Context and Perspectives for Establishing a Novel Database for Protein Quality of Human Foods, as Proposed by a Joint Food and Agriculture Organization of the United Nations/International Atomic Energy Agency Expert Technical Meeting in October 2022.

United Nations agencies have a long history of leading work on establishing global human nutrient requirements. Dietary protein contributes to metabolism and homeostasis and plays an essential role in human health for growth, maintenance, reproduction, and immune function (or immunity). Accurately defining the quantity and quality of protein provided by foods and diets required to meet human nutritional needs is essential to achieving global environmental and nutrition goals. There have been many scientific developments related to protein quality over the past decades, with the preferred method being the scoring approach that relates the capacity of protein sources to provide an adequate amount and proportion of nitrogen and indispensable amino acids (IAAs) in a bioavailable form (often referred to as digestibility). Questions surrounding the scoring approach and IAA metabolic availability have been discussed during past and recent expert consultations. Recently, an Food and Agriculture Organization of the United Nations/International Atomic Energy Agency technical meeting, held in Vienna, 10-13 October, 2022, reviewed and updated evidence and related methods on protein requirements and protein quality assessment and designed a framework for the development of a Protein Digestibility Database to aid dialog on the evaluation of protein quality and protein sufficiency in different populations. The database should be a living document and align with national food compositional databases.

Autonomic neuropathy as post-acute sequela of SARS-CoV-2 infection: a case report.

Symptoms of autonomic dysfunction, particularly those of orthostatic intolerance, continue to represent a major component of the currently recognized post-acute sequelae of SARS-CoV-2 infections. Different pathophysiologic mechanisms can be involved in the development of orthostatic intolerance including hypovolemia due to gastrointestinal dysfunction, fatigue-associated deconditioning, and hyperadrenergic state due to pandemic-related anxiety. Additionally, there has been a well-established association of a common primary autonomic disorder like postural orthostatic tachycardia syndrome, a subtype of orthostatic intolerance, with antecedent viral infections. Here we report a case of neuropathic type postural orthostatic tachycardia syndrome as a form of autonomic neuropathy that developed following COVID-19 infection.

Delayed post-hypoxic leukoencephalopathy in an adult with COVID-19.

As the novel coronavirus, SARS-CoV-2, has enveloped the world in a pandemic, it has become clear that the symptoms extend far beyond the respiratory system and have particularly caused a wide range of neurologic CNS complications, including diffuse leukoencephalopathy. Here, we describe a case of a 59-year-old male with severe COVID-19 infection who developed severe encephalopathy, which persisted well after his acute infection had subsided and had begun to improve from his respiratory dysfunction. He was found to have diffuse leukoencephalopathy with concomitant diffusion restriction on MR imaging. This case represents a delayed onset of leukoencephalopathy secondary to hypoxia in a small but growing cohort of COVID-related leukoencephalopathy due to similarities in imaging features and lack of superior alternate diagnosis. Patient's clinical improvement suggests reversibility with likely pathology being demyelination rather than infarction.

Central Nervous System Opportunistic Infections.

Opportunistic infections of the central nervous system are classically associated with immunosuppression arising from infection with human immunodeficiency virus and with various hematologic malignancies. However, over the past few years, they are increasingly associated with transplantation and various immunosuppressive treatments used to treat autoimmune diseases. They cause significant morbidity and mortality and remain a diagnostic challenge due to the absence of typical signs and symptoms of infection and mimicry by various noninfectious causes. The pathogens associated with these infections are often commonly found pathogens of low virulence in immunocompetent hosts and include various bacteria, parasites, fungi, or viruses. These infections can present as various clinical syndromes, including meningitis, encephalitis, space-occupying lesions, stroke-like presentations, or even neoplastic manifestations. Progressive multifocal leukoencephalopathy can be seen in patients with multiple sclerosis on various new immunomodulatory drugs in addition to patients with human immunodeficiency virus, transplantation, or hematologic malignancies, and is characterized by multifocal white matter lesions. Human herpesvirus-6 causes severe encephalitis in transplant recipients, known as posttransplantation acute limbic encephalitis. Neoplastic manifestations like Epstein-Barr virus-associated primary central nervous system lymphoma and posttransplantation lymphoproliferative disorders are particularly challenging to diagnose and manage. Modern diagnostic techniques, including advanced imaging techniques like magnetic resonance spectroscopy, use of polymerase chain reaction, and metagenomic sequencing, can be helpful in early recognition of pathogens. Treatment of most of these involves lowering of immunosuppression when possible and use of specific antimicrobial agents when available. Improved outcomes can be seen when early diagnosis is made.

