The hypervirulent Group B Streptococcus HvgA adhesin promotes central nervous system invasion through transcellular crossing of the choroid plexus.

BACKGROUND: Group B Streptococcus (GBS) is the leading cause of neonatal meningitis responsible for a substantial cause of death and disability worldwide. The vast majority of GBS neonatal meningitis cases are due to the CC17 hypervirulent clone. However, the cellular and molecular pathways involved in brain invasion by GBS CC17 isolates remain largely elusive. Here, we studied the specific interaction of the CC17 clone with the choroid plexus, the main component of the blood-cerebrospinal fluid (CSF) barrier. METHODS: The interaction of GBS CC17 or non-CC17 strains with choroid plexus cells was studied using an in vivo mouse model of meningitis and in vitro models of primary and transformed rodent choroid plexus epithelial cells (CPEC and Z310). In vivo interaction of GBS with the choroid plexus was assessed by microscopy. Bacterial invasion and cell barrier penetration were examined in vitro, as well as chemokines and cytokines in response to infection. RESULTS: GBS CC17 was found associated with the choroid plexus of the lateral, 3rd and 4th ventricles. Infection of choroid plexus epithelial cells revealed an efficient internalization of the bacteria into the cells with GBS CC17 displaying a greater ability to invade these cells than a non-CC17 strain. Internalization of the GBS CC17 strain involved the CC17-specific HvgA adhesin and occurred via a clathrin-dependent mechanism leading to transcellular transcytosis across the choroid plexus epithelial monolayer. CPEC infection resulted in the secretion of several chemokines, including CCL2, CCL3, CCL20, CX3CL1, and the matrix metalloproteinase MMP3, as well as immune cell infiltration. CONCLUSION: Our findings reveal a GBS strain-specific ability to infect the blood-CSF barrier, which appears to be an important site of bacterial entry and an active site of immune cell trafficking in response to infection.

Patterns of Cerebrovascular Accidents in Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is an autoimmune disease that primarily affects young adults. It is characterized by the development of antiphospholipid antibodies (APL) and a wide range of macro- and microvascular symptoms. The primary causes of morbidity and mortality in APS are cardiovascular events. Subclinical atherosclerosis and cardiovascular events are associated with high-risk APL profiles, particularly with the presence of lupus anticoagulant and triple APL positivity (all three APL subtypes), co-existence with systemic lupus erythematosus (SLE), and traditional risk factors like smoking, hypertension, obesity, and hyperlipemia. We present a case series involving three female stroke patients with APS. This series highlights the importance of immunological profiles in all stroke patients.

From Household Chemical to Medical Emergency: Stroke Induced by Hydrogen Peroxide Ingestion.

Hydrogen peroxide (H2O2) ingestion can lead to severe systemic complications, including neurological sequelae such as acute embolic stroke. We present a case of a 49-year-old male who accidentally ingested approximately 50-60 mL of 50% w/w hydrogen peroxide, resulting in encephalopathy, upper motor neuron quadriparesis, and pulmonary artery thrombosis. The patient's altered sensorium progressed to a stupor, accompanied by acute respiratory distress and abdominal gaseous distension. Imaging revealed multifocal hypodensities in the brain and saddle thrombus in the pulmonary arteries. Hyperbaric oxygen therapy initiated after diagnosis led to a significant improvement in motor power and resolution of abdominal distension during hospitalization. The pathophysiology involves gas embolization and oxidative stress-induced thrombosis. Management includes stabilizing the patient, dilution therapy, and supportive care, with hyperbaric oxygen therapy for severe cases. Prevention strategies focus on education and proper storage. Continuous monitoring and follow-up are essential for managing hydrogen peroxide poisoning. This case underscores the need for awareness and prompt intervention in hydrogen peroxide toxicity.

Beta-2 Glycoprotein I IgA Isotype: An Important Consideration in Secondary Hypertension.

Anti-beta-2 glycoprotein I antibodies are an important player in hypercoagulable states, including those that lead to antiphospholipid syndrome. Traditionally, assays have only detected IgG and IgM isotypes of this antibody. However, newer assays also detect the IgA isotype. The problem lies in the largely unknown significance of this IgA isotype. This paper describes a middle-aged male who presented with hypertensive emergency and was later found to have IgA anti-beta-2 glycoprotein I antibodies. He was treated with multiple anti-hypertensives, aspirin, and statin therapy. In addition to the case, we discuss the implications of this IgA isotype and how it may relate to antiphospholipid syndrome, despite not currently being included in the laboratory diagnostic criteria for the disease.

