Neurological Outcome of Early versus Late Surgery Following Cervical Spinal Cord Injury.

Background There are numerous retrospective studies and a few prospective studies to determine the neurologic outcome after early versus late surgical treatment for cervical spinal cord injury. Objective To compare the neurological outcome between early (within 72 hours after injury) and delayed (≥ 72 hours after injury) surgery in patients with cervical spinal injury. Method This is a retrospective analysis of the neurological outcome of early versus late surgery following cervical spinal cord trauma. Patients meeting appropriate inclusion criteria were divided into an early or a late surgical treatment group. The neurologic outcomes and other complications were recorded up to six months of follow-up. Result Overall, there was a significant difference in neurological status at presentation and at follow-up (p < 0.001). However, there was no statistically significant difference between the early versus late surgery groups (p-value 0.261) in terms of neurological outcome. Complications were found to be higher among those undergoing posterior surgical approach (OR = 23.75; 95% CI 2.65, 212.98) than those with anterior or combined approach (p=0.005). However, multivariate analysis of these variables failed to show any statistically significant difference between the two groups. Conclusion The timing of surgery does not alter the neurological outcomes and the development of complications significantly. The American Spinal Cord Injury Association (ASIA) status at the time of presentation is found to be the single most important factor correlating with the neurological outcome.

Management of Lateral Epicondylitis: A Prospective Comparative Study Comparing the Local Infiltrations of Leucocyte Enriched Platelet-Rich Plasma (L-aPRP), Glucocorticoid and Normal Saline.

Introduction: Lateral epicondylitis is a painful condition of the elbow, characterised by pain and tenderness with resisted wrist extension. This study was carried out to evaluate the comparative efficacy of the local infiltration of L-PRP, methylprednisolone and normal saline in patients with lateral epicondylitis. Materials and methods: Sixty adult patients, between the ages 30 to 50 years, diagnosed with lateral epicondylitis of more than 12 weeks, were enrolled in the prospective randomised study. Their medical history and previous conservative treatment were recorded; the clinical evaluation of the tendinitis was made with the visual analogue scale (VAS), the disabilities of the arm, shoulder, and hand (DASH) outcome scores, the modified elbow performance index (MEPS), the functional assessment by patient-rated tennis elbow evaluation (PRTEE), together with the laboratory investigations. The patients were randomised using the computer-generated alphabets into three groups of 20: group A received saline, group B received PRP, and group C received corticosteroids. Results: Patients were seen at 4, 8 and 12 weeks to evaluate the post-injection status. VAS, DASH, and PRTEE scores were significantly reduced, and MEPS was significantly improved in group B compared to group A and group C. Moreover, the reductions in VAS and PRTEE were significantly different in group C compared to group A. Conclusion: PRP leads to superior healing with long-term therapeutic advantages compared to corticosteroids though it takes a little longer to have its effect.

High-dose femtosecond-scale gamma-ray beams for radiobiological applications.

Objective. In the irradiation of living tissue, the fundamental physical processes involved in radical production typically occur on a timescale of a few femtoseconds. A detailed understanding of these phenomena has thus far been limited by the relatively long duration of the radiation sources employed, extending well beyond the timescales for radical generation and evolution.Approach. Here, we propose a femtosecond-scale photon source, based on inverse Compton scattering of laser-plasma accelerated electron beams in the field of a second scattering laser pulse.Main results. Detailed numerical modelling indicates that existing laser facilities can provide ultra-short and high-flux MeV-scale photon beams, able to deposit doses tuneable from a fraction of Gy up to a few Gy per pulse, resulting in dose rates exceeding 1013Gy/s.Significance. We envisage that such a source will represent a unique tool for time-resolved radiobiological experiments, with the prospect of further advancing radio-therapeutic techniques.

Topographic location and branching pattern of the superior mesenteric artery with its clinical relevance: a cadaveric study.

BACKGROUND: The topographic location of the superior mesenteric artery (SMA) and its branching pattern are usually arbitrary in textbooks. This study, therefore, aims to provide topographic information of SMA with reference to the vertebral bodies, ventral branches of aorta and branching pattern of SMA. MATERIALS AND METHODS: The study was conducted on 35 embalmed adult human cadavers. We performed detailed dissection of the SMA to topographically locate its origin in respect to vertebral level and other ventral branches of the abdominal aorta. We have categorised the branching pattern of SMA into three different types depending upon the number of arterial pedicles, traced from proximal to distal to look into their anastomoses and formation marginal artery of Drummond. RESULTS: Vertebral level of origin of SMA varied between the lower third of twelfth thoracic vertebra (T12) and lower third of first lumbar vertebra (L1), most commonly arose at the level of the lower third of L1 (77.14%). The average distances between the origin of SMA and coeliac trunk (CT), inferior mesenteric artery (IMA) and aortic bifurcation were 1.84 cm, 6.67 cm and 10.39 cm, respectively. Depending on the branching pattern, type A was found in 29 (82.85%) cases, type B in 5 (14.28%) and type C in 1 (2.85%). In 2 cases (both of type B), the marginal artery was incomplete. CONCLUSIONS: The most common topography of origin of the SMA was opposite the lower third of L1. The coeliac-superior mesenteric relationship was most consistent than between any other two points on the abdominal aorta; 85% of the SMAs were concentrated within a space of 1.00 cm (0.60-1.50 cm) from the CT. Type A branching pattern was most commonly seen in our study population.

