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Molecular dynamic (MD) simulation is performed using a secondneighbor Finnis-Sinclair (FS) potential to study structural and atomic mass transport properties of molybdenum in the liquid phase for a temperature (T) range of 3100 to 3800 K. The Computed results for the pair correlation function, structure factor, and coordination number are discussed with similar findings. Transport coefficients like viscosity and self-diffusion coefficient follow Arrhenius law, which estimates activation energy between 1.34 to 1.62 eV. The discrepancy in computed densities and other properties beyond 3800 K is discussed, given the nature of interaction potentials and binding in liquid molybdenum. It is shown that EAM, MEAM, and FS potentials show analogous repulsive character and therefore give comparable results for structural properties. However, the attractive part of the interaction potential, which determines the binding in molybdenum is responsible for the difference in various high-T physical properties reported in the study. The sensitivity of physical properties on the attractive part of the interaction potential thus demands to incorporate the effect of temperature dependency of electron density-of-state (e- dos) and angular forces into the interaction for a proper account of the binding in liquid molybdenum. [ABSTRACT FROM AUTHOR]

The role of phonons is important in accounting various properties of materials. Crystal potential being an anharmonic function of volume, variations are seen in phonon derived properties with a change in volume. In the present work, we employ an approximate technique of expanding phonon frequencies using Taylor series expansion upto second-order in volume to calculate the volume dependent phonon frequencies of CaO in B1 and B2 phases. Equilibrium properties are obtained by fitting Murnaghan EoS to first principles DFT based results, however. The mode Grüneisen parameter and concavity parameter are computed with the help of present ab initio phonon frequencies for both the phases. Their volume dependence are estimated analytically using the proposed scheme. We find that phonon frequencies increase by decreasing volume. Analytically calculated volume dependent phonon frequencies are compared in reasonable agreement with the frequencies obtained directly using DFT for B1-phase. Thus, the present r-space computational scheme of deriving volume dependent phonon frequency proves to be an alternative to overcome lengthy phonon calculations. [ABSTRACT FROM AUTHOR]

Accurate assessment of electrical transport for heavy polyvalent metals pause challenge due to complex electronic band structure, where s-wave scattering theory due to Ziman is failed. Improving schemes like t-matrix resistivity and self-consistent approach are proposed. In the present study, we employ selfconsistent approach to compute electrical resistivity (ρ) in liquid Bi and Sb at different temperatures (T). Structural input is estimated through charged hard-sphere reference system. Electron-ion interaction is modelled by modified empty-core pseudopotential including electron exchange and correlation effects. Since only two parameters are independent, as the core radius RC (= 0.51 RaZ-1/3) is a theoretical input, we have tuned, once and for all, the single parameter to find ρ at melting temperature. The same set of parameters is used to deduce high-T resistivity, thermal conductivity and thermo-electric power. Overall good agreement is observed for transport properties for both metals. The present fitting scheme and so deduced results are discussed in comparison with other findings. [ABSTRACT FROM AUTHOR]

Background: Dry needling (DN) is commonly used to treat various neuromuscular syndromes. It is effective in reducing spasticity in stroke and other neurological conditions. The current study explores the immediate effect of ultrasound-guided dry needling on soleus muscle spasticity and thickness in individuals with stroke., Methods: Approval was obtained from the Institutional Sub-ethics Committee of Dr. D. Y. Patil College of Physiotherapy, Pune. The trial was registered with the Clinical Trials Registry of India. Thirty stroke survivors having soleus muscle spasticity ranging from grade 1 to 4 on the Modified Modified Ashworth Scale (MMAS) were selected. Spasticity was also assessed using the Modified Tardeau Scale (MTS) and H-reflex. Soleus muscle architecture was assessed by using ultrasonography (USG). Participants received a single session of DN for the spastic soleus muscle. Pre and immediate post-DN outcome measures were assessed., Results: Based on USG findings, the thickness of the soleus muscle significantly increased by 2.67 mm (p<0.001) after dry needling treatment. The MMAS showed decreased spasticity by 1.47 (p<0.001) for ankle plantar flexors. A significant reduction of H-reflex values by 1.4 mV (p<0.001) was noted. The MTS also showed a significant increase in the range of ankle motion by 2.7 (p<0.001). All these indicate an immediate reduction of spasticity following DN., Conclusion: Based on the findings of the current study, we can conclude that a single session of USG-guided DN has an immediate beneficial effect on reducing soleus muscle spasticity and increased muscle thickness in individuals with stroke., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Committee of Dr. D. Y. Patil College of Physiotherapy, Pune issued approval DYPCPT/IEC/11/2021. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kamble et al.)

