Androsin alleviates non-alcoholic fatty liver disease by activating autophagy and attenuating de novo lipogenesis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease with therapeutic options on the horizon. Picrorhiza kurroa, enriched with iridoid glycosides like picroside I and picroside II is known for its hepatoprotective activity and anti-inflammatory properties. Androsin, the other phytochemical present in P. kurroa has been shown to have anti-inflammatory and anti-asthmatic properties. However, its role in NAFLD is yet to be investigated. PURPOSE: This study aims to identify the potent hepatoprotective agent from P. kurroa that can attenuate NAFLD in HFrD-fed ApoE-/- mice, and elucidate the underlying mechanisms governing its effects. METHODS: Classical purification methods were used to isolate seven compounds, including picroside I, picroside II and androsin from the roots of P. kurroa. NAFLD-induced ApoE-/- mice were administered orally with either picroside I, picroside II, or androsin for 7 weeks. Animals were scanned non-invasively by ultrasonography at 1st and 14th week. Gross histomorphometry was examined by HE and Sirius red staining. mRNA transcript and protein profile associated with autophagy, lipogenesis, inflammation, and fibrosis was done through RT-PCR and Western blot analysis. RESULTS: In-vitro and in-vivo studies revealed that among the seven evaluated compounds, androsin shows the most potent in-vitro activity. Oral dosing of androsin (10 mg/kg) protected the liver against HFrD-induced NAFLD in ApoE-/- mice model. Biochemical analysis revealed a reduction in ALT and AST enzymes and a significant reduction in cholesterol levels. Hepatocyte ballooning, hepatic lipid deposition, inflammation, and fibrosis were reduced. Androsin treatment significantly reduced fibrosis (α-SMA, collagens, TGF-ß) and inflammation (ILs, TNF-α, NFκB) in ApoE-/- mice. Mechanistically, androsin activated AMPKα and down-regulated the expression of SREBP-1c, resulting in ameliorating hepatic lipogenesis. CONCLUSION: Our results support autophagy as one of the therapeutic strategies to reduce steatosis and hepatic damage. We found that androsin treatment significantly ameliorated hepatic steatosis, serum lipid levels, and hepatic injury in ApoE-/- induced by HFrD. Androsin administration mitigated lipogenesis by inhibiting SREBP1c/FASN pathway and activating autophagy through AMPKα/PI3K/Beclin1/LC3 pathway.

Does This Infant Have a Dislocated Hip?: The Rational Clinical Examination Systematic Review.

Importance: Delayed diagnosis of a dislocated hip in infants can lead to complex childhood surgery, interruption to family life, and premature osteoarthritis. Objective: To evaluate the diagnostic accuracy of clinical examination in identifying dislocated hips in infants. Data Sources: Systematic search of CINAHL, Embase, MEDLINE, and the Cochrane Library from the inception of each database until October 31, 2023. Study Selection: The 9 included studies reported the diagnostic accuracy of the clinical examination (index test) in infants aged 3 months or younger and a diagnostic hip ultrasound (reference test). The Graf method of ultrasound assessment was used to classify hip abnormalities. Data Extraction and Synthesis: The Rational Clinical Examination scale was used to assign levels of evidence and the Quality Assessment of Diagnostic Accuracy Studies tool was used to assess bias. Data were extracted using the individual hip as the unit of analysis; the data were pooled when the clinical examinations were evaluated by 3 or more of the included studies. Main Outcomes and Measures: Sensitivity, specificity, and likelihood ratios (LRs) of identifying a dislocated hip were calculated. Results: Among infants screened with a clinical examination and a diagnostic ultrasound in 5 studies, the prevalence of a dislocated hip (n = 37 859 hips) was 0.94% (95% CI, 0.28%-2.0%). There were 8 studies (n = 44 827 hips) that evaluated use of the Barlow maneuver and the Ortolani maneuver (dislocate and relocate an unstable hip); the maneuvers had a sensitivity of 46% (95% CI, 26%-67%), a specificity of 99.1% (95% CI, 97.9%-99.6%), a positive LR of 52 (95% CI, 21-127), and a negative LR of 0.55 (95% CI, 0.37-0.82). There were 3 studies (n = 22 472 hips) that evaluated limited hip abduction and had a sensitivity of 13% (95% CI, 3.3%-37%), a specificity of 97% (95% CI, 87%-99%), a positive LR of 3.6 (95% CI, 0.72-18), and a negative LR of 0.91 (95% CI, 0.76-1.1). One study (n = 13 096 hips) evaluated a clicking sound and had a sensitivity of 13% (95% CI, 6.4%-21%), a specificity of 92% (95% CI, 92%-93%), a positive LR of 1.6 (95% CI, 0.91-2.8), and a negative LR of 0.95 (95% CI, 0.88-1.0). Conclusions and Relevance: In studies in which all infant hips were screened for developmental dysplasia of the hip, the prevalence of a dislocated hip was 0.94%. A positive LR for the Barlow and Ortolani maneuvers was the finding most associated with an increased likelihood of a dislocated hip. Limited hip abduction or a clicking sound had no clear diagnostic utility.

