Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Syndrome to Hemodialysis Polysulfone Membrane.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe and potentially life-threatening hypersensitivity reaction. Although commonly associated with specific drugs, there have been no reports of DRESS syndrome caused by medical devices. We report a unique case of DRESS syndrome linked to a particular hemodialysis membrane during treatment. An 83-year-old man on hemodialysis exhibited fever, rash, and elevated eosinophils. Despite medication changes and consultations with specialists, his condition persisted. A drug-induced lymphocyte stimulation test revealed a positive response to the dialysis membrane. His symptoms and lab results met DRESS syndrome diagnostic criteria. After substituting the membrane and administering glucocorticoids, the patient displayed early improvement. Diagnosing DRESS syndrome is complex due to its varied presentation and lack of specific benchmarks. This instance underscores the need to consider medical devices as potential DRESS syndrome triggers. Enhanced physician awareness can facilitate prompt detection and proper management, ultimately refining patient outcomes.

Single-Cell RNA Sequencing Reveals an Immune Landscape of CD4+ T Cells in Coronary Culprit Plaques With Acute Coronary Syndrome in Humans-Brief Report.

BACKGROUND: Acute coronary syndrome (ACS) involves plaque-related thrombosis, causing primary ischemic cardiomyopathy or lethal arrhythmia. We previously demonstrated a unique immune landscape of myeloid cells in the culprit plaques causing ACS by using single-cell RNA sequencing. Here, we aimed to characterize T cells in a single-cell level, assess clonal expansion of T cells, and find a therapeutic target to prevent ACS. METHODS: We obtained the culprit lesion plaques from 4 patients with chronic coronary syndrome (chronic coronary syndrome plaques) and the culprit lesion plaques from 3 patients with ACS (ACS plaques) who were candidates for percutaneous coronary intervention with directional coronary atherectomy. Live CD45+ immune cells were sorted from each pooled plaque samples and applied to the 10× platform for single-cell RNA sequencing analysis. We also extracted RNA from other 3 ACS plaque samples and conducted unbiased TCR (T-cell receptor) repertoire analysis. RESULTS: CD4+ T cells were divided into 5 distinct clusters: effector, naive, cytotoxic, CCR7+ (C-C chemokine receptor type 7) central memory, and FOXP3 (forkhead box P3)+ regulatory CD4+ T cells. The proportion of central memory CD4+ T cells was higher in the ACS plaques. Correspondingly, dendritic cells also tended to express more HLAs (human leukocyte antigens) and costimulatory molecules in the ACS plaques. The velocity analysis suggested the differentiation flow from central memory CD4+ T cells into effector CD4+ T cells and that from naive CD4+ T cells into central memory CD4+ T cells in the ACS plaques, which were not observed in the chronic coronary syndrome plaques. The bulk repertoire analysis revealed clonal expansion of TCRs in each patient with ACS and suggested that several peptides in the ACS plaques work as antigens and induced clonal expansion of CD4+ T cells. CONCLUSIONS: For the first time, we revealed single cell-level characteristics of CD4+ T cells in patients with ACS. CD4+ T cells could be therapeutic targets of ACS. REGISTRATION: URL: https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000046521; Unique identifier: UMIN000040747.

Structural basis for ion selectivity in potassium-selective channelrhodopsins.

KCR channelrhodopsins (K+-selective light-gated ion channels) have received attention as potential inhibitory optogenetic tools but more broadly pose a fundamental mystery regarding how their K+ selectivity is achieved. Here, we present 2.5-2.7 Å cryo-electron microscopy structures of HcKCR1 and HcKCR2 and of a structure-guided mutant with enhanced K+ selectivity. Structural, electrophysiological, computational, spectroscopic, and biochemical analyses reveal a distinctive mechanism for K+ selectivity; rather than forming the symmetrical filter of canonical K+ channels achieving both selectivity and dehydration, instead, three extracellular-vestibule residues within each monomer form a flexible asymmetric selectivity gate, while a distinct dehydration pathway extends intracellularly. Structural comparisons reveal a retinal-binding pocket that induces retinal rotation (accounting for HcKCR1/HcKCR2 spectral differences), and design of corresponding KCR variants with increased K+ selectivity (KALI-1/KALI-2) provides key advantages for optogenetic inhibition in vitro and in vivo. Thus, discovery of a mechanism for ion-channel K+ selectivity also provides a framework for next-generation optogenetics.

