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The incubation period of COVID‐19 symptoms, along with the proliferation and high transmission rate of the SARS‐CoV‐2 virus, is the cause of an uncontrolled epidemic worldwide. Vaccination is the front line of prevention, and antiinflammatory and antiviral drugs are the treatment of this disease. In addition, some herbal therapy approaches can be a good way to deal with this disease. The aim of this study was to evaluate the effect of propolis syrup with Hyoscyamus niger L. extract in hospitalized patients with COVID‐19 with acute disease conditions in a double‐blinded approach. The study was performed on 140 patients with COVID‐19 in a double‐blind, randomized, and multicentral approach. The main inclusion criterion was the presence of a severe type of COVID‐19 disease. The duration of treatment with syrup was 6 days and 30 CC per day in the form of three meals. On Days 0, 2, 4, and 6, arterial blood oxygen levels, C‐reactive protein (CRP), erythrocyte sedimentation rate, and white blood cell, as well as the patient's clinical symptoms such as fever and chills, cough and shortness of breath, chest pain, and other symptoms, were recorded and analyzed. Propolis syrup with H. niger L. significantly reduces cough from the second day, relieving shortness of breath on the fourth day, and significantly reduces CRP, weakness, and lethargy, as well as significantly increased arterial blood oxygen pressure on the sixth day compared to the placebo group (p < 0.05). The results in patients are such that in the most severe conditions of the disease 80% < SpO2 (oxygen saturation), the healing process of the syrup on reducing CRP and increasing arterial blood oxygen pressure from the fourth day is significantly different compared with the placebo group (p < 0.05). The use of syrup is associated with a reduction of 3.6 days in the hospitalization period compared with the placebo group. Propolis syrup with H. niger L. has effectiveness in the viral and inflammatory phases on clinical symptoms and blood parameters and arterial blood oxygen levels of patients with COVID‐19. Also, it reduces referrals to the intensive care unit and mortality in hospitalized patients with COVID‐19. So, this syrup promises to be an effective treatment in the great challenge of COVID‐19. [ABSTRACT FROM AUTHOR]

Two different types of hollow‐fiber membrane contactors were used for CO2 separation from the gas stream with monoethanolamine (MEA) absorbent and numerically investigated. After the model validation with experimental data, CO2 removal efficiency, MEA concentration, and pressure drop variation were examined under different conditions by variation of some effective parameters such as gas stream velocity, absorption solution velocity, membrane porosity, and membrane tortuosity. Membrane tortuosity and porosity enhancement led to light decrease and light increase in CO2 removal efficiency, respectively, but gas stream velocity enhancement significantly reduced the CO2 removal efficiency. [ABSTRACT FROM AUTHOR]

Depression and anxiety have been linked with reduced stress‐induced cardiovascular reactivity (CVR), which could be indicative of autonomic dysregulation. Less is known about the association between work‐related fatigue and CVR. Truck drivers experience high levels of depression, anxiety, and fatigue, with repeated psychophysiological stressors on the road, yet little is known about the effects of these conditions on their CVR. Three hundred eighty six truck drivers completed the Hospital Anxiety and Depression Scale (HADS) and the Occupational Fatigue Exhaustion/Recovery Scale (OFER‐15). Systolic (SBP) and diastolic (DBP) blood pressure and heart rate (HR) were measured at rest and during a stressor protocol to measure CVR. Multivariate regression analyses were used to determine relationships between variables and adjusted for nine key covariates. Higher symptoms of persistent fatigue were related to a reduced SBP reactivity (β = −.236, p =.009) and reduced DBP reactivity (β = −.257, p =.005), whereas there was a positive trend between acute fatigue and DBP reactivity (β =.169, p =.052). Higher symptoms of anxiety were related to a reduced SBP reactivity (β = −.164, p =.016). This study demonstrated in a population of truck drivers that both anxiety and persistent fatigue were related to an attenuated SBP reactivity in a combined model, whereas there was a positive trend between acute fatigue solely and DBP reactivity. These novel findings may have serious implications for cardiovascular disease risk in truck drivers, and future research should attempt to establish the causal effect of these associations and the underlying physiological mechanisms. Truck drivers experience high levels of depression, anxiety, and fatigue, as well as repeated psychophysiological stressors on the road. Our study is novel by showing that increased fatigue and symptoms of anxiety are related to attenuated cardiovascular reactivity in truck drivers. Attenuated physiological responses may have negative consequences for future health status of truck drivers. [ABSTRACT FROM AUTHOR]

