Temporal association between NRF2/HO-1 activation, endogenous BDNF up-regulation, and motor recovery in a male mouse MCAO model.

To examine the seasonal variation of invasive group A streptococcal infections (iGAS) in relation to respiratory viral circulation, with special reference to pandemic restrictions, and to assess whether increases in viral activity may explain recent increases in iGAS. We performed a time-series analysis using a multivariate negative binomial regression model, with weekly counts of respiratory virus detections as the independent variable and weekly counts of iGAS cases as the dependent variable, covering the period from January 2010 to December 2024. We found a significant association between influenza and iGAS, with increases in influenza activity followed by an increase in iGAS cases. The association was strongest at a 2-week time lag. Influenza A (incidence rate ratio 1.0050, P <0.001) and influenza B (incidence rate ratio 1.0133, P <0.001) were both independent predictors of the number of iGAS reported 2 weeks later. The proportion of iGAS cases related to influenza activity was 21.7% before and 23.4% after the pandemic. The iGAS incidence declined by 76% during the period of COVID-19 restrictions. Annual influenza epidemics appear to contribute to seasonal increases in iGAS cases. Preventive measures aimed at reducing influenza spread may have a potential to reduce iGAS incidence.

Sex- and age-specific background incidence rates for various medical events in the German population aged≥50years using a nationwide monitoring system of claims data.

Depression and cognition in adolescents: A comparison of cross-sectional and longitudinal effects.

Introduction: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome represents an uncommon yet potentially fatal clinical condition. Drug-induced hypersensitivity reaction is characterised by fever, rash, haematological abnormalities and multi-organ involvement particularly the liver. Carbamazepine is a well-known trigger. Aim: The study presents a rare but serious adverse drug reaction, carbamazepine-induced DRESS syndrome with hepatic involvement. Case Presentation: A 29-year-old male with a seizure disorder on long term carbamazepine therapy presented with high grade fever, generalized erythematous rash, abdominal pain and jaundice. Laboratory findings showed leukocytosis, eosinophilia, elevated liver enzymes and hyperbilirubinemia. Methodology: Clinical evaluation, laboratory monitoring and causality assessment using the Naranjo scale (score 7) were performed. Carbamazepine was discontinued and replaced with levetiracetam along with supportive therapy. Discussion: Temporal association, clinical features and improvement after drug withdrawal confirmed carbamazepine induced DRESS with hepatic involvement. Conclusion: The study concludes that early recognition and discontinuation of the offending drug are crucial to prevent serious complications and ensure a favourable recovery.

Accurate displacement prediction is critical for the operation and maintenance of concrete dams. Existing methods overemphasize the global pattern of displacement behavior while neglecting the temporal association in monitoring sequences. Therefore, we propose a Bayesian-augmented Gaussian process (BaGP) integrated with double clustering analysis for temporal-aware dam displacement prediction. First, a double clustering approach is employed to thoroughly explore environmental patterns and further consider temporal association in displacement sequence evolution. Specifically, a deep clustering algorithm is introduced for the first time to extract high-quality data patterns within multidimensional nonlinear environment data. Subsequently, temporal-aware similarity among displacement sequences is quantified using dynamic time warping, and an improved K -means clustering algorithm is employed to identify temporally similar displacement phases within each environment cluster, enabling cluster-wise division. A nonparametric BaGP model is developed by augmenting standard GPs through Markov chain Monte Carlo simulation, Bayesian evidence evaluation, and model selection, to comprehensively address model structural flexibility and parameter adaptability across diverse data patterns. Each cluster’s data is sequentially fed into the BaGP model, with ensemble strategies used to generate integrated, cluster-wise predictions. Validation on real-world dam monitoring datasets demonstrates that our method achieves an average R of 0.973, outperforming models that ignore temporal association. Two additional cases also confirm its generalizability, thus providing a novel tool for structural health monitoring.

