Roles of serum uric acid on the association between arsenic exposure and incident metabolic syndrome in an older Chinese population.

Growing evidences showed that heavy metals exposure may be associated with metabolic diseases. Nevertheless, the mechanism underlying arsenic (As) exposure and metabolic syndrome (MetS) risk has not been fully elucidated. So we aimed to prospectively investigate the role of serum uric acid (SUA) on the association between blood As exposure and incident MetS. A sample of 1045 older participants in a community in China was analyzed. We determined As at baseline and SUA concentration at follow-up in the Yiwu Elderly Cohort. MetS events were defined according to the criteria of the International Diabetes Federation (IDF). Generalized linear model with log-binominal regression model was applied to estimate the association of As with incident MetS. To investigate the role of SUA in the association between As and MetS, a mediation analysis was conducted. In the fully adjusted log-binominal model, per interquartile range increment of As, the risk of MetS increased 1.25-fold. Compared with the lowest quartile of As, the adjusted relative risk (RR) of MetS in the highest quartile was 1.42 (95% confidence interval, CI: 1.03, 2.00). Additionally, blood As was positively associated with SUA, while SUA had significant association with MetS risk. Further mediation analysis demonstrated that the association of As and MetS risk was mediated by SUA, with the proportion of 15.7%. Our study found higher As was remarkably associated with the elevated risk of MetS in the Chinese older adults population. Mediation analysis indicated that SUA might be a mediator in the association between As exposure and MetS.

Síndrome de Hedinger secundario a Tumor neuroendocrino bronquial. Presentación de un caso

El síndrome carcinoide es un síndrome paraneoplásico que se presenta en tumores neuroendocrinos. Aunque es una entidad infrecuente suele ser la primera manifestación de la enfermedad. La baja incidencia junto a la presentación inespecífica genera retrasos diagnósticos importantes. Se presenta el caso de una paciente con síntomas digestivos y tuforadas que posteriormente agrega insuficiencia cardíaca, logrando mediante un ecocardiograma típico y marcadores analíticos el diagnóstico de síndrome carcinoide. Posteriormente se evidencia que su origen en un tumor neuroendocrino bronquial. Conocer las características de este síndrome es fundamental para mantener una alta sospecha clínica en pacientes con síntomas sugestivos logrando un diagnóstico precoz y adecuado.

Carcinoid syndrome is a paraneoplastic syndrome that occurs in neuroendocrine tumors. Although It is an uncommon entity, it is usually the first manifestation of the disease. The low incidence besides the non-specific presentation generates important diagnostic delays. We present the case of a patient presenting digestive symptoms and flushing that subsequently adds heart failure, achieving though a typical echocardiogram and analytical markers the diagnosis of carcinoid syndrome. Later it is discovered its origin in a bronchial neuroendocrine tumor. Knowing the characteristics of this syndrome is essential to maintain a high clinical suspicion in patients with suggestive symptoms, in order to achieve an early and adequate diagnosis.

El síndrome carcinoide é um síndrome paraneoplásico que ocorre em tumores neuroendócrinos. Embora seja uma entidade rara, geralmente é a primeira manifestação da doença. A baixa incidência, juntamente com a apresentação inespecífica, resulta em atrasos importantes no diagnóstico. Apresentamos o caso de uma paciente com sintomas digestivos e ruborização cutânea, que posteriormente desenvolve insuficiência cardíaca. O diagnóstico de síndrome carcinoide foi estabelecido por meio de um ecocardiograma característico e marcadores analíticos. Posteriormente, foi evidenciada a origem em um tumor neuroendócrino brônquico. Conhecer as características deste síndrome é fundamental para manter uma alta suspeita clínica em pacientes com sintomas sugestivos, permitindo um diagnóstico precoce e adequado.

Dielectric characterisation of human adrenal glands and adrenal tumours for the development of microwave ablation technologies for hypertension treatment.