The measurement of different quality properties requires particular tools and chemical materials, most of which are time‐using. The present research was accomplished to survey the possibility of using NIRS (870–2450 nm) to predict the amylose content (AC), protein content (PC), breakdown (BDV), and setback viscosity (SBV) of white rice (Khazar variety) and its flour. Determination coefficients of calibration models to flour samples of AC, PC, BDV, and SBV generated by the partial least‐squares (PLS) regression were obtained as R2cal ≥.85 and R2pre ≥.80. Root mean square error of calibration (RMSEC) was calculated as 0.393, 0.07, 2.55, and 1.33, respectively. Similarly to grain samples, were obtained as R2cal ≥.88 and R2pre ≥.71 for calibration and prediction. RMSEC was measured as 0.303, 0.27, 2.59, and 3.11, respectively. NIRS has the potential to be used as a quick technique for predicting the quality attributes of kernel specimens. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is associated with epileptiform activity in the hippocampus; however, the underlying mechanisms have not been fully determined. The goal was to understand what changes take place in intrinsic neuronal physiology in the hippocampus after blunt force trauma to the cortex. In this context, hyperpolarization‐activated cation current (Ih) currents may have a critical role in modulating the neuronal intrinsic membrane excitability; therefore, its contribution to the TBI‐induced hyperexcitability was assessed. In a model of TBI caused by controlled cortical impact (CCI), the intrinsic electrophysiological properties of pyramidal neurons were examined 1 week after TBI induction in rats. Whole‐cell patch‐clamp recordings were performed under current‐ and voltage‐clamp conditions following ionotropic receptors blockade. Induction of TBI caused changes in the intrinsic excitability of pyramidal neurons, as shown by a significant increase and decrease in firing frequency and in the rheobase current, respectively (p <.05). The evoked firing rate and the action potential time to peak were also significantly increased and decreased, respectively (p <.05). In the TBI group, the amplitude of instantaneous and steady‐state Ih currents was both significantly smaller than those in the control group (p <.05). The Ih current density was also significantly decreased (p <.001). Findings indicated that TBI led to an increase in the intrinsic excitability in CA1 pyramidal neurons and changes in Ih current could be, in part, one of the underlying mechanisms involved in this hyperexcitability. [ABSTRACT FROM AUTHOR]

One of the major problems in predicting the quality properties of rice is that conducting experiments in the food industry can be highly expensive. The objective of this study was to predict some quality properties in varieties (Domsiah, Hashemi, Dorfak, and Kadus) via compression test at moisture levels 9 and 14% w.b. Based on historical data design, RSM was used to model and estimate of dependent variables (amylose (AC) and protein content (PC), gelatinization temperature, gel consistency GC), minimum (Min.V), final (FV), breakdown (BDV) and setback viscosity (SBV), peak time (PT) and pasting temperature (Pa.T)) through independent variables (the rate of force, deformation, rupture energy, tangent, and secant modulus). An ANOVA test showed that models were significant (p < 0.05). The most appropriate model for response variables prediction of AC and GC (Kadus 14%), PC (Domsiah 9%), Min.V, FV, and SBV (Dorfak 9%), BDV (Dorfak 14%), PT (Hashemi 14%), and Pa.T (Kadus 9%) was Rpred2 as 0.86, 0.85, 0.93, 0.955, 0.953, 0.94, 0.94, 0.86, and 0.91, respectively, with the most appropriate optimal values as 23.52%, 48, 10%, 164.95 RVU, 304.12 RVU, 162.66 RVU, 64.52 RVU, 6.09 min, and 92.45°C and desirability as 0.91, 0.95, 0.95, 0.80, 0.89, 0.83, 0.84, 0.89, and 0.96, respectively. The optimal values of the independent variables have a decreasing trend, and the optimal values of the response variables are proportional to the optimal conditions. The results indicated that the RSM could be quite useful in the optimization of the models developed for predicting the rice quality properties. [ABSTRACT FROM AUTHOR]