Amid rising cannabis use, declining perceived harm, and policy liberalization over the past 15 years, we examined whether the association between cannabis use disorder (CUD) and past-year suicidal ideation among U.S. adults changed from 2014-2023 and varied by sex, age, and race/ethnicity. Using data from 415,861 adults in the 2014-2023 National Surveys on Drug Use and Health, we examined temporal association change between past-year suicidal ideation and CUD (≥2 of 9 harmonized DSM-5 criteria). Logistic regression models, adjusted for demographic, social, clinical, and geographic covariates, tested whether survey year moderated the CUD-suicidal ideation association overall and in strata by sex, age, and race/ethnicity. Adults with cannabis use disorder had 57% higher odds of past-year suicidal ideation than those without (OR, 1.57; 95% CI, 1.44-1.72) across years. Joint Wald tests showed no evidence that the association changed over time overall (p = 0.12) nor within strata defined by sex or age. Although the joint interaction test suggested some variation among Hispanic respondents (p = 0.01), no individual year-specific interaction terms remained statistically significant after Bonferroni correction. Adults with CUD had higher odds of suicidal ideation but, contrary to expectations, the strength of this association remained stable from 2014-2023 and did not differ significantly across sex, age, or racial/ethnic groups despite widespread legalization, increased potency, and shifting norms.

Human coronavirus NL63 (HCoV-NL63) is typically associated with mild upper-respiratory infections, but rare neurological manifestations have been reported. These presentations may closely mimic acute vascular or epileptic events in children. We describe an 8-year-old previously healthy girl who developed vomiting followed by ocular deviation, limb tremors, and brief altered consciousness. On arrival, she was afebrile and hemodynamically stable, with right gaze deviation, miosis, and suspected right hemiparesis. Brain computed tomography (CT) and angiography revealed marked left-hemispheric hypoperfusion consistent with a postictal state. A multiplex respiratory viral panel was positive for HCoV-NL63, while cerebrospinal fluid, microbiological, and toxicological studies were unremarkable. Magnetic resonance imaging (MRI) performed 48 hours later demonstrated complete normalization of perfusion. The patient recovered fully without further seizures. This case highlights a temporal association between HCoV-NL63 infection and transient postictal hemispheric hypoperfusion, underscoring the importance of integrating clinical, radiologic, and virologic data to avoid misdiagnosis of stroke in pediatric patients.

Background: Pemphigus diseases are rare autoimmune blistering disorders mediated by pathogenic autoantibodies directed mainly against desmoglein 1 and desmoglein 3. Although most cases are considered idiopathic, external triggers that can disrupt immune tolerance have been described. Vaccination has been discussed as a potential precipitating factor in autoimmune skin diseases. However, the relationship between vaccination and the induction of pemphigus-related autoantibodies has not been comprehensively summarized. Methods: We conducted a narrative review of all available studies published in the last 25 years identified through medical databases, excluding studies on COVID-19 vaccinations. Reports describing either new-onset pemphigus or exacerbation of preexisting pemphigus with a temporal association to vaccination were included. Clinical characteristics, vaccine type, latency period, direct immunofluorescence findings, and ELISA results for desmoglein autoantibodies were analyzed. In addition, we present our own clinical-laboratory experience illustrating this issue. Results: The current evidence consists predominantly of case reports and small case series. Published cases describe pemphigus vulgaris and pemphigus foliaceus occurring after vaccinations against influenza, hepatitis B, tetanus, diphtheria, pertussis, rabies, and other routinely administered immunizations. The latency period most often ranged from several days to a few weeks. Immunopathological findings were consistent with classical pemphigus diseases, including intercellular IgG deposits in the epidermis and circulating autoantibodies against desmoglein 1 and/or desmoglein 3. Our patient was a 78-year-old woman who developed cutaneous form of pemphigus vulgaris, diagnosed with direct immunofluorescence (DIF) and multiplex ELISA, 10 days after diphtheria-tetanus-pertussis vaccination. The patient had a positive family history of autoimmune blistering disease, namely mucous membrane pemphigoid. Conclusions: Based on the currently available evidence, a direct causal relationship between vaccination and pemphigus diseases cannot be established. Nevertheless, accumulated clinical and serological observations suggest that vaccination may act as a triggering factor in genetically or immunologically predisposed individuals, possibly by amplifying pre-existing subclinical autoreactive immune responses. Further population-based and mechanistic studies are required to clarify this association, while the overall benefits of vaccination remain substantial.