Adrenal gland-induced hypertension results from underlying adrenal gland disorders including Conn's syndrome, Cushing's syndrome, and Pheochromocytoma. These adrenal disorders are a risk for cardiovascular and renal morbidity and mortality. Clinically, treatment for adrenal gland-induced hypertension involves a pharmaceutical or surgical approach. The former presents very significant side effects whereas the latter can be ineffective in cases where the adrenal disorder reoccurs in the remaining contralateral adrenal gland. Due to the limitations of existing treatment methods, minimally invasive treatment options like microwave ablation (MWA) have received significant attention for treating adrenal gland disorders. A precise comprehension of the dielectric properties of human adrenal glands will help to tailor energy delivery for MWA therapy, thus offering the potential to optimise treatments and minimise damage to surrounding tissues. This study reports the ex vivo dielectric properties of human adrenal glands, including the cortex, medulla, capsule, and tumours, based on the data obtained from four patients (diagnosed with Conn's syndrome, Cushing's syndrome, and Pheochromocytoma) who underwent unilateral adrenalectomy at the University Hospital Galway, Ireland. An open-ended coaxial probe measurement technique was used to measure the dielectric properties for a frequency range of 0.5-8.5 GHz. The dielectric properties were fitted using a two-pole Debye model, and a weighted least squares method was employed to optimise the model parameters. Moreover, the dielectric properties of adrenal tissues and tumours were compared across frequencies commonly used in MWA, including 915 MHz, 2.45 GHz, and 5.8 GHz. The study found that the dielectric properties of adrenal tumours were influenced by the presence of lipid-rich adenomas, and the dielectric properties of Cushing's syndrome tumour were lowest in comparison to the tumours in patients diagnosed with Conn's syndrome and Pheochromocytoma. Furthermore, a notable difference was observed in the dielectric properties of the medulla and cortex among patients diagnosed with Conn's syndrome, Cushing's syndrome, and Pheochromocytoma. These findings have significant implications for the diagnosis and treatment of adrenal tumours, including the optimisation of MWA therapy for precise ablation of adrenal masses.

IARS2 mutations lead to Leigh syndrome with a combined oxidative phosphorylation deficiency.

BACKGROUND: Leigh syndrome (LS) is a common mitochondrial disease caused by mutations in both mitochondrial and nuclear genes. Isoleucyl-tRNA synthetase 2 (IARS2) encodes mitochondrial isoleucine-tRNA synthetase, and variants in IARS2 have been reported to cause LS. However, the pathogenic mechanism of IARS2 variants is still unclear. METHODS: Two unrelated patients, a 4-year-old boy and a 5-year-old boy diagnosed with LS, were recruited, and detailed clinical data were collected. The DNA of the patients and their parents was isolated from the peripheral blood for the identification of pathogenic variants using next-generation sequencing and Sanger sequencing. The ClustalW program, allele frequency analysis databases (gnomAD and ExAc), and pathogenicity prediction databases (Clinvar, Mutation Taster and PolyPhen2) were used to predict the conservation and pathogenicity of the variants. The gene expression level, oxygen consumption rate (OCR), respiratory chain complex activity, cellular adenosine triphosphate (ATP) production, mitochondrial membrane potential (MMP) and mitochondrial reactive oxygen species (ROS) levels were measured in patient-derived lymphocytes and IARS2-knockdown HEK293T cells to evaluate the pathogenicity of the variants. RESULTS: We reported 2 unrelated Chinese patients manifested with LS who carried biallelic IARS2 variants (c.1_390del and c.2450G > A from a 4-year-old boy, and c.2090G > A and c.2122G > A from a 5-year-old boy), of which c.1_390del and c.2090G > A were novel. Functional studies revealed that the patient-derived lymphocytes carrying c.1_390del and c.2450G > A variants exhibited impaired mitochondrial function due to severe mitochondrial complexes I and III deficiencies, which was also found in IARS2-knockdown HEK293T cells. The compensatory experiments in vitro cell models confirmed the pathogenicity of IARS2 variants since re-expression of wild-type IARS2 rather than mutant IARS2 could rescue complexes I and III deficiency, oxygen consumption, and cellular ATP content in IARS2 knockdown cells. CONCLUSION: Our results not only expand the gene mutation spectrum of LS, but also reveal for the first time the pathogenic mechanism of IARS2 variants due to a combined deficiency of mitochondrial complexes I and III, which is helpful for the clinical diagnosis of IARS2 mutation-related diseases.

Association of ratios of visceral fat area/subcutaneous fat area and muscle area/standard body weight at T12 CT level with the prognosis of acute respiratory distress syndrome.

