this painful and severe condition. The development of diabetic neuropathy is influenced by factors such as impaired blood flow to the peripheral nerves and metabolic issues, including increased polyol pathway activation, myo-inositol loss, and nonenzymatic glycation. The present review article provides a brief overview of the pathological changes in diabetic neuropathy and the mechanisms and types of DPN. Various diagnostic tests and biomarkers are available to assess nerve damage and its severity. Pharmacotherapy for neuropathic pain in diabetic neuropathy is complex. This review will explore current treatment options and potential future developments to improve the quality of life for patients suffering from diabetic neuropathy.

Programming tunable active dynamics in a self-propelled robot.

We present a scheme for producing tunable active dynamics in a self-propelled robotic device. The robot moves using the differential drive mechanism where two wheels can vary their instantaneous velocities independently. These velocities are calculated by equating robot's equations of motion in two dimensions with well-established active particle models and encoded into the robot's microcontroller. We demonstrate that the robot can depict active Brownian, run and tumble, and Brownian dynamics with a wide range of parameters. The resulting motion analyzed using particle tracking shows excellent agreement with the theoretically predicted trajectories. Later, we show that its motion can be switched between different dynamics using light intensity as an external parameter. Intriguingly, we demonstrate that the robot can efficiently navigate through many obstacles by performing stochastic reorientations driven by the gradient in light intensity towards a desired location, namely the target. This work opens an avenue for designing tunable active systems with the potential of revealing the physics of active matter and its application for bio- and nature-inspired robotics.

Supraglottic Myxedema Presenting as a Complication of Hypothyroidism: A Case Report.

Myxedema is a medical emergency with high mortality rates if not treated aggressively. Here, we present a middle-aged female with complaints of generalized body swelling for one year, shortness of breath, hoarseness of voice, neck swelling, and cough for 20 days. The patient was diagnosed to be having severe hypothyroidism with polyserositis. Contrast-enhanced computed tomography (CECT) of the neck and thorax revealed extensive soft tissue edema causing airway narrowing, bilateral pleural effusion, moderate pericardial effusion, and features of atypical pneumonia. The patient was started on levothyroxine and antibiotics as per cultures to which she had initially improved; however, she developed ventilator-associated pneumonia leading to sepsis, acute respiratory distress syndrome followed by refractory type 1 respiratory failure and succumbed.

The Anti-ulcer Potential of Weissella cibaria Assisted Bio-fermented Product of Citrus limetta Waste Peel in Wistar Albino Rats.

BACKGROUND: There are patents available related to fermented food and beverages which enhance to human health. Citrus limetta (Mosambi) has a high content of flavonoids and exhibits antioxidant activity, which could stimulate the digestive system and be useful for gastroprotective activity. It supports digestion by neutralizing the acidic digestive juices and reducing gastric acidity. OBJECTIVE: This study explored the potential of using waste peel extract from Citrus limetta to prevent ulcers. The study specifically sought to assess the anti-ulcer properties of fermented and non-fermented extracts and compare them. Further, the study looked at the potential benefits of treating or preventing ulcers with Citrus limetta waste peels and whether fermentation affected the efficacy of the treatment. METHODS: Thirty female Wistar albino rats were equally distributed into five different groups. Group 1 received distilled water (20 ml/kg/b.w); Group 2 received indomethacin (mg/kg/b.w); Group 3 received omeprazole (20 mg/kg/b.w); Group 4 received aqueous extract of Mosambi peel (400 mg/kg/b.w) and Group 5 received fermented product of extract of Mosambi peel (400 mg/kg/b.w). RESULTS: Findings explored that, compared to non-fermented citrus fruit juice, biofermented exhibited less gastric volume (1.58 ± 0.10 ml vs. 1.8 ± 0.14 ml), reduced MDA levels (355.23 ± 100.70 µmol/mg protein vs. 454.49 ± 155.88 µmol/mg protein), and low ulcer index (0.49 ± 0.07 vs. 0.72 ± 0.14). CONCLUSION: The results suggest that the bio-fermented product of Citrus limetta peel has better anti-ulcer potential against peptic ulcer induced by indomethacin in Wistar albino rats compared to non-fermented.