Abstract: Background: The trisynaptic circuit ( entorhinal cortex– dentate gyrus–CA3–CA1) is a key unidirectional network in the hippocampus. Damage to the hippocampus interrupts this circuit and causes neurological disorders. Efficient delivery of therapeutic genes into this network is of great interest with respect to treating trisynaptic circuit pathologies. Methods: We generated a lentivector system pseudotyped by a variant of rabies glycoprotein, FUG‐B2. The efficiency of the vector in the retrograde transduction of the rat hippocampal neurons (i.e. the entorhinal cortex from the dentate gyrus, the dentate gyrus from CA3, and CA3 from CA1) was examined by direct injection of the vector into the dentate gyrus, CA3 and CA1. To distinguish transduction of the neuronal and glial cells, as well as selective retrograde gene transfer, double‐staining of the green fluorescent protein (GFP) expressing cells with the specific neuron biomarker NeuN (neuronal nuclear protein) and the specific glia biomarker GFAP (glial fibrillary acidic protein) was performed across the network. Results: The transgene was successfully introduced into the circuit. More than 80% of the neuronal and glial cells at the injection sites preserved GFP expression during the 2‐month period after vector injection. Importantly, GFP was expressed selectively in almost 80.0% of the presynaptic neuronal cells by retrograde axonal transport of the vector. Conclusions: The FUG‐B2‐based vector system can efficiently introduce the transgene into the rat hippocampal neurons both directly and indirectly through retrograde monosynaptic movement. This efficient and long‐lasting gene delivery might provide a tool for treating neurological disorders originating in hippocampal circuits. [ABSTRACT FROM AUTHOR]

The chemical graft copolymerization reactions were used to enhance water resistance of paper by reaction of acrylonitrile (AN) monomer onto cellulosic paper sheet in the presence of comonomer (styrene or acrylic acid or itaconic acid) 1 : 1 molar ratio in dimethyl formamide using benzoyl peroxide as free radical initiator under nitrogen atmosphere at 70°C. The infrared spectroscopy confirms that graft copolymerization reaction occurs onto the paper samples. Water absorption test was carried out following the Normal Protocol 7/81 (water absorption by complete immersion) to evaluate the protective effect of the graft treatment onto the paper sheet. It was found that the three graft copolymerization systems reduced the water absorption of the investigated paper and the reduction of water absorption is directly proportional to the grafting %. The wettability of the grafted and ungrafted paper sheet samples were investigated using the wicking time method which exhibits the decreasing of paper sheet wettability using the AN/S comonomers in the graft copolymerization reaction. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013 [ABSTRACT FROM AUTHOR]

The reversible cycling of CaO adsorbents to CaCO3 for high-temperature CO2 capture is substantially improved by mechanical treatment. The mechanical milling intensity and conditions of grinding (e.g., wet vs. dry, planetary vs. vibratory milling) were determined to be the main factors that control the effectiveness of the mechanochemical synthesis to enhance the recycling stability of the sorbents prepared. In addition, MgO was used as an example of an inert binder to help mitigate CaCO3 sintering. Wet planetary milling of MgO into CaCO3 allowed efficient particle size reduction and the effective dispersion of MgO throughout the particles. Wet planetary milling yielded the most stable sorbents during 50 cycles of carbonation-calcination. [ABSTRACT FROM AUTHOR]

The chemical graft copolymerization reaction of acrylonitrile (AN) onto paper sheet was performed. The effect of initiator concentration, monomer concentration, and temperature on the reaction rate was studied. The reaction rate equation of the graft copolymerization reaction is found to be R = K [initiator][monomer]. The apparent activation energy ( E) of the copolymerization reaction is found to be 35.99 KJ/mol. The infrared characteristic absorption bands for cellulosic paper structure and the paper gr-AN are studied. Tensile break load, porosity, and burst strength were measured for the grafted and pure paper sheet. It was found that the mechanical properties are improved by grafting. The chemical resistance of the graft product against strong acid (HCl), strong alkali (NaOH), polar and nonpolar solvents was investigated. It was found that the resistance to these chemicals is enhanced by grafting. From the TGA and DTA data, it is clear that the grafted paper sheet is more thermally stable than pure paper sheet. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011 [ABSTRACT FROM AUTHOR]

