Novel Semi‐Fluorinated Poly(ether imide)s Derived From 4‐(p‐Aminophenoxy)‐3‐trifluoromethyl‐4′‐aminobiphenyl

An unsymmetrical diamine monomer 4‐(p‐aminophenoxy)‐3‐trifluoromethyl‐4′‐aminobiphenyl has been synthesized successfully. This monomer leads to the synthesis of different novel poly(ether imide)s when reacted with different dianhydrides like pyromellatic dianhydride (PMDA), benzophenone tetracarboxylic acid dianhydride (BTDA), 2,2‐bis(3,4‐dicarboxyphenyl) hexafluoropropane (6FDA), and oxy diphthalic anhydride (ODA). The poly(ether imide) prepared from this monomer on reaction with 6FDA is soluble in several organic solvents such as N‐methylpyrolidinone (NMP), dimethylformamide (DMF), N,N‐dimethylacetamide (DMAc), tetrahydrofuran (THF), and CHCl₃. The poly(ether imide)s prepared from BTDA and ODA are soluble in NMP, DMF, and DMAc but not in THF or CHCl₃, whereas the polymer prepared from PMDA is soluble only in NMP. The water uptake value for these poly(ether imide) films is very low (0.2–0.5%), and exhibited low dielectric constants (2.81 at 1 MHz). The polymers exhibited high thermal stability up to 532 °C in air for 5% weight loss, and high glass transition temperatures up to 288 °C. The polymer exhibited high tensile strength up to 135 MPa, modulus 3.2 GPa, and elongation at break up to 25%, depending on the exact polymer structure.

The structure of the poly(ether imide) synthesised from 4‐(p‐aminophenoxy)‐3‐trifluoromethyl‐4′‐aminobiphenyl and 2,2‐bis(3,4‐dicarboxyphenyl) hexafluoropropane. This polymer was soluble in many organic solvents.     

Bilateral pneumothoraces secondary to an isolated midline zone 1 cervical stab injury

Penetrating neck trauma, though rare, carries a high morbidity and mortality risk if not recognized promptly, due to the presence of vital neurovascular and airway elements within a closed compartment. We describe the unique presentation of a high zone 1 anterior midline cervical stab injury with bilateral large pneumothoraces and extensive pneumomediastinum. Understanding the respiratory mechanics and a high clinical suspicion will help to recognize such complications of tracheobronchial injuries and their timely management is key to salvage of these patients.     

Need for Testing and Supplementation of Vitamin D3 After Release of COVID-19 Lockdown in Patients with Increased Musculoskeletal Pain

AimsTo evaluate vitamin D3 levels in patients who presented with increased musculo-skeletal pain after release of lockdown period when compared to pre-lockdown status.IntroductionDuring this COVID pandemic, many countries have implemented lockdown measures and people have to work from home and many students and workers have to restrict themselves to home. During this period, their outdoor activities were limited. After the partial release of this lockdown many of them started to have some kind of physical activity and started experiencing body pains. We evaluated such patients for vitamin D3 levels and symptoms of fibromyalgia.MethodsThis is a retrospective analysis of patients from age group 18–60 presented to outpatient department or on telephonic consultation after partial release of lockdown. All patients who had mild back ache before lockdown and had symptoms exaggerated during this lockdown release were included. All patients were investigated for vitamin D3, PTH, thyroid profile, liver functional and kidney functional tests.ResultsOut of 120 patients presented to us in a period of 3 months, 31 patients had increased symptoms when compared to pre-lockdown status. 20 out of 31 patients had low vitamin D3 levels. 14 patients also developed symptoms of fibromyalgia.ConclusionThere might be many reasons for increased pain during lockdown, but we focussed specially only on vitamin D3 because of its association with increased symptoms of COVID-19. This is a gentle reminder to test for vitamin D3 levels and supplement if found deficient.Supplementary InformationThe online version contains supplementary material available at 10.1007/s43465-021-00376-8.     

