3D Characterization of the Aortic Valve and Aortic Arch in Bicuspid Aortic Valve Patients.

Patients with bicuspid aortic valve (BAV) commonly have associated aortic stenosis and aortopathy. The geometry of the aortic arch and BAV is not well defined quantitatively, which makes clinical classifications subjective or reliant on limited 2D measurements. The goal of this study was to characterize the 3D geometry of the aortic arch and BAV using objective and quantitative techniques. Pre-TAVR computed tomography angiogram (CTA) in patients with BAV and aortic stenosis (AS) were analyzed (n = 59) by assessing valve commissural angle, presence of a fused region, percent of fusion, and calcium volume. The ascending aorta and aortic arch were reconstructed from patient-specific imaging segmentation to generate a centerline and calculate maximum curvature and maximum area change for the ascending aorta and the descending aorta. Aortic valve commissural angle signified a bimodal distribution suggesting tricuspid-like (≤ 150°, 52.5% of patients) and bicuspid-like (> 150°, 47.5%) morphologies. Tricuspid like was further classified by partial (10.2%) or full (42.4%) fusion, and bicuspid like was further classified into valves with fused region (27.1%) or no fused region (20.3%). Qualitatively, the aortic arch was found to have complex patient-specific variations in its 3D shape with some showing extreme diameter changes and kinks. Quantitatively, subgroups were established using maximum curvature threshold of 0.04 and maximum area change of 30% independently for the ascending and descending aorta. These findings provide insight into the geometric structure of the aortic valve and aortic arch in patients presenting with BAV and AS where 3D characterization allows for quantitative classification of these complex anatomic structures.

Effect of boron fertilization on productivity and sustainability of rice-wheat cropping system in Tarai region, North-West India.

Extensive global dependency on rice and wheat crops has necessitated the adoption of intensive cultivation practices, thereby compelling to closely monitor the potential yield-limiting factors, among which, boron (B) deficiency stands out to be a prime concern. The present study explores the effects of B fertilization strategies within the Rice-Wheat Cropping System (RWCS) in the Tarai region of North-West India. A comprehensive six-year field experiment was conducted (2013-2019) at G.B. Pant University of Agriculture and Technology, Uttarakhand, India. The experiment tested graded B doses (0.5, 1.0, 1.5, and 2.0 kg ha-1) at varied frequencies (single, alternate, and annual) in a factorial design. The study revealed significant impacts of alternate B application at 1.5 kg ha-1 on crop yields and the Sustainable Yield Index (SYI). The System Rice Equivalent Yield (SREY) exhibited an increase of 6.7% with B supplementation over B-deprived plots, highlighting the pivotal role of B fertilizer in enhancing productivity within the RWCS. The economic optimum B dose was found to be 1.422 kg ha-1 using a linear plus plateau model, resulting in a calculated annual SREY of 9.73 t ha-1 when applied alternately to the cropping system. Continuous application and higher B rates demonstrated substantial increases in various B fractions, while the mobility factor remained within 10%, depicting safe ecological limits. The distribution of fractions in B-treated plots on average followed the order: residual B > organically-bound B > oxide bound B > specifically adsorbed B > readily soluble B. Similarities in the distribution patterns of B fractions between B-treated plots and the control indicated potential influence of biotic or abiotic processes on B fraction dynamics, even in the absence of external B application. To sum up, B application in alternate years at 1.5 kg ha-1 was most sustainable in enhancing the SREY, SYI, available soil B, and B fractions and lowering the environmental hazards.

Deciphering the potential of Sargassum tenerrimum extract: metabolic profiling and pathway analysis of groundnut (Arachis hypogaea) in response to Sargassum extract and Sclerotium rolfsii.

Seaweed extracts have enormous potential as bio-stimulants and demonstrated increased growth and yield in different crops. The presence of physiologically active component stimulate plant stress signaling pathways, enhances growth and productivity, as well as serve as plant defense agents. The seaweed extracts can reduce the use of chemicals that harm the environment for disease management. In the present study, the Sargassum tenerrimum extract treatment was applied, alone and in combination with Sclerotium rolfsii, to Arachis hypogea, to study the differential metabolite expression. The majority of metabolites showed maximum accumulation with Sargassum extract-treated plants compared to fungus-treated plants. The different classes of metabolite compounds like sugars, carboxylic acids, polyols, showed integrated peaks in different treatments of plants. The sugars were higher in Sargassum extract and Sargassum extract + fungus treatments compared to control and fungus treatment, respectively. Interestingly, Sargassum extract + fungus treatment showed maximum accumulation of carboxylic acids. Pathway enrichment analysis showed regulation of different metabolites, highest impact with galactose metabolism pathway, identifying sucrose, myo-inositol, glycerol and fructose. The differential metabolite profiling and pathway analysis of groundnut in response to Sargassum extract and S. rolfsii help in understanding the groundnut- S. rolfsii interactions and the potential role of the Sargassum extract towards these interactions. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01418-9.