Poly(o-phenylenediamine-co-2-aminobenzothiazole), P(oPD-co-2ABT), has been synthesized electrochemically from an aqueous acid medium. The initial rate of electrocopolymerization reaction on platinum electrode is small, and the rate law is Rate = KE [Na2SO4]0.48 [HCl]1.09 [M]2.08. The apparent activation energy (Ea) is found to be 57.44 kJ mol-1. The polymer films obtained have been characterized by cyclic voltammetry, X-ray diffraction, elemental analysis, TGA, scanning electron microscopy, and IR-spectroscopy. The mechanism of the electrochemical polymerization reaction has been discussed. The monomer reactivity ratios (r1 and r2) were calculated using Fineman-Röss method. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011 [ABSTRACT FROM AUTHOR]

Objective To assess the efficacy and tolerability of ondansetron in combination with selective serotonin reuptake inhibitors (SSRIs) in patients with obsessive-compulsive disorder (OCD). Methods The study was an 8-week pilot double-blind randomized clinical trial. Forty-two adult outpatients who met the Diagnostic and Statistical Manual, Fourth Edition, Text Revision (DSM-IV-TR) criteria for OCD based on the structured clinical interview participated in the trial. In this study, patients were randomly assigned to receive either ondansetron (4 mg) plus fluoxetine or fluoxetine (20 mg/day) plus placebo. Results The results showed a significant difference between two groups in the treatment of OCD (based on t-test). There was not any significant difference between the two groups in terms of observed side effects. Conclusions The results of this study show that ondansetron has positive effects on obsession and compulsion which start two weeks after the beginning of the treatment. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aim: The clinical importance of preterm premature rupture of the membranes (PPROM) is its relationship to maternal and neonatal mortality and morbidity, especially in twin pregnancies. The aim of this study was to determine and compare the role of inflammatory factors as predictors of the PPROM outcome between singleton and twin pregnancies. Methods: The medical records of 22 twins delivered between 28 and 34 weeks and complicated by PPROM were reviewed at the Al-Zahra Hospital in Tabriz, Iran. Also among singletons, 55 cases of matched gestational age were randomly selected as a control group. Three laboratory indices of neonatal white blood cell (WBC) count and C-reactive protein (CRP) in the two groups were measured immediately after delivery and the effects of two factors on neonatal outcome were assessed. Results: In singletons, there was adverse relationship between the mean of WBC count and duration of latency ( P = 0.007). Also, a positive relationship between the means of ventilation time and WBC count in second twins was found ( P = 0.034). Positive CRP was the main predictor of neonatal intensive care unit admission in both singletons (odds ratio: 4.929, P = 0.042) and first twins (odds ratio: 9.000, P = 0.005). However, positive CRP did not influence the existence of metabolic acidosis or duration of latency in either of the two groups. Conclusion: Neonatal WBC count was a predictor for the duration of latency in singletons and for ventilation time in twins. Positive neonatal CRP was an important factor for the prediction of neonatal intensive care unit admission in both types of pregnancy; its role in twins is clearer than in singletons. [ABSTRACT FROM AUTHOR]

The article presents a study which carried out O-phenylenediamine (o-PD)'s electropolymerization on platinum (Pt)-electrode. The study made use of cyclic voltammetry method in performing the electropolymerization. Results indicate that the initial rate of P(o-PD)'s electropolymerization reaction on platinum electrode is comparatively low.

The article investigates the preparation of a new vinyl monomer containing flouorescein moiety which was covalently bonded with the vinyl group and its copolymerization with methyl methacrylate. It examines the kinetics and characterization of the resulting modified laser dye monomer, 2-(6-acryl-oyloxy-3-oxo-3H-xanthene-9-yl)-benzoic acid ethyl ester (AOXBE). It showed how an increase in the new monomer inhibited the effect on the rate of copolymerization.

