Eastern Europe and Central Asia (EECA) face a dual crisis in addiction treatment. On one side, Russian imperial legacies persist through punitive "narcology," now weaponized amid ongoing aggression. On the other, Western retrenchment, marked by abrupt aid suspensions and dwindling harm-reduction budgets, has weakened the evidence-based counterweight that once challenged authoritarian approaches. The result is a convergence of punitive logics that marginalizes people who use drugs, whether through active repression, such as the closure of methadone programs in Crimea, or sudden neglect, such as the withdrawal of donor funding for opioid agonist therapy in Tajikistan. We call for a decolonial, community-driven response grounded in non-reformist reform and transformative discomfort-one that reduces harm while dismantling punitive systems and embraces the tensions of shared authority and care. Drawing on the case of self-run addiction treatment in Kyrgyz prisons, we call for resourcing user-led infrastructures as models for decolonial directions in global health amid a splintering global health world order.
Stimuli-responsive dynamic crystals, particularly those that respond to light, offer tremendous potential for developing intelligent materials. Whereas specialized photoresponsive behaviors can be achieved through subtle optical modulation, understanding how these crystals interact with other ambient factors remains equally critical but not fully elucidated. Herein, we show crystals based on methylated pyridinium halide derivatives (MX, X═Cl, Br, I) that undergo moisture-gated photoinduced crystal-to-liquid transition (PCLT) via [2+2] photocycloaddition at the vinyl structure. Under visible-light irradiation and high local humidity, MX crystals melt rapidly within 1 min (20-50 s). In contrast, under drier conditions, the crystals display vigorous photomechanical motions, including jumping, expanding, and splintering instead. Ambient water molecules surrounding crystal surfaces are found to significantly promote photocycloaddition and stabilize the generated photodimers, leading to a crystal that fully melts outward to inward when local humidity exceeds 60% under light. This process also enables the instant recrystallization growth of photodimer single crystals via a solvent-free approach. Furthermore, we develop a facile sensor system for real-time monitoring of local humidity and for quantifying trace moisture in water-miscible solvents, such as tetrahydrofuran (THF). Our work highlights the significance of synergistic environmental conditions and light stimuli in unlocking advanced functionalities in crystalline materials.
A systematic review recommended seven multimorbidity indices for predicting mortality. However, their performance has not been assessed in a head-to-head comparison. We externally validated these indices and determined their performance compared to counting co-occurring diseases. Within the prospective Rotterdam Study in the Netherlands, we constructed seven specific sub-cohorts, selected from 14 926 community-dwelling older adults to match the target population of the selected multimorbidity indices. We calculated prediction scores according to the indices' original methods and used these as predictors in logistic regression models with all-cause mortality as outcome. We assessed their performance and compared it to four benchmark models fitted on the same index-specific samples. These models were based on (i) age and sex; (ii) counts of co-occurring diseases, age and sex; (iii) counts of co-occurring diseases associated with mortality, age and sex; and (iv) individual diseases as separate predictors, age and sex. The total population sizes of the seven sub-cohorts ranged from 2409 to 9045 participants. The mean age of the populations ranged from 59.4 to 77.0 years; the proportion of women ranged from 56.0% to 61.8% (excluding single-sex indices). The absolute risk for mortality ranged from 0.9% to 13%. Discriminative performance of the indices and corresponding count models was nearly identical across all indices (maximum difference in C-statistic: 0.06), yet higher than age-and-sex models. Absolute accuracy of the prediction scores was similar across all models (maximum improvement in Brier score: 4%). Calibration was poor in four out of seven indices, all of which had a follow-up time of 2 years or less. Counting co-occurring diseases is as accurate in predicting all-cause mortality in the general population as using multimorbidity indices. These findings imply that counting diseases is the more practical and reliable way of providing prognosis to patients with multimorbidity in a population of community-dwelling adults.