The Great Masquerader: Recurrent Ischemic Strokes Secondary to Meningovascular Syphilis in a Man With Cardiovascular Stroke Risk Factors.

A male in his 60s with stroke risk factors presented with confusion and word-finding difficulties. He was diagnosed with acute ischemic stroke in the right basal ganglia. He was started on secondary stroke prevention measures including dual antiplatelet therapy and a high-dose statin. A highly reactive rapid plasma reagin (RPR) was performed as part of the workup and found to be positive. Follow-up fluorescent treponemal antibody absorption (TPA) test was also positive, confirming a diagnosis of syphilis. He was discharged home with a scheduled course of antibiotic treatment for tertiary syphilis but returned due to a new episode of transient facial paralysis. Further workup and physical exam findings revealed the patient had neurosyphilis. He was started on the appropriate antibiotic therapy, which significantly improved his confusion and prevented new episodes of stroke.

Cognitive dysfunction, depression and serum level of brain-derived neurotrophic factor (BDNF) in Egyptian patients with rheumatoid arthritis.

AIM OF THE WORK: To evaluate serum brain-derived neurotrophic factor (BDNF) in Egyptian patients with rheumatoid arthritis (RA) and its relation with cognitive dysfunction. PATIENTS AND METHODS: The study was carried out on 60 RA patients; 30 were active (group A) and 30 were non active (group B); and 30 controls (group C). RA disease activity was assessed via DAS28 tool, cognitive function via The Montreal Cognitive Assessment and depression via the PHQ depression scale. Serum BDNF levels were measured. RESULTS: The mean age in group A was 37.8 (±9.37) years with 83.3% females, in group B was 39.97 (±8.04) years with 86.7% females and in group C was 33.17 (±3.6) years with 93.3% females. Abnormal cognitive functions test was detected in 66.7% of group A, 66.7% of group B, and in 23.3% of group C. There was a statistically significant difference in BDNF serum level between both groups of patients (1.58±0.9ng/ml for group A, 1.81±1.17ng/ml for group B) compared with the control group (3.01±1.25ng/ml, p<0.001). There was no statistically significant difference between BDNF and both disease duration and cognitive function, also no statistically significant difference regarding cognitive function, depression, and BNDF levels in patients with and without fibromyalgia. At a cut-off value of <2ng/ml, BDNF detected RA patients with cognitive dysfunction with a sensitivity of 80%, specificity of 96.67%. CONCLUSION: BDNF can be a potential biomarker of cognitive dysfunction in RA patients.

Utility of the cerebro-placental-uterine ratio in predicting composite adverse perinatal outcomes in pregestational diabetes: A prospective cohort study.

PURPOSE: To examine the cerebro-placental-uterine ratio (CPUR) in pregnant women with pregestational diabetes and determine its role in predicting adverse prenatal outcomes. METHODS: This prospective, cohort study conducted at a tertiary hospital included 65 patients with pregestational diabetes (25 with type1 diabetes, 40 with type2 diabetes) and 130 low-risk patients in the control group. The cerebroplacental (CPR) ratio and the CPUR were calculated. Composite adverse perinatal outcome (CAPO) is defined as the presence of any of the following: (1) Neonatal intensive care unit (NICU) admission, (2) Apgar at 5 min <7, and (3) umbilical cord arterial pH <7.10. The relationship of CPR and CPUR with CAPO was investigated. RESULTS: CPR and CPUR were significantly lower in the pregestational diabetes group than in the control group. The NICU admission was higher in the case group. In receiver operating characteristic analyses, the optimal cut-off value of CPUR was 1.46 (AUC = 0.72, p = 0.003, 80% sensitivity, and 69% specificity) to predict CAPO and the optimal cut-off value of CPUR was 1.50 for NICU admission (AUC = 0.70, p = 0.013, 77% sensitivity, and 66% specificity). CONCLUSION: Low CPUR values were found to be associated with adverse perinatal outcomes in women with pregestational diabetes. With the increasing number of studies, CPUR is expected to be utilized more widely in routine obstetric practice.

