Multicenter, Open-Label, Prospective Study Shows Safety and Therapeutic Benefits of a Defined Ginkgo Biloba Extract for Adults with Major Neurocognitive Disorder.

INTRODUCTION: The safety and therapeutic effects of Gingko biloba extract EGb 761® to treat cognitive decline have been demonstrated in numerous clinical trials. However, trials in Indian populations have been lacking. METHODS: This open-label, multicenter, single-arm, phase IV trial enrolled 150 patients aged ≥50 years with major neurocognitive disorder due to Alzheimer's disease, major vascular neurocognitive disorder, or mixed forms of both according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria and a Mini-Mental State Examination (MMSE) score of 12-24. Patients took 120 mg EGb 761® twice daily for 18 weeks. Therapeutic effects were assessed by CERAD constructional praxis and recall of constructional praxis (CERAD CP, CERAD recall of CP), Trail-Making Test (TMT), Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD), Clinical Global Impressions (CGI) scale, and 11-point box scales for tinnitus and vertigo. Safety assessment was based on the occurrence of adverse events as well as changes in clinical, laboratory, and functional parameters. RESULTS: After 18 weeks, significant improvements compared to baseline were found in constructional praxis (CERAD CP, p < 0.0001), memory (CERAD recall of CP, p < 0.0001), speed and executive functioning (TMT A, p < 0.0001; TMT B, p < 0.0001), and behavioral symptoms (BEHAVE-AD, p < 0.0001). Forty-five adverse events were reported in 33 (22.0%) patients in total, including ten presumed adverse drug reactions in 9 (6.0%) patients. Headache and diarrhea of mild-to-moderate severity were the most frequent events. Two serious adverse events, both considered unrelated to the study drug, occurred in 2 (1.3%) patients. CONCLUSION: This study confirmed the favorable safety profile and suggested therapeutic benefits of EGb 761® in Indian patients with major neurocognitive disorder.

A Dreaded Complication of Corrosive Poisoning Leading to Gangrene of the Stomach and Duodenum: A Rare Case.

Corrosive poisoning is common in developing countries like India. It is mainly due to accidental consumption in children, whereas suicide is the usual intent in adults. It leads to devastating injuries, to the upper gastrointestinal tract such as necrosis and perforation. The long-term complications include stricture formation and gastric outlet obstruction. Here, we present the case of a 50-year-old male with an alleged history of corrosive acid ingestion. On contrast-enhanced computed tomography (CECT) of the abdomen, there was an absence of wall enhancement of the stomach and the first part of the duodenum, which was suggestive of necrosis or gangrenous changes with signs of impending perforation of the stomach and the first part of the duodenum. The patient was immediately taken up for surgery, and the intraoperative findings were consistent with the imaging findings.

Perioperative Care in Cardiac Surgery: A Joint Consensus Statement by the Enhanced Recovery After Surgery (ERAS) Cardiac Society, ERAS International Society, and The Society of Thoracic Surgeons (STS).

Enhanced Recovery After Surgery (ERAS) programs have been shown to lessen surgical insult, promote recovery, and improve postoperative clinical outcomes across a number of specialty operations. A core tenet of ERAS involves the provision of protocolized evidence-based perioperative interventions. Given both the growing enthusiasm for applying ERAS principles to cardiac surgery and the broad scope of relevant interventions, an international, multidisciplinary expert panel was assembled to derive a list of potential program elements, review the literature, and provide a statement regarding clinical practice for each topic area. This article summarizes those consensus statements and their accompanying evidence. These results provide the foundation for best practice for the management of the adult patient undergoing cardiac surgery.

The Association of Gestational Age and Size with Management Strategies and Outcomes in Symptomatic Neonatal Tetralogy of Fallot.