Background: It is well-known that body composition metrics can influence the prognosis of various diseases. This study investigated how body composition metrics predict acute respiratory distress syndrome (ARDS) prognosis, focusing on the ratio of visceral fat area (VFA) to subcutaneous fat area (SFA), SFA to standard body weight (SBW), VFA to SBW, and muscle area (MA) to SBW. These metrics were assessed at the level of the twelfth thoracic vertebra (T12 computed tomography [CT] level) to determine their correlation with the outcomes of ARDS. The goal was to utilize these findings to refine and personalize treatment strategies for ARDS. Methods: Patients with ARDS admitted to the intensive care units (ICUs) of three hospitals from January 2016 to July 2023 were enrolled in this study. Within 24 hours of ARDS onset, we obtained chest CT scans to measure subcutaneous fat, visceral fat, and muscle area at the T12 level. We then compared these ratios between survivors and non-survivors. Logistic regression was employed to identify prognostic risk factors. Receiver operating characteristic (ROC) curve analysis was utilized to determine the optimal cutoff for predictors of in-hospital mortality. Based on this cutoff, patients with ARDS were stratified. To reduce confounding factors, 1:1 propensity score matching (PSM) was applied. We conducted analyses of clinical feature and prognostic differences pre- and post-PSM between the stratified groups. Additionally, Kaplan-Meier survival curves were generated to compare the survival outcomes of these groups. Results: Of 258 patients with ARDS, 150 survived and 108 did not. Non-survivors had a higher VFA/SFA ratio (P <0.001) and lower SFA/SBW and MA/SBW ratios (both P <0.001). Key risk factors were high VFA/SFA ratio (OR=2.081; P=0.008), age, acute physiology and chronic health evaluation (APACHE) II score, and lactate levels, while MA/SBW and albumin were protective. Patients with a VFA/SFA ratio ≥0.73 were associated with increased mortality, while those with an MA/SBW ratio >1.55 cm²/kg had lower mortality, both pre- and post-PSM (P=0.001 and P <0.001, respectively). Among 170 patients with pulmonary-origin ARDS, 87 survived and 83 did not. The non-survivor group showed a higher VFA/SFA ratio (P <0.001) and lower SFA/SBW and MA/SBW (P=0.003, P <0.001, respectively). Similar risk and protective factors were observed in this cohort. For VFA/SFA, a value above the cutoff of 1.01 predicted higher mortality, while an MA/SBW value below the cutoff of 1.48 cm²/kg was associated with increased mortality (both P <0.001 pre-/post-PSM). Conclusions: Among all patients with ARDS, the VFA to SFA ratio, MA to SBW ratio at the T12 level, age, APACHE II score, and lactate levels emerged as independent risk factors for mortality.

Paraneoplastic dermatomyositis and Hodgkin's lymphoma in a 14-year-old girl: a case report and literature review.

Background: Juvenile dermatomyositis (JDM) is a rare autoimmune myopathy whose main clinical manifestations include a characteristic rash, symmetrical proximal muscle weakness, and elevated muscle enzymes. While approximately one-third of adult patients with dermatomyositis (DM) develop malignancies, typically within a year of diagnosis, this phenomenon is not commonly observed in patients with JDM. In this study, we present a rare case of both JDM and Hodgkin's lymphoma (HL) diagnosed in an adolescent female patient. Case description: A 14-year-old girl with proximal muscle weakness and myalgia for 8 weeks was admitted to the hospital and ultimately received a diagnosis of DM. A thorough physical examination revealed enlarged lymph nodes on both sides of the cervical, and a lymph node biopsy was performed to diagnose HL. After she underwent radiotherapy and chemotherapy, her symptoms of both HL and DM were alleviated. Conclusion: The phenomenon of JDM as a paraneoplastic syndrome associated with HL is very rare. Thus, routine cancer screening for DM in adolescents is currently not recommended. The diagnosis of JDM requires a detailed physical examination, and further tumor screening is necessary for patients with unusual physical findings, such as atypical rashes, enlarged lymph nodes, and enlargement of the spleen and/or liver. Even if no malignancy is detected when JDM is diagnosed, long-term follow-up is necessary.

[Research Progress in the Pathogenesis of Polycystic Ovary Syndrome]. / å¤šå›Šåµå·¢ç»¼åˆå¾å‘ç— æœºåˆ¶ç ”ç©¶è¿›å±•.

Polycystic ovary syndrome (PCOS) is one of the most common gynecological endocrine disorders. Most pathophysiological changes of PCOS begin in the peripubertal phase, and these pathophysiological changes will continuously affect women's health in the later stages of their lives. The pathogenic mechanisms of PCOS remain unclear, involving key aspects such as the regulation of hypothalamic-pituitary function, ovarian cellular functions, androgen levels, and insulin resistance. Herein, we summarized the latest findings on the pathogenesis of PCOS from the perspectives of the genetic background, intrauterine development, neuroendocrine function, inflammatory factors, gut microbiome, and environmental factors. This review will help provide new ideas for a deeper understanding of the disease, as well as its clinical diagnosis and treatment.