Regulation of the chikungunya-virus-induced innate inflammatory response by protein tyrosine phosphatase non-receptor 6 in muscle cells.

Chikungunya virus (CHIKV)-induced myositis is an emerging affliction with high incidence globally. Given the essential regulatory role of protein tyrosine phosphatase non-receptor 6 (PTPN6) in virus-induced myositis, the expression of the PTPN6 and TNF-α genes in a CHIKV-infected muscle cell line was examined by quantitative PCR, and the expression of PTPN6 and STAT 3 was examined by immunoblotting. In addition, the effect of PTPN6 siRNA treatment on TNF-α gene expression was assessed. Increased higher expression of PTPN6 and TNF-α, and significant upregulation of TNF-α upon PTPN6 siRNA treatment were observed, suggesting that CHIKV has the ability to induce host PTPN6 gene expression, which may lead to a decreased pro-inflammatory immune response in the host.

Inflammasome-independent IL-1ß mediates autoinflammatory disease in Pstpip2-deficient mice.

Chronic recurrent multifocal osteomyelitis (CRMO) is a human autoinflammatory disorder that primarily affects bone. Missense mutation (L98P) of proline-serine-threonine phosphatase-interacting protein 2 (Pstpip2) in mice leads to a disease that is phenotypically similar to CRMO called chronic multifocal osteomyelitis (cmo). Here we show that deficiency of IL-1RI in cmo mice resulted in a significant reduction in the time to onset of disease as well as the degree of bone pathology. Additionally, the proinflammatory cytokine IL-1ß, but not IL-1α, played a critical role in the pathology observed in cmo mice. In contrast, disease in cmo mice was found to be independent of the nucleotide-binding domain, leucine-rich repeat-containing family, pyrin domain-containing 3 (NLRP3) inflammasome as well as caspase-1. Neutrophils, but not bone marrow-derived macrophages, from cmo mice secreted increased IL-1ß in response to ATP, silica, and Pseudomonas aeruginosa compared with neutrophils from WT mice. This aberrant neutrophil response was sensitive to inhibition by serine protease inhibitors. These results demonstrate an inflammasome-independent role for IL-1ß in disease progression of cmo and implicate neutrophils and neutrophil serine proteases in disease pathogenesis. These data provide a rationale for directly targeting IL-1RI or IL-1ß as a therapeutic strategy in CRMO.

Role of CT scan in diagnosis of renal lymphangiectasia: our single-center experience.

BACKGROUND: Renal lymphangiectasia is rarely reported benign renal disorder of lymphatic malformation. Though found incidentally; it presents with nonspecific symptoms and shows characteristic findings in radiological imaging studies. AIM: Here, we report eight patients with symptoms, laboratory and imaging findings compatible with renal lymphangiectasia. This report describes clinical and laboratory characteristics, treatment, Imaging findings and outcome of a series of patients with renal lymphangiectasia and reviews the literature. METHODS AND MATERIAL: Eight patients (mean age 45 years, male:female ratio 3:1) from 1st January 2011 to 30th June 2016; showing renal lymphangiectasia as incidental finding on CT IVP were included in the series. Imaging and laboratory findings were reviewed. Two out of eight patients (25%) underwent aspiration of collection and laboratory findings confirmed the diagnosis of renal lymphangiectasia. Four out of eight patients (50%) did not undergo aspiration of fluid and were offered conservative treatment. Two out of eight patients (25%) were donors for renal transplantation who were managed conservatively. RESULTS: Renal lymphangiectasia was diagnosed on CT IVP. In each case, where aspiration of collection fluid was offered, the laboratory diagnosis of renal lymphangiectasia was confirmed and patients were managed conservatively. However, large collection in one patient was relieved by percutaneous aspiration. CONCLUSIONS: Renal lymphangiectasia can be diagnosed with CT scan and confirmed by laboratory tests. As it may be confused with other cystic lesions of kidney; proper diagnosis and exclusion of other differentials can be effectively offered by CT scan IVP, which can avoid unnecessary invasive treatment options.

