Structural, surface morphological and dielectric studies of guanidinium salt incorporated poly (ethylene oxide)/poly (vinyl pyrrolidone) solid polymer electrolytes.

The research article investigates the effect of incorporating the guanidinium carbonate (GuC) salt into the poly vinylpyrrolidone (PVP) and polyethylene oxide (PEO) polymer matrix. Various weight percentages of GuC enriched PVP/PEO solid polymer electrolytes (SPEs) have been prepared by the simplest solution casting process. XRD analysis revealed that the incorporation of the GuC salt led to changes in the crystalline structure of the PVP/PEO. FTIR analysis confirms the presence of guanidinium carbonate in the blended polymeric system. FESEM imaging showed the uniform and smooth surface view of the electrolytes. DSC analysis suggests that the addition of the GuC led to a decrease in the melting temperature and an increase in the crystallisation temperature. The temperature-dependent dielectric analysis showed that the presence of the organic salt led to an increase in the dielectric constant of the polymer blend. Among all the prepared electrolytes, 25 wt.% GuC added polymer electrolyte achieved a higher conductivity of 3.00764 × 10-7 S/cm. Overall, the results of the study suggest that the incorporation of the GuC salt into the PVP/PEO can lead to significant changes in the structural, thermal, and dielectric properties of the blend. These findings have potential implications for the use of PVP/PEO blends in solid state battery applications.

99mTc-DPD scintigraphy in immunoglobulin light chain (AL) cardiac amyloidosis.

AIMS: Technetium-99m-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD scintigraphy) is recognized as highly accurate for the non-invasive diagnosis of transthyretin (ATTR) cardiac amyloidosis (CA). A proportion of patients with immunoglobulin light chain (AL) CA have also been reported to show cardiac 99mTc-DPD uptake. Herein, we assessed the frequency and degree of cardiac 99mTc-DPD uptake and its clinical significance among patients with AL CA. METHODS AND RESULTS: Between 2010 and 2017, 292 consecutive patients with AL CA underwent 99mTc-DPD scintigraphy and were included in this study: 114 (39%) had cardiac 99mTc-DPD uptake: grade 1 in 75%, grade 2 in 17%, and grade 3 in 8% of cases. Patients with cardiac 99mTc-DPD uptake had poorer cardiac systolic function and higher N-terminal pro-brain natriuretic peptide. No differences were noted in cardiac magnetic resonance parameters between patients with and without cardiac 99mTc-DPD uptake (N = 19 and 42, respectively). Patients with cardiac 99mTc-DPD uptake showed a trend to worse survival than those with no uptake (log-rank P = 0.056). Among 22 patients who underwent serial 99mTc-DPD scintigraphy, 5 (23%) showed reduction in the grade of cardiac uptake. CONCLUSIONS: In this large cohort of patients with AL CA, 99mTc-DPD scintigraphy ∼40% of cases showed cardiac uptake, including grade 2-3 in 10% of all patients (25% of those with cardiac 99mTc-DPD uptake). Cardiac 99mTc-DPD uptake was associated with poorer cardiac function and outcomes. These data highlight the critical importance of ruling out AL amyloidosis in all patients with cardiac 99mTc-DPD uptake to ensure such patients are not assumed to have ATTR CA.

Pedicled ipsilateral anterolateral thigh (ALT) with flow-through to a secondary contralateral-free ALT flap for coverage of large thigh, trochanteric, and gluteal area defects: A case report.