[Mechanism of Extracellular Histone-Induced Endothelial Dysfunction Leading to Sepsis-Induced Acute Respiratory Distress Syndrome]. / å¾ªçŽ¯ç»„è›‹ç™½è¯±å¯¼å† çš®åŠŸèƒ½éšœç¢è‡´è„“æ¯’ç—‡æ€¥æ€§å‘¼å¸çª˜è¿«ç»¼åˆå¾çš„æœºåˆ¶ç ”ç©¶.

Objective: Sepsis-induced acute respiratory distress syndrome (ARDS) is an independent risk factor for mortality in critically ill septic patients. However, effective therapeutic targets are still unavailable due to the lack of understanding of its unclear pathogenesis. With increasing understanding in the roles of circulating histones and endothelial dysfunction in sepsis, we aimed to investigate the mechanism of histone-induced endothelial dysfunction leading to sepsis-induced ARDS and to provide experimental support for histone-targeted treatment of sepsis-induced ARDS. Methods: First of all, in vitro experiments were conducted. Human umbilical vein endothelial cells (HUVEC) were stimulated with gradient concentrations of histones to explore for the optimal stimulation concentration in vitro. Then, HUVEC were exposed to histones at an optimal concentration with or without resatorvid (TAK-242), a selective inhibitor of Toll-like receptor 4 (TLR4), for 24 hours for modeling. The cells were divided into 4 groups: 1) the blank control group, 2) the blank control+TAK-242 intervention group, 3) the histone stimulation group, and 4) the histone+TAK-242 intervention group. HUVEC apoptosis was determined by flow cytometry, VE-Cadherin expression in endothelial cells was determined by Western blot, and the integrity of adhesion connections between endothelial cells was evaluated with confocal fluorescence microscopic images. Male C57BL/6 mice aged 6-8 weeks and weighing 22-25 g were used for the in vivo experiment. Then, the mice were given cecal ligation and puncture (CLP) as well as histone injection at 50 mg/kg via the tail vein for sepsis modeling. The experimental animals were divided into 6 groups: 1) the blank control group, 2) the blank control+TAK-242 intervention group, 3) the CLP model group, 4) the CLP+TAK-242 intervention group, 5) the histone model group, and 6) the histone+TAK-242 intervention group. After 24 h, the concentrations of serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were determined using ELISA kits. Western blot was performed to determine the expression of vascular endothelial (VE)-cadherin in the lung tissue. Hematoxylin and eosin (HE) staining was performed to observe the pathological changes in the lung tissue of the mice. Evans Blue was injected via the tail vein 30 min before the mice were sacrificed. Lung tissue was collected after the mice were sacrificed. Then, the concentrations of Evans blue dye per unit mass in the lung tissue from mice of different groups were evaluated, the rates of pulmonary endothelial leakage were calculated, and the integrity of the pulmonary endothelial barrier was evaluated. Results: The results of the in vitro experiment showed that, compared with those of the control group, HUVEC apoptosis was significantly increased under histone stimulation (P<0.05), the expression of VE-cadherin was decreased (P<0.05), and the integrity of adherens junctions between endothelial cells was damaged. TAK-242 can significantly inhibit histone-induced HUVEC apoptosis and VE-cadherin expression reduction and maintain the integrity of adherens junctions between endothelial cells. According to the findings from the in vivo experiments, in mice with CLP-induced and histone-induced sepsis, TAK-242 effectively alleviated the increase in serum concentrations of IL-6 and TNF-α, reduced the downregulation of VE-cadherin expression in the lung tissue (P<0.05), decreased endothelial permeability of the lung vessels, and improved pathological injury in the lung tissue. Conclusion: By binding to TLR-4, histone decreases VE-cadherin expression on the surface of vascular endothelial cells, disrupts the integrity of intercellular adherens junctions, and triggers pathological damage to lung tissue. Using TLR-4 inhibitors can prevent sepsis-induced ARDS in histone-induced sepsis.

A case report on atypical presentations of Dyke-Davidoff-Masson syndrome.