Radial artery pseudoaneurysm: A rare complication after a single arterial puncture for blood-gas analysis.

With a reported incidence of 0.048%, radial artery pseudoaneurysm (PA) is a rare but serious complication of arterial cannulation. We report a case of PA developing after a single puncture of the right radial artery for arterial blood-gas analysis diagnosed by Doppler ultrasound in young male patient. The development of PA after puncture of radial artery for continuous blood pressure monitoring and serial blood-gas analysis has been reported in the past; however, to the best of our knowledge, there is only one case report of development of PA after a single arterial puncture for blood-gas analysis is reported in the past.

A fatal case of JC virus meningitis presenting with hydrocephalus in a human immunodeficiency virus-seronegative patient.

JC virus (JCV) is the etiologic agent of progressive multifocal leukoencephalopathy, JCV granule cell neuronopathy, and JCV encephalopathy. Whether JCV can also cause meningitis has not yet been demonstrated. We report a case of aseptic meningitis resulting in symptomatic hydrocephalus in a human immunodeficiency virus-seronegative patient. Brain imaging showed enlargement of ventricles but no parenchymal lesion. She had a very high JC viral load in the cerebrospinal fluid (CSF) and developed progressive cognitive dysfunction despite ventricular drainage. She was diagnosed with pancytopenia and passed away after 5.5 months. Postmortem examination revealed productive JCV infection of leptomeningeal and choroid plexus cells, and limited parenchymal involvement. Sequencing of JCV CSF strain showed an archetype-like regulatory region. Further studies of the role of JCV in aseptic meningitis and in idiopathic hydrocephalus are warranted.

Hyperintense cortical signal on magnetic resonance imaging reflects focal leukocortical encephalitis and seizure risk in progressive multifocal leukoencephalopathy.

OBJECTIVE: To determine the frequency of hyperintense cortical signal (HCS) on T1-weighted precontrast magnetic resonance (MR) images in progressive multifocal leukoencephalopathy (PML) patients, its association with seizure risk and immune reconstitution inflammatory syndrome (IRIS), and its pathologic correlate. METHODS: We reviewed clinical data including seizure history, presence of IRIS, and MR imaging scans from PML patients evaluated at our institution between 2003 and 2012. Cases that were diagnosed either using cerebrospinal fluid JC virus (JCV) polymerase chain reaction, brain biopsy, or autopsy, and who had MR images available were included in the analysis (n=49). We characterized pathologic findings in areas of the brain that displayed HCS in 2 patients and compared them with isointense cortex in the same individuals. RESULTS: Of 49 patients, 17 (34.7%) had seizures and 30 (61.2%) had HCS adjacent to subcortical PML lesions on MR images. Of the 17 PML patients with seizures, 15 (88.2%) had HCS compared with 15 of 32 (46.9%) patients without seizures (p=0.006). HCS was associated with seizure development with a relative risk of 4.75 (95% confidence interval=1.2-18.5, p=0.006). Of the 20 patients with IRIS, 16 (80.0%) had HCS compared with 14 of 29 (49.3%) patients without IRIS (p=0.04). On histological examination, HCS areas were associated with striking JCV-associated demyelination of cortical and subcortical U fibers, significant macrophage infiltration, and a pronounced reactive gliosis in the deep cortical layers. INTERPRETATION: Seizures are a frequent complication in PML. HCS is associated with seizures and IRIS, and correlates histologically with JCV focal leukocortical encephalitis.

Neurosarcoidosis.

