Mild Form Research Articles

Systematic study of ophthalmological findings in 10 patients with PEX1-mediated Zellweger spectrum disorder

ABSTRACT Purpose This cross-sectional study describes the ophthalmological and general phenotype of 10 patients from six different families with a comparatively mild form of Zellweger spectrum disorder (ZSD), a rare peroxisomal disorder. Methods Ophthalmological assessment included best-corrected visual acuity (BCVA), perimetry, microperimetry, ophthalmoscopy, fundus photography, spectral-domain optical coherence tomography (SD-OCT), and fundus autofluorescence (FAF) imaging. Medical records were reviewed for medical history and systemic manifestations of ZSD. Results Nine patients were homozygous for c.2528 G > A (p.Gly843Asp) variants in PEX1 and one patient was compound heterozygous for c.2528 G>A (p.Gly843Asp) and c.2097_2098insT (p.Ile700TyrfsTer42) in PEX1. Median age was 22.6 years (interquartile range (IQR): 15.9 – 29.9 years) at the most recent examination, with a median symptom duration of 22.1 years. Symptom onset was variable with presentations of hearing loss (n = 7) or nyctalopia/reduced visual acuity (n = 3) at a median age of 6 months (IQR: 1.9–8.3 months). BCVA (median of 0.8 logMAR; IQR: 0.6–0.9 logMAR) remained stable over 10.8 years and all patients were hyperopic. Fundus examination revealed a variable retinitis pigmentosa (RP)-like phenotype with rounded hyperpigmentations as most prominent feature in six out of nine patients. Electroretinography, visual field measurements, and microperimetry further established the RP-like phenotype. Multimodal imaging revealed significant intraretinal fluid cavities on SD-OCT and a remarkable pattern of hyperautofluorescent abnormalities on FAF in all patients. Conclusion This study highlights the ophthalmological phenotype resembling RP with moderate to severe visual impairment in patients with mild ZSD. These findings can aid ophthalmologists in diagnosing, counselling, and managing patients with mild ZSD.

P.109 Machine learning based approach to improving the prediction of neurological deterioration in mild Degenerative Cervical Myelopathy

Background: Degenerative cervical myelopathy (DCM) is the most common form of atraumatic spinal cord injury globally, yet clinical guidelines remain unclear on surgical recommendations for patients with mild forms of DCM. This is in part due to limitations in current MR imaging interpretation and complex mechanisms of neurological deterioration. Supervised machine learning (ML) models can help to identify clinical and imaging indicators of deterioration within mild DCM patients. Methods: 127 MRI scans (T2w, Diffusion Tensor Imaging, and Magnetization transfer scans) accompanied by a series of clinical tests underwent a semi-automated analysis to derive quantitative metrics. Random forest classifier, Support Vector Machine, and Logistic Regression models were trained and tested to predict 6-month neurological deterioration within patients. Results: The ML models performed, on average, better than previous studies with a balanced accuracy ranging between 70-75%. “Advanced” imaging metrics such as diffusion tensor imaging and magnetization transfer scans played an important role in improving model accuracy but only when used near the maximally compressed disc level, suggesting that limited yet targetted imaging metrics support ML model performance. Conclusions: The inclusion of specific, targeted imaging and clinical metrics support ML model performance in predicting neurological deterioration within mild DCM patients.

Timing and risk factors associated with acute kidney injury in infants with necrotizing enterocolitis.

To evaluate the prevalence, onset, risk factors, and mortality associated with acute kidney injury (AKI) in infants with necrotizing enterocolitis (NEC). Retrospective study at 2 centers in infants with NEC, with/without AKI. AKI assessed by serum creatinine and urine output. Statistical tests used included t, Mann-Whitney U, Chi-square, and Fisher Exact tests. Among 80 eligible infants with NEC, 56 (70%) had AKI. Median onset of NEC was day 15, with median AKI onset two days (IQR, -5.75 to 0) prior to NEC onset. Vasopressors were significantly more likely to be used in infants with NEC and AKI (p = 0.009). Increased mortality (p = 0.01) was noted in infants with NEC and AKI. The onset of AKI mostly precedes NEC onset, with moderate to severe AKI more prevalent than the milder form in infants with NEC. These infants are significantly more likely to be hemodynamically unstable and have increased mortality.