Effect of Preoperative Modifiable Psychological and Behavioural Factors on Early Outcome Following Total Knee Arthroplasty in an Indian Population

BackgroundNon-surgical factors have been found to have significant impact on outcome following Total Knee Arthroplasty (TKA). The study was conducted to know the independent effect of each of the four interacting psychological factors: anxiety, depression, pain catastrophizing and kinesiophobia on early outcome following TKA in an Indian population.Materials and Methods104 consecutive patients undergoing TKA were included in the study and followed up at 6 weeks, 6 months and one year. Preoperatively, Hospital Anxiety and Depression Scale was used to diagnose and quantify anxiety and depression, pain catastrophizing and kinesiophobia were assessed using Pain Catastrophizing Scale and Tampa Scale for Kinesiophobia, respectively. Outcome was assessed on the basis of Knee Society Score and Knee Injury and Osteoarthritis Outcome Score. Regression analysis was done to know independent effect of each factor on outcome scores.ResultsNine (8.7%) patients were found to have undiagnosed psychopathology. The patients with psychopathologies were found to have significantly worse knee outcome scores on follow-up, although the rate of improvement in knee symptoms and function was not significantly different from those without psychopathology. The degree of Anxiety correlated with worse knee pain and stiffness up to 6 months while it correlated with poor knee function for a longer duration. The degree of depression and pain catastrophizing correlated with worse knee pain, stiffness and function at all visits while kinesiophobia didn’t show correlation independent other factors.ConclusionPsychopathology was found to be associated poor knee outcome scores with degree of preoperative depression and pain catastrophizing as significant independent predictors as poor outcome, whereas the effect of degree of anxiety on knee pain and stiffness was found to wane over time. Kinesiophobia didn’t show any independent correlation.Supplementary InformationThe online version of this article (10.1007/s43465-020-00325-x) contains supplementary material, which is available to authorized users.     

Liver transplantation for acute liver failure in a SARS-CoV-2 PCR-positive patient

Current guidelines recommend deferring liver transplantation (LT) in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection until clinical improvement occurs and two PCR tests collected at least 24 hours apart are negative. We report a case of an 18-year-old, previously healthy African-American woman diagnosed with COVID-19, who presents with acute liver failure (ALF) requiring urgent LT in the context of SARS-CoV-2 polymerase chain reaction (PCR) positivity. The patient was thought to have acute Wilsonian crisis on the basis of hemolytic anemia, alkaline phosphatase:bilirubin ratio <4, AST:ALT ratio >2.2, elevated serum copper, and low uric acid, although an unusual presentation of COVID-19 causing ALF could not be excluded. After meeting criteria for status 1a listing, the patient underwent successful LT, despite ongoing SARS-CoV-2 PCR positivity. Remdesivir was given immediately posttransplant, and mycophenolate mofetil was withheld initially and the SARS-CoV-2 PCR test eventually became negative. Three months following transplantation, the patient has made a near-complete recovery. This case highlights that COVID-19 with SARS-CoV-2 PCR positivity may not be an absolute contraindication for transplantation in ALF. Criteria for patient selection and timing of LT amid the COVID-19 pandemic need to be validated in future studies.     

Interaction with 14-3-3 proteins promotes functional expression of the potassium channels TASK-1 and TASK-3

The two-pore-domain potassium channels TASK-1, TASK-3 and TASK-5 possess a conserved C-terminal motif of five amino acids. Truncation of the C-terminus of TASK-1 strongly reduced the currents measured after heterologous expression in Xenopus oocytes or HEK293 cells and decreased surface membrane expression of GFP-tagged channel proteins. Two-hybrid analysis showed that the C-terminal domain of TASK-1, TASK-3 and TASK-5, but not TASK-4, interacts with isoforms of the adapter protein 14-3-3. A pentapeptide motif at the extreme C-terminus of TASK-1, RRx(S/T)x, was found to be sufficient for weak but significant interaction with 14-3-3, whereas the last 40 amino acids of TASK-1 were required for strong binding. Deletion of a single amino acid at the C-terminal end of TASK-1 or TASK-3 abolished binding of 14-3-3 and strongly reduced the macroscopic currents observed in Xenopus oocytes. TASK-1 mutants that failed to interact with 14-3-3 isoforms (V411*, S410A, S410D) also produced only very weak macroscopic currents. In contrast, the mutant TASK-1 S409A, which interacts with 14-3-3-like wild-type channels, displayed normal macroscopic currents. Co-injection of 14-3-3ζ cRNA increased TASK-1 current in Xenopus oocytes by about 70 %. After co-transfection in HEK293 cells, TASK-1 and 14-3-3ζ (but not TASK-1ΔC5 and 14-3-3ζ) could be co-immunoprecipitated. Furthermore, TASK-1 and 14-3-3 could be co-immunoprecipitated in synaptic membrane extracts and postsynaptic density membranes. Our findings suggest that interaction of 14-3-3 with TASK-1 or TASK-3 may promote the trafficking of the channels to the surface membrane.     