Respiratory depression caused by low dose of olanzapine: A case report / Depresión respiratoria causada por dosis baja de Olanzapina: informe de un caso

Objective: Olanzapine is widely used throughout the world to treat patients with schizophrenia and bipolar disorder. Olanzapine has numerous side effects, but respiratory depression has not been reported with doses as low as 5 mg. Clinical case: An elderly woman presented with severe hypercarbia, hypoxia, and impaired consciousness possibly due to low doses of oral olanzapine. There is no accepted antidote for the side effects of olanzapine, so we followed the patient with respiratory support and electrolyte correction. Symptoms improved after 2 weeks and did not recur. Results and conclusions: Elderly patients, women, and non-smokers may have elevated olanzapine concentrations and may do better with lower than usual doses. If somnolence is observed in a patient taking olanzapine, a blood gas should be obtained and appropriate respiratory care should be provided. We expect that this case report will add to the existing body of literature on the appropriate use of olanzapine. (AU)

Objetivo: Olanzapina se utiliza de manera amplia a nivel mundial para tratar a los pacientes con esquizofrenia y trastorno bipolar. Tiene numerosos efectos secundarios, pero no se había reportado depresión respiratoria con dosis bajas de 5 mg. Caso clínico: Una mujer mayor acudió con hipercarbia severa, hipoxia y deterioro de la consciencia, debido posiblemente a la administración de dosis bajas de olanzapina oral. No existe antídoto aceptado para los efectos secundarios de olanzapina, por lo que seguimos a la paciente con soporte respiratorio y corrección de electrolitos. Los síntomas mejoraron transcurridas dos semanas, no produciéndose recidiva. Resultados y conclusiones: Los pacientes mayores, mujeres, y no fumadores pueden tener concentraciones elevadas de olanzapina, siendo adecuado utilizar dosis más bajas de lo habitual. De observarse somnolencia en un paciente que toma olanzapina, deberán obtenerse gases sanguíneos, y aportarse cuidados respiratorios adecuados. Esperamos que este informe de caso ayude al cuerpo existente de la literatura con relación al uso adecuado de olanzapina. (AU)

Newly Diagnosed Sjogren Syndrome in an Elderly Patient on Dialysis: A Case Report.

Sjogren syndrome (SS) is a chronic, systemic autoimmune disease that primarily affects the exocrine glands, causing dry eyes and mouth, but also presents with a variety of other symptoms. SS is a common connective tissue disease but it can be difficult to diagnose due to the non-specific symptoms and lack of diagnostic markers in many cases. This report describes a case of an elderly patient on dialysis with newly diagnosed SS. The patient had been unable to eat a normal diet for a year, but treatment had not been initiated, presumably because of his age and the fact that he was on dialysis. The patient's symptoms improved with the administration of glucocorticoids. This is a very educational case for physicians to recognize undiagnosed SS patients presenting with non-specific symptoms.

Cardiogenic control of affective behavioural state.

Emotional states influence bodily physiology, as exemplified in the top-down process by which anxiety causes faster beating of the heart1-3. However, whether an increased heart rate might itself induce anxiety or fear responses is unclear3-8. Physiological theories of emotion, proposed over a century ago, have considered that in general, there could be an important and even dominant flow of information from the body to the brain9. Here, to formally test this idea, we developed a noninvasive optogenetic pacemaker for precise, cell-type-specific control of cardiac rhythms of up to 900 beats per minute in freely moving mice, enabled by a wearable micro-LED harness and the systemic viral delivery of a potent pump-like channelrhodopsin. We found that optically evoked tachycardia potently enhanced anxiety-like behaviour, but crucially only in risky contexts, indicating that both central (brain) and peripheral (body) processes may be involved in the development of emotional states. To identify potential mechanisms, we used whole-brain activity screening and electrophysiology to find brain regions that were activated by imposed cardiac rhythms. We identified the posterior insular cortex as a potential mediator of bottom-up cardiac interoceptive processing, and found that optogenetic inhibition of this brain region attenuated the anxiety-like behaviour that was induced by optical cardiac pacing. Together, these findings reveal that cells of both the body and the brain must be considered together to understand the origins of emotional or affective states. More broadly, our results define a generalizable approach for noninvasive, temporally precise functional investigations of joint organism-wide interactions among targeted cells during behaviour.

A Flp-dependent G-CaMP9a transgenic mouse for neuronal imaging in vivo.