THE ISSUE OF INFECTIOUS DISEASE INCIDENCE AMONG MEDICAL STUDENTS

Introduction. The training of future medical professionals involves not only development of skills and professional background, but also maintaining a sufficient health status; therefore the relevance of studying an incidence of infectious pathologies in medical students is exceptionally important. The purpose of the study is to investigate, analyze, and compare incidence of some infectious diseases among medicine students. Materials and methods. We utilized various research methods including analysis of scientific sources, synthesis and comparison of studies by other researchers, surveys, observations, interviews, and statistical data on the incidence of infectious diseases in Ukraine and worldwide. Additionally, we conducted a poll among first-year students of the medical faculty at Vinnytsia National Pirogov Memorial Medical University using Google Forms to gather data on the incidence of respiratory and digestive system infections. The study revealed that approximately 65% of the surveyed students had experienced coronavirus disease, mostly in a mild form. Among acute respiratory viral infections, flu (55.3%), sore throat (31.3%), and rhinopharyngitis (21.3%) were the most common (79.1%) among medical students. About 74% of respondents reported no chronic diseases of the upper and lower respiratory tract, while the rest mentioned conditions such as allergic rhinitis (10%), chronic tonsillitis (10%), chronic pharyngitis (3.4%), and vocal cord diseases (2%). In terms of infectious pathologies of the digestive system, food poisoning of unspecified etiology (33.3%) and viral intestinal infections (11.7%) were the most prevalent. Conclusion. The relevance of the issue of infectious disease incidence among medical students necessitates further investigation and analysis to identify contributing factors, develop monitoring methods, and promote healthy lifestyles to maintain optimal health status.

Staged Bilateral MRI-Guided Focused Ultrasound Subthalamotomy for Parkinson Disease

Unilateral magnetic resonance imaging (MRI)-guided focused ultrasound subthalamotomy (FUS-STN) improves cardinal motor features among patients with asymmetrical Parkinson disease (PD). The feasibility of bilateral FUS-STN is as yet unexplored. To assess the safety and effectiveness of staged bilateral FUS-STN to treat PD. This prospective, open-label, case series study was conducted between June 18, 2019, and November 7, 2023, at HM-CINAC, Puerta del Sur University Hospital, Madrid, Spain, and included 6 patients with PD who had been treated with unilateral FUS-STN contralateral to their most affected body side and whose parkinsonism on the untreated side had progressed and was not optimally controlled with medication. Staged bilateral FUS-STN. Primary outcomes were assessed 6 months after the second treatment and included safety (incidence and severity of adverse events after second treatment) and effectiveness in terms of motor change (measured with the Movement Disorders Society Unified Parkinson's Disease Rating Scale part III [MDS-UPDRS III]) in the off-medication state (ie, after at least 12 hours of antiparkinsonian drug withdrawal) compared with baseline (ie, prior to the first side ablation). Secondary outcomes included motor change in patients in the on-medication state (ie, after usual antiparkinsonian medication intake), motor complications (measured with the MDS-UPDRS IV), daily living activities (measured with the MDS-UPDRS I-II), quality of life (measured with the 39-item Parkinson's Disease Questionnaire), change in dopaminergic treatment, patient's global impression of change (measured with the Global Impression of Change [PGI-C] scale), and long-term (24-month) follow-up. Of 45 patients previously treated with unilateral FUS-STN, 7 were lost to follow-up, and 4 were excluded due to adverse events. Of the remaining 34 patients, 6 (median age at first FUS-STN, 52.6 years [IQR, 49.0-57.3 years]; 3 women [50%]) experienced progression of parkinsonism on the untreated body side and were included. At the time of the first FUS-STN, patients' median duration of disease was 5.7 years (IQR, 4.7-7.3 years). The median time between procedures was 3.2 years (IQR, 1.9-3.5 years). After the second FUS-STN, 4 patients presented with contralateral choreic dyskinesia, which resolved by 3 months. Four patients developed speech disturbances, which gradually improved but remained in a mild form for 2 patients at 6 months; 1 patient experienced mild imbalance and dysphagia during the first week after treatment, which subsided by 3 months. No behavioral or cognitive disturbances were found on neuropsychological testing. For patients in the off-medication state, MDS-UPDRS III scores improved by 52.6% between baseline and 6 months after the second FUS-STN (from 37.5 [IQR, 34.2-40.0] to 20.5 [IQR, 8.7-24.0]; median difference, 23.0 [95% CI, 7.0-33.7]; P = .03). The second treated side improved by 64.3% (MDS-UPDRS III score, 17.0 [IQR, 16.0-19.5] prior to the second treatment vs 5.5 [IQR, 3.0-10.2]; median difference, 9.5 [95% CI, 3.2-17.7]; P = .02). After the second procedure, all self-reported PGI-C scores were positive. Findings of this pilot study suggest that staged bilateral FUS-STN was safe and effective for the treatment of PD, although mild but persistent speech-related adverse events were observed among a small number of patients.