Dyke-Davidoff-Masson Syndrome (DDMS) is a rare neurological disease with an unknown incidence. The manifestations of DDMS are variable, while typical symptoms are seizures, hemiparesis, and mental retardation. Here, we present a case involving a 19-year-old male patient who presents with headaches, mood changes, and a history of seizures during childhood. Based on the neuroimages, a diagnosis of DDMS was established. The application of sertraline hydrochloride as a therapeutic intervention has alleviated the symptoms. This case report illustrates the importance of understanding the clinical features of DDMS based on imaging.

Disseminated Mycobacterium tilburgii infection in a person with AIDS: A case report.

Background: Mycobacterium tilburgii is a nonculturable, nontuberculous mycobacterium that occasionally causes serious infections in individuals with immune deficiencies. Owing to its nonculturable nature, its antimicrobial susceptibility has not been assessed, and the optimal treatment regimen is unclear. Herein, we report a case of disseminated M. tilburgii infection in a person with AIDS, identified using metagenomics next-generation sequencing (mNGS) and polymerase chain reaction (PCR). Case presentation: A 33-year-old man presented with a 3-month history of abdominal pain, lymphadenopathy, intermittent night hot flashes, night sweats, and weight loss. No pathogen was detected during initial routine investigations. M. tilburgii was subsequently identified in a left cervical lymph node sample using mNGS. Furthermore, M. tilburgii infection was detected in a bone marrow sample based on PCR of 16S rRNA and hsp65 gene sequencing. The person was treated with a combination of moxifloxacin, clarithromycin, ethambutol, rifabutin, and amikacin. The laboratory results improved, and the patient's symptoms resolved. Conclusion: M. tilburgii may be missed in diagnostic tests because it cannot be grown using routine culture techniques. Early diagnosis and timely and effective treatment are critical in patients with M. tilburgii infection; therefore, molecular techniques are recommended for patients with suspected M. tilburgii infection.

TMAO is involved in kidney-yang deficiency syndrome diarrhea by mediating the "gut-kidney axis".

Background: Trimethylamine-N-oxide (TMAO) is a harmful metabolite dependent on the intestinal microbiota and excreted through the kidneys. According to numerous investigations, rich circulation concentrations of TMAO have been linked to kidney and gastrointestinal disorders. Through the "gut-kidney axis" mediated by TMAO, this research attempted to clarify the microbiological causes of kidney-yang deficiency syndrome diarrhea. Methods: Adenine and Folium Sennae were used to create a mouse model of kidney-yang deficiency syndrome diarrhea. 16S rRNA sequencing was used to identify the traits of the intestinal mucosal microbiota. ELISA was used to assess TMAO, transforming growth factor-ß1 (TGF-ß1), interleukin-1ß (IL-1ß), and NOD-like receptor thermal protein domain associated protein 3 (NLRP3). Kidney tissue fibrosis was evaluated using Masson's trichrome staining, and immunohistochemical labeling was used to investigate the protein expression of occludin and Zonula Occludens-1(ZO-1) in small intestine tissue. Microbial activity was determined by using fluorescein diacetate (FDA) hydrolysis spectrophotometry. Results: TMAO showed a positive correlation with NLRP3, IL-1ß and TGF-ß1, all of which exhibited substantial increases (P < 0.05). Significant renal fibrosis and decreased ZO-1 and occludin expression in small intestine tissues were detected in the model group. The sequencing results revealed alterations in both α and ß diversities of small intestinal mucosal microbiota. Elevated TMAO concentrations were potentially associated with increasing Firmicutes/Bacteroidota (F/B) ratios, Streptococcus, Pseudomonas and unclassified Clostridia UCG 014, but with decreasing Rothia and RB41 abundances. Conclusion: This study establishes a link between intestinal microbiota dysbiosis and elevated TMAO concentrations. TMAO can activate inflammatory responses and cytokines, contributing to kidney-yang deficiency syndrome diarrhea via the "gut-kidney axis". Moreover, TMAO may coincide with disruptions in the intestinal barrier and renal fibrosis. Dysfunction of the "gut-kidney axis" further elevates TMAO levels, perpetuating a vicious cycle.

Congenital rubella syndrome, a case series.