Inflammation is central in atrial fibrillation (AF) pathophysiology, but the temporal association between inflammatory activity and AF remains uncertain. This study investigated the day-to-day relationship between plasma C-reactive protein (CRP) levels and AF occurrence in continuously monitored individuals. Post-hoc analysis of the LOOP study randomizing participants with stroke risk factors to implantable loop recorder (ILR) screening (n=1501) or usual care. ILR raw data were linked to blood samples collected within one day. The outcome was AF episodes lasting ≥60 minutes. Associations were examined using generalized and linear mixed models and as a self-controlled case series (SCCS). ILR and CRP data were available for 1065 participants combining >1.2 million days of heart rhythm monitoring (including ∼40,000 days with AF) with >7,000 CRP measurements. CRP was higher during days with AF (geometric mean 8.37 [7.11-9.86] mg/L) versus non-AF days (4.02 [3.71-4.35] mg/L). Each doubling of CRP was associated with 36% higher odds of AF (adjusted odds ratio [aOR] 1.36 [1.26-1.47]). Compared with CRP ≤3 mg/L, the odds of AF increased for CRP >10-50 mg/L and >50 mg/L (aOR 3.50 [2.18-5.60] and 5.75 [3.48-9.50], respectively). In SCCS analyses, CRP >10 mg/L was associated with higher incidence of AF compared to lower levels (incidence rate ratio 2.41 [1.53-3.80]). This exploratory study found a temporal and dose-response relationship between CRP levels and AF occurrence, supporting inflammation as an acute trigger and underscoring the need to evaluate inflammatory markers as potential targets in AF management.

Chronic pain is associated with maladaptive reorganization of brain networks, particularly in the anterior cingulate cortex (ACC), contributing to the affective dimension of pain. Although peripheral capsaicin administration relieves neuropathic pain in clinics, its effects on central pain networks remain unclear. In this study, we determined the resting-state functional connectivity of ACC (ACC FC) rearrangement after infraorbital nerve chronic constriction injury (ION-CCI) and subsequent peripheral administration of capsaicin through longitudinal resting-state functional magnetic resonance imaging (fMRI) in male rats. We also conducted functional silencing of the ACC using inhibitory chemogenetic receptors to determine ACC networks commonly reversed by peripheral capsaicin and chemogenetic silencing. Infraorbital nerve chronic constriction injury produced orofacial mechanical allodynia accompanied by ACC FC changes compared to sham. A single injection of capsaicin into the maxillary skin decreased mechanical allodynia. Five days after capsaicin injection, CCI-enhanced ACC FC was significantly reduced compared to the time point before the injection in the same rats or to the rats with vehicle injection. Subsequent chemogenetic silencing of ACC in the previously vehicle-treated CCI rats reduced mechanical allodynia and suppressed CCI-enhanced ACC FC. Peripheral capsaicin and chemogenetic inhibition of ACC commonly reversed approximately one-third of the CCI-enhanced ACC FC. Affected regions included the bilateral cingulate areas, primary and secondary somatosensory cortex, primary and secondary auditory areas, hippocampus, and temporal association cortex. We conclude that peripheral capsaicin administration reverses maladaptive ACC networks in male rats with nerve injury and that peripheral nociceptors contribute to the maintenance chronic pain and peripherally targeted treatment can produce long-lasting analgesia.