Serotonin Transporter Deficiency Induces Metabolic Alterations in the Ileal Mucosa.

Serotonin transporter (SERT) deficiency has been implicated in metabolic syndrome, intestinal inflammation, and microbial dysbiosis. Interestingly, changes in microbiome metabolic capacity and several alterations in host gene expression, including lipid metabolism, were previously observed in SERT-/- mice ileal mucosa. However, the precise host or microbial metabolites altered by SERT deficiency that may contribute to the pleiotropic phenotype of SERT KO mice are not yet understood. This study investigated the hypothesis that SERT deficiency impacts lipid and microbial metabolite abundances in the ileal mucosa, where SERT is highly expressed. Ileal mucosal metabolomics was performed by Metabolon on wild-type (WT) and homozygous SERT knockout (KO) mice. Fluorescent-activated cell sorting (FACS) was utilized to measure immune cell populations in ileal lamina propria to assess immunomodulatory effects caused by SERT deficiency. SERT KO mice exhibited a unique ileal mucosal metabolomic signature, with the most differentially altered metabolites being lipids. Such changes included increased diacylglycerols and decreased monoacylglycerols in the ileal mucosa of SERT KO mice compared to WT mice. Further, the ileal mucosa of SERT KO mice exhibited several changes in microbial-related metabolites known to play roles in intestinal inflammation and insulin resistance. SERT KO mice also had a significant reduction in the abundance of ileal group 3 innate lymphoid cells (ILC3). In conclusion, SERT deficiency induces complex alterations in the ileal mucosal environment, indicating potential links between serotonergic signaling, gut microbiota, mucosal immunity, intestinal inflammation, and metabolic syndrome.

Manual Instruments as an Alternative to Drilling for Bony Exposure in Skull Base Surgery: Concept and Technique.

Background Drilling in neurosurgery is an integral part of surgical exposure, especially in skull base approaches and craniovertebral junction (CVJ) surgeries. Most of such drillings are done in close proximity to the neurovascular structures in skull base surgeries and cervical-medullary junction or facet/pedicle in CVJ surgeries. Reluctance to drilling among young neurosurgeons is due to less hands-on experience during training and also, in the early part of the career, due to fear of injury to neurovascular structures. Methods Five commonest bone removals for skull base region and CVJ surgeries that can be safely done using manual instruments were identified based on experiences of senior authors. The authors highlight key technical nuances to widen surgical corridors using manual instruments safely for skull base surgical approaches. Results Basic neuroanatomical concepts and basic physics help in using manual instruments safely for bone removals in various skull base surgical approaches. Conclusions Manual instruments may be used for bone removals in selected skull base surgical approaches, which help young neurosurgeons to perform these surgeries in limited-resource settings.

Picture Perfect: Standardizing and Safekeeping Clinical Photography in Plastic Surgery.

Plastic surgery relies heavily on clinical photography to document preoperative and postoperative changes, visualize surgical approaches, and evaluate outcomes. However, the contemporary landscape of plastic surgery photography faces challenges, including a lapse in standards due to the prevalence of smartphones, social media platforms, and security concerns related to data storage and cyberattacks. In this comprehensive review, the authors aim to provide plastic surgeons with practical guidelines for achieving standardized, high-quality clinical photography while navigating the evolving landscape of technology, security, and ethical considerations. We explore the security challenges associated with storing clinical photographs, emphasizing the legal obligations under the Health Insurance Portability and Accountability Act (HIPAA). We also discuss various storage options, including HIPAA-compliant cloud services, electronic medical records, and emerging technologies like blockchain and artificial intelligence.

Donor-transmitted cystinuria in a renal transplant recipient.

Cystinuria is an autosomal recessive disorder associated with defective proximal tubular reabsorption of divalent amino acids. It leads to increased cystine, ornithine, lysine, and arginine excretion in the urine. Cystine is insoluble in physiological pH, and cystinuria leads to crystalluria and nephrolithiasis. We present a case of acquired cystinuria in a renal transplant recipient, that is, to the best of our knowledge, the first case of acquired cystinuria ever documented in the literature.

Comparison of the effects of dexmedetomidine and nitroglycerin on cerebral oxygen saturation using near-infrared spectroscopy in patients undergoing controlled hypotensive anaesthesia: A randomised controlled non-inferiority trial.