 In neonatal, symptomatic tetralogy of Fallot (sTOF), data are lacking on whether high-risk groups would benefit from staged (SR) or complete repair (CR). We studied the association of gestational age (GA) at birth and z-score for birth weight (BWz), with management strategy and outcomes in sTOF. California population-based cohort study (2011-2017) of infants with sTOF (defined as catheter or surgical intervention prior to 44 weeks corrected GA) was performed, comparing management strategy and timing by GA and BWz categories. Multivariable models evaluated composite outcomes and days alive and out of hospital (DAOOH) in the first year of life. Among 345 patients (SR = 194; CR = 151), management strategy did not differ by GA or BWz with complete repair defined as prior to 44 weeks corrected gestational age; however, did differ by GA with regard to complete/timely repair (defined as complete repair within first 30 days of life). Full-term and early-term neonates underwent CR 20 (95%CI: - 27.1, - 14.1; p < 0.001) and 15 days (95%CI: - 22.1, - 8.2; p < 0.001) sooner than preterm neonates. Prematurity and major anomaly were associated with mortality or non-cardiac morbidity, while only major anomaly was associated with mortality or cardiac morbidity (OR = 3.5, 95%CI: 1.8,6.7, p < .0001). Full-term infants had greater DAOOH compared to preterm infants (35.2 days, 95%CI: 4.0, 66.5, p = 0.03). LGA infants and those with major anomaly had significantly lower DAOOH. In sTOF, patient specific risk factors such as prematurity and major anomaly were more associated with outcomes than management strategy.

A two-centre experience of tonsil biopsies in the investigation of patients with tonsillar asymmetry.

INTRODUCTION: We aim to evaluate our experience of tonsil biopsies in the investigation of patients presenting with asymmetrical tonsils. METHODS: A two-centre retrospective analysis of all patients who underwent histology sampling of the palatine tonsils between 1 January 2013 and 31 December 2018 was completed. Data collected included patient demographics, method of obtaining tonsil tissue, histological diagnosis and need for repeat tissue sampling. A follow-up period of 36 months was allowed to establish whether any patients re-presented with missed diagnoses. RESULTS: In total, 937 patients were included for analysis: 375 (40.0%) had a biopsy, of which 191 (50.9%) were performed in clinic. The mean duration from initial appointment with the ear, nose and throat clinic to tissue sample collection was 17.6 days (range 0-327 days) for all biopsies, reducing to 0.2 days (range 0-17 days) for biopsies performed in clinic. This was significantly shorter than for tonsillectomies (mean 38.9 days, range 0-444 days; p<0.05). Of the patients who underwent tonsil biopsy, six (1.6%) had malignancy that was not unequivocally diagnosed on initial biopsy. In all six patients, prior clinical suspicion was high, and repeat tissue sampling was undertaken on receipt of negative histology results. CONCLUSIONS: Tonsil biopsy is a viable alternative to tonsillectomy for histology in the assessment of tonsil asymmetry. Tonsil biopsy in the outpatient setting has reduced surgical morbidity, significantly less delay in diagnosis, less inconvenience for patients and lower healthcare costs compared with formal tonsillectomy. Although tonsil biopsies should not be used in isolation, they can be useful in the investigation of patients presenting with tonsillar asymmetry.

Virtual clinic for hearing loss and non-pulsatile tinnitus: initial experience of 210 cases.

OBJECTIVE: Patients with hearing loss and tinnitus face lengthy waits to be seen in the ENT clinic. SHOEBOX Audiometry is an iPad-based, audiometric screening tool. A virtual hearing loss and non-pulsatile tinnitus clinic involving an ENT specialist virtually assessing cases based on the SHOEBOX audiogram, a patient symptom questionnaire and the primary care referral letter were implemented. This service evaluation explored the outcomes of the virtual clinic in reducing the need for a face-to-face ENT appointment. METHOD: This was a retrospective service evaluation of the first six months of the virtual hearing loss and non-pulsatile tinnitus clinic. RESULTS: A total of 210 patients were included: 34.8 per cent (73) were discharged without requiring audiologist assessment or an ENT appointment, 51.9 per cent (109) required formal audiological assessment, 36.7 per cent (77) required imaging and only 13.8 per cent (29) required a face-to-face ENT appointment. CONCLUSION: A virtual hearing loss and non-pulsatile tinnitus clinic minimised the number of patients requiring a traditional face-to-face clinic appointment within ENT.