Rubella, or German measles, is a vaccine-preventable disease. Rubella infection is usually mild; however, infection in pregnancy is associated with severe outcomes for the baby, including pregnancy loss or a combination of developmental defects called congenital rubella syndrome. Within the last ten-year period, two cases of congenital rubella syndrome in Saskatchewan were reported to the provincial ministry and the Public Health Agency of Canada of the newborns of mothers who had recently arrived from Sub-Saharan Africa. Both infants had multiple health complications at birth consistent with congenital rubella and tested positive for the rubella virus. The article discusses the challenges encountered by the healthcare system in diagnosing, investigating, monitoring and managing cases of congenital rubella syndrome to prevent further sporadic transmission. The article emphasizes the need to provide additional support for cases and their households, especially new Canadians with less support to comply with public health advice and the importance of routine immunization to eliminate rubella globally.

Tumor necrosis factor inhibitors enhance corticosteroid therapy for Stevens-Johnson syndrome and toxic epidermal necrolysis linked to immune checkpoint inhibitors: a prospective study.

Introduction: Immune-related epidermal necrolysis (irEN), including Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN), represents a potentially lethal reaction to immune checkpoint inhibitors. An optimal treatment strategy remains undefined. This study evaluates the effectiveness and safety of combination therapy with corticosteroids and tumor necrosis factor inhibitors (TNFi) in treating irEN patients. Methods: In this single-center, prospective, observational study, patients with irEN received either corticosteroid monotherapy or a combination therapy of corticosteroids and TNFi (etanercept for SJS, infliximab for TEN). The primary endpoint was re-epithelization time, with secondary endpoints including corticosteroid exposure, major adverse event incidence, acute mortality rates, and biomarkers indicating disease activity and prognosis. The study was registered at the Chinese Clinical Trial Registry (ChiCTR2100051052). Results: Thirty-two patients were enrolled (21 SJS, 11 TEN); 14 received combination therapy and 18 received corticosteroid monotherapy. IrEN typically occurred after 1 cycle of ICI administration, with a median latency of 16 days. Despite higher SCORTEN scores in the combination group (3 vs. 2, p = 0.008), these patients experienced faster re-epithelization (14 vs. 21 days; p < 0.001), shorter corticosteroid treatment duration (22 vs. 32 days; p = 0.005), and lower prednisone cumulative dose (1177 mg vs. 1594 mg; p = 0.073). Major adverse event rates were similar between groups. Three deaths occurred due to lung infection or disseminated intravascular coagulation, with mortality rates for both groups lower than predicted. Potential risk factors for increased mortality included continuous reduction in lymphocyte subset counts (CD4+ T cells, CD8+ T cells, natural killer cells) and consistent rises in inflammatory markers (serum ferritin, interleukin-6, TNF-α). Re-epithelization time negatively correlated with body mass index and positively correlated with epidermal detachment area and serum levels of interleukin-6 and TNF-α. Conclusions: Corticosteroids combined with TNFi markedly promote re-epithelization, reduce corticosteroid use, and decrease acute mortality in irEN patients without increasing major adverse events, offering a superior alternative to corticosteroid monotherapy. Inflammatory markers and lymphocyte subsets are valuable for assessing disease activity and prognosis.

Advancing the early detection of canine cognitive dysfunction syndrome with machine learning-enhanced blood-based biomarkers.

Up to half of the senior dogs suffer from canine cognitive dysfunction syndrome (CCDS), the diagnosis method relies on subjective questionnaires such as canine cognitive dysfunction rating (CCDR) scores. Therefore, the necessity of objective diagnosis is emerging. Here, we developed blood-based biomarkers for CCDS early detection. Blood samples from dogs with CCDR scores above 25 were analyzed, and the biomarkers retinol-binding protein 4 (RBP4), C-X-C-motif chemokine ligand 10 (CXCL10), and NADPH oxidase 4 (NOX4) were validated against neurodegenerative models. Lower biomarker levels were correlated with higher CCDR scores, indicating cognitive decline. Machine-learning analysis revealed the highest predictive accuracy when analyzing the combination of RBP4 and NOX4 using the support vector machine algorithm and confirmed potential diagnostic biomarkers. These results suggest that blood-based biomarkers can notably improve CCDS early detection and treatment, with implications for neurodegenerative disease management in both animals and humans.

Coffin-Siris Syndrome and SMARCB1 Mutation Presenting With Schwannomatosis: A Case Report and Literature Review.