Background and Aims: There is limited literature wherein the hypotensive drugs have been compared to know the cerebral effects by monitoring regional cerebral oxygen saturation (rScO2). This study aimed to compare the effects of dexmedetomidine and nitroglycerin on rScO2 during controlled hypotensive anaesthesia using near-infrared spectroscopy (NIRS). The primary objective was to evaluate the non-inferiority of dexmedetomidine versus nitroglycerin in the occurrence of cerebral desaturation events (CDEs) during hypotensive anaesthesia. Methods: Adult patients scheduled to undergo head and neck surgery under general anaesthesia randomised to receive either dexmedetomidine or nitroglycerin infusion for controlled hypotensive anaesthesia. Cerebral oximetry was monitored with NIRS, and data regarding CDEs, bilateral rScO2, and peri-operative haemodynamics were collected. Continuous data were analysed using unpaired Student's t-tests except for intra-group analyses, which were analysed using paired t-tests. Categorical data were analysed using the Chi-square test. For comparison of time to CDEs, Kaplan-Meier survival analysis with log-rank test was performed. Results: Of the 82 patients in both groups, CDEs were observed in 15 patients each. A decrease from baseline by 20% was observed in three patients: one in Group N and two in Group D. Statistically, there was an equal risk of getting CDEs in the groups. The time to CDE was comparable (P > 0.05). The difference in heart rate was statistically significant (P < 0.001). Conclusion: Dexmedetomidine is non-inferior to nitroglycerin in terms of the occurrence of cerebral desaturation events when used for controlled hypotensive anaesthesia in head and neck surgeries.

Combinatorial Ubiquitination REal-time PROteolysis (CURE-PROs): A Modular Platform for Generating Reversible, Self-Assembling Bifunctional Targeted Degraders.

Proteolysis-Targeting Chimeras (PROTACs) are bifunctional molecules that bring a target protein and an E3 ubiquitin ligase into proximity to append ubiquitin, thus directing target degradation. Although numerous PROTACs have entered clinical trials, their development remains challenging, and their large size can produce poor drug-like properties. To overcome these limitations, we have modified our Coferon platform to generate Combinatorial Ubiquitination REal-time PROteolysis (CURE-PROs). CURE-PROs are small molecule degraders designed to self-assemble through reversible bio-orthogonal linkers to form covalent heterodimers. By modifying known ligands for Cereblon, MDM2, VHL, and BRD with complementary phenylboronic acid and diol/catechol linkers, we have successfully created CURE-PROs that direct degradation of BRD4 both in vitro and in vivo. The combinatorial nature of our platform significantly reduces synthesis time and effort to identify the optimal linker length and E3 ligase partner to each target and is readily amenable to screening for new targets.

A critical review on the biotechnological potential of Brewers' waste: Challenges and future alternatives.

In order to comply with the stringent discharge guidelines issued by governmental organizations to protect the ecosystem, the substantial amounts of effluent and sturdy wastes produced by the beer brewing process need to be discarded or handled in the most affordable and secure manner. Huge quantities of waste material released with each brew bestow a significant opportunity for the brewing sector to move towards sustainability. The concept of circular economy and the development of technological advancements in brewery waste processing have spurred interest to valorize brewery waste for implementation in various sectors of medical and food science, industrial science, and many more intriguing fields. Biotechnological methods for valorizing brewery wastes are showing a path towards green chemistry and are feasible and advantageous to environment. The study unfolds most recent prospectus for brewery waste usage and discusses major challenges with brewery waste treatment and valorization and offers suggestions for further work.

Complex architecture of cardiac muscle thick filaments revealed.

Muscle contraction is orchestrated by the well-understood thin filaments and the markedly complex thick filaments. Studies by Dutta et al. and Tamborrini et al., discussed here, have unravelled the structure of the mammalian heart thick filament in exquisite near-atomic detail and pave the way for understanding physiological modulation pathways and mutation-induced dysfunction and for designing potential drugs to modify defects.

Ion Transport Basis of Diarrhea, Paneth Cell Metaplasia, and Upregulation of Mechanosensory Pathway in Anti-CD40 Colitis Mice.

BACKGROUND: Anti-Cluster of differentiation (CD)-40-induced colitis, driven by innate inflammatory responses in the intestine, is a potent animal model exhibiting IBD pathophysiology including diarrhea. However, the ion transport basis of diarrhea and some key mucosal pathways (Paneth cells, stem cell niche, and mechanosensory) in this model have not been investigated. METHODS: Mucosal scrapings and intestinal tissue from control and CD40 antibody (150 µg) treated Rag2-/- mice were examined for gut inflammation, Paneth cell numbers, expression of key transporters, tight/adherens junction proteins, stem cell niche, and mechanosensory pathway via hematoxylin and eosin staining, quantitative polymerase chain reaction, and western blotting. RESULTS: Compared with control, anti-CD40 antibody treatment resulted in a significant loss of body weight (P < .05) and diarrhea at day 3 postinjection. Distal colonic tissues of anti-CD40 mice exhibited increased inflammatory infiltrates, higher claudin-2 expression, and appearance of Paneth cell-like structures indicative of Paneth cell metaplasia. Significantly reduced expression (P < .005) of downregulated in adenoma (key Cl- transporter), P-glycoprotein/multidrug resistantance-1 (MDR1, xenobiotic transporter), and adherens junction protein E-cadherin (~2-fold P < .05) was also observed in the colon of anti-CD40 colitis mice. Interestingly, there were also marked alterations in the stem cell markers and upregulation of the mechanosensory YAP-TAZ pathway, suggesting the activation of alternate regeneration pathway post-tissue injury in this model. CONCLUSION: Our data demonstrate that the anti-CD40 colitis model shows key features of IBD observed in the human disease, hence making it a suitable model to investigate the pathophysiology of ulcerative colitis (UC).