Sarcoidosis is an idiopathic multisystem granulomatous disorder. Neurologic manifestations in sarcoidosis are varied and making a diagnosis of neurosarcoidosis can be difficult as it mimics various other neurologic diseases. Knowledge of the syndromes associated with neurosarcoidosis can help guide the diagnostic evaluation. Definitive diagnosis requires neurologic tissue evidence of noncaseating granuloma, but in practice probable diagnosis is often made through nonneurologic biopsy and a characteristic syndrome and imaging. Treatment remains empiric, but new advances in immunologic therapy hold promise for effective and less-toxic regimens.

Transformation of Mandatory Physiotherapy Internship into A Structured Competency-Based Program: A Pilot Study.

Introduction: Health professions education is challenging in terms of developing ways to construct and assess the amalgamation of knowledge, skills and attitudes that result in novice graduates to be self-aware and confident to practice without supervision. Currently, the Physiotherapy internship program in India does not have a comprehensive competency-based framework. With the current batch of interns facing the wrath of the COVID-19 pandemic during their undergraduate training, it is a matter of concern to ensure they have developed the required competencies to handle patients independently. Methods: This is a single-group interventional study using convenience sampling. A competency framework inclusive of a comprehensive assessment and training module was developed and introduced to 27 physiotherapy interns. Every intern underwent 10 training sessions along with 8 competency assessments during 6 months of internship training. A pre-post indigenous questionnaire was used to assess their self-perceived competency along with feedback questionnaire taken at the end of the module. Results: Implementation of the competency framework revealed a statistically significant difference in the self-perceived competency (pre=84.36±10.98, post=98.55±8.74, p≤0.000). Having uniformity in assessment techniques among the faculty, being exposed to challenging cases during assessment, having training module at the beginning of the internship were some of the suggestions given by the participants. Conclusion: Competency based education offers to be an effective technique in health professional program. Incorporating a competency-based training would help the learners to understand their strengths and weaknesses that would go a long way to develop competent health-care professionals. Developing such framework in curriculum will emphasize standardization of learning outcomes, thereby resulting in quality education, further enhancing patient care, and improving the health outcomes worldwide.

UVB emitting phosphors based on singly and co-doped Ce3+, Gd3+ in Li4ZrF8 phosphors.

Preparation of Li4ZrF8:Ce3+ and Li4ZrF8:Ce3+,Gd3+ phosphors is described. Data on luminescence characteristics are presented. Hydrothermal route was employed for the synthesis. Li4ZrF8 crystallizes in orthorhombic system with Pnma space group. Li atoms are distributed over two sites, both having same coordination of six. Zr is also similarly distributed over two 8 coordinated sites. Li4ZrF8:Ce3+ emits a broad band UVB light, while the emission of Li4ZrF8:Ce3+,Gd3+ is in form of a narrow line around 311 nm attributed to 6P7/2 â†’ 8S7/2. Both phosphors exhibited a broad excitation spectrum with a peak at 253 nm. The excitation and emission properties are thus adequate enough to obtain UVB light sources using a conventional high pressure mercury vapour lamp or an ultraviolet LED.

Short Report: Clinical Features and Epilepsy Monitoring in an Adult With 22q11.2 Deletion Syndrome.

Background: 22q11.2 microdeletion is the most common microdeletion syndrome in humans with a prevalence of 13 per 100 000 live births, and it is a multisystem condition with variable phenotypic presentations. Methods: We present a case of an adult patient with Dandy-Walker syndrome who presented to our epilepsy clinic with 2 years of new-onset seizures and cognitive decline and 1 year of psychotic symptoms. Results: Patient had a non-revealing autoimmune and malignancy work-up. Continuous scalp vEEG study showed bursts of 1-2 Hz generalized fronto-centrally predominant spike or polyspike and slow wave discharges. Several myoclonic jerks were time-locked with the generalized discharges indicative of cortical myoclonus. MRI brain revealed periventricular nodular heterotopia in addition to findings suggestive of Dandy-Walker syndrome. Array-based comparative genomic hybridization demonstrated a 22q11.2 microdeletion seen in 22q11.2 deletion syndrome. Conclusion: Our case illustrates the challenges of diagnosing genetic disorders in adults especially when the initial diagnosis is dependent on a number of factors, including the patient's age, the severity of the phenotypic features, and the awareness of the physician.