BackgroundDolutegravir based antiretroviral therapy (ART) is widely recommended as first line treatment for people living with HIV because of its potent viral suppression, high genetic barrier to resistance, and a favorable tolerability profile. Haematological adverse effects of ART are well recognized, most commonly anemia, particularly with zidovudine-containing regimens. However, erythrocytosis or polycythaemia is rarely described in association with dolutegravir, and available literature on this possible association remains limited. Case-presentationsWe describe a case series of four male patients living with HIV who developed persistent polycythemia after transition to dolutegravir-based regimens in accordance with National AIDS Control Organization guidelines. All our patients had been on long-term ART since childhood and were virologically suppressed with stable CD4 counts prior to regimen change. Haemoglobin levels progressively increased to >16.5g/dL within 1 to 3years of initiating dolutegravir, with peak values ranging from 17.4 to 17.8g/dL. The patients remained asymptomatic, and leukocyte and platelet counts were largely within normal limits. Evaluation excluded common secondary causes of erythrocytosis including smoking, dehydration, renal dysfunction, and clinical features suggestive of myeloproliferative neoplasms. Liver and renal function parameters were stable, and no evidence of hypoxia or exogenous androgen use was identified. DiscussionThe temporal association between initiation of dolutegravir and rising haemoglobin levels is possibly suggestive of a drug-related effect or a haematological recovery phenomenon following sustained viral suppression. Proposed mechanisms include ART-associated increases in testosterone levels, enhanced erythropoietin production, reduced haemolysis, and improved bone marrow function. Although the patients were clinically stable, persistent polycythaemia may increase long term thrombotic risk and therefore may warrant periodic complete blood count monitoring. ConclusionThis case series highlights the need for awareness of this uncommon but potentially significant haematological observation in patients receiving dolutegravir-based ART and underscores the importance of systematic evaluation to exclude alternative aetiologies.

Air pollution is a major global public health concern and has been increasingly linked to cardiovascular diseases, including acute coronary syndrome (ACS). This study investigated the temporal association between air pollution and the case counts of ACS in ***, northern Türkiye. In this retrospective study, the medical records of 6185 ACS patients at a single hospital, including cases of ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI) and unstable angina pectoris were analyzed. Environmental air pollutants (e.g., PM10, PM2.5, NO, NOx) levels were collected and their temporal correlations with the case counts of ACS were determined. Seasonal variations in both the number of hospital admissions of ACS cases and pollutant concentrations were also evaluated. Seasonal analysis revealed a significantly higher number of hospital admissions for acute coronary syndrome during winter compared with other seasons in this single-center study conducted in northern Türkiye (p<0.05). The levels of particulate matter (PM10 and PM2.5) were also elevated in winter, with PM2.5 showing a moderate positive correlation with the case counts of STEMI (r=0.38, p=0.0005) and a strong positive correlation with NSTEMI (r=0.55, p<0.0001). Nitrogen oxides (NO and NOx) exhibited elevations in winter but did not show significant correlations with overall ACS case counts. Targeted public health strategies are required to mitigate pollution exposure, particularly during high-risk seasons. Further research with more accurate and higher-resolution pollution metrics and longitudinal data is warranted to deepen our understanding of the cardiovascular impacts of specific pollutants and to develop effective intervention strategies.

Gitelman syndrome (GS) is an inherited renal tubulopathy characterized by chronic hypokalemia, hypomagnesemia, and metabolic alkalosis. We report a case of a 36-year-old GS woman, who experienced recurrent respiratory tract infections over three years, and each episode was associated with severe hypokalemia and variable potassium requirements across episodes. Despite intermittent potassium supplementation, mild hypokalemia persisted between episodes. During a recent acute respiratory infection, the serum potassium dropped to as low as 1.80 mmol/L, accompanied by elevated inflammatory markers, including interleukin-6(IL-6). This observation describes a temporal association between infection and hypokalemic episodes but does not establish a causal relationship. The genetic testing identified compound heterozygous variants in SLC12A3. After initiation of regular oral potassium supplementation and infection-prevention measures, no further hospitalizations occurred during follow-up. This case illustrates how recurrent infection-associated hypokalemia may unmask previously unrecognized Gitelman syndrome and underscores the importance of early recognition of Gitelman syndrome and adequate long-term potassium supplementation to mitigate complications of chronic hypokalemia.

Exploring the dynamics of symptom networks in esophageal cancer patients during chemotherapy: a cross-lagged panel network analysis.