Ventricular tachycardia (VT) dynamics in myocardial infarction and heart failure patients could be influenced by heterogeneous sprouting of sympathetic nerves or alteration of β-adrenergic receptors to disrupt normal β-adrenergic receptor signalling (BARS). Because sympathetic remodelling is challenging to control experimentally, we created and validated a novel ionic model incorporating the macroscopic effects of BARS on intracellular Ca2+ dynamics and handling for tissue-scale simulations. Using our model we created ventricular sheets with varying spatial densities and gradients to study VT behaviour, represented as a rotor. We demonstrated that our BARS model reduces action potential durations (APDs) by 16% due to drastic changes in K+ and Ca2+ regulation, consistent with experimental data from animal and human studies. We also demonstrated that the ventricular substrate with spatial BARS density > 15 % $ > 15{\mathrm{\% }}$ for ≥ 0.1 $ \ge 0.1\;$ µM (ISO) could host faster (4.5 Hz vs. 3.7 Hz) and more stable (5.6 mm2 vs. 14 mm2) VTs than non-BARS substrates. We also showed that VTs hosted in substrates with spatial BARS gradients ( ≥ Δ 15 % $ \ge {{\Delta}}15{\mathrm{\% }}$ could splinter into multiple slow and disorganized wavelets, indicative of fibrillation. Our model and simulation findings may help predict and enhance the effectiveness of neuromodulatory interventions for sympathetically modulated VTs. KEY POINTS: A novel human ventricular model is used for tissue-scale simulation of sympathetic activity Sympathetically remodelled substrates may have fast and stable rotors Spatial gradients of sympathetic stimulation could break rotors into wavelets Simulations may help inform interventions for sympathetically modulated arrhythmias.
ObjectiveTo describe the prevalence, clinical manifestations, histopathological features, and antibody profile associated to skin involvement in patients with catastrophic antiphospholipid syndrome (CAPS).MethodsWe performed a cross-sectional study of the patients included in the "CAPS Registry," a registry developed by the European Forum on Antiphospholipid Antibodies (aPL)1,2 This database contains data from patients with CAPS collected from April 1992 to December 2024. Demographic clinical manifestations, laboratory features (including aPL antibodies), pathological findings in involved skin, and outcome were retrieved.ResultsCutaneous involvement was described in 377 episodes (47%) from 361 patients. A female sex prevalence of 49.4% was observed. The average age was 39.4 (SD ± 17.9) years. The more frequent skin manifestations observed were livedo reticularis (17.6%), skin necrosis (13%), ischemic ulcers (10.4%), skin ischemic (9.7%), skin purpura (7.1%), gangrene (5%), splinter haemorrhages (2.6%), and Raynaud's phenomenon (1.5%). The most frequently affected organs in CAPS episodes with skin involvement were kidneys (72%), lungs (61%), central nervous system (54.5%), and heart (54.4%). Thrombocytopenia and hemolysis features were more common in patients with skin involvement (p < 0.05 for all). Thrombotic microangiopathy was the predominant pathological finding, present in 82 (68.3%) episodes. No difference regarding mortality were found in episodes with or without skin involvement (29.3% vs 32.1%, p = 0.42).ConclusionThe presence of skin involvement in patients with CAPS is frequent. The most frequent manifestations were livedo reticularis and skin necrosis. Skin involvement does not seem to be associated to mortality.