Background and Purpose: Acute graft-versus-host disease (GVHD) remains a major barrier to successful transplantation outcomes. Recent studies have shown that pharmacotherapy for GVHD should target both the innate and adaptive inflammatory immune responses. Juglone, a redox-active phytochemical found in walnuts, has shown potent anti-inflammatory effects in models of colitis and inflammatory bowel disease. However, its effects on T-cell-mediated immune responses remain largely unknown. Considering the overlapping mediators of inflammation in GVHD and the aforementioned conditions, we investigated the use of juglone as a prophylactic agent for GVHD., Experimental Approach: Immunomodulatory activity and mechanism of action of juglone were studied using murine splenic leukocytes in vitro. The GVHD prophylactic efficacy of orally administered juglone was evaluated using a murine model of allogeneic haematopoietic stem cell transplantation based on an MHC mismatch., Key Results: Juglone exhibited immunomodulatory activity by (i) inhibiting the activation of dendritic cells and CD4 + T-cells, (ii) inhibiting cytokine secretion and lymphocyte proliferation, and (iii) inducing exhaustion of CD4 + T-cells, as shown by increased expression of CTLA-4 (CD152) and Fas (CD95). Oral administration of juglone significantly reduced mortality and morbidity associated with GVHD while maintaining graft-versus-leukaemia activity. This was accompanied by a decrease in the number of naïve CD4 + cells, and an increase in the number of CD4 + and CD8 + central memory T-cells., Conclusion and Implications: Juglone is a potent immunomodulator for GVHD prophylaxis. Our study is the first to provide a dosage framework for the oral administration of juglone that can be used for clinical development., (© 2024 British Pharmacological Society.)

Anti-inflammatory and immune suppressive agents are required to moderate hyper-activation of lymphocytes under disease conditions or organ transplantation. However, selective disruption of mitochondrial redox has not been evaluated as a therapeutic strategy for suppression of T-cell-mediated pathologies. Using mitochondrial targeted curcumin (MitoC), we studied the effect of mitochondrial redox modulation on T-cell responses by flow cytometry, transmission electron microscopy, transcriptomics, and proteomics, and the role of Nrf2 was studied using Nrf2 - / - mice. MitoC decreased mitochondrial TrxR activity, enhanced mitochondrial ROS (mROS) production, depleted mitochondrial glutathione, and suppressed activation-induced increase in mitochondrial biomass. This led to suppression of T-cell responses and metabolic reprogramming towards T reg differentiation. MitoC induced nuclear translocation and DNA binding of Nrf2, leading to upregulation of Nrf2-dependent genes and proteins. MitoC-mediated changes in mitochondrial redox and modulation of T-cell responses are abolished in Nrf2 - / - mice. Restoration of mitochondrial thiols abrogated inhibition of T-cell responses. MitoC suppressed alloantigen-induced lymphoblast formation, inflammatory cytokines, morbidity, and mortality in acute graft-versus-host disease mice. Disruption of mitochondrial thiols but not mROS increase inculcates an Nrf2-dependent immune-suppressive disposition in T cells for the propitious treatment of graft-versus-host disease., (© 2024 John Wiley & Sons Ltd.)