Cognitive dysfunction, depression and serum level of brain-derived neurotrophic factor (BDNF) in Egyptian patients with rheumatoid arthritis / Disfunción cognitiva, depresión y nivel sérico del factor neurotrófico derivado del cerebro (BDNF) en pacientes egipcios con artritis reumatoide

Aim of the work: To evaluate serum brain-derived neurotrophic factor (BDNF) in Egyptian patients with rheumatoid arthritis (RA) and its relation with cognitive dysfunction. Patients and methods: The study was carried out on 60 RA patients; 30 were active (group A) and 30 were non active (group B); and 30 controls (group C). RA disease activity was assessed via DAS28 tool, cognitive function via The Montreal Cognitive Assessment and depression via the PHQ depression scale. Serum BDNF levels were measured. Results: The mean age in group A was 37.8 (±9.37) years with 83.3% females, in group B was 39.97 (±8.04) years with 86.7% females and in group C was 33.17 (±3.6) years with 93.3% females. Abnormal cognitive functions test was detected in 66.7% of group A, 66.7% of group B, and in 23.3% of group C. There was a statistically significant difference in BDNF serum level between both groups of patients (1.58±0.9ng/ml for group A, 1.81±1.17ng/ml for group B) compared with the control group (3.01±1.25ng/ml, p<0.001). There was no statistically significant difference between BDNF and both disease duration and cognitive function, also no statistically significant difference regarding cognitive function, depression, and BNDF levels in patients with and without fibromyalgia. At a cut-off value of <2ng/ml, BDNF detected RA patients with cognitive dysfunction with a sensitivity of 80%, specificity of 96.67%. Conclusion: BDNF can be a potential biomarker of cognitive dysfunction in RA patients.(AU)

Objetivo: Evaluar el factor neurotrófico derivado del cerebro (BDNF) en suero en pacientes egipcios con artritis reumatoide (AR) y su relación con la disfunción cognitiva. Pacientes y métodos: El estudio se realizó en 60 pacientes con AR; 30 eran activos (grupo A) y 30 no activos (grupo B); y 30 controles (grupo C). La actividad de la enfermedad de AR se evaluó a través de la herramienta DAS28, la función cognitiva a través de la Evaluación Cognitiva de Montreal y la depresión a través de la escala de depresión PHQ. Se midieron los niveles de BDNF en suero. Resultados: La edad media en el grupo A fue de 37,8 (±9,37) años con 83,3% de mujeres, en el grupo B de 39,97 (±8,04) años con 86,7% de mujeres y en el grupo C de 33,17 (±3,6) años con 93,3% de mujeres. La prueba de funciones cognitivas anormales se detectó en 66,7% del grupo A, 66,7% del grupo B y 23,3% del grupo C. Hubo una diferencia estadísticamente significativa en el nivel sérico de BDNF entre ambos grupos de pacientes (1,58±0,9ng/mL para grupo A, 1,81±1,17ng/mL para el grupo B) en comparación con el grupo control (3,01±1,25ng/mL, p<0,001). No hubo diferencias estadísticamente significativas entre el BDNF y la duración de la enfermedad y la función cognitiva, tampoco hubo diferencias estadísticamente significativas con respecto a la función cognitiva, la depresión y los niveles de BDNF en pacientes con y sin fibromialgia. A un valor de corte de <2ng/mL, BDNF detectó pacientes con AR con disfunción cognitiva con una sensibilidad de 80% y una especificidad de 96,67%. Conclusión: BDNF puede ser un biomarcador potencial de disfunción cognitiva en pacientes con AR.(AU)

Temperature management in acute brain injury: A narrative review.

Temperature management has been used in patients with acute brain injury resulting from different conditions, such as post-cardiac arrest hypoxic-ischaemic insult, acute ischaemic stroke, and severe traumatic brain injury. However, current evidence offers inconsistent and often contradictory results regarding the clinical benefit of this therapeutic strategy on mortality and functional outcomes. Current guidelines have focused mainly on active prevention and treatment of fever, while therapeutic hypothermia (TH) has fallen into disuse, although doubts persist as to its effectiveness according to the method of application and appropriate patient selection. This narrative review presents the most relevant clinical evidence on the effects of TH in patients with acute neurological damage, and the pathophysiological concepts supporting its use.

Understanding the role of AMPA receptors in autism: insights from circuit and synapse dysfunction.