The Genetic Architecture of the Human Corpus Callosum and its Subregions.

The corpus callosum (CC) is the largest set of white matter fibers connecting the two hemispheres of the brain. In humans, it is essential for coordinating sensorimotor responses, performing associative/executive functions, and representing information in multiple dimensions. Understanding which genetic variants underpin corpus callosum morphometry, and their shared influence on cortical structure and susceptibility to neuropsychiatric disorders, can provide molecular insights into the CC's role in mediating cortical development and its contribution to neuropsychiatric disease. To characterize the morphometry of the midsagittal corpus callosum, we developed a publicly available artificial intelligence based tool to extract, parcellate, and calculate its total and regional area and thickness. Using the UK Biobank (UKB) and the Adolescent Brain Cognitive Development study (ABCD), we extracted measures of midsagittal corpus callosum morphometry and performed a genome-wide association study (GWAS) meta-analysis of European participants (combined N = 46,685). We then examined evidence for generalization to the non-European participants of the UKB and ABCD cohorts (combined N = 7,040). Post-GWAS analyses implicate prenatal intracellular organization and cell growth patterns, and high heritability in regions of open chromatin, suggesting transcriptional activity regulation in early development. Results suggest programmed cell death mediated by the immune system drives the thinning of the posterior body and isthmus. Global and local genetic overlap, along with causal genetic liability, between the corpus callosum, cerebral cortex, and neuropsychiatric disorders such as attention-deficit/hyperactivity and bipolar disorders were identified. These results provide insight into variability of corpus callosum development, its genetic influence on the cerebral cortex, and biological mechanisms related to neuropsychiatric dysfunction.

Unilateral K-F ring in Wilson's disease.

Wilson's disease, also called hepatolenticular degeneration, has varied clinical manifestations and poses diagnostic challenges. Kayser-Fleischer ring, when present, is considered pathognomic of Wilson's disease. Although its presence is most commonly seen with the neuro-psychiatric form of the disease, it can also be present in hepatic form and asymptomatic patients. We report a case of unilateral Kayser-Fleischer ring in the normal, functional eye of a patient which subsequently led to the diagnosis of Wilson's disease in the patient. This case also highlights the examination of the normal appearing eye in all the patients presenting with complaints in only one eye.

Trehalose and its Diverse Biological Potential.

Trehalose, a disaccharide molecule of natural origin, is known for its diverse biological applications, like in drug development, research application, natural scaffold, stem cell preservation, food, and various other industries. This review has discussed one such diverse molecule 'trehalose aka mycose', and its diverse biological applications with respect to therapeutics. Due to its inertness and higher stability at variable temperatures, it has been developed as a preservative to store stem cells, and later, it has been found to have anticancer properties. Trehalose has recently been associated with modulating cancer cell metabolism, diverse molecular processes, neuroprotective effect, and so on. This article describes the development of trehalose as a cryoprotectant and protein stabilizer as well as a dietary component and therapeutic agent against various diseases. The article discusses its role in diseases via modulation of autophagy, various anticancer pathways, metabolism, inflammation, aging and oxidative stress, cancer metastasis and apoptosis, thus highlighting its diverse biological potential.

Safety and feasibility of pulmonary rehabilitation in patients hospitalized with post-COVID-19 fibrosis: A feasibility study.