The article discusses a study which investigated the kinetics, optimum conditions, and mechanism of the electrochemical copolymerization of a binary mixture of pyrrole and o-aminobenzoic acid in aqueous hydrochloride (HCl) solution on platinum electrode. The results of the characterization of the obtained copolymer films by hydrogen nuclear magnetic resonance (H-NMR), infrared (IR), elemental analysis, thermogravimetric analysis (TGA), and cyclic voltammetry are discussed.

The protection of some poly(methyl methacrylate) (PMMA) samples against γ rays was investigated in the absence and presence of poly(p‐sulfanilamide). Pure PMMA (without additives) and PMMA–poly(p‐sulfanilamide) blend samples were irradiated with γ rays for different exposure doses (5, 15, 25, 35, 50, 75, and 100 kGy). The viscosity‐average molecular weights were determined and thin‐layer chromatography measurements were carried out after each irradiation dose. The maximum protection against γ rays was found when 1% poly(p‐sulfanilamide) was used. The radiation chemical yield for main scission (Gs) was calculated and had lower values in the case of 1% poly(p‐sulfanilamide). The energy absorption per scission was maximum for 1% poly(p‐sulfanilamide), and this confirmed the obtained Gs data. From thin‐layer chromatography studies, it was observed that both the retention factor (Rf) values and polydispersity of the PMMA samples increased with an increasing exposure dose. The effect of γ irradiation on PMMA films doped with 1% poly(p‐sulfanilamide) was investigated with UV spectroscopy after the extraction of the additives. A change in the intensity of the absorption bands with an increasing irradiation dose was recorded. It is suggested that PMMA films doped with this type of polymer can be used as dosimeters. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007 [ABSTRACT FROM AUTHOR]

Electrochemical copolymerization of a binary mixture of pyrrole and 2‐amino‐4‐phenylthiazole on platinum electrode in acid medium was carried out. The kinetic parameters were calculated using ex situ microgravimetric and electrochemical data. The experimentally obtained kinetic equations were RP,W = kW [acid]1.16 [monomer]1.85 from microgravimetric data and RP,E = kE [acid]1.1 [monomer]1.9 from the values of the anodic current density using cyclic voltammetry technique. The apparent activation energy was calculated by the two techniques and is found to be 32.55 and 29.6 kJ/mol from microgravimetric and electrochemical data respectively. The monomer reactivity ratios (r1 and r2) were calculated according to Fineman–Ross method and the copolymer structure was determined from the obtained data, which is found to be a block copolymer structure. The applications of the prepared copolymer as corrosion protection of mild steel in acid medium are studied. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 4047–4058, 2007 [ABSTRACT FROM AUTHOR]

Background: Most of deaths from cervical cancer occur in low and medium income countries and opportunistic screening for cervical cancer does not decrease the incidence rate, thus organized mass screening is needed for control of the disease. Methods: Pathology reports of cervical smears, biopsies, endocervical curettings, and hysterectomy specimens were collected from 22 pathology centers in East Azarbayjan during 2003–2004. Incidence rates for low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL) and cervical carcinoma were calculated by (Incidence/Population at risk) ×100 000. At risk population for cervical intraepithelial neoplasia (CIN) (between 18 and 64 years old) and invasive carcinoma of the cervix (between 30 and 64 years old) were 1 103 109 and 537 217 respectively. Result: The adjusted incidence rates for LSIL, HSIL and cervical carcinoma were 3.68, 1.19 and 5.11 per 100 000 women at risk, respectively. Conclusion: In contrast to developed countries we identified a higher incidence rate of cervical invasive cancers than preinvasive lesions, therefore, the importance and necessity of well organized mass screening in our country must be emphasized. [ABSTRACT FROM AUTHOR]