Acute graft versus host disease (aGvHD) is the major contributor of nonrelapse mortality in alloHSCT. It is associated with an inflammatory immune response manifesting as cytokine storm with ensuing damage to target organs such as liver, gut, and skin. Prevention of aGvHD while retaining the beneficial graft versus leukemia (GvL) effect remains a major challenge. Withania somnifera extract (WSE) is known for its anti-inflammatory, immune-modulatory, and anticancer properties, which are appealing in the context of aGvHD. Herein, we demonstrated that prophylactic and therapeutic use of WSE in experimental model of alloHSCT mitigates aGvHD-associated morbidity and mortality. In the prophylaxis study, a dose of 75 mg/kg of WSE offered greatest protection against death due to aGvHD (hazard ratio [HR] = 0.15 [0.03-0.68], P ≤ .01), whereas 250 mg/kg was most effective for the treatment of aGvHD (HR = 0.16 [0.05-0.5], P ≤ .01). WSE treatment protected liver, gut, and skin from damage by inhibiting cytokine storm and lymphocytic infiltration to aGvHD target organs. In addition, WSE did not compromise the GvL effect, as alloHSCT with or without WSE did not allow the leukemic A20 cells to grow. In fact, WSE showed marginal antileukemic effect in vivo . WSE is currently under clinical investigation for the prevention and treatment of aGvHD., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: LH is the managing director of Pharmanza Herbal Pvt. Ltd. which is licensed to manufacture WSE for human use as a nutraceutical. He had no role in the design or conduct of the study, nor in the interpretation of results. Other authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Knot configuration is an important but relatively neglected topic in microvascular anastomosis literature., Objective: To study the differences between end-to-end microvascular anastomosis performed with two-throw reef knots as compared to traditional three-throw knots in a rat femoral artery model at the histological level., Material and Methods: Sprague Dawley rats underwent end-to-end microvascular anastomosis of the right femoral artery (one-way-up method). The rats were divided into two groups: two-throw reef knots versus traditional three-throw knots. The patency was checked by the standard empty refill method. After 2 weeks, the rats underwent re-exploration. An anastomotic segment was sent for histological analysis. Histological alterations including luminal patency and changes in Tunica intima, Tunica media, and Tunica adventitia were compared between the two groups., Results: Twenty-nine rats were operated on by the senior author (17 by three-throw and 12 by two-throw reef knots). In the two-throw reef knot group versus the traditional three-throw knot group, the immediate patency rates were 100% versus 82.4%, and the delayed patency rates were 90.9% versus 62.5%, respectively. The histopathological patency rates were concordant with delayed patency rates. Subintimal proliferation and fibrosis were comparable in both groups. Adventitial granulomas were noted in all, irrespective of the knotting technique. Tunica media preservation rates for the two-throw reef knot versus the traditional three-throw knot group were 63.6% versus 0%. Five rats were operated by the beginner in the field, all by two-throw reef knots (to assess the safety of this new method in the hands of a beginner)., Conclusion: Microvascular anastomosis performed with two-throw reef knots appears not only feasible but better in terms of anastomosis patency. Histological superiority in terms of Tunica media preservation further validates the technique., Competing Interests: None

Base excision repair (BER) corrects forms of oxidative, deamination, alkylation, and abasic single-base damage that appear to have minimal effects on the helix. Since its discovery in 1974, the field has grown in several facets: mechanisms, biology and physiology, understanding deficiencies and human disease, and using BER genes as potential inhibitory targets to develop therapeutics. Within its segregation of short nucleotide (SN-) and long patch (LP-), there are currently six known global mechanisms, with emerging work in transcription- and replication-associated BER. Knockouts (KOs) of BER genes in mouse models showed that single glycosylase knockout had minimal phenotypic impact, but the effects were clearly seen in double knockouts. However, KOs of downstream enzymes showed critical impact on the health and survival of mice. BER gene deficiency contributes to cancer, inflammation, aging, and neurodegenerative disorders. Medicinal targets are being developed for single or combinatorial therapies, but only PARP and APE1 have yet to reach the clinical stage.