BACKGROUND: Emerging data suggest a spectrum of pulmonary complications from COVID-19, ranging from dyspnea to difficult ventilator weaning and fibrotic lung damage. Prolonged hospitalization is known to significantly affect activity levels, impair muscle strength and reduce cardiopulmonary endurance. OBJECTIVE: To assess the feasibility and safety of inpatient pulmonary rehabilitation (PR) and to explore effects on functional capacity, physical performance, fatigue levels, and functional status. DESIGN: A prospective feasibility study. SETTING: Inpatient unit of a tertiary care hospital. PARTICIPANTS: Twenty-five hospitalized patients diagnosed with post-COVID-19 fibrosis referred for PR. INTERVENTION: Individualized PR intervention including breathing exercises, positioning, strengthening, functional training, and ambulation twice a day for 6 days a week. OUTCOME MEASURES: One-minute sit-to-stand test (STST), Short Physical Performance Battery (SPPB), Fatigue Assessment Scale (FAS), and Post-COVID-19 Functional Status Scale (PCFS). RESULTS: Twenty-five participants (19 males, 6 females) with a mean age of 54.2 ± 13.4 years were enrolled. Sixteen completed the two-point assessment after undergoing in-patient PR of mean duration 14.8 ± 9 days. PR led to a significant improvement in all functional outcomes that is, STST (from 7.1 ± 4.3 repetitions to 14.2 ± 2.1 repetitions, SPPB (from 5 ± 2.8 to 9.4 ± 1.5), FAS (from 33.3 ± 10.8 to 25.8 ± 4.7) at the p ≤ .001, and PCFS (from 3.6 ± 0.9 to 2.9 ± 1.2, p ≤ .05). CONCLUSION: Early initiation of PR for hospitalized patients with COVID-19 fibrosis was safe, well tolerated, and feasible and may improve functional status.

The Relationship between Whole-Grain Intake and Measures of Cognitive Decline, Mood, and Anxiety-A Systematic Review.

Greater intake of whole grains, compared to refined grains, is consistently associated with a reduced risk of cardiovascular disease and type 2 diabetes, both of which are associated with cognitive decline. To better understand the relationship between whole-grain intake, cognition, mood, and anxiety, a systematic review was conducted to synthesize available evidence linking whole grains to these outcomes. Four electronic databases were searched from inception to August 2021 for potentially relevant observational and interventional studies. Risk of bias (RoB) assessments were performed using the newly developed Nutrition Quality Evaluation Strengthening Tools, and the Grades of Recommendation, Assessment, Development, and Evaluation approach was used to determine the strength of evidence for each outcome. In total, 23 studies [4 randomized controlled trials (RCTs) and 19 observational studies] met the predefined eligibility criteria. Of these,12 studies included analysis of whole-grain intake and cognitive decline, 9 included mood outcomes, and 2 included both cognition and mood outcomes. The overall evidence for an association between whole-grain intake and cognition is inconclusive. With respect to mood outcomes, evidence from RCTs prospective cohort and case-control studies suggest that higher intake is linked to improved outcomes for mood and depression although the evidence is mixed for cross-sectional studies. Reporting of whole-grain intake fell short of suggested standards, and the strength of available evidence was low or very low for all outcomes. A high RoB toward studies reporting results was also noted, complicating both the interpretation of some studies and the combined evidence. Of note, few well-designed RCTs assessing the effect of whole-grain intake on measures of cognition, mood, and anxiety were identified, highlighting the need for more studies in this area. The available, although limited, evidence suggests that greater whole-grain intake is associated with better mood and anxiety-related scores and is inconclusive regarding cognitive outcomes. PROSPERO registration: CRD42021266355.

A Comprehensive Corpus Callosum Segmentation Tool for Detecting Callosal Abnormalities and Genetic Associations from Multi Contrast MRIs.

Structural alterations of the midsagittal corpus callosum (midCC) have been associated with a wide range of brain disorders. The midCC is visible on most MRI contrasts and in many acquisitions with a limited field-of-view. Here, we present an automated tool for segmenting and assessing the shape of the midCC from T1w, T2w, and FLAIR images. We train a UNet on images from multiple public datasets to obtain midCC segmentations. A quality control algorithm is also built-in, trained on the midCC shape features. We calculate intraclass correlations (ICC) and average Dice scores in a test-retest dataset to assess segmentation reliability. We test our segmentation on poor quality and partial brain scans. We highlight the biological significance of our extracted features using data from over 40,000 individuals from the UK Biobank; we classify clinically defined shape abnormalities and perform genetic analyses.