Our studies demonstrate the ion transport basis of diarrhea, downregulation of MDR1 and E-cadherin, Paneth cell metaplasia, and induction of claudin-2 and mechanosensory pathway in anti-CD40 colitis (innate immune-based model of IBD), similar to the human disease.

Islet Dimensions and Its Impact on the Cellular Composition and Insulin-Secreting Capacity: Insights Into the Role of Non-beta Cells.

Studies have underscored the significance of islet dimensions, encompassing i) the necessity for islets to maintain an optimal diameter to sustain functional activity; ii) larger islets exhibit an intermingled architecture of alpha and beta cells, enhancing functional activity through paracrine effects; iii) non-alpha/beta (NAB) cells play a significant role in regulating beta cells; and iv) there is a preferential loss of larger islets in cases of type 2 diabetes mellitus. To delve deeper into these aspects, the authors documented the cellular composition in islets of various dimensions and regions of the pancreas, along with their secreting capacity, using the expression of the myosin Va motor protein in nine non-diabetic adult human pancreases. The proportion of NAB cells was found to be higher in intermediate islets and significantly lower in smaller and larger islets. By comparing the differences in islet composition, where NAB cells increase from smaller to intermediate islets, leading to a decrease in the proportion of alpha and beta cells, and in larger islets, there is a higher proportion of beta and alpha cells similar to smaller islets, we propose the hypothesis that NAB cells proliferate as islets increase in size. Furthermore, in larger islets, these NAB cells convert into alpha and beta cells, resulting in the scattered, intermingled arrangement observed in larger islets. The higher intensity of myosin Va expression in the islets of the tail region, along with a similar proportion of NAB cells in intermediate islets of the tail region compared to larger islets, leads to decreased inhibitory stimuli to beta cells and an increased insulin-secreting capacity.

Osteoarthritis Increases the Frequency and Duration of Postoperative Hand Clinic Visits after Carpal Tunnel Release.

Background: Carpal tunnel syndrome affects up to 6% of the general population, and surgical intervention is often required to ameliorate symptoms. Osteoarthritis (OA) is a common condition that often coexists with carpal tunnel syndrome. We hypothesized that patients with preexisting OA use more healthcare resources after carpal tunnel release (CTR) than patients without arthritis. Methods: This was a retrospective cohort study at a single academic center between January 1, 2018 and November 1, 2021. Patients who underwent CTR were included. Preoperative carpal tunnel symptoms, diagnostic tests, medications, and concomitant OA were abstracted. Hand, wrist, and basal joint arthritis were specified. The primary outcome was healthcare utilization represented by duration and frequency of hand clinic and occupational therapy (OT) follow-up. In total, 312 hands were included. Multivariable analysis was performed. Results: The average duration of hand clinic follow-up among patients without arthritis was 25.3 days compared with 87.1 days for patients with any arthritis (P = 0.0375) and 172 days for patients with wrist arthritis (P = 0.012). The average number of postoperative surgeon visits was increased in patients with hand arthritis, with an average of 2.3 visits versus 1.34 visits for patients without arthritis (P = 0.003). Both the number of OT visits and the duration of OT follow-up did not differ between cohorts. Conclusion: After CTR, patients with preexisting OA use more healthcare resources than patients without OA.

Emerging frontiers in microbial-mediated utilization of crop residues for economically valuable biomaterials.

Agricultural crop residues include leftover and unmarketable materials, such as crop stover, weeds, leaf litter, sawdust, forest litter, and livestock manure originating from crop cultivation, and post-harvest activities. Such residues are a storehouse of plant nutrients and several other resources and therefore need to be managed in an environment- friendly manner with minimum loss of plant nutrients and other resources that can be recovered. Microbial starter consortia are a key component in the rapid recycling of farm residue wastes and the production of other valuable products, such as biogas, bioethanol/biofuel, enzymes, molecules, and metabolites. Recent advances in microbial biotechnology can also facilitate the conversion of farm residues into economically valuable materials, i.e. soil additives, adsorbents, energy, and enzymes, thereby contributing to a circular economy. This special issue attempts to compile the latest advancements in the field of agricultural crop residue management for enhanced nutrient recycling and resource recovery by the use of compost starters and inoculant formulations.