Reconstruction of the trochanteric area can be difficult in extensive defects postsarcoma resection. It requires a robust flap. In reconstructing the upper thigh, trochanteric, and gluteal area, a pedicled anterolateral thigh (ALT) flap is a good option. If the defect extends further than the pivot point of a single pedicled ALT, this can be used a flow-through for a secondary free flap. Here we describe a case of a 66-year-old gentleman with a 25 cm × 15 cm defect in the trochanteric and gluteal area where a single pedicled ALT was insufficient for coverage and hence a second ALT from the contralateral leg is anastomosed to the distal runoff of the descending branch of the lateral circumflex femoral vessel of the pedicled ALT, using it as the flow-through donor vessel. This method requires less time if a second free flap is required and a smaller range of dissection, and it also facilitates anastomosis, as the vessel can be brought to the surface for anastomosis while supine before inset. The patient healed with no complications and received radiotherapy to the area. On 1-year follow-up, the area has healed well despite some contraction secondary to the radiotherapy. Using the pedicled ALT as a flow-through for a second free flap is a useful adjunct to large defects in the gluteal and trochanteric area, which is a difficult area to reconstruct with limited donor vessels.

Necrotizing fasciitis of the periorbital region: from presentation to reconstructive journey.

Periorbital necrotizing fasciitis is a very rare condition with a UK incidence of 0.24 cases per million per annum. Outcomes can range from disfigurement to sight loss and even death. Debridement is crucial when sight or life is threatened and the subsequent reconstructive stages can be challenging. We describe two cases of periocular necrotizing fasciitis demonstrating the progression of the disease as well as the surgical debridement for both pre-septal and post-septal disease and the reconstructive steps leading to outcome. Level of evidence: Level V, therapeutic study.

Potential Repurposed Therapeutics and New Vaccines against COVID-19 and Their Clinical Status.

SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), was first reported in Wuhan, China, in December 2019. Since then, the virus has stretched its grip to almost all the countries in the world, affecting millions of people and causing enormous casualties. The World Health Organization (WHO) declared COVID-19 a pandemic on March 11, 2019. As of June 12, 2020, almost 7.30 million people have already been infected globally, with 413,000 reported casualties. In the United States alone, 2.06 million people have been infected and 115,000 have succumbed to this pandemic. A multipronged approach has been launched toward combating this pandemic, with the main focus on exhaustive screening, developing efficacious therapies, and vaccines for long-term immunity. Several pharmaceutical companies in collaboration with various academic institutions and governmental organizations have started investigating new therapeutics and repurposing approved drugs so as to find fast and affordable treatments against this disease. The present communication is aimed at highlighting the efforts that are currently underway to treat or prevent SARS-CoV-2 infection, with details on the science, clinical status, and timeline for selected investigational drugs and vaccines. This article is going to be of immense help to the scientific community and researchers as it brings forth all the necessary clinical information of the most-talked-about therapeutics against SARS-CoV-2. All the details pertaining to the clinical status of each therapeutic candidate have been updated as of June 12, 2020.

Preparation of Cu2ZnSnS4 Thin Films by Successive Ionic Layer Adsorption and Reaction (SILAR) Method for Supercapacitor Applications.

The Cu2ZnSnS4 (CZTS) thin films have been prepared at different deposition cycles, deposited on a glass substrate by successive ionic layer adsorption and reaction (SILAR) method followed by the annealing process at elevated temperature. The investigations on the films have been carried out to understand and confirm its structure, functional group present, crystalline morphology, optical and electrochemical behavior. The powder X-ray diffraction patterns recorded indicate that the deposited films are formed in the tetragonal structure. Other parameters like grain size, dislocation density, and microstrain are also calculated. The uniform surface of the films with spherical shaped morphology has been observed by Scanning Electron Microscopy, and the elemental compositions have been confirmed by EDAX. Electrochemical behavior such as cyclic voltammetry, electrochemical impedance spectroscopy and galvanostatic charge-discharge analysis have been carried out by electrochemical workstation. The modified electrode exhibits maximum specific capacitance value as 416 F/g for a pure sample. Optical studies have shown that the band gaps are estimated between 1.40 eV and 1.57 eV.

Synthesis, 17α-hydroxylase-C17,20-lyase Inhibitory and 5AR Reductase Activity of Novel Pregnenolone Derivatives.