Neuroprotective role of vitamin B12 in streptozotocin-induced type 1 diabetic rats.

Chronic hyperglycemia-induced neuropathological changes include neuronal apoptosis, astrogliosis, decrease in neurotrophic support, impaired synaptic plasticity, and impaired protein quality control (PQC) system. Vitamin B12 is indispensable for neuronal development and brain function. Several studies reported the neuroprotective effect of B12 supplementation in diabetic patients. However, the underlying molecular basis for the neuroprotective effect of B12 supplementation in diabetes needs to be thoroughly investigated. Two-month-old Sprague-Dawley rats were randomly assigned into three groups: Control (CN), diabetes (D; induced with streptozotocin; STZ), and diabetic rats supplemented with vitamin B12 (DBS; vitamin B12; 50 µg/kg) for four months. At the end of 4 months of experimentation, the brain was dissected to collect the cerebral cortex (CC). The morphology of CC was investigated with H&E and Nissl body staining. Neuronal apoptosis was determined with TUNEL assay. The components of neurotrophic support, astrogliosis, synaptic plasticity, and PQC processes were investigated by immunoblotting and immunostaining methods. H& E, Nissl body, and TUNEL staining revealed that diabetes-induced neuronal apoptosis and degeneration. However, B12 supplementation ameliorated the diabetes-induced neuronal apoptosis. Further, B12 supplementation restored the markers of neurotrophic support (BDNF, NGF, and GDNF), and synaptic plasticity (SYP, and PSD-95) in diabetic rats. Interestingly, B12 supplementation also attenuated astrogliosis, ER stress, and ameliorated autophagy-related proteins in diabetic rats. Overall, these findings suggest that B12 acts as a neuroprotective agent by inhibiting the neuropathological changes in STZ-induced type 1 diabetes. Thus, B12 supplementation could produce beneficial outcomes including neuroprotective effects in diabetic patients.

Oxidative Stress in Health and Disease.

Oxidative stress, resulting from the excessive intracellular accumulation of reactive oxygen species (ROS), reactive nitrogen species (RNS), and other free radical species, contributes to the onset and progression of various diseases, including diabetes, obesity, diabetic nephropathy, diabetic neuropathy, and neurological diseases, such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Oxidative stress is also implicated in cardiovascular disease and cancer. Exacerbated oxidative stress leads to the accelerated formation of advanced glycation end products (AGEs), a complex mixture of crosslinked proteins and protein modifications. Relatively high levels of AGEs are generated in diabetes, obesity, AD, and other I neurological diseases. AGEs such as Ne-carboxymethyllysine (CML) serve as markers for disease progression. AGEs, through interaction with receptors for advanced glycation end products (RAGE), initiate a cascade of deleterious signaling events to form inflammatory cytokines, and thereby further exacerbate oxidative stress in a vicious cycle. AGE inhibitors, AGE breakers, and RAGE inhibitors are therefore potential therapeutic agents for multiple diseases, including diabetes and AD. The complexity of the AGEs and the lack of well-established mechanisms for AGE formation are largely responsible for the lack of effective therapeutics targeting oxidative stress and AGE-related diseases. This review addresses the role of oxidative stress in the pathogenesis of AGE-related chronic diseases, including diabetes and neurological disorders, and recent progress in the development of therapeutics based on antioxidants, AGE breakers and RAGE inhibitors. Furthermore, this review outlines therapeutic strategies based on single-atom nanozymes that attenuate oxidative stress through the sequestering of reactive oxygen species (ROS) and reactive nitrogen species (RNS).

Post-quantum distributed ledger technology: a systematic survey.

