Search

Recent advances in neuroscience have illuminated the central role of glutamate dysregulation in various neurological disorders. The glutamatergic system has emerged as a central player in the pathophysiology of various neurological disorders. The dysregulation of glutamate signaling, leading to excitotoxicity and neuronal cell death, has been a focal point in understanding the underlying mechanisms of these conditions. This has prompted a paradigm shift in neuroprotection research, with a growing emphasis on targeting ionotropic glutamate receptors (iGluRs) to restore glutamatergic homeostasis. This review provides a comprehensive overview of recent advancements in the field of iGluR-targeted neuroprotection. We further investigate the implications of glutamate dysregulation in the central nervous system (CNS) disorders, highlighting the complex interplay between excitotoxicity and neuroprotection. We elucidate the multifaceted factors that render neurons vulnerable to excitotoxic damage, emphasizing the need for innovative therapeutic approaches. This review provides an extensive survey of the burgeoning field of iGluR-targeted neuroprotection. It showcases the significant potential of a wide array of compounds, encompassing both natural and synthetic agents, to modulate iGluRs and ameliorate excitotoxicity and oxidative stress-induced neuronal damage. These compounds have demonstrated impressive neuroprotective effects in diverse experimental models, from glutamate-induced toxicity to traumatic brain injuries. We advocate for further research and clinical investigations to harness the full therapeutic potential of iGluR modulation, heralding a promising era in neuroprotection and CNS disorder management. Glutamate dysregulation leads to neurological disorders, which has prompted a paradigm shift towards neuroprotection targeting ionotropic glutamate receptors (iGluRs). Neurons may be less susceptible to excitotoxic damage with interventions targeting iGluRs. In this work we highlight natural and synthetic compounds with remarkable neuroprotective effects in various experimental models. This opens a broad research scenery to fully exploit their beneficial potential in CNS disorders. Targeting ionotropic glutamate receptors (iGluRs) holds significant promise for restoring glutamatergic balance in CNS disorders.Personalized therapies based on biomarkers and genomic profiling are on the horizon, revolutionizing neuroprotection.Potential for preventing and delaying neurodegenerative diseases through iGluR modulation. Targeting ionotropic glutamate receptors (iGluRs) holds significant promise for restoring glutamatergic balance in CNS disorders. Personalized therapies based on biomarkers and genomic profiling are on the horizon, revolutionizing neuroprotection. Potential for preventing and delaying neurodegenerative diseases through iGluR modulation.

Hidradenocarcinomas are rare cutaneous adnexal malignancies with sweat gland differentiation that can show a broad spectrum of histomorphologic appearances, ranging from low to high grade. The diagnosis of low-grade hidradenocarcinoma can be challenging and may be mistaken for benign hidradenomas, especially on superficial and partial samples. We performed a retrospective analysis of 16 low-grade hidradenocarcinomas, obtained from 4 large academic institutions. All neoplasms presented clinically as nodular lesions that ranged in size from 1.5 to 6.0 cm. All patients were adults and their age ranged from 33 to 74 years of age. All cases shared features similar to hidradenomas in the surface and mid portion of the tumors and all tumors had 1 or more histomorphologic clues to malignancy, including the presence of an asymmetric and infiltrative growth pattern (especially at the base of the tumors), perineurial invasion, and a desmoplastic stromal reaction. In the tumors evaluated for immunohistochemistry, the tumor cells were positive for p63, EMA, AE1/AE3, MNF116, and CK7. Three patients underwent sentinel lymph node biopsy, and 2 cases showed metastatic disease to regional lymph nodes. All cases (including the 2 cases that had regional lymph node metastasis), showed no local recurrence or distant metastasis observed after a complete re-excision of the tumors (follow-up range from 6 to 72 mo). Our study highlights the salient clinical and histopathologic features of low-grade hidradenocarcinomas and emphasizes the potential diagnostic pitfalls in distinguishing this entity from other neoplasms. Our results indicate that a combination of thorough histopathologic inspection is necessary to support the diagnosis of this rare neoplasm. These tumors can be exceedingly difficult to diagnose and awareness of the subtle features of low-grade hidradenocarcinoma is of importance are as it remains a diagnostic challenge for practicing pathologists.