BACKGROUND: The potential of steroids for development into lead pharmacological molecules lies in the regulation of a variety of biological processes by these molecules and also because of these being a fundamental class of signaling molecules. Steroid based scaffolds have been extensively used as active pharmaceutical agents for the treatment of various diseases including the deadly disease of cancer which despite the recent advances in the early diagnosis, prevention and therapy, remains a clinical challenge affecting millions of people world over and is one of the leading causes of death. It thus warrants the development of new drugs against this dreadful disease through exploitation of emerging molecularly defined targets. METHODS: The present study explores the effect of novel steroidal pyrazolines as presumed inhibitors of 5α- reductase (5AR) and 17α-hydroxylase-C17,20-lyase as a target for treatment of prostate cancer. A series of 1,5- diaryl pyrazoline pregnenolones were synthesized and screened for 5α-reductase inhibitory activities. Synthesis of the analogs is multistep and proceeds in good overall yields. The key step in the synthesis of 1,5- disubstituted pyrazolinyl pregnenolones is the heterocyclization of bezylidine derivatives (3) in presence of phenylhydrazines (4) through the initial formation of the phenylhydrazones, which undergo concomitant cyclization to generate the stable pyrazoline derivatives. RESULTS: All the synthesised D-ring 1,5-disubstituted pyrazolinyl pregnenolone derivatives (5a-l) were screened for prostate cancer cell inhibitory, 5α-reductase and 17α-hydroxylase-C17,20-lyase inhibitory activity. Amongst all the compounds screened for their 5α-reductase inhibitory activities, compound 5c, 5e, 5g and 5l were found to be the most active. Further, compounds 5g and 5h were found to have moderate 17α-hydroxylase-C17,20-lyase inhibitory activities. CONCLUSION: A series of D-ring 1,5-disubstituted pyrazolinyl pregnenolone derivatives (5a-l) were synthesized and screened for their prostate cancer cell inhibitory, 5a-reductase and 17α-hydroxylase-C17,20-lyase inhibitory activity. Amongst all the compounds screened for their 5α-reductase inhibitory activities, compound 5c, 5e, 5g and 5l were found to be the most active whereas compounds 5g and 5h were found to have moderate 17α- hydroxylase-C17,20-lyase inhibitory activities.

A radiographic review of the subacromial architecture: a South African study

The subacromial space, which is occupied by the subacromial bursa, rotator cuff complex and the long head of the biceps brachii tendon, is a well-known area of study due to its association with subacromial disease. Although it is demarcated by the coraco-acromial arch and the supraglenoid tubercle, degenerative changes in these osteological components often lead to mechanical narrowing and subsequent tendon abrasion. In addition to the morphological characteristics, the morphometry of the subacromial architecture is considered to play an important role in maintaining glenohumeral stability. Accordingly, the present study outlined the morphometry of the subacromial architecture and the acromial morphology from a radiological perspective. A total of 120 true lateral-outlet view radiographs (n = 120), representative of 58 males and 62 females of the Black (12), Coloured (10), Indian (27) and White (71) race groups, were analysed. In addition to calculation of the standard and population-specific means, the acromial classification scheme of Bigliani et al. (1986) was adopted. A trend of ascending values from Type III (16.7%) to Type II (37.5%) to Type I (45.8%) acromia was noted. Various shapes of the subacromial space were observed, viz. rhomboidal (20.0%), trapezoidal (65.8%) and triangular (14.1%). Since a statistically significant P value of 0.030 was recorded for the comparison of acromial type with the shape of the subacromial space, the shape of the subacromial space appeared to be dependent on the acromial type. While the parameters were determined with regard to the demographic representation of South Africa, this study also provided standard mean values which were not previously reported. Furthermore, the correlation of the acromio-glenoidal length with side, gender and shape of the subacromial space reflected levels of significance and highlighted this parameter as a diagnostic determinant of subacromial disease due to its tendency to change in accordance with the demographic and morphological factors

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Immunoparesis defined by heavy+light chain suppression is a novel marker of long-term outcomes in cardiac AL amyloidosis.