Acute graft versus host disease (aGvHD) contributes to a significant proportion of non-relapse mortality and morbidity in patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT). Withaferin-A (WA), a phytomolecule obtained from Withania somnifera (Ashwagandha), is known to have anti-inflammatory, anti-proliferative and immunomodulatory properties. The efficacy of WA for the prevention and treatment of aGvHD was evaluated using a murine model of alloHSCT. Prophylactic administration of WA to mice mitigated the clinical symptoms of aGvHD and improved survival significantly compared to the GvHD control [HR = 0.07 (0.01-0.35); P < 0.001]. Furthermore, WA group had better overall survival compared to standard prophylactic regimen of CSA + MTX [HR = 0.19 (0.03-1.1), P < 0.05]. At the same time, WA did not compromise the beneficial GvL effect. In addition, WA administered to animals after the onset of aGvHD could reverse the clinical severity and improved survival, thus establishing its therapeutic potential. Our findings suggest that WA reduced the systemic levels of Th1, Th2 and Th17 inflammatory cytokine and increased the anti-inflammatory cytokine IL-10 levels significantly (P < 0.05). WA also inhibited lymphocytes migration to gut, liver, skin and lung and protected these organs from damage. Ex-vivo, WA inhibited proliferation of human peripheral blood mononuclear cells (hPBMCs), modulated immune cell phenotype and decreased cytokine release. In addition, WA inhibited pJAK2 and pSTAT3 protein levels in mouse splenocytes and hPBMCs. In conclusion, our study demonstrates the utility of WA for the prevention and treatment of aGvHD, which should be further evaluated in a clinical setting., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘Dr. Lal Hingorani is the managing director of Pharmza Herbal Pvt. Ltd., which manufactures Witahferin-A containing nutraceuticals for human use. He had no role in the design or conduct of the study nor in the interpretation of results. Other authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.’, (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: A narrow working space, small diameters, and the tendency to collapse with clamps make cerebral microvascular anastomosis challenging. A retraction suture (RS) is a novel technique to keep the recipient vessel lumen open during the bypass., Objective: To provide a step-by-step overview of RS for end-to-side (ES) microvascular anastomosis on rat femoral vessels and successful use for superficial temporal artery to middle cerebral artery (STA-MCA) bypass in Moyamoya disease patients., Methods: A prospective experimental study with approval from the Institutional Animal Ethics Committee. Femoral vessels ES anastomoses were performed on Sprague Daley rats. The rat model used 3 types of RS (adventitial, luminal, and flap RSs). An ES-interrupted anastomosis was done. The rats were observed for an average period of 16.18 ± 5.65 days; the patency was assessed by reexploration. The immediate patency on the STA-MCA bypasses was confirmed with intraoperative indocyanine green angiography and micro-Doppler; delayed patency with magnetic resonance imaging and digital subtraction angiography after 3-6 months., Results: In the rat model, 45 anastomoses were performed, 15 each using the 3 subtypes. The immediate patency was 100%. Delayed patency was 42/43 (97.67%), and 2 rats died during observation. In the clinical series, 59 STA-MCA bypasses were done in 44 patients (average age, 18.14 ± 11.09 years) using RS. The follow-up imaging was available for 41/59 patients. Both immediate patency and delayed patency (41/41 at 6 months) were 100%., Conclusion: The RS allows continuous visualization of the vessel lumen, reduces the handling of intimal edges, and avoids incorporating the back wall in sutures, thus improving anastomosis patency., (Copyright © 2023 Elsevier Inc. All rights reserved.)

5-hydroxy-1,4-naphthoquinone (5NQ) or juglone is a bioactive molecule found in walnuts and has shown therapeutic effects in various disease models. Limited information is available regarding the toxicity of 5NQ, thereby limiting the clinical development of this drug. In the present study, oral acute (50, 300 and 2000   mg/kg) and sub-acute toxicity (5, 15 and 50   mg/kg) was assessed in mice to evaluate the safety of 5NQ. The acute toxicity study identified 118   mg/kg as the point-of-departure dose (POD) for single oral administration of 5NQ using benchmark dose modeling (BMD). Repeated administration of 5NQ at doses of 15 and 50   mg/kg/day caused reduction in food consumption and body weight of mice along with alterations in liver and renal function. Histopathological assessment revealed significant damage to hepatic and renal tissues at all doses in the acute toxicity study, and at higher doses of 15 and 50   mg/kg in the sub-acute toxicity study. We observed dose dependent mortality in sub-acute toxicity study and the no observed adverse effect level (NOAEL) was established as < 5   mg/kg/day. Modeling the survival response in sub-acute toxicity study identified 1.74   mg/kg/day as the POD for repeated administration of 5NQ. Serum levels of aspartate aminotransferase (AST) were most sensitive to 5NQ administration with a lower limit of BMD interval (BMDL) of 1.1 × 10 -3   mg/kg/day. The benchmark doses reported in the study can be further used to determine a reference dose of 5NQ for human risk assessment.