Risk factors and associated pathway for rural and urban unmet dental prosthetic needs among older adults in Central India.

AIM: This study was undertaken to evaluate the risk factors and associated pathways for unmet dental prosthetic needs among older adult population in Central India. METHODS: A total of 11,145 randomly selected older adults participated in the study; 4613 from urban region and 6532 form rural region. Oral examinations were conducted at individual households for recording dental caries, periodontal disease, prosthetic status and needs. Structural Equation Modelling (SEM) was used to examine relationship between a set of exogenous variables and unmet dental prosthetic needs with variables that remained significant in the adjusted multilevel logistic model. Path coefficients were calculated for all variables with 95% confidence interval. Goodness of fit of the model was assessed by several indices. RESULTS: A total of 8433 (75.7%) participants had never visited a dentist and 9139 (82%) had unmet dental prosthetic needs. Dental caries was observed among 3207 (69.5%) and 4644 (71.1%) study participants from urban and rural regions respectively (p < .05). Low utilization of dental services was associated with high dental prosthetic needs in upper arch and lower arch (PC = -0.05, 0.001) and DMFT was associated with lower utilization of dental services (PC = -0.09, 0.001). DMFT was also associated with age, annual income, level of education, paternal education, type of family, tobacco consumption and CPI score in the hypothesized model. The fit indices used indicated that the model was adequate. CONCLUSIONS: Dental prosthetic needs in the proposed pathway model was associated with low utilization of dental services, dental caries, periodontal disease and other socio-demographic factors.

Neuromodulation of spinal reflex pathway for the treatment of detrusor overactivity by medial plantar nerve stimulation at surface of sole of foot in patients with spinal cord injury.

Objectives: Suprasacral spinal cord lesions are prone to have neurogenic detrusor overactivity leading to urinary incontinence. Current medical management has known side-effects and often surgical managements are irreversible. Electrical stimulation to modulate spinal reflex pathway having same nerve root as urinary bladder is reported in the literature. This study aimed to reduce detrusor overactivity in patients with spinal cord injury (SCI) using surface electrical stimulation of medial plantar nerve at the sole of foot. Materials and Methods: Twenty adults with SCI having episode of at least 1 leak/day due to detrusor overactivity as diagnosed by cystometrogram (CMG), were on clean intermittent catheterization and ankle jerk was present consented for the study. Participants were asked to maintain bladder diary a week before and during 2 weeks of treatment. CMG was done on day-0 and day-14. cmcUroModul@tor®, an inhouse developed electrical stimulator was used for ½ h daily for period of 2 weeks. Patient satisfaction feedback questionnaire was taken on completion of treatment. CMG data were analyzed using Wilcoxon signed-ranked test while bladder diary was analyzed using binomial distribution. P < 0.05 was considered as statistically significant. Institutional Review Board (IRB) and ethics committee of Christian Medical College, Vellore, approved the study (CMC/IRB/11061). Results: Statistical significant improvement in maximum detrusor pressure (P = 0.03) and cystometric capacity (P = 0.04) was observed. Of 20 subjects, 18 showed improvement in bladder diary. Conclusion: Neuromodulation of medial plantar nerve at sole of foot by surface electrical stimulation is non-invasive, cost-effective, and alternative simple treatment modality for urinary incontinence due to detrusor overactivity.