The leaf essential oil of Laurus nobilis Linn. (Lauraceae) has been evaluated for antinociceptive and anti-inflammatory activities in mice and rats. The essential oil exhibited: (1) a significant analgesic effect in tail-flick and formalin tests; (2) a dose-dependent anti-inflammatory effect in the formalin-induced edema and (3) a moderate sedative effect at the anti-inflammatory doses. The analgesic and anti-inflammatory effect of the essential oil was comparable to reference analgesics and non-steroid anti-inflammatory drugs: morphine and piroxicam. Present results make the essential oil worthy of further investigations. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Summary: Purpose: There is some structural similarity between the androgen receptor antagonist, flutamide (Flut) and benzodiazepines (BZDs). We evaluated the possible anticonvulsant effect and interaction of Flut with BZD receptors in common seizure models. Methods: (a) Different groups of mice each were pretreated i.p. with Flut, and after 0.5 h, they received chemoconvulsants [pentylenetetrazole (PTZ), bicuculline, aminophylline, strychnine or kainic acid]. Latency and incidence of a clonic seizure were recorded. (b) Mice were pretreated i.p. with Flut, and after 0.5 h, transauricular electroshock was applied. Occurrence of a tonic seizure was observed. (c) Amygdala-kindled rats were pretreated i.p. with Flut, and 0.5, 1, or 2 h later, they were stimulated at afterdischarge threshold. Then the seizure parameters (afterdischarge duration, seizure severity, and stage 5 duration) were recorded. (d) The effect of Flut on clonic seizure threshold was determined by i.v. infusion of bicuculline or PTZ to different groups of Flut-receiving mice. To determine the possible interaction of Flut with BZD receptors, the flumazenil (FMZ)+Flut effect on clonic seizure threshold was compared with the effect of Flut. (e) Neurotoxicity of Flut was evaluated by rotarod test at 30 min after administration. Results: Flut produced a dose-dependent anticonvulsant effect against PTZ-induced seizures [median effective dose (ED50 ), 67.0 mg/kg]. Moreover, Flut elevated the clonic seizure threshold induced by bicuculline or PTZ. FMZ reversed the effect of Flut on the threshold of PTZ seizures. A median toxic dose (TD50 ) value of 124.8 mg/kg was obtained for Flut. Conclusions: Flut both blocks PTZ-induced clonic seizures and elevates the threshold of PTZ or bicuculline-induced clonic seizures, through interaction with BZD receptors. [ABSTRACT FROM AUTHOR]

Abstract Background: Accumulation of endogenous opioids and overproduction of nitric oxide has been reported in cholestatic mice. It is well known that endogenous opioids and nitric oxide alter the susceptibility of experimental animals to different models of seizure. Methods: The alterations in clonic seizure thresholds, induced by pentylenetetrazole from 1 to 6 days after bile duct ligation, were evaluated in mice. Whether the pretreatment of cholestatic mice with different doses of opioid receptor antagonist naltrexone, or nitric oxide inhibitor N ω -nitro-L-arginine methyl ester would have changed the clonic seizure threshold was also examined. Results: While in sham-operated mice the clonic seizure threshold was similar to that of the thresholds in unoperated controls, a time-dependent increase in the threshold was observed in cholestatic mice, reaching a peak on day 3 after bile duct ligation and declining partially after the 4th day. Chronic pretreatment with naltrexone (2, 5 and 10 mg/kg, i.p.) reversed the increased threshold in cholestatic mice on day 3 after operation in a dose-dependent manner with the highest doses used restoring the threshold to that of the control animals. A similar reversal of the increased threshold was observed after acute (1, 3 and 10 mg/kg, i.p.) or chronic (10 mg/kg, i.p. for 4 days) pretreatment with N ω -nitro-L-arginine methyl ester. Moreover, concurrent administration of doses of N ω -nitro-L-arginine methyl ester and naltrexone that each separately induced a partial reversal of increased seizure threshold in cholestasis caused a complete restoring of the threshold to the control level. Conclusions: Based on these findings, both opioid receptors and nitric oxide may be involved in the dramatic increase in pentylenetetrazole-induced seizure threshold in cholestasis. [ABSTRACT FROM AUTHOR]