Withaferin-A (WA) is the principle component of Withania somnifera (Ashwagandha). It has several biological activities including anti-cancer, anti-diabetic, neuroprotective, hepatoprotective and immune-modulatory properties. The acute and sub-acute toxicity of oral WA was investigated in mice. In the acute toxicity study, up to 2000 mg/kg of WA was well tolerated without any signs of toxicity or death. In the sub-acute toxicity study, mice were orally administered 10, 70 and 500 mg/kg of WA respectively, daily for 28 days. Upon physiological, serum chemistry, hematology and histopathogical examination, no features suggestive of drug-induced toxicity were observed at any dose levels, thereby confirming the No-Observed Adverse Effect Level (NOAEL) to be at least 500 mg/kg. Furthermore, the oral bioavailability of WA was evaluated using single intravenous and oral doses of 10 mg/kg and 70 mg/kg respectively using sparse sampling strategy. Bioanalysis was carried out using a validated LC-MS/MS method. The AUC of WA was found to be 3996.9 ± 557.6 ng/mL*h and 141.7 ± 16.8 ng/mL*h for the intravenous and oral routes of administration respectively. The oral bioavailability was determined to be 1.8%. To conclude, WA was found to be extremely safe even at high doses, with a low oral bioavailability., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Objectives: Autoanalyzers are used in clinical haematology for analysis of blood samples in clinical as well as in nonclinical studies. The results from these analyzers vary from machine to machine. In this study, we compared the lymphocyte and neutrophil count of mouse blood between ADVIA 2120i, Horiba Yumizen H2500 and CellaVision analyzers against manual counting as gold standard., Methods: Blood samples from 28 female BALB/c mice were collected and analyzed. Agreement between different autoanalyzers and manual counting were determined by Bland-Altman method., Results: A high level of agreement was found between CellaVision and manual technique for lymphocyte (bias=4.75, 95% limits of agreement -14 to 24) and neutrophil count (bias=0.68 [-17 to 19]). Agreement in lymphocyte count was also observed between ADVIA and manual counting, but to a lesser extent compared to CellaVision (bias=13.9 [-10.45 to 38.27]). However, no agreement was observed for ADVIA (Neutrophils), Horiba (lymphocytes and neutrophils) with manual counting., Conclusions: Our data suggests that CellaVision could be used for the differential counting of neutrophil and lymphocytes in mouse blood sample., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Background: The use of the classic 2-ends anchoring technique is common in end-to side (ES) microvascular anastomosis. The literature on the toe-first (TF) technique is limited. In the current study we present the successful outcomes with the TF technique in ES anastomoses in rat femoral vessels model., Methods: ES microvascular anastomosis with the tf technique was performed in the femoral vessels of 10 Sprague Dawley rats. Two-throw reef knot interrupted sutures were used in all cases. Individual parameters during the procedure were recorded for analysis. The immediate and delayed (cut open technique after 2 weeks) patencies were confirmed. An illustrative case showing the use of this technique in superficial temporal artery to middle cerebral artery bypass in a pediatric moyamoya disease case is included., Results: The average suturing time was 40.14 ± 5.30 minutes, the procedures were completed with an average of 14.57 ± 1.90 sutures. The average time per suture was 2.78 ± 0.43 minutes. The immediate patency was 100% (10 of 10 cases). Two rats died of unknown cause in the observation period. The delayed patency was 100% in the remaining 8 cases (average observation: 29.6 days)., Conclusions: The TF interrupted suture technique of ES microvascular anastomosis with 2-throw reef knots is feasible with excellent immediate and delayed patency rates. The distinct advantages of the TF are the continuous visualization of the recipient lumen during anastomoses, avoiding back-wall bites, and the ability to correct any discrepancy in the recipient-donor lumens during the procedure., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The use of a 3-throw knot for anastomosis by microvascular neurosurgeons is the usual standard. There is an inherent belief that the third throw adds extra security to the knot; however, the third throw can make the knot heavy and unbalanced and can exert undue extra pressure on the opposing walls of the small-caliber intracranial vessels. This study evaluated the feasibility and efficiency of 2-throw reef knot interrupted sutures for an end-to-side microvascular anastomosis., Methods: A prospective observational study of end-to-side anastomosis using a femoral artery-to-vein model was performed in 30 Sprague-Dawley rats. All anastomoses were done using 2-throw reef knot interrupted sutures. Ten procedures each were done by the heel-first, toe-first, and classic 2-ends techniques. Individual parameters were recorded for analysis. The delayed patency was confirmed by reexploration after a mean duration of 19.82 ± 8.12 days., Results: The overall patency rates were 100% in the immediate period and 96.43% (27 of 28) in the delayed period. The average clamping time, average suturing time, and the average time per suture were 65.48 ± 16.93 minutes, 40.94 ± 11.22 minutes, and 3.18 ± 1.10 minutes, respectively. Two rats died in the postoperative period., Conclusions: The end-to-side microvascular anastomosis with 2-throw reef knots is feasible, with excellent immediate and delayed patency rates., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Introduction: Intraoperative neuromonitoring for eloquent cortical lesions is irreplaceable in present-day neurosurgery., Objective: We report a novel technique of combining awake craniotomy with direct cortical stimulation of the motor cortex using the NIM © nerve monitoring system., Technique: A 17-year-old boy presenting with focal motor seizures, diagnosed with left perirolandinc cavernoma, underwent awake craniotomy and complete excision under direct cortical stimulation with NIM monopolar stimulator electrode to locate the motor cortex., Result: The patient developed transient weakness of handgrip during surgery, which improved by the same day evening. At 3 months follow-up, he could perform all the activities with his dominant right hand., Conclusion: Cortical stimulation using a nerve monitoring system is a useful technique in case of nonavailability of standard evoked potential monitoring system for motor cortex mapping., Competing Interests: None