Autism spectrum disorders represent a diverse etiological spectrum that converge on a syndrome characterized by discrepant deficits in developmental domains often highlighted by concerns in socialization, sensory integration, and autonomic functioning. Importantly, the incidence and prevalence of autism spectrum disorders have seen sharp increases since the syndrome was first described in the 1940s. The wide etiological spectrum and rising number of individuals being diagnosed with the condition lend urgency to capturing a more nuanced understanding of the pathogenic mechanisms underlying the autism spectrum disorders. The current review seeks to understand how the disruption of AMPA receptor (AMPAr)-mediated neurotransmission in the cerebro-cerebellar circuit, particularly in genetic autism related to SHANK3 or SYNGAP1 protein dysfunction function and autism associated with in utero exposure to the anti-seizure medications valproic acid and topiramate, may contribute to the disease presentation. Initially, a discussion contextualizing AMPAr signaling in the cerebro-cerebellar circuitry and microstructural circuit considerations is offered. Subsequently, a detailed review of the literature implicating mutations or deletions of SHANK3 and SYNGAP1 in disrupted AMPAr signaling reveals how bidirectional pathogenic modulation of this key circuit may contribute to autism. Finally, how pharmacological exposure may interact with this pathway, via increased risk of autism diagnosis with valproic acid and topiramate exposure and potential treatment of autism using AMPAr modulator perampanel, is discussed. Through the lens of the review, we will offer speculation on how neuromodulation may be used as a rational adjunct to therapy. Together, the present review seeks to synthesize the disparate considerations of circuit understanding, genetic etiology, and pharmacological modulation to understand the mechanistic interaction of this important and complex disorder.

Cerebral Haemodynamic Changes in Type 2 Diabetes Mellitus Following a Three-Month Yoga Intervention: A Randomized Controlled Trial.

Background and purpose Cerebral haemodynamics and cognitive performance may be adversely affected in type 2 diabetes mellitus (T2DM). Previous studies reported reduced cerebral blood flow (CBF) and altered cerebrovascular reactivity (CVR) in T2DM. Yoga, an ancient holistic health approach, is known to be beneficial for T2DM. We hypothesized that yoga practice may alter CBF and the flow resistance in the middle cerebral artery (MCA) and improve cognition in T2DM. Our secondary objective was to explore the relationship between changes in cerebral haemodynamics and cognition in T2DM. Materials and methods Participants were randomly allotted into the yoga and control groups based on the eligibility criteria. One hour of yoga intervention specific to type 2 diabetes was provided to the yoga group for three months, while conventional treatment was provided to the control group. A transcranial Doppler was used to evaluate longitudinal changes in cerebral haemodynamics in MCA. A Corsi block tapping test was used to assess visio-spatial working memory. Results There were 75 participants recruited, of whom 38 participated in yoga and 37 participated in a control group. Both intention to treat and per protocol analysis showed significant results. At day 90, intention-to-treat analysis showed significant changes in CBF velocities (mean difference -10.85%, 95% CI (-13.26, -6.15), p<0.001), cerebral vasodilatory reserve (mean difference -0.23%, 95% CI (-0.43, -0.03), p=0.02) and cognition (mean difference -12.13%, 95% CI (-17.48, -6.78), p≤0.001). There was no between-group effect. Also, the correlation between the CBF and cognition did not show any significant results. Conclusion The three-month yoga intervention was associated with an improvement in cerebral hemodynamics. The study also revealed an improvement in visio-spatial working memory among patients with T2DM. The study did not show any correlation between the improvement in cerebral haemodynamics and working memory. We recommend larger and longer studies on yoga intervention for T2DM patients to evaluate whether such benefits are sustained and improve their quality of life.

Factores asociados a la función cognitiva de los adultos mayores indonesios que viven en residencias de ancianos / Associated factors to the cognitive function among indonesian older adult living in nursing home