A case of granulomatos is with polyangiitis (Wegener’s) after a patient’s suffering from a new coronavirus infection COVID-19

A case of granulomatos is with polyangiitis (Wegener’s) after a patient’s suffering from a new coronavirus infection COVID-19

Factors Associated with Length of Hospitalization in Patients with Diabetes and Mild COVID-19: Experiences from a Tertiary University Center in Serbia.

Background and Objectives: During the COVID-19 pandemic, there was an increased number of hospitalized COVID-19-positive patients suffering from type 2 diabetes mellitus (T2DM). The objective of this research study was to explore factors associated with the length of hospitalization of patients with T2DM and the mild form of COVID-19. Material and Methods: This retrospective cohort study involved all patients who tested positive for COVID-19 and those who were treated in the dedicated COVID-19 department of the University Clinical Center (UCC) in Nis between 10 September 2021 and 31 December 2021. Upon admission, patients underwent blood tests for biochemical analysis, including blood count, kidney and liver function parameters (C-reactive protein (CRP), creatinine kinase, and D-dimer), and glycemia and HbA1c assessments. Additionally, all patients underwent lung radiography. Univariate and multivariate regression analyses were employed to assess the impact of specific factors on the length of hospitalization among patients with T2DM. Results: Out of a total of 549 treated COVID-19-positive patients, 124 (21.0%) had T2DM, while 470 (79.0%) did not have diabetes. Among patients with T2DM, men were significantly younger than women (60.6 ± 16.8 vs. 64.2 ± 15.3, p < 0.01). The average hospitalization length of patients with diabetes was 20.2 ± 9.6 (5 to 54 days), and it was significantly longer than for patients without diabetes, at 15.0 ± 3.4, which ranged from 3 days to 39 (t-test ≈ 5.86, p < 0.05). According to the results of the univariate regression analysis, each year of age is associated with an increase in the length of hospital stay of 0.06 days (95% CI: 0.024 to 0.128, p = 0.004). Patients who received oxygen therapy were treated for 2.8 days longer than those who did not receive oxygen treatment (95% CI: 0.687 to 4988, p = 0.010), and each one-unit increase in CRP level was associated with a 0.02-day reduction in the length of hospitalization (95% CI: 0.004 to 0.029, p = 0.008). Based on the results of the multivariate regression analysis, each year of age is associated with an increase in the length of hospitalization by 0.07 days (95% CI: 0.022 to 0.110, p = 0.003). Patients who received oxygen therapy were treated for 3.2 days longer than those who did not receive oxygen therapy (95% CI: 0.653 to 5726, p = 0.014), and each unit increase in CRP level was associated with a 0.02-day reduction in the length of hospitalization (95% CI: 0.005 to 0.028, p = 0.004). Conclusions: Based on the presented results, COVID-19-positive patients with diabetes had, on average, longer hospitalizations than COVID-19 patients without diabetes. The hospital treatment of patients with T2DM and a milder form of COVID-19 was associated with older age, the use of oxygen therapy, and elevated CRP values. Patients who received oxygen therapy were treated approximately 3 days longer than those who did not receive this therapy.

Echocardiographic differences between the mild form of subclinical hypothyroidism and healthy subjects

Echocardiographic differences between the mild form of subclinical hypothyroidism and healthy subjects

A study to assess the health care utilization and the activities of the daily living status amongst the geriatric population residing in urban and rural field practice areas of a medical college in Tamil Nadu

Background: The prevalence of disability in the activities of daily living (ADL), could probably have a significant impact on the healthcare utilization amongst the geriatric population with disability. Methods: A cross-sectional study in the urban and rural field practice areas of a medical college in Tamil Nadu, using a sample size of 402 elderly individuals. Using the pre-tested, semi-structured questionnaire; the socio-demographic variables, healthcare utilization variables and a comprehensive Katz ADL assessment were used. Results: The overall prevalence of ADL limitation amongst the elderly was seen in 49 (12.2%) elderly individuals mostly with a score of 5 (mildest form) was found in 36 (74%) of the elderly. There was an association found between the follow-up care at health centres, frequency of visits, distance from home to health centres and the ADL limitation with a P- value less than 0.05 (C.I.-95%) using the Pearson chi-square test using SPSS v.26.0. Conclusions: The association between ADL limitation and healthcare utilization calls for initiatives at the family and community level.