Genetically encoded calcium indicators (GECIs) are widely used to measure calcium transients in neuronal somata and processes, and their use enables the determination of action potential temporal series in a large population of neurons. Here, we generate a transgenic mouse line expressing a highly sensitive green GECI, G-CaMP9a, in a Flp-dependent manner in excitatory and inhibitory neuronal subpopulations downstream of a strong CAG promoter. Combining this reporter mouse with viral or mouse genetic Flp delivery methods produces a robust and stable G-CaMP9a expression in defined neuronal populations without detectable detrimental effects. In vivo two-photon imaging reveals spontaneous and sensory-evoked calcium transients in excitatory and inhibitory ensembles with cellular resolution. Our results show that this reporter line allows long-term, cell-type-specific investigation of neuronal activity with enhanced resolution in defined populations and facilitates dissecting complex dynamics of neural networks in vivo.

Systemic capillary leak syndrome (SCLS) after receiving BNT162b2 mRNA COVID-19 (Pfizer-BioNTech) vaccine.

Systemic capillary leak syndrome (SCLS), also known as Clarkson's disease, is a rare disorder of unknown aetiology. Since SCLS was first described in 1960, fewer than 500 cases have been reported. SCLS is diagnosed by the classic triad of hypotension, haemoconcentration and hypoalbuminaemia resulting from fluid extravasation. Some reports show that SCLS may sometimes occur as a side effect of adenoviral vector COVID-19 vaccines, although there is only one report (two cases) of SCLS after receiving a messenger RNA vaccine. Survival rates for SCLS are very poor without treatment, so it is crucial for clinicians to recognise this disorder. A middle-aged woman who presented with generalised malaise and anasarca after receiving the BNT162b2 COVID-19 vaccine was diagnosed with SCLS. Treatment with methylprednisolone and intravenous immunoglobulin was commenced and her symptoms resolved. We expect that this case report will add to the existing literature on this rare disorder and the side effects of vaccinations.

Structural basis for channel conduction in the pump-like channelrhodopsin ChRmine.

ChRmine, a recently discovered pump-like cation-conducting channelrhodopsin, exhibits puzzling properties (large photocurrents, red-shifted spectrum, and extreme light sensitivity) that have created new opportunities in optogenetics. ChRmine and its homologs function as ion channels but, by primary sequence, more closely resemble ion pump rhodopsins; mechanisms for passive channel conduction in this family have remained mysterious. Here, we present the 2.0 Å resolution cryo-EM structure of ChRmine, revealing architectural features atypical for channelrhodopsins: trimeric assembly, a short transmembrane-helix 3, a twisting extracellular-loop 1, large vestibules within the monomer, and an opening at the trimer interface. We applied this structure to design three proteins (rsChRmine and hsChRmine, conferring further red-shifted and high-speed properties, respectively, and frChRmine, combining faster and more red-shifted performance) suitable for fundamental neuroscience opportunities. These results illuminate the conduction and gating of pump-like channelrhodopsins and point the way toward further structure-guided creation of channelrhodopsins for applications across biology.

Proliferative Glomerulonephritis with Monoclonal IgG Deposits and Refractory Ascites: Successful Treatment with Rituximab and Cell-free and Concentrated Ascites Reinfusion Therapy.

A 49-year-old woman presented with nephrotic-range proteinuria, microhematuria, and moderate renal dysfunction. Diuretic-resistant refractory ascites associated with nephrotic syndrome were observed. Based on the histopathological findings, the patient was diagnosed with proliferative glomerulonephritis with monoclonal immunoglobulin G deposits (PGNMID). Rituximab was administered due to steroid and immunosuppressive drug resistance, and partial remission was achieved after six months. Cell-free and concentrated ascites reinfusion therapy (CART) performed to treat the refractory ascites improved the ascites and anasarca. Rituximab successfully treated the PGNMID, while CART effectively treated the refractory ascites associated with nephrotic syndrome.

Synchronous gastric cancer and primary lymphoma of right adrenal gland: a case report.

This report presents an extremely rare case of synchronous gastric cancer and primary adrenal diffuse large B-cell lymphoma (DLBCL). An 82-year-old man underwent computed tomography, which revealed a heterogeneous appearing and hypodense adrenal mass and a gastric mass with no enlarged lymph nodes in the neck, mediastinum, abdomen, and inguinal region. Upper gastrointestinal endoscopy revealed a protruding gastric tumor. The specimens obtained from endoscopic biopsy were histologically confirmed to be adenocarcinoma. The hormonal findings eliminated functional adrenal tumor. The patient underwent distal gastrectomy with regional lymph node resection for gastric cancer and incisional biopsy of the adrenal mass. Based on the pathological findings, diagnoses of mixed mucinous and tubular adenocarcinomas of the stomach and adrenal DLBCL were confirmed. Postoperation, the patient received rituximab combined with low-dose doxorubicin, cyclophosphamide, vincristine, and prednisone (R-miniCHOP). Six courses of R-miniCHOP were planned, but were completed in only one course at the patient's request. The patient died 2 months after surgery.