Blockchain technology finds widespread application across various fields due to its key features such as immutability, reduced costs, decentralization, and transparency. The security of blockchain relies on elements like hashing, digital signatures, and cryptography. However, the emergence of quantum computers and supporting algorithms poses a threat to blockchain security. These quantum algorithms pose a significant threat to both public-key cryptography and hash functions, compelling the redesign of blockchain architectures. This paper investigates the status quo of the post-quantum, quantum-safe, or quantum-resistant cryptosystems within the framework of blockchain. This study starts with a fundamental overview of both blockchain and quantum computing, examining their reciprocal influence and evolution. Subsequently, a comprehensive literature review is conducted focusing on Post-Quantum Distributed Ledger Technology (PQDLT). This research emphasizes the practical implementation of these protocols and algorithms providing extensive comparisons of characteristics and performance. This work will help to foster further research at the intersection of post-quantum cryptography and blockchain systems and give prospective directions for future PQDLT researchers and developers.

State of the art: Proceedings of the American Association for Thoracic Surgery Enhanced Recovery After Cardiac Surgery Summit.

Despite the benefits established for multiple surgical specialties, enhanced recovery after surgery has been underused in cardiac surgery. A cardiac enhanced recovery after surgery summit was convened at the 102nd American Association for Thoracic Surgery annual meeting in May 2022 for experts to convey key enhanced recovery after surgery concepts, best practices, and applicable results for cardiac surgery. Topics included implementation of enhanced recovery after surgery, prehabilitation and nutrition, rigid sternal fixation, goal-directed therapy, and multimodal pain management.

Generating high-fidelity cochlear organoids from human pluripotent stem cells.

Mechanosensitive hair cells in the cochlea are responsible for hearing but are vulnerable to damage by genetic mutations and environmental insults. The paucity of human cochlear tissues makes it difficult to study cochlear hair cells. Organoids offer a compelling platform to study scarce tissues in vitro; however, derivation of cochlear cell types has proven non-trivial. Here, using 3D cultures of human pluripotent stem cells, we sought to replicate key differentiation cues of cochlear specification. We found that timed modulations of Sonic Hedgehog and WNT signaling promote ventral gene expression in otic progenitors. Ventralized otic progenitors subsequently give rise to elaborately patterned epithelia containing hair cells with morphology, marker expression, and functional properties consistent with both outer and inner hair cells in the cochlea. These results suggest that early morphogenic cues are sufficient to drive cochlear induction and establish an unprecedented system to model the human auditory organ.

Sublattice spin reversal and field induced Fe3+spin-canting across the magnetic compensation temperature in Y1.5Gd1.5Fe5O12rare-earth iron garnet.

In the present work Fe3+sublattice spin reversal and Fe3+spin-canting across the magnetic compensation temperature (TComp) are demonstrated in polycrystalline Y1.5Gd1.5Fe5O12(YGdIG) by means of in-field57FeMössbauer spectroscopy measurements. Corroborating in-field57FeMössbauer measurements, both Fe3+& Gd3+sublattice spin reversal has also been manifested in hard x-ray magnetic circular dichroism (XMCD) measurements. From in-field57FeMössbauer measurements, estimation and analysis of effective internal hyperfine field (Heff), relative intensity of absorption lines in a sextet elucidated unambiguously the signatures of Fe3+spin reversal and field induced spin-canting of Fe3+sublattices across TComp. Gd L3-edge XMCD signal is observed to consist of an additional spectral feature, identified as Fe3+magnetic contribution to XMCD spectra of Gd L3-edge, enabling us the extraction of both the sublattices (Fe3+& Gd3+) information from a single absorption edge analysis. The evolution of the XMCD amplitudes, which is proportional to magnetic moments, as a function of temperature for both magnetic sublattices extracted at the Gd L3-edge reasonably match with values that are extracted from bulk magnetization data of YGdIG and YIG (Y3Fe5O12) and corresponding Fe K-edge XMCD amplitudes for Fe contribution. These measurements pave new avenues to investigate how the magnetic behavior of such complex system acts across the compensation point.

Adult Cardiac Surgery-Associated Acute Kidney Injury: Joint Consensus Report.