Platelet factor 4-polyanion enzyme-linked immunosorbent assays (ELISAs) are considered highly sensitive for diagnosing heparin-induced thrombocytopenia (HIT), such that current practice guidelines recommend use of ELISA-negative results to exclude HIT. Once HIT is ruled out, alternative, non-heparin-based anticoagulant treatments are ceased, and heparin reintroduction frequently occurs. Antigen-based and PF4-dependent functional testing were used to study PF4/polyvinylsulfonate ELISA-negative platelet-activating antibodies in HIT-suspected patients. Three patients with clinical presentations consistent with HIT tested negative in an ELISA using PF4-polyvinylsulfonate (PF4/PVS), an antigenic target very commonly used for HIT antibody screening. All three patients demonstrated PF4-dependent platelet activation in functional testing that was sensitive to blockade of platelet FcγRIIa receptors and inhibited by high concentrations of heparin, consistent with pathogenic HIT antibodies. Functional testing-based screening of 500 ELISA-negative patients identified three additional patients whose sera activated platelets in a PF4- and FcγRIIa-dependent manner and had clinical histories consistent with HIT. Five of the six ELISA-negative HIT patients were re-exposed to heparin, which precipitated a decrease in platelet counts in all re-exposed patients, and one patient developed a new thrombus. Recognition of ELISA-negative HIT is critical to avoid harm due to the cessation of alternative anticoagulation therapy and re-exposure of these patients to heparin.
Delayed presentation of retained foreign bodies with sequelae of chronic inflammation is a rare but well documented phenomenon. Here we present the unusual case of a 23-year-old female with a retained wooden splinter in the buttock region presenting more than 10 years post injury. A foreign body was not identified on initial imaging. Only after surgical exploration and targeted ultrasound was a wooden splinter identified and removed.
Systemic amyloid light-chain (AL) amyloidosis is a multisystem disorder caused by extracellular deposition of monoclonal immunoglobulin light chains. Cutaneous manifestations are diverse, but nail involvement is uncommon and may lead to diagnostic delay. We report the case of a 53-year-old man presenting with progressive dystrophy affecting all 20 nails for 18 months. Clinical examination revealed marked nail plate atrophy and onychorrhexis. Dermoscopy demonstrated nail plate atrophy, subungual hyperkeratosis, and splinter hemorrhages. A longitudinal lateral nail-bed biopsy revealed abundant amorphous eosinophilic deposits in the papillary dermis on hematoxylin and eosin staining. Congo red staining confirmed amyloid deposition. Subsequent systemic evaluation revealed markedly elevated free lambda light chains and bone marrow plasmacytosis, establishing the diagnosis of systemic AL amyloidosis associated with multiple myeloma. This case highlights that unexplained progressive pan-ungual dystrophy may represent an early manifestation of systemic amyloidosis. Early recognition and nail-unit biopsy can facilitate prompt diagnosis of this potentially fatal systemic disease.
Onychomatricoma is a rare benign tumor of the nail matrix that is often misdiagnosed due to its resemblance to other nail conditions, particularly onychomycosis. A giant variant, which affects the entire nail structure, is even more uncommon, with fewer than 20 cases documented. We present the case of a 62-year-old male with a 5-year history of a slow-growing, asymptomatic tumor on the third nail of his left hand. Clinical examination revealed a papillomatous mass originating from the nail matrix, accompanied by nail thickening and xanthonychia. Dermoscopy showed longitudinal yellow, white, and gray lines, splinter hemorrhages, and a honeycomb pattern. Mycological testing suggested onychomycosis, but due to the size and persistence of the lesion, a multidisciplinary team recommended a complete nail avulsion and proximal matricectomy. Histopathological analysis revealed fibroepithelial projections covered by squamous epithelium and thickened nail plate fragments, confirming the diagnosis of giant onychomatricoma. The patient underwent surgical management and has shown no signs of recurrence after 2 years of follow-up. This case highlights the diagnostic and therapeutic challenges posed by giant onychomatricoma, particularly when coexisting with fungal infection. It also underscores the need for thorough clinical, dermoscopic, and histopathological evaluation in cases of chronic nail deformities.