Neuroinflammation generated by HIV-infected microglia promotes dysfunction and death of neurons in human brain organoids.

Despite the success of combination antiretroviral therapy (ART) for individuals living with HIV, mild forms of HIV-associated neurocognitive disorder (HAND) continue to occur. Brain microglia form the principal target for HIV infection in the brain. It remains unknown how infection of these cells leads to neuroinflammation, neuronal dysfunction, and/or death observed in HAND. Utilizing two different inducible pluripotent stem cell-derived brain organoid models (cerebral and choroid plexus [ChP] organoids) containing microglia, we investigated the pathogenic changes associated with HIV infection. Infection of microglia was associated with a sharp increase in CCL2 and CXCL10 chemokine gene expression and the activation of many type I interferon stimulated genes (MX1, ISG15, ISG20, IFI27, IFITM3 and others). Production of the proinflammatory chemokines persisted at low levels after treatment of the cell cultures with ART, consistent with the persistence of mild HAND following clinical introduction of ART. Expression of multiple members of the S100 family of inflammatory genes sharply increased following HIV infection of microglia measured by single-cell RNA-seq. However, S100 gene expression was not limited to microglia but was also detected more broadly in uninfected stromal cells, mature and immature ChP cells, neural progenitor cells and importantly in bystander neurons suggesting propagation of the inflammatory response to bystander cells. Neurotransmitter transporter expression declined in uninfected neurons, accompanied by increased expression of genes promoting cellular senescence and cell death. Together, these studies underscore how an inflammatory response generated in HIV-infected microglia is propagated to multiple uninfected bystander cells ultimately resulting in the dysfunction and death of bystander neurons.

Molecular Characteristics of Blood Serum After Covid-19 Vaccination in a Remote Period