Sodium fluorescein dye as an adjunct in vitrectomy for rhegmatogenous retinal detachment in oculocutaneous albinism.

A 48-year-old male with oculocutaneous albinism (OCA) presented with bilateral diminution of vision. Ocular examination revealed bilateral central corneal thinning, scarring with ectasia, depigmented irides, transillumination defects, and pseudophakia. Examination of the right eye also revealed a hyperoleon, emulsified silicon oil in the vitreous cavity, and an attached retina, while the left eye had a total rhegmatogenous retinal detachment (RRD). This case describes a unique set of challenges (the presence of an ectatic scarred cornea and a hypopigmented fundus) and sodium fluorescein dye as an adjunct in the surgical management of a complex RRD. A review of literature highlighting the association of keratoconus and RRD in OCA is also presented in this report.

Retinal vascular pathology in a mouse model of Lafora progressive myoclonus epilepsy.

Neurodegenerative diseases (ND) affect distinct populations of neurons and manifest various clinical and pathological symptoms. A subset of ND prognoses has been linked to vascular risk factors. Consequently, the current study investigated retinal vascular abnormalities in a murine model of Lafora neurodegenerative disease (LD), a fatal and genetic form of progressive myoclonus epilepsy that affects children. Here, arterial rigidity was evaluated by measuring pulse wave velocity and vasculature deformations in the retina. Our findings in the LD mouse model indicate altered pulse wave velocity, retinal vascular thinning, and convoluted retinal arteries.

Genomic attributes of airway commensal bacteria and mucosa.

Microbial communities at the airway mucosal barrier are conserved and highly ordered, in likelihood reflecting co-evolution with human host factors. Freed of selection to digest nutrients, the airway microbiome underpins cognate management of mucosal immunity and pathogen resistance. We show here the initial results of systematic culture and whole-genome sequencing of the thoracic airway bacteria, identifying 52 novel species amongst 126 organisms that constitute 75% of commensals typically present in heathy individuals. Clinically relevant genes encode antimicrobial synthesis, adhesion and biofilm formation, immune modulation, iron utilisation, nitrous oxide (NO) metabolism and sphingolipid signalling. Using whole-genome content we identify dysbiotic features that may influence asthma and chronic obstructive pulmonary disease. We match isolate gene content to transcripts and metabolites expressed late in airway epithelial differentiation, identifying pathways to sustain host interactions with microbiota. Our results provide a systematic basis for decrypting interactions between commensals, pathogens, and mucosa in lung diseases of global significance.

Minimally invasive endoscopic management of tubercular tenosynovitis of the anterior tibial tendon.

The incidence of tubercular tenosynovitis around the foot and ankle is rare even in endemic areas. We present an unusual case involving the isolated tubercular tenosynovitis of the Anterior Tibial tendon, which was successfully managed through a combination of medical treatment and endoscopic intervention. Our patient, a 30-year-old female, sought medical attention due to a gradually worsening painful swelling localized to the anterior aspect of her left ankle. Diagnostic imaging, specifically Magnetic Resonance Imaging (MRI), revealed alterations in signal intensity within the Anterior Tibial tendon. Importantly, the infection had not spread to involve the ankle joint. We performed both diagnostic and therapeutic tenosynovectomy endoscopically and subsequently sent the tissue for histopathological examination. The histopathological findings revealed the presence of histiocytic granulomas containing Langhans' giant cells, which strongly suggested a tuberculosis infection. Consequently, we initiated anti-tubercular chemotherapy as the treatment approach. Our patient exhibited a positive response to the treatment, and after one year, she experienced complete resolution of the disease. This case underscores the importance of maintaining a high level of clinical suspicion for tuberculosis, especially in endemic areas, when encountering unusual presentations. Level of evidence: V.

Small molecules that disrupt RAD54-BLM interaction hamper tumor proliferation in colon cancer chemoresistance models.

