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Background: Despite the growth of physical medicine and rehabilitation (PM&R) in recent years, the same cannot be said for its workforce conditions. Although various issues regarding the reality of the physiatry workforce have been reported, no studies were found that have evaluated it in Peru., Objective: To assess characteristics, proficiency profile, and specialty perceptions of Peruvian physiatrists., Design: Cross-sectional survey, designed and validated by the Peruvian Society of PM&R., Setting: Online anonymous and voluntary questionnaire., Participants: One hundred five Peruvian physiatrists., Interventions: During August 2023, after approval from the ethics committee, a Google Forms questionnaire was shared with the participants via WhatsApp, providing information about study details. Responses were monitored through direct communication with each participant., Main Outcome Measures: Twenty-four questions covering sociodemographic data, training-related characteristics, work-related characteristics, proficiency perceptions, and specialty perceptions., Results: Most surveyed physiatrists were females (80%) and completed residency between 2017 and 2022 (46.7%). Only 2.8% had pursued a subspecialty fellowship; 41.9% were involved in teaching and easily found employment after residency. Most worked in the public sector (82.9%) and had a permanent employment status under the 728 regime (33.3%). Most reported having much proficiency (Level 3) in all competency domains. Mastery in ultrasound (US) (10.2%) and electrodiagnostic medicine (EDX) (4.1%) was reported mainly by those completing residency between 2017 and 2022. Only 2.9% reported ability to conduct scientific research. Overall satisfaction with the specialty was high (75.2%)., Conclusions: The survey found that most of surveyed Peruvian physiatrists worked in the public sector, had permanent employment status, considered themselves highly proficient in all evaluated domains, reported low mastery in US and EDX, and were very satisfied with the specialty. Given the lack of literature, these findings provide valuable insights for policymakers and educators, highlighting key areas for improving conditions for the physiatry workforce., (© 2025 American Academy of Physical Medicine and Rehabilitation.)

Background and Purpose: Abacavir, an antiretroviral drug used in HIV therapy associated with myocardial infarction, promotes thrombosis through P2X7 receptors. The role of platelets as pro-thrombotic cells is acknowledged whereas that of neutrophils-due to their secretory capacity-is gaining recognition. This study analyses the role of neutrophils-specifically the secretome of abacavir-treated neutrophils (SN ABC )-in platelet activation that precedes thrombosis., Experimental Approach: Effects of abacavir or SN ABC on platelet activation and platelet-leukocyte interactions and expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) were analysed by flow cytometry. The secretome was analysed by proteomics. The role of leukocytes in the actions of abacavir was evaluated in a mouse model of thrombosis., Key Results: Abacavir induced platelet-leukocyte interactions, not directly via effects of abacavir on platelets, but via activation of neutrophils, which triggered interactions between platelet P-selectin and neutrophil P-selectin glycoprotein ligand-1 (PSGL-1). SN ABC stimulated platelet activation and platelet-leukocyte interactions through a process that was dependent on LOX-1, neutrophil P2X7 and platelet P2Y1, P2Y12 and P2X1 receptors. Abacavir induced the expression of LOX-1 on neutrophils and of the soluble form of LOX-1 (sLOX-1) in SN ABC . Neutrophils, LOX-1, P2X7, P2Y1, P2Y12 and P2X1 receptors were required for the pro-thrombotic actions of abacavir in vivo., Conclusion and Implications: Neutrophils are target cells in abacavir-induced thrombosis. Abacavir released sLOX-1 from neutrophils via activation of their P2X7 receptors, which in turn activated platelets. Hence, sLOX-1 could be the missing link in the cardiovascular risk associated with abacavir., (© 2022 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Cells selectively activated by a particular view of an environment have been found in the primate hippocampus (HPC). Whether view cells are present in other brain areas, and how view selectivity interacts with other variables such as object features and place remain unclear. Here, we explore these issues by recording the responses of neurons in the HPC and the lateral prefrontal cortex (LPFC) of rhesus macaques performing a task in which they learn new context-object associations while navigating a virtual environment using a joystick. We measured neuronal responses at different locations in a virtual maze where animals freely directed gaze to different regions of the visual scenes. We show that specific views containing task relevant objects selectively activated a proportion of HPC units, and an even higher proportion of LPFC units. Place selectivity was scarce and generally dependent on view. Many view cells were not affected by changing the object color or the context cue, two task relevant features. However, a small proportion of view cells showed selectivity for these two features. Our results show that during navigation in a virtual environment with complex and dynamic visual stimuli, view cells are found in both the HPC and the LPFC. View cells may have developed as a multiarea specialization in diurnal primates to encode the complexities and layouts of the environment through gaze exploration which ultimately enables building cognitive maps of space that guide navigation., (© 2023 The Authors. Hippocampus published by Wiley Periodicals LLC.)