Acute Graft versus Host Disease (aGVHD) is a frequent and serious complication in patients receiving allogeneic bone marrow transplantation (allo-BMT) and often requires rigorous prophylaxis. The current treatment regimens for aGVHD are associated with several side effects which necessitates the development of novel interventions that prevent aGVHD without precluding graft-versus-tumor effects. In the present study, we show that treatment of donor graft with plant steroidal lactone Withaferin A (WA) prior to transplantation markedly reduced aGVHD mediated damage in target organs without compromising the graft-versus.-tumor activity of the transplanted lymphocytes. WA abrogated post-transplant cytokine storm associated with allo-activation of donor lymphocytes. This was attributed to the ability of WA to inhibit early signaling events in T-cell activation including lymphoblast formation and activation of AKT/mTOR pathway. Mortality and morbidity related to allo-transplantation was significantly reduced in recipients of WA treated donor splenocytes compared to recipient of vehicle treated donor splenocytes. Further, WA treatment did not have any effect on reconstitution of lymphoid and myeloid lineages in recipients, resulting in stable and complete donor chimerism. In agreement with previous reports showing the effectiveness of WA in a mouse model of partial chimerism, our data further establishes that WA is able to attenuate aGVHD in an MHC-mismatched high dose chemo-conditioned murine model without compromising engraftment. This study provides compelling scientific basis for possible application of WA for prevention and treatment of aGVHD in patients receiving allo-BMT., Competing Interests: Declaration of Competing Interest All the authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Vascular surgery is the largest (non-cardiac) user of blood transfusion which is associated with increased risk to patients. Patient Blood Management (PBM) is a quality improvement programme in transfusion medicine involving educational change and recommendations through preoperative, operative, and postoperative surgery. We wished to assess the feasibility to implement a PBM programme in vascular surgery. A multidisciplinary programme was developed at a vascular unit by PBM experts. The PBM programme involved a series of educational lectures, consultations, and discussions with doctors, nurses, and theatre staff. A one-page PBM checklist of recommendations was developed for all patients undergoing vascular surgery. Prospective audits were conducted before (October 2014 to March 2015) and after (November 2015 to February 2016) PBM implementation. Outcomes were blood transfusion and haemoglobin concentration (Hb) trigger threshold. A total of 211 patients were admitted under vascular surgery: 127 for Audit 1 and 84 for Audit 2. Overall, 30% of patients were transfused, with 193 units transfused in Audit 1 and 85 in Audit 2. PBM implementation was associated with a reduction in patients receiving a blood transfusion (37% to 20%; p = 0.01). However, there was no difference in Hb trigger threshold (76 g/L vs 72 g/L, p = 0.051). A PBM programme is feasible and can be implemented in vascular surgery. PBM was associated with an improvement in transfusion use and length of patient stay that merits further investigation.

Objective: The aim of this study was to report the etiology, clinical features, microbiology, surgical outcome, and predictors of outcome of spontaneous subdural empyema (SDE)., Methods: The authors conducted a retrospective study in a tertiary hospital. Children up to 18 years of age, with a diagnosis of SDE with infective etiology, were included in the present cohort. Patients with posttraumatic, postsurgery, and tubercular origin of SDE were excluded from the study. The Glasgow Outcome Scale was used for outcome assessment at the end of 3 months. For analysis purposes, the demographic data, clinical features, radiological data, microbiology, type of surgery, and complication data were categorized, and univariate and multivariable logistic regression analyses were performed to identify the factors associated with outcome., Results: Ninety-eight children were included in the study and the mean age was 10.9 years. Otogenic origin (34.7%) was the most common source of infection, followed by meningitis (14.3%). The mean duration of symptoms was 12 days. Seventy-six children presented with Glasgow Coma Scale (GCS) score > 8 and the supratentorial location was the most common location. Almost 75% of the children underwent craniotomy or craniectomy and the rest had burr-hole evacuation. Beta-hemolytic Streptococcus (10%) was the most common organism isolated. Cerebral venous thrombosis (CVT; 10.2%) was the most frequent complication in this cohort. The other complications were infarction (6.1%), new-onset seizure (4.1%), and bone flap osteomyelitis (4.1%). Thirteen cases had a recurrence of pus collection, which was more common in the craniotomy group than in the burr-hole group. Age (p = 0.02), GCS score ≤ 8 (OR 8.15, p = 0.001), CVT (OR 15.17, p = 0.001), and presence of infarction (OR 7, p = 0.05) were strongly associated with unfavorable outcome. In multivariable logistic regression analysis, only GCS score ≤ 8 (p = 0.01), CVT (p = 0.02), and presence of infarction (p = 0.04) had a significant impact on unfavorable outcome., Conclusions: Prompt diagnosis and immediate intervention is the goal of management of SDE, especially in children as a delay in diagnosis can result in unconsciousness and secondary complications such as CVT and infarction, which adversely affect outcome.