Postoperative solitary liver metastasis from esophageal squamous cell carcinoma achieving a clinical complete response to chemotherapy with cisplatin and 5-fluorouracil followed by stereotactic body radiotherapy: A case report.

Treatment strategies for distant organ metastasis have changed markedly since the concept of oligometastasis was introduced. The perception that distant organ metastasis is a systemic disease and not eligible for local therapy is now a thing of the past. Therefore, the present report details a case of postoperative solitary liver metastasis from esophageal squamous cell carcinoma (ESCC), which achieved a clinical complete response to chemotherapy with cisplatin and 5-fluorouracil (5-FU) followed by stereotactic body radiotherapy (SBRT). A 76-year-old male patient underwent esophagectomy for lower thoracic ESCC. At 7 months after surgery, abdominal CT revealed a solitary hypovascular mass, 28 mm in size, in segment 7 of the liver. After three courses of chemotherapy with cisplatin and 5-FU, abdominal CT revealed that the liver mass had shrunk to 7 mm in size. SBRT was then administered with a 6 MV X-ray beam generated by a linear accelerator. A total dose of 50 Gy was given in 5 fractions of 10 Gy to the liver mass. At 1 month after SBRT, abdominal CT revealed that the liver mass had disappeared. The patient received no further adjuvant chemotherapy and had no recurrence at 18 months after diagnosis of liver metastasis and 13 months after SBRT.

Genetically encoded calcium indicators to probe complex brain circuit dynamics in vivo.

Over the past two decades, genetically encoded calcium indicators (GECIs) have been used extensively to report intracellular calcium (Ca2+) dynamics in order to readout neuronal and network activity in living tissue. Single wavelength GECIs, such as GCaMP, have been widely adapted due to advances in dynamic range, sensitivity, and kinetics. Additionally, recent efforts in protein engineering have expanded the GECI color palette to enable direct optical interrogation of more complex circuit dynamics. Here, I discuss the engineering, application, and future directions of the most recently developed GECIs for in vivo neuroscience research.

Occult follicular lymphoma in a swollen regional lymph node of gastric schwannoma.

BACKGROUND: Regional lymphadenopathy is more commonly noted in gastric schwannomas than in other gastric submucosal tumors. Most of the swollen lymph nodes associated with gastric schwannomas are non-metastatic lymphadenopathy. CASE PRESENTATION: A 69-year-old Japanese woman was referred to our hospital with a chief complaint of abdominal discomfort. Contrast-enhanced computed tomography (CT) of the abdomen revealed an extraluminal tumor with heterogeneous enhancement at the middle stomach on the lesser curve, accompanied with one swollen lymph node approximately 10 mm in size and several small lymph nodes in the perigastric region. These lymph nodes were flat; therefore, we considered them to be non-metastatic. The main tumor was removed via wedge resection. Soft and slightly swollen lymph nodes, which were compatible with the lymph nodes noted in the preoperative CT, were found near the main tumor in the fatty tissue at the lesser curvature of the stomach. An excisional biopsy of the largest lymph node was performed for the diagnosis. Based on pathological findings, a diagnosis of gastric schwannoma and follicular lymphoma (FL) was confirmed. The patient is doing well without recurrence of either the gastric schwannoma or FL 28 months postsurgery. CONCLUSIONS: The present report detailed an extremely rare case of FL coincidentally discovered in the swollen regional lymph node of gastric schwannoma.

A Case of Pathological Complete Response Following FOLFIRINOX Therapy for Pancreatic Adenocarcinoma with Synchronous Distant Lymph Node Metastases.