COVID-19 is a dangerous disease with long-lasting consequences. Vaccination contributes to the accumulation of neutralizing anti-S IgG antibodies, reducing the incidence of COVID-19 and its complications. However, in some individuals, the inflammatory process can persist for an indefinite period and lead to a wide range of dysfunctions. The current task is to investigate molecular markers for their detection. The aim of this study is to examine the levels of anti-S IgG antibodies, lactate, glucose, lactate dehydrogenase, and C-reactive protein in the peripheral blood of individuals who have and have not been affected by COVID-19 after vaccination. The research subject is venous blood. Among 547 employees of the Neurosurgery Institute (481 vaccinated against COVID-19 and 66 unvaccinated individuals), levels of anti-S IgG antibodies were investigated, as well as levels of lactate, lactate dehydrogenase, glucose, and C-reactive protein. At the time of the study, among 372 individuals, 16 months had passed from the first vaccination, and 12 months had passed from the second vaccination; in 21 individuals, 12 months had passed after a single vaccination, and in 88 individuals, 16 months had passed from the first vaccination, 12 months from the second, and 6 months from the third vaccination. Methods. Quantitative determination of IgG antibodies to the S protein of the SARS-CoV-2 virus. Confirmation of COVID-19 using the RT-PCR method (Allplex 2019-nCoV kit, SeeGene, Korea). Levels of lactate, lactate dehydrogenase, glucose, and C-reactive protein were determined using reagents from BioSystems (Spain). Statistical analysis of the obtained data was performed using Jamovi software (USA) and the following criteria: χ2 ‒ Kruskal-Wallis, W ‒ Dwass-Steel-Critchlow-Fligner (DSCF), χ2 ‒ Pearson, t ‒ Student, rs ‒ Spearman, τb ‒ Kendall. A statistically significant difference was considered at p &lt; 0.05. Results. The level of anti-S IgG antibodies to the SARS-CoV-2 virus was higher in vaccinated individuals compared to unvaccinated individuals (Kruskal-Wallis χ2=14.09; p &lt; 0.001). A higher level of antibodies to the S protein of the virus was observed when using the Comirnaty vaccine compared to vaccination with Moderna, AstraZeneca, Pfizer, and CoronaVac (Dwass-Steel-Critchlow-Fligner (DSCF): W 4.26, p=0.002; W 4.62, p=0.010; W 4.84, p=0.006, respectively). Vaccination reduces the likelihood of contracting the disease by 1.84 times (Odds Ratio (OR) 1.84; 95% Confidence Interval (CI) 1.02‒3.30; χ2=4.129; p=0.043). However, no statistically significant dependence on the prevention of COVID-19 incidence based on the type of vaccines used was found (Kruskal-Wallis χ2=2.072; p=0.72). A statistically significant difference in C-reactive protein levels is observed between groups with early mild complications and early moderate-severity complications (DSCF: W=4.193, p=0.009). A statistically significant difference in LDH levels is noted between individuals without chronic diseases and those with chronic diseases at the time of the study (Kruskal-Wallis χ2=6.08, p=0.014). In individuals vaccinated against the SARS-CoV-2 virus, a positive correlation is found between the levels of C-reactive protein and lactate dehydrogenase (Kendall's τb 0.134, p &lt; 0.001). The mean levels of lactate among individuals with mild, moderate, and severe forms of COVID-19 are higher than the reference mean; similarly, the mean levels of glucose in these same groups are higher than the reference mean. A positive correlation exists between the levels of lactate and glucose among individuals vaccinated against the SARS-CoV-2 virus (Kendall's τb 0.082, p &lt; 0.01). Conclusions. Vaccination contributes to an increase in antibody levels. The level of antibodies after the third vaccination exceeded the levels after the first (Dwass-Steel-Critchlow-Fligner (DSCF): W 4.42, p=0.005) and second vaccinations (W 4.24, p=0.008). Vaccination reduces the likelihood of COVID-19 infection by 1.84 times (Odds Ratio ‒ 1.84; 95% Confidence Interval 1.02‒3.30; Pearson χ2=4.129; p=0.043). The frequency of COVID-19 incidence is not dependent on the type of vaccine used: AstraZeneca, Comirnaty, CoronaVac, Moderna, Pfizer (Kruskal-Wallis χ2=2.072; p=0.723), and the level of antibodies in the vaccinated individuals' serum. In the post-COVID-19 remote period, regardless of vaccination status, various complications are observed. However, among the vaccinated, the number of individuals without complications or with minimal complications is greater than in the unvaccinated group, while the number of individuals with early and severe complications is lower (Kruskal-Wallis χ2=6.127; p=0.047). A high level of C-reactive protein (DSCF: W=4.19, p=0.009), a tendency toward increased levels of lactate dehydrogenase (DSCF: W=3.27, p=0.054), elevated levels of lactate (2.17+1.23, t=3.34; p=0.002), and glucose (6.06+0.048, t=10.54; p &lt; 0.001) indicate that after recovering from COVID-19, regardless the type of vaccines used, in individuals with distant symptoms there are metabolic changes that are signs of a chronic inflammatory process. Individuals with chronic diseasees show an increase in the level of lactate dehydrogenase (χ2=6.08; p=0.014) and a tendency toward increased levels of C-reactive protein (χ2=3.74; p=0.053). Molecular markers of inflammation such as increased levels of lactate, glucose, C-reactive protein, and lactate dehydrogenase are informative for identifying individuals with an inflammatory process in the post-COVID-19 remote period.

Isolated REM Sleep without Atonia Is Not Equivalent to REM Sleep Behavior Disorder in Early-Stage Parkinson's Disease.

In early-stage Parkinson's disease (PD), rapid eye movement (REM) sleep behavior disorder (RBD) predicts poor cognitive and motor outcome. However, the baseline significance and disease evolution associated with isolated REM sleep without atonia (iRWA, ie, enhanced muscle tone during 8.7% of REM sleep, but no violent behavior) are not well understood. The objective is to determine whether iRWA was a mild form of RBD and progressed similarly over time. Participants with early PD (<4 years from medical diagnosis) were included from 2014 to 2021 in a longitudinal study. They underwent interviews and examinations in the motor, cognitive, autonomous, psychiatric, sensory, and sleep domains every year for 4 years along with a video polysomnography and magnetic resonance imaging examination of the locus coeruleus/subcoeruleus complex (LC/LsC) at baseline. The clinical characteristics were compared between groups with normal REM sleep, with iRWA and with RBD, at baseline and for 4 years. Among 159 PD participants, 25% had RBD, 25% had iRWA, and 50% had normal REM sleep. At baseline, the non-motor symptoms were less prevalent and the LC/LsC signal intensity was more intense in participants with iRWA than with RBD. Over 4 years, participants with normal REM sleep and with iRWA had a similar cognitive and motor trajectory, whereas participants with RBD had greater cognitive and motor decline. We demonstrated that iRWA is frequent in early PD, but is not a milder form of RBD. Both groups have distinct baseline characteristics and clinical trajectories. They should be distinguished in clinical routine and research protocols. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Familial adenomatous polyposis associated with malignancy