In side to side anastomosis and end to end (one way up) microvascular anastomosis, the back wall of the vessel is sutured first with inverted/buried knots. A common mistake made by surgeons during this step is the formation of a granny knot. In inverted suturing, cut ends of granny knot points inside the vessel lumen and interfere with the suture line. This additional Intraluminal thread may promote foreign body reaction and may act as a nidus for thrombus formation. Hence, this subtle mistake in knot formation may cause immediate and/or delayed anastomosis failure. The purpose of the study was to describe principles of inverted/buried reef knot formation. We describe in detail the methodology to form an inverted reef knot in microsurgery using paracords and a glove model.

In macrosurgery creating a knot with at least three throws is an established practice. The potential disadvantages of this practice in microsurgery include the following: the direction of the cut ends interfere with the suture line, unbalanced nature of knot disturbs the apposition of delicate vessel ends and the excessive knot weight. A reef knot with only 2 throws may thus be a better alternative. We have described our technique of end to end anastomosis with 2-throw reef knots in a rat femoral artery model using one way up method. Judging from the surgical outcome the practice of two throw reef knot seems feasible and appealing.

In this study, design of experiments (DoE) was employed to develop a single injection method using a headspace gas chromatograph with flame ionization detector for resolution of residual solvents of United States Pharmacopeia (USP) listed classes 1 and 2, against current recommendation of independent injections. G43 column (6% cyanopropylphenyl and 94% dimethylpolysiloxane) and nitrogen were used as the stationary phase and carrier gas, respectively. Initial temperature, hold time, temperature ramp and carrier gas velocity were the critical method parameters. Resolution of 1,1,1-trichloroethane and tetrahydrofuan (THF); THF and chloroform; benzene and 1,2-dichloroethane (DCE), and 1,2-dimethoxyethane and DCE were selected as critical quality attributes. These were optimized by DoE that resulted in resolution of >1.34 among various solvents. The separation of all the solvents was achieved within total run time of 77 min. A better resolution of 2.66 was observed in the case of acetonitrile and methylene chloride; there was improved Signal/Noise ratio of 8.86 for 1,1,1-trichloroethane; tailing factor for pyridine was 1.00, and the method showed acceptable repeatability of peak areas (%RSDmax = 11.53) and retention times (%RSDmax = 0.45). Thus, while system suitability criteria and validation results very well met the USP requirements, the optimized method proposed in this study proved advantageous additionally in terms of single injection; short run time, and use of nitrogen as a carrier gas instead of costly helium in the USP method.

The objective of this work was to utilize a potential of microemulsion for the improvement in oral bioavailability of raloxifene hydrochloride, a BCS class-II drug with 2% bioavailability. Drug-loaded microemulsion was prepared by water titration method using Capmul MCM C8, Tween 20, and Polyethylene glycol 400 as oil, surfactant, and co-surfactant respectively. The pseudo-ternary phase diagram was constructed between oil and surfactants mixture to obtain appropriate components and their concentration ranges that result in large existence area of microemulsion. D-optimal mixture design was utilized as a statistical tool for optimization of microemulsion considering oil, S mix , and water as independent variables with percentage transmittance and globule size as dependent variables. The optimized formulation showed 100 ± 0.1% transmittance and 17.85 ± 2.78 nm globule size which was identically equal with the predicted values of dependent variables given by the design expert software. The optimized microemulsion showed pronounced enhancement in release rate compared to plain drug suspension following diffusion controlled release mechanism by the Higuchi model. The formulation showed zeta potential of value -5.88 ± 1.14 mV that imparts good stability to drug loaded microemulsion dispersion. Surface morphology study with transmission electron microscope showed discrete spherical nano sized globules with smooth surface. In-vivo pharmacokinetic study of optimized microemulsion formulation in Wistar rats showed 4.29-fold enhancements in bioavailability. Stability study showed adequate results for various parameters checked up to six months. These results reveal the potential of microemulsion for significant improvement in oral bioavailability of poorly soluble raloxifene hydrochloride.

