Notes

Multiple myeloma in Armenia during the time period 2006-2018: facts along with dialogue.
Glia modulate neuronal excitability and seizure sensitivity by maintaining potassium and water homeostasis. A salt inducible kinase 3 (SIK3)-regulated gene expression program controls the glial capacity to buffer K+ and water in Drosophila, however upstream regulatory mechanisms are unknown. Here, we identify an octopaminergic circuit linking neuronal activity to glial ion and water buffering. Under basal conditions, octopamine functions through the inhibitory octopaminergic G-protein-coupled receptor (GPCR) OctβR to upregulate glial buffering capacity, while under pathological K+ stress, octopamine signals through the stimulatory octopaminergic GPCR OAMB1 to downregulate the glial buffering program. Failure to downregulate this program leads to intracellular glia swelling and stress signaling, suggesting that turning down this pathway is glioprotective. In the eag shaker Drosophila seizure model, the SIK3-mediated buffering pathway is inactivated. Reactivation of the glial buffering program dramatically suppresses neuronal hyperactivity, seizures, and shortened life span in this mutant. These findings highlight the therapeutic potential of a glial-centric therapeutic strategy for diseases of hyperexcitability.The mechanistic target of rapamycin complex 1 (mTORC1) stimulates a coordinated anabolic program in response to growth-promoting signals. Paradoxically, recent studies indicate that mTORC1 can activate the transcription factor ATF4 through mechanisms distinct from its canonical induction by the integrated stress response (ISR). However, its broader roles as a downstream target of mTORC1 are unknown. selleck products Therefore, we directly compared ATF4-dependent transcriptional changes induced upon insulin-stimulated mTORC1 signaling to those activated by the ISR. In multiple mouse embryo fibroblast and human cancer cell lines, the mTORC1-ATF4 pathway stimulated expression of only a subset of the ATF4 target genes induced by the ISR, including genes involved in amino acid uptake, synthesis, and tRNA charging. We demonstrate that ATF4 is a metabolic effector of mTORC1 involved in both its established role in promoting protein synthesis and in a previously unappreciated function for mTORC1 in stimulating cellular cystine uptake and glutathione synthesis.Interleukin-4-induced-1 (IL4i1) is an amino acid oxidase secreted from immune cells. Recent observations have suggested that IL4i1 is pro-tumorigenic via unknown mechanisms. As IL4i1 has homologs in snake venoms (L-amino acid oxidases [LAAO]), we used comparative approaches to gain insight into the mechanistic basis of how conserved amino acid oxidases regulate cell fate and function. Using mammalian expressed recombinant proteins, we found that venom LAAO kills cells via hydrogen peroxide generation. By contrast, mammalian IL4i1 is non-cytotoxic and instead elicits a cell protective gene expression program inhibiting ferroptotic redox death by generating indole-3-pyruvate (I3P) from tryptophan. I3P suppresses ferroptosis by direct free radical scavenging and through the activation of an anti-oxidative gene expression program. Thus, the pro-tumor effects of IL4i1 are likely mediated by local anti-ferroptotic pathways via aromatic amino acid metabolism, arguing that an IL4i1 inhibitor may modulate tumor cell death pathways.
PRP is produced by centrifugation of whole blood containing highly concentrated platelets, associated growth factors, and other bioactive agents which has been shown to provide some symptomatic relief in early knee osteoarthritis (OA). The principal objective of our study was to evaluate the effectiveness and safety of standardized intra-articular injection of autologous PRP in early osteoarthritis knee.

A total of 98 eligible symptomatic patients received two injections of standardized PRP 3 weeks apart. Clinical outcomes were evaluated using the VAS and Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire before treatment and at 6 weeks, 3 months, 6 months, and 1 year after treatment. Secondary objectives were safety (side effects), and the effect of PRP on the different grades of knee degeneration.

There was a statistically significant improvement in mean VAS and WOMAC scores at 6 weeks, 3 months, 6 months, and slight loss of improvement at 1 year follow-up. There was also a correlation between the degree of degeneration and improvement in the mean scores. The decrease in mean pain score is more in grades 1 and 2 (early OA) than in grade 3. The intraarticular injection is safe, with no major complications.