BACKGROUND: Neuroretinitis (NR) is an uncommon inflammatory optic neuropathy characterized by optic disc edema and macular exudates. Although NR may arise from infectious or idiopathic causes, its association with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is exceptionally rare in children. Early recognition is critical, as MOGAD-related ocular involvement can respond favorably to prompt immunotherapy. CASE PRESENTATION: We report an 11-year-old girl presenting with acute, painless visual loss in the right eye following one week of ocular pain with eye movements. Ophthalmologic evaluation revealed marked optic disc edema, splinter hemorrhages, and early macular exudation. MRI demonstrated right optic nerve thickening with T2-FLAIR hyperintensity, and optical coherence tomography showed subretinal fluid extending to the fovea. Extensive infectious testing was negative. Serum MOG-IgG was positive, supporting a diagnosis of MOGAD-associated NR. The patient received high-dose intravenous corticosteroids followed by intravenous immunoglobulin (IVIG), resulting in rapid visual improvement. A partial macular star developed during the early recovery phase. Maintenance therapy with mycophenolate mofetil was initiated due to IVIG intolerance and continued for 24 months. Over a 3-year follow-up period, the patient experienced full visual recovery without clinical relapses, although residual optic nerve thinning was observed on MRI. CONCLUSION: This case highlights a rare pediatric presentation of MOGAD manifesting as NR and underscores the importance of considering MOG-IgG testing in children presenting with optic disc edema and macular exudation. Early and sustained immunotherapy can lead to complete visual recovery and may reduce the risk of recurrent demyelinating episodes.
Infective endocarditis carries high mortality in hemodialysis patients, particularly when caused by methicillin‑resistant Staphylococcus aureus. Concomitant fungemia further worsens prognosis but remains rare. A 52‑year‑old woman with type 2 diabetes mellitus and stage V chronic kidney disease on thrice‑weekly hemodialysis presented with atypical chest pain, fatigue, night sweats, and splinter hemorrhages. She was afebrile. Transthoracic echocardiography showed preserved left‑ventricular ejection fraction and grade II mitral/tricuspid regurgitation; transesophageal echocardiography revealed a 0.7 × 2.1 cm pedunculated vegetation on the septal leaflet of the tricuspid valve. Three sets of peripheral and catheter blood cultures were drawn, and empiric renally adjusted daptomycin plus gentamicin were started. On day 3, C‑reactive protein had fallen. Cultures grew methicillin‑resistant Staphylococcus aureus in two peripheral sets and in the tunneled catheter, and Candida tropicalis in one peripheral set. The infected catheter was removed and a brachio‑axillary graft was placed. Gentamicin was discontinued; daptomycin was continued for six weeks. Voriconazole was administered for 21 days, ending 14 days after negative fungal cultures. Follow‑up echocardiography at week 6 showed complete resolution of the vegetation. The patient remained asymptomatic at three‑month follow‑up. In immunocompromised hemodialysis patients, dual bacterial‑fungal bloodstream infections can occur, yet not every positive fungal culture indicates endocardial involvement. Serial cultures, prompt removal of infected hardware, and targeted antimicrobial therapy can achieve cure without surgery even in the presence of sizable vegetations.
A 17-year-old previously healthy girl presented with 7 days of fever and classical peripheral findings including Osler's nodes, Janeway lesions, splinter hemorrhages, and Roth's spots. Echocardiography revealed a large vegetation attached to the posterior mitral leaflet. Blood culture later grew methicillin-sensitive Staphylococcus aureus. Despite antibiotic therapy, the vegetation increased in size with splenic embolization, requiring urgent mitral valve replacement. This case highlights the enduring diagnostic value of classical clinical signs, now rarely seen in high-income settings but still encountered in resource-limited regions, and emphasizes the importance of early echocardiographic evaluation in such presentations.
To report a case of foveal micro-embolism in the setting of subacute bacterial endocarditis following routine dental cleaning. Retrospective case report and literature review. A 45-year-old man presented with subacute bacterial endocarditis and a small distortion of vision his left eye. Aside from renal, splenic, and brain embolization the patient showed no splinter hemorrhages, Roth spots, Osler's nodes, and Janeway lesions. Further examination demonstrated a discrete, non-hemorrhagic lesion which corresponded to hyperreflective foci disrupting the inner and outer retinal layers on optical coherence tomography. This lesion resolved with observation and intravenous antibiotics. We propose this case represents a distinct embolic mechanism mediated by neutrophil extracellular traps. Recognition of this mechanism may help expand our understanding of the spectrum of embolic phenomena in endocarditis.