Pandemic influenza A (H1N1) 2009 virus was first detected in India in May 2009 which subsequently became endemic in many parts of the country. Influenza A viruses have the ability to evade the immune response through its ability of antigenic variations. The study aims to characterize influenza A (H1N1) pdm 09 viruses circulating in Mumbai during the pandemic and post-pandemic period. Nasopharyngeal swabs positive for influenza A (H1N1) pdm 09 viruses were inoculated on Madin-Darby canine kidney cell line for virus isolation. Molecular and phylogenetic analysis of influenza A (H1N1) pdm 09 isolates was conducted to understand the evolution and genetic diversity of the strains. Nucleotide and amino acid sequences of the HA gene of Mumbai isolates when compared to A/California/07/2009-vaccine strain revealed 14 specific amino acid differences located at the antigenic sites. Amino acid variations in HA and NA gene resulted in changes in the N-linked glycosylation motif which may lead to immune evasion. Phylogenetic analysis of the isolates revealed their evolutionary position with vaccine strain A/California/07/2009 but had undergone changes gradually. The findings in the present study confirm genetic variability of influenza viruses and highlight the importance of continuous surveillance during influenza outbreaks.

Redox potential has been identified by the Organisation for Economic Co-operation and Development (OECD) as one of the parameters that should be investigated for the testing of manufactured nanomaterials. There is still some ambiguity concerning this parameter, i.e., as to what and how to measure, particularly when in a nanoecotoxicological context. In this study the redox potentials of six nanomaterials (either zinc oxide (ZnO) or cerium oxide (CeO(2))) dispersions were measured using an oxidation-reduction potential (ORP) electrode probe. The particles under testing differed in terms of their particle size and dispersion stability in deionised water and in various ecotox media. The ORP values of the various dispersions and how they fluctuate relative to each other are discussed. Results show that the ORP values are mainly governed by the type of liquid media employed, with little contributions from the nanoparticles. Seawater was shown to have reduced the ORP value, which was attributed to an increase in the concentration of reducing agents such as sulphites or the reduction of dissolved oxygen concentration. The lack of redox potential value contribution from the particles themselves is thought to be due to insufficient interaction of the particles at the Pt electrode of the ORP probe.

We describe a practical method of fabricating surface-enhanced Raman spectroscopy (SERS) substrates based on dip-coating poly-L-lysine derivatized microscope slides in a gold colloidal suspension. The use of only commercially available starting materials in this preparation is particularly advantageous, aimed at both reducing time and the inconsistency associated with surface modification of substrates. The success of colloid deposition has been demonstrated by scanning electron microscopy (SEM) and the corresponding SERS response (giving performance comparable to the corresponding traditional colloidal SERS substrates). Reproducibility was evaluated by conducting replicate measurements across six different locations on the substrate and assessing the extent of the variability (standard deviation values of spectral parameters: peak width and height), in response to either Rhodamine 6G or Isoniazid. Of particular interest is the observation of how some peaks in a given spectrum are more susceptible to data variability than others. For example, in a Rhodamine 6G SERS spectrum, spectral parameters of the peak at 775 cm(-1) were shown to have a relative standard deviation (RSD) % of <10%, while the peak at 1573 cm(-1) has a RSD of >or=10%. This observation is best explained by taking into account spectral variations that arise from the effect of a chemisorption process and the local nature of chemical enhancement mechanisms, which affects the enhancement of some spectral peaks but not others (analogous to resonant Raman phenomenon).

W/C emulsions were stabilized using hydrophobic silica particles adsorbed at the interface, resulting in average droplet diameters as low as 7.5 microm. A porous cross-linked shell was formed about a hydrophilic (colloidal and fumed) silica core with a trifunctional silylating agent, (heptadecafluoro-1,1,2,2-tetrahydrodecyl)triethyoxysilane, to render the particles CO(2)-philic. The stability of emulsions comprising equal weights of CO(2) and water was assessed with visual observations of settling fronts and the degree of emulsion coalescence, and the average drop size was measured by optical microscopy. The effect of CO(2) density on both emulsion stability and droplet size was determined quantitatively. The major destabilizing mechanism of the emulsions was settling, whereas Ostwald ripening and coalescence were not visible at any density, even over 7 days. Flocculation of the settling droplets did not occur, although gelation of the emulsions through particle interactions resulted after longer periods of time. CO(2)-philic particles offer a new route to highly stable W/C emulsions, with particle energies of attachment on the order of 10(6)kT, even at CO(2) densities as low as 0.78 g ml(-1). At these low densities, surfactants rarely stabilize emulsions as the result of poor surfactant tail solvation.