Hidradenocarcinoma (HAC) is a rare adnexal tumor associated with the potential for locoregional recurrence and systemic metastasis. The clinical appearance of HAC is nonspecific, frequently presenting as a solitary firm subcutaneous nodule or plaque on the head and neck region or distal extremities. These tumors show histomorphologic heterogeneity, as they can be low and high grade. Distinguishing HAC from hidradenoma, especially the low-grade variant of HAC, can be challenging as both tumors can show histologic overlapping features. In this article, we describe a case of a 33-year-old patient presenting with a low-grade HAC of the plantar foot who was subsequently found to have lymph node metastasis.

•Mineralogical composition and moisture content govern energy consumption.•Dehydroxylation and drying use around one-third of the energy input.•Energy and exergy efficiencies amount to 66.4% and 32.3%, respectively.•Dehydroxylation, drying, and size define intraparticle temperature gradient.

Development of effective, scenario-driven training exercises requires both an instructional design and a delivery system that match the subject domain and needs of the students. The Training Research Team at Los Alamos National Laboratory conducts research and development of prototype training systems. One of the Team's efforts is a joint research project, supported with funding and behavioral science guidance from the Army Research Institute, to develop a prototype part-task trainer for student helicopter pilots. The Team designed a “trilevel interaction” model and a Level III interactive videodisc delivery system for this project. The model, founded on instructional and psychological theory, should be transferable to other domains where part-task training is appropriate.

We compared verapamil and propranolol hydrochloride for monotherapy of hypertension. Verapamil lowered blood pressure (BP) more effectively than propranolol in black and white patients. Verapamil was equally effective in blacks and whites, whereas propranolol was more effective in whites. Heart rate was reduced by 6.0 beats per minute by verapamil, and by 13.6 beats per minute by propranolol. In blacks, verapamil lowered systolic BP 16.9 vs 8.1 mm Hg for propranolol; verapamil reduced diastolic BP 12.8 vs 8.6 mm Hg for propranolol. In whites, verapamil lowered systolic BP 19.0 vs 12.7 mm Hg for propranolol; verapamil reduced diastolic BP 16.7 vs 12.3 mm Hg for propranolol. Increases in systolic BP were observed in 22% and 3.4% of patients receiving propranolol and verapamil, respectively. The PR interval was increased from 163.5 to 174.9 ms for verapamil vs 160.3 to 164.4 ms for propranolol. Constipation (15%) and headaches (10%) were most frequent complaints for verapamil vs fatigue (18%) and dizziness (7%) for propranolol. Changes in blood biochemistry values were of small magnitude. We conclude that verapamil monotherapy is a safe and effective means of achieving BP control in patients with essential hypertension.(JAMA 1986;256:2214-2221)

One of the main complications of the double-cuffed chronic peritoneal dialysis catheters is cuff erosion, with or without exit-site infection. We present a simple technique, which allows partial replacement of the external catheter segment with splicing. In addition it can be used to replace the intraperitoneal segment, leaving undisturbed the external segment and exit site.This technique can be carried out under local anesthesia, as an outpatient procedure, without interrupting treatment and with less trauma than total catheter replacement.This paper describes our experience with 20 external catheter replacements in 17 patients followed up to 20 months.

We present the clinical course of a patient who has been treated with CAPD since 1979. He developed dialysis encephalopathy and fracturing osteomalacia, and was found to have a serum aluminum concentration of 560 μg/L. Treatment with desferrioxamine over a six month's period reduced his serum aluminum concentration to a non-toxic level, and his symptoms abated. One year after his initial encephalopathy this patient has a normal EEG, the bone fractures have healed, and serum aluminum concentration is 38 μg/ L. Apparently the hyperaluminemia was due to the ingestion of prescribed aluminum hydroxide.

To the Editor.—Pierce et al (219:1593, 1972) reported lymphomas as a complication of renal transplantation. They stated that in two of their three cases of reticulum cell sarcoma the earliest manifestation of the tumor was a macrocytic anemia which occurred in the presence of maintenance folic acid (PGA) therapy and which, in one case, responded to treatment with folinic acid.Dossetor et al, in 19641 described in one patient the presence of macrocytic anemia and megaloblastic marrow with normal serum levels of vitamin B12 and folate but reduced red blood cell (RBC) folate levels, in the absence of tumor. They commented on the lack of information on azathioprine interfering with vitamin B12 action.In 1965, Mowbray et al2 reported four transplant patients treated with azathioprine, who developed macrocytic megaloblastic anemia. In one patient, an abnormal formiminoglutamic acid excretion after histidine load suggested interference with folic