Systemic AL amyloidosis is rarely reported in temporal association with immune checkpoint inhibitor use. We report a 69-year-old man with resectable stage IIB right upper lobe lung adenocarcinoma who received neoadjuvant pembrolizumab, carboplatin, and pemetrexed followed by robotic-assisted lobectomy. Pathology showed a 4.6-cm treated tumour bed with residual invasive adenocarcinoma (50% viable), negative margins, and no nodal metastasis (0/9). Tumour profiling demonstrated a PD-L1 tumour proportion score of 100%, a high tumour mutational burden (18 mut/Mb), microsatellite stability, and variants in BRAF, TP53 and PTPRT. In addition to the treatment effect, widespread Congo red-positive deposits were identified in lung parenchyma and multiple nodal stations. Laser microdissection with LC-MS/MS confirmed AL (λ) amyloid. Subsequent workup revealed a λ-restricted plasma cell clone (6.4%) with t (11;14), establishing systemic AL amyloidosis. He received adjuvant pembrolizumab and daratumumab-CyBorD with partial hematologic response. This case highlighted that amyloid can unexpectedly be a second diagnosis after post-neoadjuvant lung resections and that proteomic subtyping is essential for prompt haematologic staging and treatment.

WCN26-5025 MPO ANCA-ASSOCIATED VASCULITIS RELAPSE IN A LIVING KIDNEY DONOR PRECIPITATED BY HYDRALAZINE RE-INTRODUCTION

Hypertensive urgency is commonly attributed to medication nonadherence, progression of essential hypertension, or secondary causes. However, in some patients, no clear precipitating factor is identified, despite repeated evaluations and the absence of target organ damage. Subclinical inflammatory conditions have been hypothesized as potential, underrecognized contributors to acute blood pressure destabilization. We describe three cases of elderly women with previously diagnosed and treated essential hypertension who presented with episodes of hypertensive urgency without evidence of acute target organ damage. In each case, blood pressure remained persistently elevated despite optimization of oral antihypertensive therapy and exclusion of common secondary causes. Lung ultrasound performed during evaluation revealed pulmonary parenchymal infiltrates suggestive of an inflammatory process, despite minimal or absent respiratory symptoms and unremarkable laboratory tests, electrocardiograms, and chest radiographs. Although microbiological confirmation and inflammatory biomarker elevation were not documented, empirical antibiotic therapy was initiated based on clinical judgment. Follow-up lung ultrasound demonstrated progressive improvement of pulmonary findings, temporally associated with stabilization and improved blood pressure control, allowing simplification or return to baseline antihypertensive regimens. These cases suggest a temporal association between lung ultrasound-detected pulmonary infiltrates and hypertensive urgency in patients with essential hypertension. While causality cannot be established, subclinical inflammatory pulmonary processes may represent potential contributors to acute blood pressure elevation in some patients. Lung ultrasound may serve as a useful adjunctive tool in the evaluation of unexplained hypertensive urgency. Prospective studies incorporating microbiological and inflammatory markers are needed to further clarify this possible association.

Bilateral Auricular Blastomycosis-like Pyoderma: A Rare Presentation Histologically Misinterpreted as Squamous Cell Carcinoma.

Diabetes is associated with microvascular complications in multiple tissues. Nailfold capillaries (NFCs) provide a noninvasive window for assessing microvascular alterations; however, their temporal association with skeletal muscle microvascular changes during diabetes progression remains unclear. This study aimed to determine whether NFC structural changes reflect skeletal muscle microvascular alterations and muscle-type-specific vulnerability in a non-obese type 2 diabetes model. Spontaneously Diabetic Torii (SDT) rats, a non-obese type 2 diabetes model, and age-matched Sprague-Dawley rats were studied. NFC morphology was evaluated by capillaroscopy at 12, 18, and 28 weeks of age. Soleus and plantaris muscles were collected for histological and gene expression analyses, and glucose tolerance was evaluated by oral glucose tolerance testing at each time point. At 12 weeks of age, SDT rats exhibited mild glucose intolerance without significant abnormalities in NFC morphology or skeletal muscle capillary indices. At 18 weeks, when glucose intolerance became evident in the absence of persistent hyperglycemia, NFC narrowing and reduced density were observed, accompanied by capillary rarefaction in the predominantly fast-twitch plantaris muscle, whereas the slow-twitch soleus muscle remained relatively preserved. By 28 weeks, persistent hyperglycemia was present, and overt muscle atrophy was observed exclusively in the plantaris muscle. NFC structural alterations emerge alongside skeletal muscle microvascular rarefaction at the stage of glucose intolerance and precede overt muscle atrophy in fast-twitch muscle. NFC assessment may serve as a noninvasive indicator of early microvascular alterations relevant to diabetes-associated skeletal muscle deterioration.