Critical Evaluation of Lateral Calcaneal Artery Fascio-Cutaneous Flap in Re-Surfacing Posterior Heel Defects: A Review of 24 Cases.

Purpose and background: To assess feasibility and functional acceptability of lateral calcaneal artery fascio-cutaneous flap (LCAFCF) in providing cover to posterior heel defects in single stage. Aims and objectives: To provide stable and sensate cover to small and moderate posterior heel defects. Materials and methods: This review was conducted in department of Burns & Plastic Surgery of Postgraduate Institute of Medical Sciences (PGIMS), Rohtak, Haryana between October 2021 and September 2022 to analyse the clinical outcome of LCAFCF in 24 patients (18 males, 6 females) aged between 20 and 35 years who had chronic dry wounds n = 9, failed primary reconstruction by reverse sural flap n = 1, granulated wounds n = 8, exposed achilles tendons n = 4 and scarred tissue restricting ankle joint movements n = 2 in region of posterior heel following trauma, while riding motor-cycle. Course of lateral calcaneal artery was marked with hand-held doppler. Flap size ranged from 3 to 3.5 cm in width and 5.5-7.5 cm length. The donor sites were split skin grafted. Sutures were removed on 22nd day of surgery. Mean follow up was 13 months. Results: All flaps survived. Two had partial loss of skin graft and two developed hyperkeratosis on grafted site. Sensations in flap, regain of movements of ankle joint, comfort of walking and driving were acceptable. Conclusions: LCAFCF is handy, safe and reliable flap for re-surfacing difficult wounds of posterior heel, therefore should be included in surgical armamentarium.

Clinical Classification of Urethrocutaneous Fistulas Developing after Hypospadias Repair.

Background Clinical classification of the urethrocutaneous fistulas (UCFs) was designed to help the surgeons in (1) categorizing the fistulas, (2) selecting appropriate treatments, (3) keeping record at presentation and discharge, and (4) transferring information while referring a patient with recurrent fistula to a higher center. Methods This retrospective study comprised of 68 patients with UCFs who reported in the "Hypospadias and VVFs Clinic" between 2004 and 2016. The study was performed to determine the incidence or etiology of the UCFs. It was rather performed to classify fistulas into different categories depending on the number of fistulas: A (5 fistulas), B (16 fistulas), C-a (28 fistulas), C-b (4 fistulas), D (4 fistulas), and E (11 fistulas). Category A fistulas healed conservatively. Category B fistulas underwent transection of the fistula tracts (tractotomy), purse-string closure, or multilayered closure (fistulorrhaphy). Category C-a fistulas were reenforced by preputial or penile skin flaps or waterproofing flaps. Category C-b fistulas underwent re-tubularization of their neourethral plates and eccentric closure of peno-preputial skin. The urethral plates of category D fistulas were re-tubularized after 3 to 6 months and cover was provided by the Cecil-Culp procedure. Category E fistulas had associated hairy urethra, stricture distal urethra, stricture with diverticulum, perifistular scar-induced chordee, long narrow urethral plate, balanitis xerotica obliterans (BXO), and short reconstructed neourethra. Accordingly, appropriate corrective measures were taken. Miscellaneous category F was excluded from the study. Results Except for one in category D, none of the patients had any recurrence of fistula. One patient of category E had residual diverticulum. Conclusion The designed clinical classification of UCFs is simple. Treatment was in accordance with reconstructive ladder wherein complexity of treatment paralleled with increasing complexity of fistulas.

Design and development of benzyl piperazine linked 5-phenyl-1,2,4-triazole-3-thione conjugates as potential agents to combat Alzheimer's disease.