OBJECTIVES: Acute kidney injury (AKI) is increasingly recognized as a source of poor patient outcomes after cardiac surgery. The purpose of the present report is to provide perioperative teams with expert recommendations specific to cardiac surgery-associated AKI (CSA-AKI). METHODS: This report and consensus recommendations were developed during a joint, in-person, multidisciplinary conference with the Perioperative Quality Initiative and the Enhanced Recovery After Surgery Cardiac Society. Multinational practitioners with diverse expertise in all aspects of cardiac surgical perioperative care, including clinical backgrounds in anesthesiology, surgery and nursing, met from October 20 to 22, 2021, in Sacramento, California, and used a modified Delphi process and a comprehensive review of evidence to formulate recommendations. The quality of evidence and strength of each recommendation were established using the Grading of Recommendations Assessment, Development, and Evaluation methodology. A majority vote endorsed recommendations. RESULTS: Based on available evidence and group consensus, a total of 13 recommendations were formulated (4 for the preoperative phase, 4 for the intraoperative phase, and 5 for the postoperative phase), and are reported here. CONCLUSIONS: Because there are no reliable or effective treatment options for CSA-AKI, evidence-based practices that highlight prevention and early detection are paramount. Cardiac surgery-associated AKI incidence may be mitigated and postsurgical outcomes improved by focusing additional attention on presurgical kidney health status; implementing a specific cardiopulmonary bypass bundle; using strategies to maintain intravascular euvolemia; leveraging advanced tools such as the electronic medical record, point-of-care ultrasound, and biomarker testing; and using patient-specific, goal-directed therapy to prioritize oxygen delivery and end-organ perfusion over static physiologic metrics.

Early Failure of Primary Total Knee Arthroplasty Due to Massive Osteolysis Caused by Bio-Absorbable Interference Screws.

We report an unusual case in which an unabsorbed bio-absorbable screw in the tibial tunnel of anterior cruciate ligament reconstruction (ACLR) performed 11 years ago caused massive osteolysis and subsequent failure of total knee arthroplasty (TKA). ACLR was performed using suspensory fixation on the femoral side and a bio-absorbable interference screw on the tibial side. Fragmentation of the bio-absorbable screw at the time of tibial component implantation is thought to have evoked an accelerated inflammatory response, causing osteolysis, which finally resulted in early failure of the TKA.

RAGE Inhibitors in Neurodegenerative Diseases.

Nonenzymatic reactions of reducing sugars with primary amino groups of amino acids, proteins, and nucleic acids, followed by oxidative degradations would lead to the formation of advanced glycation endproducts (AGEs). The AGEs exert multifactorial effects on cell damage leading to the onset of neurological disorders. The interaction of AGEs with the receptors for advanced glycation endproducts (RAGE) contribute to the activation of intracellular signaling and the expression of the pro-inflammatory transcription factors and various inflammatory cytokines. This inflammatory signaling cascade is associated with various neurological diseases, including Alzheimer's disease (AD), secondary effects of traumatic brain injury (TBI), amyotrophic lateral sclerosis (ALS), and diabetic neuropathy, and other AGE-related diseases, including diabetes and atherosclerosis. Furthermore, the imbalance of gut microbiota and intestinal inflammation are also associated with endothelial dysfunction, disrupted blood-brain barrier (BBB) and thereby the onset and progression of AD and other neurological diseases. AGEs and RAGE play an important role in altering the gut microbiota composition and thereby increase the gut permeability and affect the modulation of the immune-related cytokines. The inhibition of the AGE-RAGE interactions, through small molecule-based therapeutics, prevents the inflammatory cascade of events associated with AGE-RAGE interactions, and thereby attenuates the disease progression. Some of the RAGE antagonists, such as Azeliragon, are currently in clinical development for treating neurological diseases, including AD, although currently there have been no FDA-approved therapeutics based on the RAGE antagonists. This review outlines the AGE-RAGE interactions as a leading cause of the onset of neurological diseases and the current efforts on developing therapeutics for neurological diseases based on the RAGE antagonists.

Robotic infraclavicular approach for minimally invasive neck dissection in head-neck cancers.