Objetivo: Muchos adultos mayores en Indonesia deciden vivir en residencias de ancianos. Vivir en un hogar de ancianos ha sido asociado al deterioro cognitivo en adultos mayores, afectando a la capacidad para llevar a cabo actividades de la vida diaria. Este estudio tuvo como objetivo determinar la asociación entre características demográficas y clínicas y la función cognitiva en adultos mayores que viven una residencia de ancianos en Indonesia. Método: Este estudio utilizó un diseño transversal, participando 60 adultos mayores de una residencia de ancianos. La función cognitiva se evaluó utilizando el instrumento Montreal Cognitive Assessment. Se evaluaron características demográficas y clínicas como edad, nivel educativo, tiempo de permanencia en la residencia, así como niveles séricos de factor neurotrófico derivado del cerebro y dopamina. Se utilizó la prueba de Spearman-rank para el análisis de datos. Resultados: La función cognitiva de atención se correlacionó positivamente con la edad (r=0,314, p=0,015) y el tiempo de permanencia en la residencia (r=0,268, p=0,038), y negativamente con los niveles séricos de dopamina (r=–0,425, p=0,001). La función cognitiva de denominación se relacionó positivamente con la edad (r=0,263, p=0,042). Conclusiones: Edad, tiempo de internado y niveles de dopamina se asociaron a la función cognitiva en adultos mayores que viven en una residencia de ancianos. El adulto mayor debe ser evaluado en cuanto a factores asociados a la función cognitiva, para realizar los programas de mejora cognitiva en residencias de ancianos.(UA)

Objective: Many older adults in Indonesia decide to live in nursing homes. Living in a nursing home has been associated with the incidence of cognitive decline in older adult that leads to decreasing ability to perform daily activity. This study aimed to determine the association between demographic and clinical characteristics with cognitive functions in older adults living in nursing homes in Indonesia. Methods: This study used a cross-sectional design and involved 60 older adults in a nursing home. Cognitive function was evaluated using the Montreal Cognitive Assessment instrument. Demographic and clinical characteristics such as age, education level, length of stay in the nursing home, as well as serum levels of brain-derived neurotrophic factor and dopamine were studied. Spearman-Rank test was used for data analysis. Results: Cognitive function of attention had a positive correlation with age (r=0.314, p=0.015), length of stay in the nursing home (r=0.268, p=0.038), and negative correlation with dopamine serum levels (r=-0.425, p=0.001). The cognitive function of naming has a positive correlation with age (r=0.263, p=0.042). Conclusions: Age, length of stay, and dopamine levels associated with cognitive function in older adult living in nursing homes. The older adult should be assessed in term of factors associated with cognitive function to make the cognitive improvement programs in nursing homes.(AU)

DNA repair-related heritable photosensitivity syndromes: Mutation landscape in a multiethnic cohort of 17 multigenerational families with high degree of consanguinity.

Inherited photosensitivity syndromes are a heterogeneous group of genetic skin disorders with tremendous phenotypic variability, characterized by photosensitivity and defective DNA repair, especially nucleotide excision repair. A cohort of 17 Iranian families with heritable photosensitivity syndromes was evaluated to identify their genetic defect. The patients' DNA was analyzed with either whole-exome sequencing or RNA sequencing (RNA-Seq). The interpretations of the genomic results were guided by genome-wide homozygosity mapping. Haplotype analysis was performed for cases with recurrent mutations. RNA-Seq, in addition to mutation detection, was also utilized to confirm the pathogenicity. Thirteen sequence variants, including six previously unreported pathogenic variants, were disclosed in 17 Iranian families, with XPC as the most common mutated gene in 10 families (59%). In one patient, RNA-Seq, as a first-tier diagnostic approach, revealed a non-canonical homozygous germline variant: XPC:c.413-9 T > A. The Sashimi plot showed skipping of exon 4 with dramatic XPC down-expression. Haplotype analysis of XPC:c.2251-1 G>C and XPC:1243 C>T in four families showed common haplotypes of 1.7 Mb and 2.6 Mb, respectively, denoting a founder effect. Lastly, two extremely rare cases were presented in this report: a homozygous UVSSA:c .1990 C>T was disclosed, and ERCC2-related cerebro-oculo-facio-skeletal (COFS) syndrome with an early childhood death. A direct comparison of our data with the results of previously reported cohorts demonstrates the international mutation landscape of DNA repair-related photosensitivity disorders, although population-specific differences were observed.

Neuronal pentraxin 2 correlates with neurodegeneration but not cognition in idiopathic normal pressure hydrocephalus (iNPH).