Our present work demonstrates the molecular hybridization-assisted design, synthesis, and biological evaluation of 22 benzylpiperazine-linked 1,2,4-triazole compounds (PD1-22) as AD modifying agents. All the compounds were tested for their in vitro hChEs, hBACE-1, and Aß-aggregation inhibition properties. Among them, compound PD-08 and PD-22 demonstrated good hChE and hBACE-1 inhibition as compared to standards donepezil and rivastigmine. Both compounds displaced PI from PAS at 50 µM concentration which was comparable to donepezil and also demonstrated anti-Aß aggregation properties in self- and AChE-induced thioflavin T assay. Both compounds have shown excellent BBB permeation via PAMPA-BBB assay and were found to be non-neurotoxic at 80 µM concentration against differentiated SH-SY5Y cell lines. Compound PD-22 demonstrated an increase in rescued eye phenotype in Aß-phenotypic drosophila AD model and amelioration of behavioral deficits in the Aß-induced rat model of AD. The in-silico docking studies of compound PD-22 revealed a good binding profile towards CAS and PAS residues of AChE and the catalytic dyad of the BACE-1. The 100 ns molecular dynamics simulation studies of compound PD-22 complexed with AChE and BACE-1 enzymes suggested stable ligand-protein complex throughout the simulation run. Based on our findings compound PD-22 could further be utilized as a lead to design a promising candidate for AD therapy.

Carbon dioxide flushing versus saline flushing of thoracic aortic stents (INTERCEPTevar): protocol for a multicentre pilot randomised controlled trial.

INTRODUCTION: Thoracic endovascular aortic repair (TEVAR) carries a 3%-6.1% stroke risk, including risk of 'silent' cerebral infarction (SCI). Stent-grafts are manufactured in room air and retain air. Instructions for use recommend saline flushing to 'de-air' the system prior to insertion, but substantial amounts of air are released when deploying them, potentially leading to downstream neuronal injury and SCI. Carbon dioxide (CO2) is more dense and more soluble in blood than air, without risk of bubble formation, so could be used in addition to saline to de-air stents. This pilot trial aims to assess the feasibility of a full-scale randomised controlled trial (RCT) investigating the neuroprotective benefit against SCI with the use of CO2-flushed aortic stent-grafts. METHODS AND ANALYSIS: This is a multicentre pilot RCT, which is taking place in vascular centres in the UK, USA and New Zealand. Patients identified for TEVAR will be enrolled after informed written consent. 120 participants will be randomised (1:1) to TEVAR-CO2 or TEVAR-saline, stratified according to TEVAR landing zone. Participants will undergo preoperative neurocognitive tests and quality of life assessments, which will be repeated at 6 weeks, or first outpatient appointment, and 6 months. Inpatient neurological testing will be performed within 48 hours of return to level 1 care for clinical stroke or delirium. Diffusion-weighted MRI will be undertaken within 72 hours postoperatively (1-7 days) and at 6 months to look for evidence and persistence of SCI. Feasibility will be assessed via measures of recruitment and retention, informing the design of a full-scale trial. ETHICS AND DISSEMINATION: The study coordination centre has obtained approval from the London Fulham Research Ethics Committee (19/LO/0836) and Southern Health and Disability Ethics Committee (NZ) and UK's Health Regulator Authority (HRA). The study has received ethical approval for recruitment in the UK (Fulham REC, 19/LO/0836), New Zealand (21/STH/192) and the USA (IRB 019-264, Ref 378630). Consent for entering into the study will be taken using standardised consent forms by the local study team, led by a local PI. The results of the trial will be submitted for publication in an open access journal. TRIAL REGISTRATION NUMBER: NCT03886675.

Evaluation of serum interleukin-33 and soluble suppression of tumorigenicity 2 (sST2) receptors in patients with and without periodontal disease.