RAD54 and BLM helicase play pivotal roles during homologous recombination repair (HRR) to ensure genome maintenance. BLM amino acids (aa 181-212) interact with RAD54 and enhance its chromatin remodeling activity. Functionally, this interaction heightens HRR, leading to a decrease in residual DNA damage in colon cancer cells. This contributes to chemoresistance in colon cancer cells against cisplatin, camptothecin, and oxaliplatin, eventually promoting tumorigenesis in preclinical colon cancer mouse models. ChIP-Seq analysis and validation revealed increased BLM and RAD54 corecruitment on the MRP2 promoter in camptothecin-resistant colon cancer cells, leading to BLM-dependent enhancement of RAD54-mediated chromatin remodeling. We screened the Prestwick small-molecule library, with the intent to revert camptothecin- and oxaliplatin-induced chemoresistance by disrupting the RAD54-BLM interaction. Three FDA/European Medicines Agency-approved candidates were identified that could disrupt this interaction. These drugs bound to RAD54, altered its conformation, and abrogated RAD54-BLM-dependent chromatin remodeling on G5E4 and MRP2 arrays. Notably, the small molecules also reduced HRR efficiency in resistant lines, diminished anchorage-independent growth, and hampered the proliferation of tumors generated using camptothecin- and oxaliplatin-resistant colon cancer cells in both xenograft and syngeneic mouse models in BLM-dependent manner. Therefore, the 3 identified small molecules can serve as possible viable candidates for adjunct therapy in colon cancer treatment.

Cataract progression after primary pars plana vitrectomy for uncomplicated rhegmatogenous retinal detachments in young adults.

BACKGROUND: Scleral buckling is typically implemented to repair rhegmatogenous retinal detachments (RRD) in young patients. Therefore, there is limited data on post-pars plana vitrectomy (PPV) cataract formation in this cohort. We report the rates and risk factors of cataract progression after PPV for RRD repair in young eyes. METHODS: Retrospective single-center cohort study. Medical records of patients between the ages of 15 to 45 undergoing PPV for uncomplicated RRD between 2014 and 2020 were reviewed. RESULTS: Twenty-eight eyes from 26 patients met inclusion criteria. Cataracts developed in 20/28 (71%) eyes after PPV. After PPV, nuclear sclerotic cataract (NSC) rates were higher in patients above 35 (65%) compared to below 35 years (18%) (p = 0.024). Cataracts developed more frequently after macula-off RRDs (88%) compared to macula-on RRDs (50%) (p = 0.044) with NSC more common in macula-off detachments (p = 0.020). At postoperative month 2, all eyes with C3F8 gas developed cataracts compared to 59% of eyes with no gas (p = 0.040). CONCLUSIONS: Cataract formation was common and frequent after PPV. After PPV, young eyes and macula-on detachments developed cataracts less frequently than older eyes and macula-off detachments. If appropriate, a shorter acting gas tamponade should be considered in young eyes to minimize cataract formation.

Burkholderia-associated polymyositis.

A diagnosis of polymyositis can readily be made when there is a typical history of proximal muscle weakness together with clinical findings, and there is corroboratory evidence in the form of elevated creatine kinase lactate dehydrogenase, aldolase, and serum glutamic-oxaloacetic transaminase (aspartate aminotransferase). A muscle biopsy usually helps in making the confirmatory diagnosis. A female in her 50s presented with non-healing multiple deep necrotic ulcers with muscle weakness. The initial possibility of vasculitis ulcers remained. Later, this proved to be a case of polymyositis with mildly elevated creatine kinase (which is usually not the case), atypical skin manifestations (usually there is no skin involvement), and negative extended myositis specific antibody panel with the growth of Burkholderia cepacia (perhaps the triggering factor). Hence, polymyositis can present with a myriad of atypical findings. Thus, thorough clinical examination and an integrated approach are necessary for early identification and treatment of the disease.

Implications of siRNA Therapy in Bone Health: Silencing Communicates.

The global statistics of bone disorders, skeletal defects, and fractures are frightening. Several therapeutic strategies are being used to fix them; however, RNAi-based siRNA therapy is starting to prove to be a promising approach for the prevention of bone disorders because of its advanced capabilities to deliver siRNA or siRNA drug conjugate to the target tissue. Despite its 'bench-to-bedside' usefulness and approval by food and drug administration for five siRNA-based therapeutic medicines: Patisiran, Vutrisiran, Inclisiran, Lumasiran, and Givosiran, its use for the other diseases still remains to be resolved. By correcting the complications and complexities involved in siRNA delivery for its sustained release, better absorption, and toxicity-free activity, siRNA therapy can be harnessed as an experimental tool for the prevention of complex and undruggable diseases with a personalized medicine approach. The present review summarizes the findings of notable research to address the implications of siRNA in bone health for the restoration of bone mass, recovery of bone loss, and recuperation of bone fractures.