Cardiac involvement and presenting dFLC (difference between involved and uninvolved free light chains) are independent predictors of outcome in systemic AL amyloidosis. These markers have limited prognostic utility in patients surviving the initial months following diagnosis. Here we assessed immunoparesis, as determined by novel heavy+light chain (HLC) immunoassays, as a prognostic marker for survival in AL amyloidosis. HLC measurements identified immunoparesis of at least one immunoglobulin (Ig) isotype in 145 (85%) patients; and severe immunoparesis (≥2 Ig isotypes suppressed by >50% below normal levels) in 29 (17%) patients. Median overall survival (OS) on intention to treat (ITT) analysis was 26·2 months. In the ITT cohort, dFLC >180 mg/l was associated with shorter OS (P = 0·05); whereas HLC immunoparesis was not prognostic. On a landmark analysis of 127 patients alive at 6 months, presenting dFLC was not prognostic for OS (P = 0·33) and severe HLC immunoparesis trended towards poorer survival (20·2 vs. 42·8 months; P = 0·09). In the subset of patients with cardiac involvement, severe HLC immunoparesis conferred very poor outcome (median OS 8·8 vs. 29·9 months, P = 0·007). In conclusion, severe HLC immunoparesis is an independent marker of long-term poor prognosis in AL patients with cardiac involvement. The pathophysiological significance of this observation needs further study.

Clinical profile and treatment outcome of older (>75 years) patients with systemic AL amyloidosis.

Systemic AL amyloidosis, a disease with improving outcomes using novel therapies, is increasingly recognized in the elderly but treatment and outcomes have not been systematically studied in this group of patients in whom comorbidities and frailty may compound morbidity and mortality. We report the outcomes of 295 patients with systemic AL amyloidosis ≥75 years seen at the UK National Amyloidosis Centre from 2005-2012. The median age was 78.5 years. The median overall survival was 20 months. Two hundred and thirty-eight patients received chemotherapy and 57 elected for supportive care only (overall survival - 24 and 8.4 months, respectively). On intention-to-treat analysis, 44% achieved a hematologic response including a very good partial response or better in 23%. The median overall survival was 6.2 years in patients achieving very good partial response or better at the 6-month landmark analysis and 1.5 years in non-responders. Factors independently indicating a poor prognosis were: cardiac involvement, performance status ≥2; systolic blood pressure <100 mmHg and, on landmark analysis, achieving less than a very good partial response. Treatment of systemic AL amyloidosis in the elderly is challenging. Deep clonal responses are associated with excellent survival and organ responses. Achieving a response to the first-line regimen appears particularly important as outcomes of non-responders are similar to those of untreated patients. Prospective trials with lower toxicity, outpatient treatment regimens are needed.

Trabecular orientation in the human femur and tibia and the relationship with lower-limb alignment for patients with osteoarthritis of the knee.

Wolff׳s Law suggests that the orientation of trabeculae in human bone changes in response to altered loading patterns. The aim of this study was to investigate trabecular orientation in both the femur and tibia and to compare this with the mechanical axis of the leg. The study involved analysis of radiographs from patients with osteoarthritis of the knee (n=91). For each patient, the trabecular orientation in both the distal femur and proximal tibia was measured from a standard anteroposterior radiograph of the knee and the mechanical axis of the leg was calculated from a long leg view taken while weight bearing. There was a significant correlation between the mechanical axis and the trabecular orientation in each of the regions considered in the femur (r=-0.41, -0.30, 0.52, and 0.23) and tibia (r=-0.27 and 0.31). Multiple regression analysis, with mechanical axis as the dependent variable, produced an R(2) of 0.62. Greater trabecular anisotropy (i.e. greater alignment) was observed in the medial femur and tibia compared to the lateral side (p<0.01). The results give an insight into the trabecular changes that may take place during development of osteoarthritis and following surgery. In particular, we propose that the orientation of the trabeculae in both the distal femur and proximal tibia will reflect the angle of mechanical loading through the knee.