Background Familial adenomatous polyposis (FAP) is a rare genetic disorder that is inherited in an autosomal dominant fashion. This disease is caused by a germline mutation in the APC gene, but in 20-30% of cases the disease occurs due to de novo mutations. There are several forms of the disease from severe, which is characterized by a pronounced number of polyps throughout the gastrointestinal tract (GIT) to a mild (attenuated) form of FAP, with less than 100 colonic polyps. According to various scientific literature, the risk of malignancy of epithelial formations reaches 100%. Identified epithelial formations of the gastrointestinal tract will lie down for endoscopic or surgical treatment. FAP is also characterized by neoplasms of extraintestinal localization, which characterizes it as a multisystem syndrome. There is a high risk of developing congenital retinal pigment epithelium hypertrophy, bone osteoma, fibroma, angiofibroma of the nose, thyroid carcinoma, hepatoblastoma, brain tumor and pancreatic tumor. Congenital retinal hypertrophy is the earliest extraintestinal manifestation of FAP. Thyroid cancer in young people, as a rule, is diagnosed first and serves as the basis for a comprehensive endoscopic diagnosis of the gastrointestinal tract. We present a rare case of FAP in a 14-year-old child associated with malignant neoplasms of extraintestinal localizations.

Signatures of CD4+ T and B cells are associated with distinct stages of chronic chagasic cardiomyopathy.

Chagas disease is a neglected parasitic disease caused by Trypanosoma cruzi. While most patients are asymptomatic, around 30% develop Chronic Chagasic Cardiomyopathy (CCC). Here, we employed high-dimensional flow cytometry to analyze CD4+ T and B cell compartments in patients during the chronic phase of Chagas disease, presenting the asymptomatic and mild or moderate/severe cardiac clinical forms. Effector CD27-CD4+ T cells were expanded in both CCC groups, and only mild CCC patients showed higher frequencies of effector memory and T follicular helper (Tfh) cells than healthy donors (CTL) and asymptomatic patients. Unsupervised analysis confirmed these findings and further revealed the expansion of a specific subpopulation composed of Tfh, transitional, and central memory CD4+ T cells bearing a phenotype associated with strong activation, differentiation, and exhaustion in patients with mild but not moderate/severe CCC. In contrast, patients with mild and moderate/severe CCC had lower frequencies of CD4+ T cells expressing lower levels of activation markers, suggesting resting status, than CTL. Regarding the B cell compartment, no alterations were found in naïve CD21-, memory cells expressing IgM or IgD, marginal zone, and plasma cells in patients with Chagas disease. However, expansion of class-switched activated and atypical memory B cells was observed in all clinical forms, and more substantially in mild CCC patients. Taken together, our results showed that T. cruzi infection triggers changes in CD4+ T and B cell compartments that are more pronounced in the mild CCC clinical form, suggesting an orchestrated cellular communication during Chagas disease. Overall, these findings reinforce the heterogeneity and complexity of the immune response in patients with chronic Chagas disease and may provide new insights into disease pathology and potential markers to guide clinical decisions.

Genetic Landscape and Clinical Features of Hyperphenylalaninemia in North Ossetia-Alania: High Frequency of P281L and P211T Genetic Variants in the PAH Gene.

This study, conducted in the Republic of North Ossetia-Alania (RNOA), aimed to explore the genetic landscape of hyperphenylalaninemia (HPA) and phenylketonuria (PKU) in the Ossetian population using data from newborn screening (NBS). Through comprehensive molecular genetic analysis of 29 patients with HPA from diverse ethnic backgrounds, two major genetic variants in the PAH gene, P281L and P211T, were identified, constituting 50% of all detected pathogenic alleles in Ossetian patients. Remarkably, these variants exhibited an exceptionally high frequency in the Ossetian population, surpassing global prevalence rates. This study unveiled a notable prevalence of mild forms of HPA (78%), underscoring the importance of genetic counseling for carriers of pathogenic variants in the PAH gene. Moreover, the findings emphasized the necessity for ongoing monitoring of patients with mild forms, as they may lack significant symptoms for diagnosis, potentially impacting offspring. Overall, this research offers valuable insights into the genetic landscape of HPA and PKU in the Ossetian population.