This study focuses on the development of a laser desorption/ionization mass spectrometric method for analyzing carbonaceous chondrites, meteorites that may hold clues to the origin of life. Since carbonaceous chondrites are only available in small quantities, we initially designed an artificial meteorite material (the mineral forsterite) doped with an organic material system (the amino acid tryptophan, the sugar 2-deoxy-D-ribose, and the polycyclic aromatic hydrocarbon triphenylene) as meteorite-like material to develop an LDI-MS method. This simulates a simplified artificial meteoritic composition to study the behavior of organic compounds in an inorganic environment. Experiments with meteorite-like material were performed on four different LDI-MS instruments (reflectron TOF-MS and QTOF-MS) with different performance characteristics (e.g., different lasers and laser repetition rates, different ion source pressure) in positive- and negative-ion mode and compared the data with those obtained on a TOF-SIMS instrument. Real meteoritic samples were also analyzed using our previously developed LDI-MS method and the TOF-SIMS method. For sample preparation, we used an in-house built micro-press, enabling the fixing of both meteorite-like material and real meteoritic splinters onto a target plate. Our unique target system, a universal in-house-designed adapter target holder, facilitated compatibility with all instruments including SIMS from different manufacturers. In the real meteorite samples a variety of elements, including potential detections of rubidium (85Rb:87Rb = 3:1), cesium (133Cs only), and tentatively holmium (165Ho only) was predominantly detected in positive-ion mode. Utilizing LDI with a reflectron TOF-MS in negative-ion mode, we identified distinct carbon clusters ranging from C2 to C13 in the Allende and Jbilet Winselwan meteorites originating most likely from high molecular weight organic carbon compounds. Background analysis confirmed a minimal impact of external contamination with carbon cluster ions validating the authenticity of these findings. No distinct other carbon-containing material could be identified.
Tetanus is a serious infectious disease characterized by muscle rigidity and autonomic storm. In severe cases, long-term deep sedation is required, resulting in a high risk of post-intensive care syndrome (PICS). However, criteria for determining the timing of early rehabilitation intervention have not yet been established. We report the case of a woman in her 70s who developed tetanus following a wood-splinter injury to her right forearm and subsequently suffered bilateral humeral fractures due to muscle rigidity and convulsions. She was admitted to the intensive care unit (ICU) with an Ablett classification of Grade III, which progressed to Grade IV following ICU admission. On Day 11, rehabilitation was initiated after confirming the resolution of muscle hypertonicity and opisthotonos, a downward trend in creatine kinase (CK) levels, and the stabilization of hemodynamic parameters. No apparent recurrence of autonomic symptoms was observed during rehabilitation. The patient was gradually mobilized from edge-of-bed sitting to wheelchair use, and then to standing and walking. With multidisciplinary collaboration, she was discharged home on Day 114. The findings from this case may provide a basis for determining the timing of safe rehabilitation intervention in patients with severe tetanus.
Herpes zoster (HZ) predominantly affects sensory nerves and can lead to postherpetic neuralgia. A motor deficit in the corresponding myotome is a rare but severe complication. Objectives: The objective of this study was to further characterize patients with HZ-related motor deficits and to explore potential risk factors. This retrospective cohort study in the tertiary pain clinic of the University Medical Center Utrecht, includes a comparative analysis of patients presenting with and without motor deficit resulting from HZ. Patient characteristics including psychological distress were assessed using standardized questionnaires, and Quantitative Sensory Testing outcomes were analysed between the 2 groups. The study population included 158 patients with postherpetic neuralgia, of whom 17 patients had motor paralysis. In the motor paralysis group, most were male (94.1%). The median pain intensity was NRS 7, similar in both groups. Anxiety, depression, Pain Catastrophizing Scale, and DN4 scores did not differ significantly between groups. Tampa Scale of Kinesiophobia, indicating kinesiophobia did significantly differ between both groups (P = 0.043). Patients with motor deficit showed distinct sensory profiles characterized by sensory loss in 70.6% of patients compared with 35.5% in the group without motor deficit (P = 0.017). Motor deficit may be more common than we realize and is a serious complication of HZ. Patients who experienced motor deficit as a complication of herpes zoster demonstrated more severe nerve damage, with sensory loss being the most frequent sensory phenotype. More awareness is needed for this serious complication accompanied with research guiding treatment and rehabilitation protocols.