INTRODUCTION: We report a case of conversion surgery for pancreatic ductal adenocarcinoma (PDAC) with synchronous distant metastases showing pathological complete response (pCR) after FOLFIRINOX therapy. PRESENTATION OF CASE: A 46-year-old woman with obstructive jaundice was referred to our hospital. A CT scan revealed a hypo-vascular mass in the head of the pancreas with multiple para-aortic lymph nodes and a Virchow's node swollen. The serum CA 19-9 level was 71795.1 U/mL. The result of tumor biopsy from the biliary stenotic site was concordant with adenocarcinoma. She was diagnosed with PDAC with distant metastases. After 10 courses of FOLFIRINOX followed by 4 courses of FOLFIRI, a CT scan showed that distant lymph node swellings disappeared, and CA19-9 level became almost normal. She underwent pancreaticoduodenectomy with dissection of para-aortic lymph nodes 8 months after the initiation of chemotherapy. Pathologically, no evidence of residual adenocarcinoma was observed in neither pancreas nor lymph nodes. Adjuvant chemotherapy using S-1 was administered for 6 months, and no recurrence has been observed 4 years after surgery. BRCA1/2 mutations were not detected in patient's DNA. DISCUSSION: With the induction of intensive chemotherapies such as FOLFIRINOX, an increasing number of patients with synchronous distant metastases could become suitable candidates for surgery of the primary lesion because of the potential complete response of metastatic lesions. CONCLUSION: This case presented a rare occurrence of pCR in a patient with unresectable PDAC with distant metastases who received FOLFIRINOX. The feasibility and benefits of conversion surgery in such patients must be investigated in future trials.

Cell Culture on Low-Fluorescence and High-Resolution Photoresist.

2D and 3D topographic cues made of photoresist, a polymer, are used for cell culture and cell analysis. Photoresists used for cell analysis provide the surface conditions necessary for proper cell growth, along with patterning properties of a wide range and high precision, and low auto-fluorescence that does not affect fluorescence imaging. In this study, we developed a thick negative photoresist SJI-001 possessing the aforementioned properties. We evaluated the surface conditions of SJI-001 affecting cell culture. First, we studied the wettability of SJI-001, which was changed by plasma treatment, conducted as a pretreatment on a plastic substrate before cell seeding. SJI-001 was more chemically stable than SU-8 used for fabricating the micro-electromechanical systems (MEMS). Furthermore, the doubling time and adhesion rate of adherent HeLa cells cultured on untreated SJI-001 were 25.2 h and 74%, respectively, thus indicating its suitability for cell culture over SU-8. In addition, we fabricated a cell culture plate with a 3D lattice structure, three micrometers in size, using SJI-001. HeLa cells seeded on this plate remained attached over five days. Therefore, SJI-001 exhibits surface conditions suitable for cell culture and has several bioapplications including microstructures and cell chips for cell culture and cell analysis.

Comprehensive Dual- and Triple-Feature Intersectional Single-Vector Delivery of Diverse Functional Payloads to Cells of Behaving Mammals.

The resolution and dimensionality with which biologists can characterize cell types have expanded dramatically in recent years, and intersectional consideration of such features (e.g., multiple gene expression and anatomical parameters) is increasingly understood to be essential. At the same time, genetically targeted technology for writing in and reading out activity patterns for cells in living organisms has enabled causal investigation in physiology and behavior; however, cell-type-specific delivery of these tools (including microbial opsins for optogenetics and genetically encoded Ca2+ indicators) has thus far fallen short of versatile targeting to cells jointly defined by many individually selected features. Here, we develop a comprehensive intersectional targeting toolbox including 39 novel vectors for joint-feature-targeted delivery of 13 molecular payloads (including opsins, indicators, and fluorophores), systematic approaches for development and optimization of new intersectional tools, hardware for in vivo monitoring of expression dynamics, and the first versatile single-virus tools (Triplesect) that enable targeting of triply defined cell types.

Isolated myeloid sarcoma presenting with small bowel obstruction: a case report.

BACKGROUND: Myeloid sarcoma (MS) is a solid tumor consisting of myeloid blasts or immature myeloid cells, which are unusual outside the bone marrow. CASE PRESENTATION: We present a rare case of isolated myeloid sarcoma of the small bowel in a 54-year-old man who was admitted to our hospital with repeated symptoms of intestinal obstruction. A small bowel series via an ileus tube revealed severe jejunal obstruction. Computed tomography revealed that the obstruction was likely caused by a jejunal tumor. The patient underwent laparoscopy-assisted partial resection of the jejunum with lymphadenectomy. Histopathological examination of the surgical specimen confirmed that MS had been responsible for the obstruction. CONCLUSIONS: Patients with MS require systemic chemotherapy, as do patients with acute myeloid leukemia. Hence, an early, accurate diagnosis is imperative for treating this malignancy. It is also important to list MS in the differential diagnosis of a small bowel tumor, even in nonleukemic patients.