Objectives: To perform a radio-anatomical evaluation of the nasal cavity floor free mucosal graft (endonasal extended mucoplasty, EEM) to repair mucosal defects after an extended ethmoid-sphenoidotomy., Methods: A human cadaveric study (radiological and anatomical dissection) and an in vivo study in surgical patients with CRSwNP were performed. The EEM areas were compared between 3D reconstruction from CT scans and anatomical/surgical dissections, both in cadaver specimens and in patients. Feasibility was assessed by correlation between the EEM area on CT scans and when harvested in cadavers and when grafted in patients. Usefulness was assessed by the degree of coverage of the EEM in the surface exposed after an extended ethmoid-sphenoidotomy. Both feasibility and usefulness were assessed in cadaveric specimens (n = 15) and patients (n = 4)., Results: Fifteen cadaveric specimens and 4 patients with bilateral CRSwNP were included. The mean (SD) areas obtained in the cadaveric radiological and anatomical studies were 9.44 (2.07) cm 2 and 8.03 (1.36) cm 2 , respectively (intraclass correlation coefficient 0.59, moderate correlation), and in 3D reconstruction for operated patients were 10.32 (0.98) cm 2 and 11.27 (2.44) cm 2 , respectively. The coverage of the ethmoidal roof in the cadaveric dissection study was 100%, from the anterior ethmoidal artery to the posterior ethmoidal artery, covering the planun sphenoidale up to 75% in the case series. In 87.5% of the cases, up to 50% of the papiracea lamina was covered., Conclusion: The EEM have shown to be a feasible and useful grafting technique to repair skull base defects after performing an extended ethmoid-sphenoidotomy during surgery for CRSwNP., Level of Evidence: NA., Competing Interests: The authors declare no potential conflict of interest., (© 2020 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Although diet and exercise clearly have an influence on immune function, studies are scarce on the effect caused by exercise and the consumption of a carbohydrate-rich or fat-rich diet on the peripheral immune system. The aim of the present study was to evaluate the effect of exercise and the two aforementioned unbalanced diets on young Balb/c mice, especially in relation to BMI, the level of glucose, and the percentage of lymphocyte subpopulations in peripheral blood. The changes found were then related to the synthesis of leptin and adiponectin as well as the production of oxidative stress. The increase in BMI found with the carbohydrate-rich and fat-rich diets showed correlation with the levels of leptin and adiponectin. An increase in leptin and a decrease in adiponectin directly correlated with an increase in total lymphocytes and CD4+ cells and with a decrease in B cells. The increase in leptin also correlated with an increase in CD8+ cells. Glycemia and oxidative stress increased with the two unbalanced diets, negatively affecting the proliferation of total lymphocytes and the percentage of B cells, apparently by causing alterations in proteins through carbonylation. These alterations caused by an unbalanced diet were not modified by moderate exercise.