Steroidal pyrazolines and pyrazoles as potential 5α-reductase inhibitors: synthesis and biological evaluation.

Taking pregnenolone as the starting material, two series of pyrazolinyl and pyrazolyl pregnenolones were synthesized through different routes. The synthesis of the analogs of both series is multistep and proceeds in good overall yields. While the key step in the synthesis of pyrazolinyl pregnenolones is the heterocyclization of benzylidine derivatives (3) in presence of hydrazine hydrate, it is the condensation of 3ß-hydroxy-21-hydroxymethylidenepregn-5-en-3ß-ol-20-one (5) with phenylhydrazine in the synthesis of pyrazolyl derivatives. Compounds of both the series were tested for their 5α-reductase inhibitory activities. Amongst all the compounds screened for their 5α-reductase inhibitory activities, compound 4b, 4c and 6b were found to be the most active.

Benzylidine pregnenolones and their oximes as potential anticancer agents: synthesis and biological evaluation.

The present study reveals the anticancer activity of benzylidine pregnenolones and their oxime derivatives. The synthesis of the analogs of both series is very simple and involves aldol condensation in the first step followed by nucleophillic addition of hydroxylamine across carbonyl in the second step. Quantitative yields of more than 80% are obtained in both the steps. All the compounds were tested for their cytotoxic activities against a panel of six human cancer cell lines. Amongst all the compounds of both the series screened for their cytotoxic activity, compound 3e, 3f and 4e are very potent especially against HCT-15 and MCF-7 cancer cell lines.

Anxiolytic and anticonvulsant activity of methanol extract of leaves of Alternanthera brasiliana (L.) Kuntze (Amaranthaceae) in laboratory animals.

Anxiety related disorders are the most common mental illnesses and major cause of disability in man. Anxiolytic activity of methanol extract of leaves of A. brasiliana (L.) Kuntze (MEAB) was evaluated using hole board (HB), open field (OF), elevated plus maze (EPM) and light/dark exploration test (LDE) in mice. Its locomotor activity was studied using actophotometer and anticonvulsant effect was studied using maximal electroshock-induced seizures and pentylenetetrazole-induced seizures in mice. Single oral administration of MEAB at different doses (100, 300 and 600 mg/kg, ip) significantly increased the number and duration of head poking in the HB test; rearing, assisted rearing and number of square traveled in the OF test; entries and time spent in open arm in the EPM test; time spent in lighted box, and numbers of crossings and transfer latency time in the LDE test. There was significant reduction in the time spent in close arm in the EPM test and time spent in dark box in LDE test. In the actophotometer, the activity count was reduced in MEAB and diazepam treated group than control group. All the three doses of the extract significantly reduced the duration of seizures induced by pentylenetetrazole (chemoshock convulsion). However, the extract did not show any appreciable effect in electroshock convulsion model. The results of the present study suggest promising anxiolytic and anticonvulsant activity of MEAB which might be accredited to different phytoconstituents like alkaloids, steroids and triterpenes present in the methanol extract of A. brasiliana.

Antimicrobial studies of unsymmetrical bis-1,2,3-triazoles.

Aryl azides were treated with allenylmagnesium bromide to generate 1,5-disubstituted butynyl 1,2,3-triazoles in a domino fashion, which upon Cu(I) catalyzed 1,3-dipolar cycloaddition with aryl azides afforded novel bis-1,2,3-triazoles in quantitative yields. The final products were analyzed for their antimicrobial activities against a panel of bacterial and fungal strains which revealed the products to be potent antimicrobials.

Effect of Alternanthera brasiliana (L) Kuntze on healing of dermal burn wound.