Context: : Interleukin-33 and its receptor soluble suppression of tumorigenicity 2. (: sST2) play an important role in inflammation and its role in periodontal disease is yet unclear. The role of both IL-33 and sST2 together in periodontal disease as biomarkers has never been studied. Aim: : To assess the levels of IL-33 and sST2 in serum samples of patients with periodontitis and healthy subjects. Methods: : A total of 71 subjects (30 healthy subjects and 41 patients with periodontal disease) were included in the cross-sectional study. Community Periodontal Index (CPI) was used to assess periodontal health by utilizing a mouth mirror and a CPI probe. Venous blood was collected and serum was separated. Serum levels of IL-33 and sST2 were determined by the enzyme-linked immunosorbent assay (ELISA) assay. Statistical Analysis: Graph Pad Prism 5 was used for statistical analysis. Mann Whitney test was applied to compare the two groups. Results: : The level of IL-33 was not found to be elevated among healthy subjects and sST2 was found elevated among patients with periodontal disease. The serum concentration of IL-33 was found at 472 ± 114 pg/ml and 282 ± 77 pg/ml among healthy subjects and patients with periodontal disease respectively. Significantly higher values of sST2 at 28 ± 2 ng/ml were found among periodontal patients as compared to healthy subjects with values of 18 ± 1 ng/ml. No significant differences were noted between mild to moderate and severe periodontitis for IL-33 and sST2 between the two groups. Conclusion: This study shows alteration in serum levels of IL-33 and sST2 in periodontitis patients. IL-33 and sST2 may be potential inflammatory markers of periodontitis. Further studies are required on a large sample size for better understanding. This pilot study is the first to assess the serum levels of both IL-33 and sST2 together among patients with and without periodontal disease.

Missile embolisation to the right common femoral artery following thoracic injury, without any conspicuous source of entry.

Embolisation of a projectile metallic body in the arterial system is not an unusual entity and has been reported off and on, in literature. We report the successful treatment and survival of a patient with thoracic injury, with a metallic projectile embolisation to the right common femoral artery and acute limb ischemia. Curiously, there was no identifiable entry point, on multiple imaging. The patient remained functionally independent, and without any complication on discharge. Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-021-01291-1.

Comparative metabolic profiling, isolation of alkylated phenols and antioxidant activity of roots of Plumbago species using GC-MS and NMR based metabolomics study.

In this study, NMR and GC-MS based comparative metabolomic profiling of the roots of three different species namely, Plumbago indica, P. auriculata and P. zeylanica were investigated followed by multivariate statistical analyses and their antioxidant activity. Also, two alkylated phenols i.e., 2,6-di-tert-butyl phenol and 2,4-di-tert-butyl phenol not reported earlier from this taxon were isolated from P. indica. This metabolic study resulted in the identification of 25 and quantification of 18 metabolites. Principal component analysis showed the clear distinction among the three species. The antioxidant activity in the extracts was tested by free radical scavenging method. The three Plumbago species revealed interesting antioxidant potential, in particular, P. indica, which was rich in naphthoquinones, coumarins, alkylated phenols, sterols, triterpenes, fatty acids showed lowest IC50 value. The results highlighted the role of P. indica in the management of oxidative stress especially when they are utilized in the formation of fermented food products.

Rotational stability of Toric intraocular lenses.

BACKGROUND: A prospective study to evaluate the rotational stability of toric intraocular lenses (IOLs). METHODS: A prospective study of 30 eyes in 29 patients. All patients with regular astigmatism of range 0.75-4 D were included in the study. Exclusion criteria included irregular corneal astigmatism, post-refractive surgery and corneal dystrophies. All patients underwent uncomplicated phacoemulsification cataract surgery by the same surgeon. Three eyes with corneal astigmatism of 0.75-1.5 D were implanted with the AcrySof SA60T3 IOL, eight eyes with astigmatism between 1.5 and 2.0 D received the SA60T4 IOL and eight eyes with astigmatism between 2.0 and 2.50 D received the SA60T5 and rest with astigmatism of 2.5 D and higher received SA60T6 and above models. Main outcome measure was the post-operative position of the lens, assessed at day 1, 1 week, 1 month and 6 months, using toric marker and the slit lamp. RESULTS: There was no significant rotation of IOL observed during a follow-up period of 6 months. Overall, the post-operative rotation was within 5° in 95% of cases. There was no trend for either clockwise or anti-clockwise rotation. However, IOL rotation happens mostly within the first month of surgery, and if it is significant, it requires early repositioning. CONCLUSION: Toric IOLs are very effective and consistent in correcting astigmatism during the cataract surgery. Once placed to its position, toric IOLs demonstrate rotational stability in the capsular bag.