The three most common Cys-loop receptors expressed by myenteric neurons are nACh, 5-HT3 and GABAA . To investigate the function of these proteins researchers have used channel inhibitors such as hexamethonium (antagonist of nACh receptors), ondansetron (antagonist of 5-HT3 receptors), picrotoxin and bicuculline (both antagonists of GABAA receptors). The aim of this study was to investigate the specificity of these inhibitors on Cys-loop receptors of primary cultured neurons obtained from the guinea-pig small intestine. The whole-cell configuration of the patch clamp techniques was used to record membrane currents induced by ACh (IACh ), 5-HT (I5-HT ) and GABA (IGABA ) in the absence and the presence of various concentrations of hexamethonium, ondansetron, picrotoxin or bicuculline. The three Cys-loop receptors present in enteric neurons are expressed independently and they do not cross-desensitized. Hexamethonium inhibited IACh without affecting I5-HT and IGABA . Ondansetron inhibited I5-HT and also IACh but did not affect IGABA . Picrotoxin and bicuculline inhibited I5-HT , IACh and IGABA with different potency, being the lowest potency on 5-HT3 receptors. All these inhibitory effects were concentration dependent and reversible. Our observations showed that except for hexamethonium, all other inhibitors used here show different degrees of selectivity, which has to be considered when these antagonists are used in experimental studies aimed to investigate the functions of these receptors. In particular, in tissues expressing nACh receptors because these are the targets of all other inhibitors used here. The low potency of picrotoxin and bicuculline to inhibit 5-HT3 receptors suggests that these receptors are heteromeric proteins., (© 2013 John Wiley & Sons Ltd.)

Amyloid beta (Aβ) is a peptide of 39-43 amino acids found in large amounts and forming deposits in the brain tissue of patients with Alzheimer's disease (AD). For this reason, it has been implicated in the pathophysiology of damage observed in this type of dementia. However, the role of Aβ in the pathophysiology of AD is not yet precisely understood. Aβ has been experimentally shown to have a wide range of toxic mechanisms in vivo and in vitro, such as excitotoxicity, mitochondrial alterations, synaptic dysfunction, altered calcium homeostasis, oxidative stress, and so forth. In contrast, Aβ has also shown some interesting neuroprotective and physiological properties under certain experimental conditions, suggesting that both physiological and pathological roles of Aβ may depend on several factors. In this paper, we reviewed both toxic and protective mechanisms of Aβ to further explore what their potential roles could be in the pathophysiology of AD. The complete understanding of such apparently opposed effects will also be an important guide for the therapeutic efforts coming in the future.

Background: Adenovirus (Ad)-mediated E2F-1 gene transfer induces apoptosis in cancer cells in vitro and in vivo, but clinical application of E2F-1 in cancer gene therapy remains controversial because of the oncogenic potential of E2F-1. This barrier can be circumvented by using the truncated form of the E2F-1 gene (E2Ftr) (amino acids 1 through 375), which lacks the E2F-1 transactivation domain and cell cycle-promoting effects., Methods: The authors constructed 3 adenoviral vectors that expressed E2Ftr under regulation of the tetracycline (Tet)-off system (AdTet-E2Ftr1, AdTet-E2Ftr2, and AdTet-E2Ftr3). These vectors were compared for E2Ftr expression and apoptosis induction in cancer cells and normal cells. E2Ftr antitumor activity in vivo also was assessed in a melanoma xenograft model., Results: One of the 3 vectors, AdTet-E2Ftr3, had the highest E2Ftr protein expression levels, which were correlated with the greatest induction of apoptosis and inhibition of cancer cell growth. E2Ftr induced apoptosis in a variety of cancer cell lines independent of p53 status with little cytotoxicity in normal cell lines. In a mouse melanoma xenograft model, AdTet-E2Ftr3 exhibited an approximately 80% decrease in tumor size compared with controls in vivo., Conclusions: The current results indicated that AdTet-E2Ftr3 is a novel anticancer agent that has significant therapeutic activity in vitro and in vivo., (© 2010 American Cancer Society.)