Wound healing activity of methanol extract of Alternanthera brasiliana [5% (w/w) ointment] was evaluated in experimental burn wound model in rats. Healing potential was assessed by the rate of wound contraction, estimation of anti-oxidants like catalase, superoxide dismutase, reduced glutathione, protein, vitamin C and hydroxyproline, along with histopathological examination on 8th day post wounding. The statistical data indicated that there was significant increase in wound contraction along with augmented level of antioxidants in granulation tissues in A. brasiliana treated group. Histopathological assessment of the granulation tissue revealed formation of epidermis with keratin layer and deposition of collagen fibers after treatment with the plant extract.

Measurement of transurethral bladder neck displacement during tension-free vaginal tape procedure.

INTRODUCTION AND HYPOTHESIS: The rigid catheter guide is used during the tension-free vaginal tape (TVT) procedure to direct the bladder neck away from the retropubic passage of the sling arm. Our aim was to measure, using transperineal ultrasound, the amount of bladder neck displacement by the rigid catheter guide during TVT placement. METHODS: This is a prospective cohort of 28 patients undergoing the TVT procedure, with or without concomitant pelvic organ prolapse repair. Spearman's correlation was used to analyze the bladder neck displacement from the midline. RESULTS: The median right-sided bladder neck displacement distance was 1.4 cm (0.6-2.0), and the median left-sided bladder neck displacement distance was 1.4 cm (0.8-2.0). The overall perforation rate was 14% (4/28). CONCLUSIONS: Bladder neck displacement with the Mandarin guide results in ~1.4 cm of lateral movement.

D-ring substituted 1,2,3-triazolyl 20-keto pregnenanes as potential anticancer agents: Synthesis and biological evaluation.

A facile synthesis of 21-triazolyl derivatives of pregnenolone and their potential antitumour activity is reported. The scheme involves the transformation of the starting pregnenolone acetate into pregnenolone, conversion of pregnenolone to 21-bromo pregnenolone and finally the one-pot, two-step in situ conversion of the bromo derivative to the 21-triazolyl pregnenolone using the 'click chemistry' approach. These derivatives were screened for their anticancer activity against seven human cancer cell lines. The compounds especially 5a, 5b, 5c, 5e, 5g and 5h exhibited significant anticancer activity with compound 5e as the most active in this study.

Antinociceptive activity of methanolic extract of leaves of Achyranthes aspera Linn. (Amaranthaceae) in animal models of nociception.

Antinociceptive activity of methanolic extract of leaves of A. aspera was studied by peripheral/non-narcotic model of nociception like acetic acid induced writhing syndrome test and central/narcotic models like hot plate and tail flick tests. The methanolic extract of the plant, administered orally (@ 300, 600 and 900 mg/kg, body weight) and the standard drug (piroxicam; 10 mg/kg body weight, po) produced significant analgesic activity in acetic acid induced writhing syndrome as compared to the vehicle treated control group. In the hot plate analgesic test, in A. aspera at the above doses and the standard drug treated group (morphine sulphate @ 1.5 mg/kg, ip), the duration of reaction time (sec) increased dose dependently and significantly compared to the control group. In the tail flick test, the plant extract produced dose dependant increase in reaction time which was significantly higher in the test and standard group compared to the control group. The plant possesses significant antinociceptive property as evidenced in all the animal models of nociception. It might possibly exert its effect through diverse mechanism that may involve both central and peripheral pathways. The preliminary phytochemical investigation revealed the presence of steroids, alkaloids and triterpene in the methanolic extract of leaves of A. aspera which may be responsible for its antinociceptive activity.

Experience curve compared with manufacturing processes for TKA.

In the experience curve concept set forth by the National Aeronautics and Space Administration (NASA), production time falls by a set percentage every time cumulative production doubles. NASA has established benchmark figures for different manufacturing processes, and we have used these figures in analyzing our first 240 navigated total knee arthroplasties for varus knees. Our experience curve was 93% (P < .001), which is similar to the experience curve (90%) for processes consisting of 25% hand assembly and 75% machining. We suggest that the experience curve may provide a guide for comparing different surgical teams and navigation systems and for resource allocation.