Reagent-controlled chemo/stereoselective glycosylation of ʟ-fucal to access rare deoxysugars.

2,6-Dideoxy sugars constitute an important class of anticancer antibiotics natural products and serve as essential medicinal tools for carbohydrate-based drug discovery and vaccine development. In particular, 2-deoxy ʟ-fucose or ʟ-oliose is a rare sugar and vital structural motif of several potent antifungal and immunosuppressive bioactive molecules. Herein, we devised a reagent-controlled stereo and chemoselective activation of ʟ-fucal, enabling the distinctive glycosylation pathways to access the rare ʟ-oliose and 2,3-unsaturated ʟ-fucoside. The milder oxo-philic Bi(OTf)3 catalyst induced the direct 1,2-addition predominantly, whereas B(C6F5)3 promoted the allylic Ferrier-rearrangement of the enol-ether moiety in ʟ-fucal glycal donor, distinguishing the competitive mechanisms. The reagent-tunable modular approach is highly advantageous, employing greener catalysts and atom-economical transformations, expensive ligand/additive-free, and probed for a diverse range of substrates comprising monosaccharides, amino-acids, bioactive natural products, and drug scaffolds embedded with susceptible or labile functionalities.

A systematic review of techniques for step cut osteotomy in cubitus varus: A comprehensive analysis.

Background: Cubitus varus, a common post-traumatic deformity of the elbow in children, poses challenges for both patients and surgeons. Step cut osteotomy has emerged as a reasonable surgical technique to address this condition, offering multiple approaches and modifications. Methods: We present a comprehensive systematic review of techniques for step cut osteotomy in cubitus varus, analyzing 13 studies that meet our inclusion criteria. These studies encompass diverse patient populations, including pediatric and adult cases, and span different geographical regions. Results: Our systematic review explores three primary osteotomy techniques-Classic Step-Cut Osteotomy, Reverse V Osteotomy, and Modified Step Cut Osteotomy-along with their modifications, providing surgeons with valuable options for individualized correction. Functional outcomes showcase improvements in range of motion, functional scores, and carrying angle, highlighting the technique's efficacy in restoring elbow function and enhancing quality of life. Radiological evaluations demonstrate successful corrections of various angles and achievement of bony union, reinforcing the stability and anatomical improvements achieved through step cut osteotomy. Conclusions: Complication rates are notably low, with transient nerve palsies being the most commonly encountered, often resolving within months. Implant failure and other complications are infrequent, underlining the safety and reliability of step cut osteotomy as a surgical intervention for cubitus varus.While the predominance of retrospective studies and heterogeneity across included studies warrant caution, our systematic review provides a robust and diverse synthesis of evidence. It underscores the significance of step cut osteotomy in managing cubitus varus deformity, emphasizing its versatility, favourable outcomes, and safety profile. Further research with rigorous designs and longer follow-up periods will enhance our understanding of step cut osteotomy's role in cubitus varus correction.

Ruthenium-Catalyzed Self-Coupling of Secondary Alcohols.

A simple catalytic method for self-coupling of secondary alcohols leading to the synthesis of ß-branched ketones under mild conditions is reported. Well-defined ruthenium pincer complex catalyzed the reactions. Optimization studies revealed that sodium tert-butoxide is an appropriate base for this transformation. Functionalized aryl methanols, heteroaryl methanols, and linear and branched aliphatic secondary alcohols underwent facile catalytic self-coupling reactions. Mechanistic studies revealed that both catalyst and base are crucial to achieve dehydrogenation of secondary alcohols to ketones, their subsequent controlled aldol condensation, and further hydrogenation of α,ß-unsaturated intermediates, leading to the selective formation of ß-branched ketone products. Notably, the noninnocent PNP ligand which displays amine-amide metal-ligand cooperation operative in a catalyst played a key role in facilitating this catalytic self-coupling of secondary alcohols. Liberated molecular hydrogen and water are the only byproducts.