Coffin-Siris syndrome (CSS) is a rare genetic condition associated with mutations in genes responsible for the modulation of gene expression and chromatin remodeling. Patients with CSS commonly present with congenital anomalies, intellectual disabilities, and developmental delays. We describe a case of a 28-year-old woman with a confirmed diagnosis of CSS and SMARCB1 mutation who presents with multiple schwannomas and an intra-abdominal neurofibroma. The patient underwent embolization and resection of an enlarging, symptomatic schwannoma of her left medial upper arm. In detailing the patient's presentation, this case report underscores the association between SMARCB1 mutations, CSS, and tumorigenesis.

Malignant Hip Flexion Failure Syndrome: An Oncologic Disease Compared to Malignant Psoas Syndrome.

Malignant psoas syndrome (MPS) causes painful hip immobilization when a malignant tumor reaches the psoas muscle. However, there exists a different condition in which a malignant tumor invades the psoas muscle, leading to hip flexion failure without painful hip immobilization. This study aimed to define malignant hip flexion failure syndrome (MHFFS) as tumors located in the upper lumbar region or at the lesser trochanter of the femur, near the origin or termination of the psoas muscle, and to compare its prevalence, characteristics, and outcomes with those of classical MPS. We analyzed 291 patients who received palliative radiotherapy (RT) in the lumbar, pelvic, and lower leg regions from 2013 to 2023. The prevalence of MPS and MHFFS, pathological features, distinctive clinical presentations, treatment modalities, and treatment outcomes have been summarized. We also defined the 'Clinical sign reported by Ishikawa and Teramura (IT sign)' to describe the characteristic action of lifting the affected lower leg with both hands in MHFFS cases and assessed its clinical significance. Among the 291 patients, 6 (2.1%) had MHFFS and 11 (3.8%) had MPS. MHFFS resulted from metastatic tumors in the 11th and 12th thoracic vertebrae, as well as the 1st and 2nd lumbar vertebrae or the lesser trochanter of the femur, and it was characterized by hip and groin pain along with hip flexion dysfunction. All cases showed a positive IT sign. The response to RT varied, with symptomatic improvement observed in 50% of the patients. MPS is characterized by tumor invasion of the psoas muscle, causing severe lumbosacral nerve pain. Strong opioids were used for pain management in all patients, and epidural anesthesia was required in some patients. The median survival time of patients with MPS and MHFFS was 13.2 months. MPS required opioids more potently than MHFFS, but MHFFS responded relatively well to early RT.

Metabolic alkalosis in cystic fibrosis: from vascular volume depletion to impaired bicarbonate excretion.

Cystic fibrosis (CF) is the most common life-threatening genetic disease in the United States and among people of European descent. Despite the widespread distribution of the cystic fibrosis transmembrane conductance regulator (CFTR) along kidney tubules, specific renal phenotypes attributable to CF have not been well documented. Recent studies have demonstrated the downregulation of the apical Cl-/HCO3 - exchanger pendrin (Slc26a4) in kidney B-intercalated cells of CF mouse models. These studies have shown that kidneys of both mice and humans with CF have an impaired ability to excrete excess HCO3 -, thus developing metabolic alkalosis when subjected to excess HCO3 - intake. The purpose of this minireview is to discuss the latest advances on the role of pendrin as a molecule with dual critical roles in acid base regulation and systemic vascular volume homeostasis, specifically in CF. Given the immense prevalence of vascular volume depletion, which is primarily precipitated via enhanced chloride loss through perspiration, we suggest that the dominant presentation of metabolic alkalosis in CF is due to the impaired function of pendrin, which plays a critical role in systemic vascular volume and acid base homeostasis.

Radiological manifestations of nail-patella syndrome in a 56-year-old female: A case report.

Nail-patella syndrome (NPS) is a rare autosomal dominant pleiotropic disorder characterized by dysplasia of the nails, patellar aplasia or hypoplasia, iliac horns and dysplasia of the elbows. We present a case of a 56-year-old female presenting with bilateral knee pain, where initial radiographic findings of hypoplastic patellae prompted further investigation, revealing characteristic skeletal anomalies consistent with NPS. This case underscores the importance of recognizing radiological clues and conducting thorough clinical evaluation to diagnose rare genetic conditions such as NPS.

Validation of the follicular and ovarian thresholds by an 18-MHz ultrasound imaging in polycystic ovary syndrome: a pilot cutoff for North African patients.