AIM OF THE STUDY: Neuronal pentraxin-2 (NPTX2) is a synaptic protein responsible for modulating plasticity at excitatory synapses. While the role of NPTX2 as a novel synaptic biomarker in cognitive disorders has been elucidated recently, its role in idiopathic normal pressure hydrocephalus (iNPH) is not yet understood. CLINICAL RATIONALE FOR STUDY: To determine if NPTX2 predicts cognition in patients with iNPH, and whether it could serve as a predictive marker for shunt outcomes. MATERIAL AND METHODS: 354 iNPH patients underwent cerebrospinal fluid drainage (CSF) as part of the tap test or extended lumbar drainage. Demographic and clinical measures including age, Evans Index (EI), Montreal Cognitive Assessment (MoCA) score, Functional Activities Questionnaire (FAQ) score, and baseline and post-shunt surgery Timed Up and Go (TUG) test scores were ascertained. CSF NPTX2 concentrations were measured using an ELISA. CSF ß-amyloid 1-40 (Aß1-40), ß-amyloid 1-42 (Aß1-42), and phosphorylated tau-181 (pTau-181) were measured by chemiluminescent assays. Spearman's correlation was used to determine the correlation between CSF NPTX2 concentrations and age, EI, MoCA and FAQ, TUG, Aß1-40/Aß1-42 ratio, and pTau-181 concentrations. Logistic regression was used to determine if CSF NPTX2 values were a predictor of short-term improvement post-CSF drainage or long-term improvement post-shunt surgery. RESULTS: There were 225 males and 129 females with a mean age of 77.7 years (± 7.06). Average CSF NPTX2 level in all iNPH patients was 559.97 pg/mL (± 432.87). CSF NPTX2 level in those selected for shunt surgery was 505.61 pg/mL (± 322.38). NPTX2 showed modest correlations with pTau-181 (r = 0.44, p < 0.001) with a trend for Aß42/Aß40 ratio (r = -0.1, p = 0.053). NPTX2 concentrations did not correlate with age (r = -0.012, p = 0.83) or MoCA score (r = 0.001, p = 0.87), but correlated negatively with FAQ (r = -0.15, p = 0.019). CONCLUSIONS: While CSF NPTX2 values correlate with neurodegeneration, they do not correlate with cognitive or functional measures in iNPH. CSF NPTX2 cannot serve as a predictor of either short-term or long-term improvement after CSF drainage. CLINICAL IMPLICATIONS: These results suggest that synaptic degeneration is not a core feature of iNPH pathophysiology.

Navigating Complexity: A Case Report of Concurrent Central Cord Syndrome and Stroke in an Elderly Gentleman.

Central cord syndrome (CCS) predominantly manifests in elderly individuals with pre-existing cervical spondylosis resulting from hyperextension mechanisms. However, it is not exclusive to the older population and can occur in younger individuals following traumatic cervical spine injuries or, less frequently, due to nontraumatic causes. The impact of this syndrome is more pronounced in the upper extremities, where motor function experiences greater impairment compared to sensory function. CCS presents itself along a spectrum of severity. At one end, individuals may exhibit weakness confined to the hands and forearms while preserving sensory function. At the other extreme, complete quadriparesis may occur, albeit with sacral sparing being the sole indication of an incomplete spinal cord injury. This spectrum underscores the varied and nuanced clinical presentations within CCS. Moreover, concurrent acute stroke presentations can mimic CCS symptoms, further complicating the diagnostic process. The challenge lies in differentiating these two distinct conditions, particularly in an elderly population with overlapping risk factors. This diagnostic challenge adds a layer of complexity to clinical decision-making and underscores the importance of comprehensive evaluations in patients presenting with neurological symptoms. This case report presents a 73-year-old gentleman with a history of a recent stroke and motor vehicle accidents, highlighting the diagnostic challenges and multidisciplinary management required for concurrent CCS and stroke mimicry. This report is unique, as there are no existing case report publications detailing concurrent CCS and stroke. It emphasizes the necessity for a comprehensive diagnostic approach and coordinated care in managing such intricate cases.

Associated factors to the cognitive function among indonesian older adult living in nursing home.

OBJECTIVE: Many older adults in Indonesia decide to live in nursing homes. Living in a nursing home has been associated with the incidence of cognitive decline in older adult that leads to decreasing ability to perform daily activity. This study aimed to determine the association between demographic and clinical characteristics with cognitive functions in older adults living in nursing homes in Indonesia. METHODS: This study used a cross-sectional design and involved 60 older adults in a nursing home. Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA) instrument. Demographic and clinical characteristics such as age, education level, length of stay in the nursing home, as well as serum levels of brain-derived neurotrophic factor (BDNF) and dopamine were studied. Spearman-Rank test was used for data analysis. RESULTS: Cognitive function of attention had a positive correlation with age (r=0.314, P=.015), length of stay in the nursing home (r=0.268, P=.038), and negative correlation with dopamine serum levels (r=-0.425, P=.001). The cognitive function of naming has a positive correlation with age (r=0.263, P=.042). CONCLUSIONS: Age, length of stay, and dopamine levels associated with cognitive function in older adult living in nursing homes. The older adult should be assessed in term of factors associated with cognitive function to make the cognitive improvement programs in nursing homes.