Blood Count and Renal Functionality Assessments in the Emergency Section Disclose Morbidity and Mortality in Omicron COVID-19 Patients: A Retrospective Study.

Background: SARS-CoV-2 is the coronavirus responsible for the COVID-19 pandemic. Even though we are no longer in a pandemic situation, people are still getting infected, some of them need hospitalization and a few of them die. Methods: We conducted a retrospective study including 445 patients who accessed the Emergency Section of Policlinico Umberto I, Rome, Italy, where they had routine blood exams. In this study, we focused on the complete blood count, serum creatinine and azotemia. The data were analyzed using ANOVA, Spearman correlation and ROC analyses. They were divided into four groups based on their clinical outcomes: (1) the emergency group (patients who had mild forms and were quickly discharged); (2) the hospital ward group (patients who were admitted to the emergency section and were then hospitalized in a COVID-19 ward); (3) the intensive care unit (ICU) group (patients who required intensive assistance after the admission in the emergency section); (4) the deceased group (patients who had a fatal outcome after admission to the emergency section). Results: We found significant changes for creatinine, azotemia, hematocrit, mean corpuscular hemoglobin concentration, basophils, monocytes, red blood cell distribution width, hemoglobin, hematocrit and red blood cell numbers using ANOVA according to their clinical outcomes, particularly for the deceased group. Also, we found linear correlations of clinical outcomes with eosinophils, hemoglobin, hematocrit, mean corpuscular hemoglobin concentration, lymphocyte, neutrophil, platelet and red blood cell number and red blood cell distribution width. Conclusions: This study discloses an early association between "classical" routine blood biomarkers and the severity of clinical outcomes in Omicron patients.

Multimodal Approach to Neurocognitive Function in People Living with HIV in the cART Era: A Comprehensive Review.

Combination antiretroviral treatment (cART) has revolutionized the management of human immunodeficiency virus (HIV) and has markedly improved the disease burden and life expectancy of people living with HIV. HIV enters the central nervous system (CNS) early in the course of infection, establishes latency, and produces a pro-inflammatory milieu that may affect cognitive functions, even in the cART era. Whereas severe forms of neurocognitive impairment (NCI) such as HIV-associated dementia have declined over the last decades, milder forms have become more prevalent, are commonly multifactorial, and are associated with comorbidity burdens, mental health, cART neurotoxicity, and ageing. Since 2007, the Frascati criteria have been used to characterize and classify HIV-associated neurocognitive disorders (HAND) into three stages, namely asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), and HIV-associated dementia (HAD). These criteria are based on a comprehensive neuropsychological assessment that presupposes the availability of validated, demographically adjusted, and normative population data. Novel neuroimaging modalities and biomarkers have been proposed in order to complement NCI assessments, elucidate neuropathogenic mechanisms, and support HIV-associated NCI diagnosis, monitoring, and prognosis. By integrating neuropsychological assessments with biomarkers and neuroimaging into a holistic care approach, clinicians can enhance diagnostic accuracy, prognosis, and patient outcomes. This review interrogates the value of these modes of assessment and proposes a unified approach to NCI diagnosis.

Changes in the avids of IgG antibodies to the S protein of SARS-CoV-2 after coronavirus infection in medical workers of a temporary infections hospital