Most perceptual tasks require sequential steps to be carried out. This must be the case, for example, when subjects discriminate the difference in frequency between two mechanical vibrations applied sequentially to their fingertips. This perceptual task can be understood as a chain of neural operations: encoding the two consecutive stimulus frequencies, maintaining the first stimulus in working memory, comparing the second stimulus to the memory trace left by the first stimulus, and communicating the result of the comparison to the motor apparatus. Where and how in the brain are these cognitive operations executed? We addressed this problem by recording single neurons from several cortical areas while trained monkeys executed the vibrotactile discrimination task. We found that primary somatosensory cortex (S1) drives higher cortical areas where past and current sensory information are combined, such that a comparison of the two evolves into a decision. Consistent with this result, direct activation of the S1 can trigger quantifiable percepts in this task. These findings provide a fairly complete panorama of the neural dynamics that underlies the transformation of sensory information into an action and emphasize the importance of studying multiple cortical areas during the same behavioural task.

1. Whole-cell and outside-out patch clamp recordings were used to characterize the physiological and pharmacological properties of the P2x-purinoceptors of myenteric neurones from the guinea-pig ileum. 2. Adenosine 5'-triphosphate (ATP) and analogues (1-3000 microM) evoked a rapid inward current in > 90% of all recorded neurones. The reversal potential of this current was dependent on the extracellular sodium concentration, at +14 +/- 1.9, 0 +/- 1.6 and -12 +/- 1 mV for 166, 83 and 42 mM of sodium, respectively. The fast activation and inactivation of this current occurred even when guanosine 5'-triphosphate (GTP) was omitted from the pipette solution or substituted with an equimolar concentration of guanosine 5'-o-[2-thiotriphosphate] (GTP-gamma-S). Single channel currents were observed when these outside-out membrane patches were exposed to ATP (10-30 microM). These channels have a unitary conductance of about 17 picosiemens. 3. The rank-order of potency of the agonists used to induce the whole-cell currents was: ATP-gamma-S = ATP = 2-methylthio-ATP (2-Me-S-ATP) > > alpha, beta-methylene ATP = beta, gamma-methylene ATP; adenosine and uridine 5'-triphosphate (UTP) (up to 1 mM) were inactive. 4. Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) (1-30 microM) antagonized the effects of ATP (1 mM) with an IC50 of 4 microM. alpha, beta-Methylene ATP (100 microM) did not affect the ATP (30 microM)-induced current. Cibacron Blue 3GA increased the ATP activated cationic current whereas Basilen Blue E-3G had a very weak antagonistic effect (IC50 > or = 3 mM). Suramin potentiated the currents induced by ATP through a mechanism that was independent of its inhibitory effect on ectonucleotidase activity, as suramin also potentiated the effect of alpha, beta-methylene ATP (an ATP analogue that is resistant to nucleotidases). 5. In conclusion, the myenteric P2x-purinoceptor shares some properties with other purinoceptors in particular with the P2x4- and P2x6-purinoceptors. This receptor has also some unusual pharmacological properties suggesting that myenteric neurones express a novel subtype of P2x-purinoceptors. The properties of this receptor, however, might be a result of the combination of two or more of the homomeric purinoceptors so far characterized.

We cared for 124 pediatric patients with a histologic diagnosis of Langerhans' cell histiocytosis (histiocytosis X) over a period of 14 years. Clinical, laboratory, and radiographic findings were analyzed. The most frequent manifestations were bone lesions, lymph node involvement, and skin infiltration. Liver disease was noted in 50% of patients and lung disease in 23%; hematologic changes were also frequent. Dysfunction and involvement of these three organ systems, plus age of onset, distinguished the group of patients with the highest mortality. All patients with generalized disease or organ dysfunction were treated with systemic chemotherapy. The actuarial survival curve at 10 years was 63%.

A case of hepatic myelolipoma is described, including the angiographic and computed tomographic appearance. Only three such cases have been reported previously.