Background: In the recent years, there has been a rapid increase in the use of robot assisted neck dissection (RAND) as an alternative method for conventional neck dissection. Several recent reports have emphasized upon the feasibility and effectiveness of this technique. However, substantial technical and technological innovation is still essential in spite of the availability of multiple approaches for RAND. Materials and Methods: The present study describes a novel technique, i.e., Robotic Infraclavicular Approach for Minimally Invasive Neck Dissection (RIA MIND) used in head and neck cancers with the help of Intuitive da Vinci Xi Surgical System. Results: After RIA MIND procedure, the patient was discharged on the third post operative day. Also, the total wound size was less than 3.5 cm which enhanced the patient recovery time and required minimal post operative care. The patient was further reviewed 10 days after the procedure for the removal of sutures. Conclusion: RIA MIND technique was effective and safe for performing neck dissection for oral, head and neck cancers. However, additional detailed studies will be required for establishing this technique.

A novel and efficient one-pot strategy for the synthesis of 1,2,4-triazoles: access to synthesis of penipanoid A and its analogues.

We developed a novel one-pot strategy for synthesizing biologically important 1,2,4-triazole motifs from easily accessible 4-hydroxy phenylacetic acid, formamidine hydrochloride and hydrazine derivatives under mild conditions. This strategy enabled us to synthesize the natural penipanoid A and its analogues in one step.

Experimental and Computational Investigation upon Combustion Characteristics of Liquid Fuel in a Novel Combustor with Hybrid Swirl and Recirculation Bowl.

In the present study, a novel hybrid swirl combustor is designed to reduce the size and complexity of a conventional gas turbine combustor. In this combustor, a dual-swirl pattern is adopted by providing the central vane swirler (45° vane angle) and circumferential tangential injection scheme to achieve higher recirculation of heat and combustion products inside the combustor. Numerical and experimental studies are carried out to understand the flow patterns and combustion characteristics in this high mass-heat interacting environment. Initially, computational studies were carried out to find the optimum geometry for greater recirculation and interaction among the reacting species inside the combustor. Liquid fuel (kerosene) is sprayed into the combustor for two thermal inputs of 25 and 50 kW. Three cases were studied to analyze the effect of bowl recirculation and tangential air inputs in addition to the swirlers. The hybrid swirl, formed by the counter-flow pattern, helps in achieving low and uniform temperature throughout and assists in flame anchoring. The tangential air flow provides a push to the combustion products from the downstream to the central recirculation zone of the combustor. The combined effect of central and tangential swirlers helps in attaining a more distributed combustion. The CO and NO emissions reduced with the use of hybrid swirl.

Declining Incidence of Postoperative Neonatal Brain Injury in Congenital Heart Disease.

BACKGROUND: Brain injury is common in neonates with complex neonatal congenital heart disease (CHD) and affects neurodevelopmental outcomes. OBJECTIVES: Given advancements in perioperative care, we sought to determine if the rate of preoperative and postoperative brain injury detected by using brain magnetic resonance imaging (MRI) and associated clinical risk factors have changed over time in complex CHD. METHODS: A total of 270 term newborns with complex CHD were prospectively enrolled for preoperative and postoperative brain MRIs between 2001 and 2021 with a total of 466 MRI scans. Brain injuries in the form of white matter injury (WMI) or focal stroke and clinical factors were compared across 4 epochs of 5-year intervals with logistic regression. RESULTS: Rates of preoperative WMI and stroke did not change over time. After adjusting for timing of the postoperative MRI, site, and cardiac group, the odds of newly acquired postoperative WMI were significantly lower in Epoch 4 compared with Epoch 1 (OR: 0.29; 95% CI: 0.09-1.00; P = 0.05). The adjusted probability of postoperative WMI declined significantly by 18.7% from Epoch 1 (24%) to Epoch 4 (6%). Among clinical risk factors, lowest systolic, mean, and diastolic blood pressures in the first 24 hours after surgery were significantly higher in the most recent epoch. CONCLUSIONS: The prevalence of postoperative WMI has declined, whereas preoperative WMI rates remain constant. More robust postoperative blood pressures may explain these findings by minimizing periods of ischemia and supporting cerebral perfusion. These results suggest potential modifiable clinical targets in the postoperative time period to minimize the burden of WMI.