BACKGROUND: The effector capabilities of humoral immunity are determined not only by the amount of specific antibodies produced in response to an antigenic effect, but also by their qualitative characteristics, which include avidity ― the total strength of binding to the antigen, which determines the duration and effectiveness of post-infectious immunity to SARS-CoV-2.&#x0D; AIM: Is a selective study of the quantity and avidity of IgG antibodies to SARS-CoV-2 over time among medical workers of a temporary infectious diseases hospital in Kazan ― convalescents of COVID-19, during the period from July 2020 to July 2021.&#x0D; MATERIALS AND METHODS: Determination of IgG to the S antigen of SARS-CoV-2 by ELISA was carried out using the test system SARS-CoV-2-IgG quantitative-ELISA-BEST (Vector-Best, Russia) and expressed in BAU/ml (binding antibody units). Antibody avidity was determined using a 4.0 M urea solution and expressed as avidity indices. 1, 4 and 7 months after COVID-19 asymptomatic (n=34); mild severity (n=42); moderate severity (n=29); reinfected (n=34). When statistically processing the data, descriptive statistics methods and the Wilcoxon matched data test were used. Differences were considered significant at p 0.05.&#x0D; RESULTS: IgG avidity to SARS-CoV-2 depended on the severity of COVID-19. The highest rates of avidity indices were found in the group of those who had a moderate form of COVID-19. If in mild and asymptomatic forms there was a parallel decrease in avidity indices and IgG titer, then in moderate forms an increase in antibody titer was accompanied by a decrease in their avidity 4 months after the infection. 7 months after seroconversion, the IgG level decreased almost twofold, both in mild, asymptomatic and moderate forms. In the group of medical workers who had COVID-19 repeatedly, the initially low levels of avidity indices and antibody titers increased in parallel, while avidity indices after 7 months did not decrease, but remained high. Differences in avidity indices determined the subsequent formation of different trends in the development of the humoral immune response, which were mainly characterized by an uneven decrease in IgG and persistence of IgM antibodies for more than 1 month.&#x0D; CONCLUSIONS: The research results expand the understanding of the mechanisms of formation of the humoral immune response and the avidity of IgG antibodies against SARS-CoV-2 in the risk group ― medical workers. The level of humoral immunity decreases in the first six months and varies depending on the severity of COVID-19. The data obtained can be used to identify categories of increased risk of SARS-CoV-2 infection among healthcare workers, make decisions about immunorehabilitation and revaccination against COVID-19.

Hypophosphatasia Presenting as a Chronic Diffuse Pain Syndrome with Extra-Articular Calcifications.

Hypophosphatasia is a rare genetic disease characterized by abnormal alkaline phosphatase activity and deficiency of bone and teeth mineralization. Hypophosphatasia is well known in pediatrics with typical presentations in children, but mild forms can also be present in adults and are difficult to detect. We present the case of a 50-year-old woman referred for pain management, with a previous diagnosis of fibromyalgia. The association of clinical features (diffuse pain syndrome, early dental loosening, personal history of two fractures with osteoporosis, and family history of osteoporosis) with radiographic (heterotopic calcifications of the yellow and interspinous lumbar ligaments) and biological (low levels of total alkaline phosphatase) indices was suggestive of hypophosphatasia, which was confirmed by genetic analysis. We review and discuss the association between hypophosphatasia, musculoskeletal pain, and calcium pyrophosphate deposition and the importance of raising the diagnosis of adult-onset hypophosphatasia when facing these two rheumatologic entities.

Mild hyponatremia is not associated with degradation of trabecular bone microarchitecture despite bone mass loss.

Hyponatremia is associated with increased risk of osteoporosis and fractures. The impact of hyponatremia on non-invasive indices of bone quality, however, is unknown. To evaluate whether trabecular bone microarchitecture, assessed non-invasively by trabecular bone score (TBS), is altered in patients with hyponatremia. We conducted a cross-sectional analysis of the population-based 2005-2008 cycles of the National Health and Nutrition Examination Survey (NHANES), in which TBS measurement was performed. The main outcome measures were TBS values and bone mineral density (BMD) T-scores at the lumbar spine, total hip and femoral neck. A total of 4204 subjects aged 50 years or older were included (4041 normonatremic, 163 hyponatremic - 90.8% with mild hyponatremia). Univariate analyses did not show any difference in TBS between patients with and without hyponatremia (1.308 ± 0.145 vs 1.311 ± 0.141, p = 0.806). Hyponatremic subjects had lower BMD T-score at total hip (-0.70 ± 1.46 vs -0.13 ± 1.32, p < 0.001) and femoral neck (-1.11 ± 1.26 vs -0.72 ± 1.14, p = 0.004), while no difference was observed at lumbar spine (-0.27 ± 1.63 vs -0.31 ± 1.51, p = 0.772). After adjustment for relevant confounders, hyponatremia was confirmed as an independent predictor of lower BMD T-score at the total hip (β=-0.20, 95%CI:[-0.39, -0.02], p = 0.029), while the significance was lost at the femoral neck (p = 0.308). Again, no association between hyponatremia and lumbar spine BMD (p = 0.236) or TBS (p = 0.346) was observed. Hyponatremia, at least in mild forms, is not associated with a degradation of trabecular microarchitecture, assessed non-invasively by TBS. An independent association between hyponatremia and loss of bone mass is confirmed, particularly at the total hip.