PRP is a safe and effective biological regenerative therapy for early OA Knees. It provides a significant clinical improvement in patients with some loss of improvement with time. More studies will be needed to confirm our findings.
PRP is a safe and effective biological regenerative therapy for early OA Knees. It provides a significant clinical improvement in patients with some loss of improvement with time. More studies will be needed to confirm our findings.In December 2019, in Wuhan, China, scientists observed a sudden and sharp increase in the number of cases of pneumonia and acute respiratory distress syndrome of an unknown origin. By the end of January 2020, the outbreak had spread to Asia, Europe, America, and Australia. In this article, we have outlined the pandemic action plan of our university hospital.Although the sensitivity of reverse transcriptase-polymerase chain reaction (RT-PCR) is low in the diagnosis of coronavirus disease 2019 (COVID-19), it is the gold standard. Clinical improvement is prioritized in the follow-up of patients with COVID-19 who are followed as possible or definitive cases. Although the priority in the discharge decision is the resolution of complaints, it is also important to see radiological improvement and RT-PCR negativity. A total of 2 of our patients who were hospitalized and treated in our clinic with a diagnosis of COVID-19 were discharged after their complaints were resolved and their treatment was completed. The patients had 2 negative RT-PCR results at discharge. Both of them presented to the hospital with symptoms such as fever, cough, and shortness of breath after the discharge, and both showed positive RT-PCR results. Considering recurrent COVID-19 infection, we aimed to present treatment and the 2 cases we followed.Pulmonary aluminosis (PA) is a rare form of pneumoconiosis caused by aluminum powders and vapors. Although the pathogenesis is not fully elucidated, it is thought to make a number of changes in the lungs, resulting in fibrosis. Our patient, who had cough, sputum, and dyspnea and had thorax computed tomography results showing reticular density changes and symmetrical ground-glass opacity in the bilateral upper and middle zones, informed us that he had worked in aluminum casting for 20 years and was exposed to iron, aluminum, and zinc vapors, and dust in the workplace. The patient was scheduled for bronchoscopy; aluminum analysis in bronchoalveolar lavage revealed 0.256 mg/kg of aluminum. The patient, with a history of occupational exposure, was diagnosed with aluminum metal fume-induced PA. This case shows that, even if it is preventable, PA can still occur if the occupational health and safety regulations are not met and also emphasizes the importance of the detailed occupational history in interstitial lung diseases.Modulation of human lung airway physiology by commensal microbiota has become one of the key mechanisms involved in the pathogenesis of adult asthma. link2 Recent evidence suggests that the composition of respiratory microbiota plays a significant role in the manifestation of adult asthma; however, scientific evidence about the relationship between airway microbial diversity and phenotypes of adult asthma is limited. Further research is needed to understand the interactions between the airway microbiota and host immune response to develop microbiota-based strategies in management of adult asthma. This study reviews the advances in culture-independent methods for detection of airway microbiome, the current data about airway microbiota in healthy individuals and in adult patients with asthma with a focus on bacterial communities, and the future research directions in airway microbiome.Biological lung volume reduction (BioLVR) is a novel and low-cost endobronchial treatment method aimed at reducing the volume of the target lung lobe using biological agents, including fibrin-based hydrogel, fibrinogen, and autologous blood (AB) with thrombin. BioLVR induces local inflammation, resulting in acute airway obstruction, resorption atelectasis, fibrosis, and finally tissue remodeling by contraction of the target lobe and reduction in the lung volume, similar to the application of hot water vapor and foam. In addition, patients with severe impairment in lung function and quality of life may refuses to undergo surgery, resulting in limited treatment options. In such complex clinical scenarios, BioLVR with AB appears to be a good therapeutic option. These treatment modalities resulted in favorable outcomes in patients with heterogeneous and bullous emphysema, pulmonary lymphangioleiomyomatosis, and giant bullous lesions. AB applications result in functional improvement, improvement in the quality of life, decrease in dyspnea scores, and reduction in the size of bullae. Based on the available evidence, application of AB for lung volume reduction is minimally invasive and well tolerated by patients. There was no incidence of pneumothorax or mortality. This review aimed to investigate the benefits, complications, and future perspectives of AB application as BioLVR in the treatment of hyperinflated lung diseases.
There is no consensus on a certain drug therapy for COVID-19 infection. Growing reports argue about the potential benefits of hydroxychloroquine (HCQ) in reducing morbidity and mortality in patients hospitalized with COVID-19, but with inconsistent results.This study aimed to assess the potential benefits of HCQ on viral conversion, reducing the need for ICU or mechanical ventilation, and its impact on mortality.

This retrospective observational study was conducted enrolling confirmed SARS-CoV2 patients. They were subjected to plain CXR (HRCT of chest if needed), routine laboratory tests for COVID-19 (including CBC, CRP, LDH, D-Dimer, ferritin, and blood sugar), ECG, and blood gases. They were allocated to either HCQ or non-HCQ groups. Both groups were followed-up for symptoms resolution, need for ICU admission, non-invasive or invasive ventilation, duration till conversion, and mortality.

A total of 202 patients with moderate COVID-19 were enrolled with a mean age of 55.05±10.15, out of whom 80% were male patients. link3 The most common presenting symptom was fever (87.38% in the control group versus 92% in the HCQ group), followed by cough (82.52% versus 89.9%). In total, 24.27% of patients in the control group versus 28.3% in the HCQ group deteriorated and necessitated ICU admission (p=0.52), 13.6% of the control group versus 19.2% in the HCQ group required mechanical ventilation (p=0.28), and 69.9% of the control group versus 68.9% in the HCQ group converted negative on day 7 (p=0.85). No significant mortality difference between both groups was observed (4.9% versus 6.1%, p=0.47).

This work did not support any benefits of using HCQ in patients with COVID-19, neither in reducing the need for ICU, mechanical ventilation, nor mortality.
This work did not support any benefits of using HCQ in patients with COVID-19, neither in reducing the need for ICU, mechanical ventilation, nor mortality.
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