Summary People with COVID‐19 infection continue to have their symptoms or develop new ones after recovery. This is called long‐COVID syndrome. We aimed to examine the association of general and abdominal obesity with long COVID. This study was conducted using Isfahan COVID Cohort (ICC). Totally 4008 including 3213 hospitalized and 795 non‐hospitalized patients with positive RT‐PCR were included. Body mass index (BMI) and waist circumference (WC) were calculated. BMI >25 kg/m2 and WC >88 cm in women and 102 cm in men were considered generally and abdominally obese, respectively. By using an open‐ended questionnaire, subjects were asked whether they had any new or persistent symptom. Reported symptoms were categorized in three different fields including general, cardiac, and respiratory symptoms. Higher BMI and WC tended to increase general symptoms (odds ratio [OR] for BMI = 1.16, 95 % confidence interval (95% CI): 0.97, 1.38, and OR for WC = 1.14, 95% CI: 0.99, 1.32). Higher BMI significantly increased cardiovascular (OR = 1.38, 95% CI: 1.14, 1.67) and respiratory symptoms (OR = 1.43, 95% CI: 1.15, 1.78). Compared with patients with normal WC, the risk of cardiovascular (OR = 1.44, 95% CI: 1.24, 1.69) and respiratory symptoms was significantly higher in subjects with abdominal obesity (OR = 1.31, 95% CI: 1.10, 1.56). We found that general and abdominal obesity were associated with increased risk of cardiovascular and respiratory symptoms in patients with long‐COVID symptoms. However, only general obesity was associated with increased risk of general symptoms. [ABSTRACT FROM AUTHOR]

Janus Kinase 2 (Jak2) is a non-receptor tyrosine kinase that links ligand/receptor interactions at the cell surface to transcriptional alterations in the nucleus. Phosphotyrosine residues play an important role in regulationg Jak2 function. Here, we sought to determine the role of a novel phosphotyrosine, Y972, on Jak2 function. We hypothesized that phosphorylation of Jak2 at position 972 is critical for achieving full Jak2 function. To test this, we produced a mutant Jak2 expressing a tyrosine to phenylalanine point mutation at position 972 (Y972F) and investigated the effects of this mutation on several aspects of Jak2 function. Specifically, we determined that the Y972F mutation significantly reduced Jak2 autophosphorylation. We showed that this loss results from a decrease in Jak2 kinase function. The Y972F loss of function impaired the ability of Jak2 to phosphorylate SH2B-β, but did not hinder the ability of Jak2 to bind SH2B-β. We also found that the Y972F mutation significantly affected the ability of Jak2 to become activated by SH2B-β. The Y972F mutation hindered growth hormone dependent Jak2 activation and STAT1 nuclear translocation. In conclusion, phosphorylation at Y972 is critical for maximal Jak2 function and in turn affects Jak2-dependent signaling. [ABSTRACT FROM AUTHOR]

Recently, a Jak2 mutation (V617F) was identified in several myeloproliferative disorders. Here, we used an in silico approach to identify novel Jak2-specific inhibitors. Specifically, we used a high-throughput program called DOCK to predict the ability of 20,000 small molecules to interact with a structural pocket adjacent to the ATP binding site of murine Jak2. The top six scoring compounds were tested for their ability to inhibit Jak2 tyrosine kinase function in vitro. One compound, Z3, effectively inhibited Jak2-V617F and Jak2-WT autophosphorylation. Z3 inhibits total Jak2 tyrosine phosphorylation as well as phosphorylation of the critical tyrosine 1007 residue in both a dose-and time-dependent manner. Z3 reduces growth hormone-dependent Jak2 activation and is a direct inhibitor of Jak2-WT and Jak2-V617F tyrosine kinase autophosphorylation as measured by an in vitro kinase assay. In addition, Z3 inhibits proliferation of human erythroleukemia (HEL) cells, which express the Jak2-V617F mutation. Furthermore, Z3 is not cytotoxic to cells at concentrations that inhibit both Jak2-WT and Jak2-V617F autophosphorylation as measured by their ability to exclude propidium iodide. In summary, this work demonstrates proof-of-principle concept that in silico molecular modeling can be used as a means to identify specific tyrosine kinase inhibitors such as those directed against Jak2. [ABSTRACT FROM AUTHOR]