Evidence for the existence of two forms of α2A-adrenoceptors in the rat

Summary The _2A-adrenoceptors in rat spleen, kidney, spinal cord and cerebral cortex were studied using [³H]-RX821002 radioligand binding. In the spleen, spinal cord and cerebral cortex, the ligand bound to saturable sites with a K _d of about 1 nmol/l and capacities of 134, 240 and 290 fmol/mg protein, respectively. Computer modelling competition curves for 39 drugs, including those for _2A-, _2B- or _2C-adrenoceptor selective drugs, indicated that the sites labelled by [³H]-RX821002 in the spleen consisted of a single population of _2A-adrenoceptors. However, the competition curves for guanoxabenz were definitely biphasic and resolved into two site fits, indicating that guanoxabenz was binding to both high affinity (K _d = 35 nmol/1) and low affinity (K _d = 8900 nmol/1) _2A-adrenoceptor sites in the proportions 57% and 43%, respectively. The K _d ^Sfor a number of ₂-adrenoceptor subtype selective drugs, measured in competition with [³H]-RX821002 in cerebral cortex and spinal cord, were highly correlated with those obtained in the spleen indicating their _2A-adrenoceptor nature. However, by contrast to the results with the spleen, the guanoxabenz competition curves for the spinal cord and cerebral cortex were monophasic and resolved only into one site fits, the K _d of guanoxabenz being about 4000 nmol/l for both tissues. Drug K _d ^Sfor kidney _2A-adrenoceptors were also determined using [³H]-RX821002. For nearly all drugs tested, the K _d ^Swere highly correlated with those found for the _2A-adrenoceptors in the other rat tissues. However, for guanoxabenz, the data indicated that it competed with [³H]-RX821002 at a single _2A-adrenoceptor site with a K _d of 39 nmol/1. When the rat _2A-adrenoceptor gene RG20 was transiently expressed in COS-7 cells and its ligand binding properties probed using [³H]-RX821002, the drug K _d ^Sobtained were also highly correlated with those found for the _2A-adrenoceptors in the spleen, cerebral cortex, spinal cord and kidney of the rat. For the RG20 encoded receptor, the guanoxabenz competition curves were steep and monophasic and modelled best into one site fits, with the Kd of guanoxabenz being 5200 nmol/1.It is suggested that guanoxabenz can differentiate between two forms of _2A-adrenoceptors in the rat: _2A1 and _2A2. The _2A1-form is present in the spleen and kidney where it shows a high apparent affinity for guanoxabenz. The _2A2-form shows a low apparent affinity for guanoxabenz and is present in the spleen, cerebal cortex and spinal cord. The _2A2-form of the rat ₂-adrenoceptor appears to be encoded by the RG20 gene. The _2A, and _2A2-adrenoceptor forms do not represent high and low affinity receptor forms for agonists because assays included EDTA, Gpp(NH)p and Na⁺, which eliminated the high affinity receptors for agonists.     

T-cell signature cytokines distinguish pulmonary sarcoidosis from pulmonary tuberculosis

Sarcoidosis is a systemic inflammatory disorder characterized by tissue infiltration due to mononuclear phagocytes and lymphocytes and associated noncaseating granuloma formation. Pulmonary sarcoidosis (PS) shares a number of clinical, radiological, and histopathological characteristics with that of pulmonary tuberculosis (PTB). Due to this, clinicians face issues in differentiating between PS and PTB in a substantial number of cases. There is a lack of any specific biomarker that can diagnose PS distinctively from PTB. We compared T-cell-based signature cytokines in patients with PS and PTB. In this study, we proposed a serum biomarker panel consisting of cytokines from cells: T helper (Th) 1 [interferon-gamma (IFN-γ); tumor necrosis factor-alpha (TNF-α)], Th9 [interleukin (IL)-9], Th17 [IL-17], and T regulatory (Treg) [IL-10; transforming growth factor-beta (TGF-β)]. We performed the principal component analysis that demonstrated that our serum cytokine panel has a significant predictive ability to differentiate PS from PTB. Our results could aid clinicians to improve the diagnostic workflow for patients with PS in TB endemic settings where the diagnosis between PS and PTB is often ambiguous.