Background: Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrinopathies among young women. Ultrasound evidence of polycystic ovaries is one of its crucial diagnostic criteria. Objectives: Our main objective is to study the contribution of ultrasound data in diagnosing PCOS. In addition, we aim to establish a new cutoff point for the use of ultrasound and to determine its sensitivity as well as its specificity. Design: It was a prospective study, including all patients presenting with clinical hyperandrogenism. Methods: The ultrasound examination of these patients was performed using a novel ultrasound machine (18 MHz) compared to an older ultrasound machine (2 Hz-8 MHz). Inclusion criteria encompassed adult female patients over 18 years presenting symptoms suggestive of PCOS, particularly hyperandrogenism and oligo-anovulation, meeting Rotterdam's diagnostic criteria. Prior to inclusion, assessments were conducted to eliminate other potential causes explaining hyperandrogenism or menstrual disorders in both groups. Results: We examined 92 patients diagnosed with PCOS. Menstrual disorders were the main symptoms, with amenorrhea being more frequent in the PCOS group (G1) (48.9% vs the control group (G2): 11.1%). The follicle number was significantly lower in the control group, as assessed by both ultrasound machines (p < 10-3). The accuracy of the new ultrasound device was evaluated compared to the old one using the receiver operating characteristic (ROC) curve, revealing a cutoff of 18 follicles (sensitivity of 68.1%, specificity of 100%) and an area under the curve of 0.955. We found a significant difference between the median values of the number of follicles (NF) by both ultrasound machines (18 vs 12). It was positively correlated with an index of r = 0.916. For the volume, it was distinctively higher in G1 (p < 10-3). ROC curve analysis revealed an ovarian volume cutoff of 9.25 ml with a sensitivity of 48.9% and a specificity of 100%. Both ultrasound machines were positively correlated with an index of r = 0.979 (p < 10-3). Conclusion: In conclusion, we were able to establish significant correlations between the new and the old ultrasound devices for both the NF and ovarian volume. Our study is distinctive as it represents the first on the African continent to re-evaluate the ultrasound criterion for PCOS.

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is often diagnosed using ultrasound in North African women. Current ultrasound standards may not be accurate enough for this group. This study aimed to improve PCOS diagnosis by setting new standards for measuring ovarian sizes and follicle numbers. METHODS: We reviewed a new ultrasound method. We then established new measurement thresholds specific to North African women. These new standards were tested for accuracy in diagnosing PCOS. RESULTS: Our new measurement thresholds were more accurate in diagnosing PCOS. The improved standards led to better identification of PCOS in North African women. This suggests that current ultrasound methods might need adjustments based on population-specific data. CONCLUSIONS: Using ultrasound with new measurement standards can improve PCOS diagnosis in North African women. Adjusting diagnostic criteria to specific populations may enhance overall healthcare outcomes.

Validating ultrasound criteria for PCOS in North African patients In this study, we explored patients using ultrasound to better diagnose Polycystic Ovary Syndrome (PCOS) in North African women. Ovarian follicles are small sacs in a woman's ovaries that not only release eggs but also produce important hormones like estrogen and progesterone. These hormones regulate the menstrual cycle, prepare the body for pregnancy, and influence many aspects of a woman's health and well-being. We set new standards for measuring follicles and ovaries to improve diagnosis accuracy.

Complimentary Role of [18F]FDG and [18F]NaF-PET/CT in Evaluating Synchronous Thyroid Carcinoma and Parathyroid Adenoma with Brown Tumors.

We herein present a patient initially suspected of multiple lytic skeletal metastasis of unknown primary on anatomical imaging. Metabolic imaging by [18F]-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) detected focal [18F]FDG uptake in the right thyroid nodule, mild [18F]FDG uptake in soft tissue lesion in the left inferior parathyroid region, and multiple nonavid osteolytic skeletal lesions. Fine-needle aspiration cytology of the right thyroid nodule showed papillary thyroid carcinoma (PTC). The patient had raised serum parathyroid hormone and serum calcium levels, suggesting parathyroid disease. [18F]-sodium fluoride (NaF)-PET/CT showed a metabolic superscan pattern of hyperparathyroidism with brown tumors rather than metastatic lytic skeletal lesions. Patient underwent total thyroidectomy and bilateral central compartment clearance, along with soft tissue lesion resection in the left inferior parathyroid region. Finally, histopathology confirmed PTC classical variant with no aggressive histology features (pT1N0) for thyroid nodule and parathyroid adenoma for soft tissue lesion in the left inferior parathyroid region. The findings of the [18F]FDG and [18F]NaF-PET/CT imaging were helpful for making a final diagnosis of synchronous thyroid cancer and parathyroid adenoma, which in turn guided the appropriate treatment strategy.