Imidazopyridine, a promising scaffold with potential medicinal applications and structural activity relationship (SAR): recent advances.

Imidazopyridine scaffold has gained tremendous importance over the past few decades. Imidazopyridines have been expeditiously used for the rationale design and development of novel synthetic analogs for various therapeutic disorders. A wide variety of imidazopyridine derivatives have been developed as potential anti-cancer, anti-diabetic, anti-tubercular, anti-microbial, anti-viral, anti-inflammatory, central nervous system (CNS) agents besides other chemotherapeutic agents. Imidazopyridine heterocyclic system acts as a key pharmacophore motif for the identification and optimization of lead structures to increase medicinal chemistry toolbox. The present review highlights the medicinal significances of imidazopyridines for their rationale development as lead molecules with improved therapeutic efficacies. This review further emphasis on the structure-activity relationships (SARs) of the various designed imidazopyridines to establish a relationship between the key structural features versus the biological activities.Communicated by Ramaswamy H. Sarma.

Principles of Bracing in the Early Management of Developmental Dysplasia of the Hip.

Bracing is considered a gold standard in treating Developmental Dysplasia of the Hip (DDH) in infants under 6 months of age with reducible hips. A variety of braces are available that work on similar principles of limiting hip adduction and extension. This paper summarises the current evidence regarding bracing in DDH. Most of the literature pertains to the Pavlik harness (PH) and there are few studies for other brace types. Bracing eliminates dislocating forces from the hamstrings, the block to reduction of the psoas and improves the muscle line of pull to stabilise the hip joint. Recent studies have shown no benefit in bracing for stable dysplasia. The rates of PH treatment failure in Ortolani-positive hips have been reported to be high. Barlow positive hips have lower Graf grades and are more amenable to PH treatment. There is consensus that the earlier the diagnosis of DDH and initiation of PH treatment, the better the outcome. Failure rates due to unsuccessful reduction and AVN are higher with treatment initiated after age 4-6 months. Studies have shown no benefits of staged weaning of braces. While there is no maximum time in brace, current consensus suggests a minimum of 6 weeks. The key to successful bracing lies in education and communication with the family.

Operative intervention for a central pulmonary artery pseudoaneurysm.

Pulmonary artery (PA) pseudoaneurysms are a rare but potentially lethal diagnosis. They can be further categorized by etiology or location and are typically successfully treated with endovascular therapies. However, they occasionally require operative intervention. Here, we present a case of a patient who presented with a central PA pseudoaneurysm on computed tomography scan with unclear etiology that was initially treated with conservative management. However, this was noted to have rapid enlargement on interval imaging necessitating urgent surgical intervention. The patient underwent a median sternotomy, anterior PA arteriotomy for exposure, exclusion of the posterior artery pseudoaneurysm with a bovine pericardial patch, and closure of the anterior arteriotomy with a bovine pericardial patch. The patient did well and was discharged on postoperative day 11 with repeat imaging showing resolution.

ABO Blood Groups and Its Association with Oral Cancer, Oral Potentially Malignant Disorders and Oral Submucous Fibrosis- A Systematic Review and Meta-Analysis.

OBJECTIVE: The study aimed to evaluate the association between ABO blood groups and oral cancer, other potentially malignant disorders (OPMD), and oral submucous fibrosis (OSMF). MATERIALS AND METHODS: A search was conducted in Medline, Cochrane databases, Google Scholar, Scopus, Web of Science and Directory of Open Access Journals (DOAJ) for studies evaluating ABO blood groups as risk factors for oral cancer and OPMD among cases and controls. The PRISMA guidelines were followed for the meta-analysis. Participants included patients with oral cancer, and OPMD diagnosed using histopathologic investigations.  Sub-group analysis was conducted to evaluate the association between blood groups and OSMF. Quality was evaluated using the Risk of Bias Assessment tool. Fixed effects model was used to assess the odds ratio for the association. RESULTS: There were 1352, 414, and 299 cases of oral cancer, OPMD, and OSMF and 11,699, 7382 and 7307 controls for analysis respectively. Blood group A was significantly associated with both oral cancer (Odds ratio: 1.27 [95% CI, 1.10, 1.47], P= 0.001) and OPMD (Odds ratio: 1.33 [95% CI, 1.01, 1.47], P= 0.04).  No association was noted between blood group B and AB with oral cancer, OPMD, and OSMF. Blood group O was significantly associated with lower chances of oral cancer (Odds ratio: 0.81 [95% CI, 0.71, 0.93], P= 0.002). CONCLUSION: Meta-analysis suggests blood group A has a greater risk for developing oral cancer and OPMD. Blood group O was associated with lower chances of oral cancer. No association was noted between ABO blood group system with OSMF.