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Mycobacterium marinum is an acid-fast bacillus. Human infection can occur when damaged skin is exposed to an aqueous environment that is contaminated by the organism. An infection with M marinum can present as painless purple nodules that spread along the lymphatics. Sporotrichosis presents similarly. We present a case of cutaneous M marinum infection in a patient from rural central Texas who developed lesions initially suspected to be sporotrichosis after she sustained a splinter wound of her right hand. Despite empirical treatment for sporotrichosis with itraconazole, the patient's condition worsened, prompting further investigation. A positive culture for M marinum altered the treatment plan. After a course of minocycline, the patient's cutaneous lesions resolved. This case highlights the diagnostic challenge of M marinum infections, which can mimic conditions such as sporotrichosis. M marinum is an incredibly slow-growing organism in culture and requires a high degree of foresight for accurate diagnosis. Clinicians should consider M marinum in the differential diagnosis for patients with apparent sporotrichosis lesions, particularly those with a history of appropriate environmental exposure, even in regions distant from bodies of water or occupations not routinely in contact with aquatic organisms.
Subungual squamous cell carcinoma is a rare malignancy of the nail unit that is frequently misdiagnosed as benign nail disease, leading to prolonged diagnostic delays and sometimes invasive spread. To synthesize the dermoscopic features of histologically confirmed subungual squamous cell carcinoma and to compare patterns between invasive and in situ disease. We performed a systematic review and meta-analysis (PROSPERO CRD42023470387) following PRISMA and MOOSE guidance. PubMed, Scopus and Cochrane CENTRAL were searched. Extracted data included study design, lesion counts, histologic subtype and specific dermoscopic signs. Random-effects meta-analysis (DerSimonian-Laird with Freeman-Tukey transformation) produced pooled prevalences with 95% confidence intervals. Between-study heterogeneity was assessed with Cochran's Q and I2. We used subgroup and meta-regression analyses to explore the influence of histologic subtype, sample size and publication year. When the data allowed, diagnostic odds ratios were calculated versus common benign mimickers. Twenty studies comprising 121 lesions (96 invasive, 25 in situ) were included. In invasive lesions, the most common dermoscopic findings were subungual hyperkeratosis (pooled prevalence 89%; 95% CI 78-97; I2 = 0%), onycholysis (85%; 75-93; I2 = 28%), irregular borders (72%; 50-90; I2 = 42%), and splinter hemorrhages (52%; 40-65; I2 = 36%). In situ lesions more often presented with melanonychia (89%) and showed lower rates of hyperkeratosis (50%). Meta-regression identified histologic subtype as a significant predictor of feature prevalence (p < 0.01). Key comparative performance estimates included a diagnostic odds ratio of 12.6 (95% CI 8.3-19.1) for polymorphous vessels distinguishing squamous cell carcinoma from warts and 6.8 (95% CI 3.2-14.5) for hyperkeratosis versus onychomycosis. Dermoscopy reliably identifies features, particularly hyperkeratosis, onycholysis, irregular margins and hemorrhagic spots, that are common in invasive subungual squamous cell carcinoma; in situ disease more commonly presents with pigmentary changes. Recognition of these signs should lower the threshold for biopsy of suspicious single-digit nail lesions and may facilitate earlier diagnosis and treatment.