Importance of the Vegetable and Fruit Intake for Health Based on the Relationship between Urinary Potassium Excretion and Cerebro-cardiovascular-renal Events or All-cause Mortality.

Since it is widely accepted that there is a positive correlation between the salt intake and hypertension or cerebro-cardiovascular-renal events, salt intake restriction is currently widely recommended, especially in patients with hypertension. However, salt intake restriction does not always have beneficial effects. Indeed, an excessively low salt intake has been reported to be harmful to health. While a reasonable vegetable and fruit intake reportedly decreases blood pressure, whether or not vegetable and fruit intake truly leads to reductions in cerebro-cardiovascular-renal events or all-cause mortality remains unclear. We reviewed the importance of vegetable and fruit intake for health, focusing on the relationship between urinary potassium excretion, a marker of vegetable and fruit intake, and cerebro-cardiovascular-renal events or all-cause mortality. In conclusion, vegetable and fruit intake may be essential for reducing cerebro-cardiovascular-renal events and all-cause mortality.

Defects of the spliceosomal gene SNRPB affect osteo- and chondro-differentiation.

Although gene splicing occurs throughout the body, the phenotype of spliceosomal defects is largely limited to specific tissues. Cerebro-costo-mandibular syndrome (CCMS) is one such spliceosomal disease, which presents as congenital skeletal dysmorphism and is caused by mutations of SNRPB gene encoding Small Nuclear Ribonucleoprotein Polypeptides B/B' (SmB/B'). This study employed in vitro cell cultures to monitor osteo- and chondro-differentiation and examined the role of SmB/B' in the differentiation process. We found that low levels of SmB/B' by knockdown or mutations of SNRPB led to suppressed osteodifferentiation in Saos-2 osteoprogenitor-like cells, which was accompanied by affected splicing of Dlx5. On the other hand, low SmB/B' led to promoted chondrogenesis in HEPM mesenchymal stem cells. Consistent with other reports, osteogenesis was promoted by the Wnt/ß-catenin pathway activator and suppressed by Wnt and BMP blockers, whereas chondrogenesis was promoted by Wnt inhibitors. Suppressed osteogenic markers by SNRPB knockdown were partly rescued by Wnt/ß-catenin pathway activation. Reporter analysis revealed that suppression of SNRPB results in attenuated Wnt pathway and/or enhanced BMP pathway activities. SNRPB knockdown altered splicing of TCF7L2 which impacts Wnt/ß-catenin pathway activities. This work helps unravel the mechanism underlying CCMS whereby reduced expression of spliceosomal proteins causes skeletal phenotypes.

Consideration of the thoracic phenotype of cerebro-costo-mandibular syndrome.

Cerebro-costo-mandibular syndrome (CCMS) is a congenital condition with skeletal and orofacial abnormalities that often results in respiratory distress in neonates. The three main phenotypes in the thorax are posterior rib gaps, abnormal costovertebral articulation and absent ribs. Although the condition can be lethal, accurate diagnosis, and subsequent management help improve the survival rate. Mutations in the causative gene SNRPB have been identified, however, the mechanism whereby the skeletal phenotypes affect respiratory function is not well-studied due to the multiple skeletal phenotypes, lack of anatomy-based studies into the condition and rarity of CCMS cases. This review aims to clarify the extent to which the three main skeletal phenotypes in the thorax contribute to respiratory distress in neonates with CCMS. Despite the posterior rib gaps being unique to this condition and visually striking on radiographic images, anatomical consideration, and meta-analyses suggested that they might not be the significant factor in causing respiratory distress in neonates. Rather, the increase in chest wall compliance due to the rib gaps and the decrease in compliance at the costovertebral complex was considered to result in an equilibrium, minimizing the impact of these abnormalities. The absence of floating ribs is likely insignificant as seen in the general population; however, a further absence of ribs or vestigial rib formation is associated with respiratory distress and increased lethality. Based on these, we propose to evaluate the number of absent or vestigial ribs as a priority indicator to develop a personalized treatment plan based on the phenotypes exhibited.