Prophylactic administration of podophyllotoxin and rutin combination assists the revival of radiation-induced hematopoietic suppression in lethally irradiated mice.

Hematopoietic syndrome contributes to mortality after exposure to high doses of low LET radiation. In this context, we have earlier demonstrated the potential of G-003 M (a combination of podophyllotoxin and rutin) in alleviating radiation-induced bone marrow suppression. Similarly, we here demonstrate that G-003 M protected mice from death (>83% protection) and increased the populations of CD 34 (Cluster of differentiation 34) as well as CD 117 (Cluster of differentiation 117) positive cell population and their colony forming capacity. This was accompanied with increase in the serum titre of granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF). Interestingly, G-003 M lowered down the titre of fms-like tyrosine kinase (Flt-3) ligands. Our results furthermore demonstrates that G-003 M facilitated the nuclear translocation of ß-catenin and upregulated the expression of Wnt 10b. Conditioning of animal with G-003 M activated the expression of survivin, inhibited the activation of Caspase-3 in CD 34/117+ progenitor stem cells and protected the bone marrow vascularity and splenic colonies in lethally irradiated animals, which collectively promoted hemopoietic recovery in lethally irradiated mice.

Increased perioperative mortality for femoral neck fractures in patients with coronavirus disease 2019 (COVID-19): experience from the United Kingdom during the first wave of the pandemic.

BACKGROUND: The coronavirus disease 19 (COVID-19) pandemic has presented modern healthcare with an unprecedented challenge. At the peak of the pandemic, trauma and orthopaedic services at our institutions undertook internal restructuring, diverting resources to frontline medical care. Consequently, we sought to assess the impact on the elderly and comorbid patients presenting with femoral neck fractures, with a particular focus on 30-day mortality, length of stay, multidisciplinary team involvement and departmental structuring. METHOD: A retrospective analysis of patients presenting with femoral neck fractures at three separate West London NHS Trusts was undertaken between March 11, 2020, to April 30, 2020. Length of stay, 30-day mortality and adherence to parameters constituting the best care evidence-based practice tariffs were compared between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive and negative patients. A similar comparison was also conducted between our cohort and the equivalent period in 2018 using data from the National Hip Fracture Database. RESULTS: A total of 68 patients presenting with femoral neck fractures were identified, mean age 81 (range 38-98), 73% female. There were 10 confirmed/suspected cases of COVID-19 on admission and a further seven confirmed as inpatients. The 30-day mortality within our cohort was 11.76% compared to 6% nationally in 2018 (p = 0.045). Orthogeriatric reviews occurred within 72 h in 71% of cases compared to 88% in the equivalent 2018 period. Within the cohort, mean length of stay was 17.13 days (SD 5.6, range 8-27 days) for SARS-CoV-2 positive patients compared to 10 days (SD 8.7, range 1-53 days) for negative patients (p < 0.05). Thirty-two patients (47%) required increased packages of care on discharge or rehabilitation. CONCLUSIONS: The increase in 30-day mortality for SARS-CoV-2 positive patients presenting with femoral neck fractures is multifactorial, resulting from a combination of the direct effects of COVID-19 pneumonia as well as changes to the delivery of orthopaedic services. The provision of multidisciplinary care was directly affected by staff redeployment, particularly reorganisation of orthogeriatric services and lack of continuity of ward based clinical care. Our experiences have re-directed efforts towards the management of theatre teams, patient services and staffing, should we be faced with either a resurgence of COVID-19 or a future pandemic.