Assessing the effects of common topical exposures on skin bacteria associated with atopic dermatitis.

BACKGROUND: While patients and families struggling with atopic dermatitis (AD) have documented concerns for a contributory role of skin care products in AD pathology, nearly all the skin microbiome studies to date have asked participants to avoid topical products (such as soaps or select medications) for the preceding days to weeks prior to sample collection. Thus, given the established role of the microbiome in AD, the interactions between topical exposures, dysbiosis and AD remains underrepresented in the academic literature. OBJECTIVES: To address this knowledge gap, we expanded our previous evaluations to test the toxicological effects of a broader range of common chemicals, AD treatment lotions, creams and ointments using both health- and AD-associated strains of Roseomonas mucosa and Staphylococcus spp. METHODS: Use of in vitro culture techniques and mouse models were deployed to identify chemicals with dysbiotic or pre-biotic potential. A proof-of-concept study was subsequently performed in healthy volunteers to assess global microbiome shifts after exposure to select chemicals using dermatologic patch testing. RESULTS: Numerous chemicals possessed antibiotic properties, including many not marketed as anti-microbials. Through targeted combination of potentially beneficial chemicals, we identified combinations which promoted the growth of health-associated isolates over disease-associated strains in bacterial culture and enhanced microbe-specific outcomes in an established mouse model of AD; the most promising of which was the combination of citral and colophonium (often sold as lemon myrtle oil and pine tar). Additional studies would likely further optimize the combination of ingredients use. Similar results were seen in the proof-of-concept human studies. CONCLUSIONS: Our results could offer a systematic, multiplex approach to identify which products carry dysbiotic potential and thus may guide formulation of new topicals to benefit patients with AD.

Sources of SARS-CoV-2 and Other Microorganisms in Dental Aerosols.

On March 16, 2020, 198,000 dentists in the United States closed their doors to patients, fueled by concerns that aerosols generated during dental procedures are potential vehicles for transmission of respiratory pathogens through saliva. Our knowledge of these aerosol constituents is sparse and gleaned from case reports and poorly controlled studies. Therefore, we tracked the origins of microbiota in aerosols generated during ultrasonic scaling, implant osteotomy, and restorative procedures by combining reverse transcriptase quantitative polymerase chain reaction (to identify and quantify SARS-CoV-2) and 16S sequencing (to characterize the entire microbiome) with fine-scale enumeration and source tracking. Linear discriminant analysis of Bray-Curtis dissimilarity distances revealed significant class separation between the salivary microbiome and aerosol microbiota deposited on the operator, patient, assistant, or the environment (P < 0.01, analysis of similarities). We also discovered that 78% of the microbiota in condensate could be traced to the dental irrigant, while saliva contributed to a median of 0% of aerosol microbiota. We also identified low copy numbers of SARS-CoV-2 virus in the saliva of several asymptomatic patients but none in aerosols generated from these patients. Together, the bacterial and viral data encourage us to conclude that when infection control measures are used, such as preoperative mouth rinses and intraoral high-volume evacuation, dental treatment is not a factor in increasing the risk for transmission of SARS-CoV-2 in asymptomatic patients and that standard infection control practices are sufficiently capable of protecting personnel and patients from exposure to potential pathogens. This information is of immediate urgency, not only for safe resumption of dental treatment during the ongoing COVID-19 pandemic, but also to inform evidence-based selection of personal protection equipment and infection control practices at a time when resources are stretched and personal protection equipment needs to be prioritized.

Thyroid hormone and thyromimetics inhibit myelin and axonal degeneration and oligodendrocyte loss in EAE.

We have previously demonstrated that thyromimetics stimulate oligodendrocyte precursor cell differentiation and promote remyelination in murine demyelination models. We investigated whether a thyroid receptor-beta selective thyromimetic, sobetirome (Sob), and its CNS-targeted prodrug, Sob-AM2, could prevent myelin and axonal degeneration in experimental autoimmune encephalomyelitis (EAE). Compared to controls, EAE mice receiving triiodothyronine (T3, 0.4 mg/kg), Sob (5 mg/kg) or Sob-AM2 (5 mg/kg) had reduced clinical disease and, within the spinal cord, less tissue damage, more normally myelinated axons, fewer degenerating axons and more oligodendrocytes. T3 and Sob also protected cultured oligodendrocytes against cell death. Thyromimetics thus might protect against oligodendrocyte death, demyelination and axonal degeneration as well as stimulate remyelination in multiple sclerosis.

Cadaverless anatomy: Darkness in the times of pandemic Covid-19.

The pandemic Covid-19 is responsible for a major education crisis globally and has a drastic impact on medical training as well. The objective of the present study was to envision the present and future impact of Covid-19 on anatomy learning and research. The virtual education is the only mode of teaching in current scenario. Every anatomist is unlocking technology to deliver best education however understanding of the subject without dissections or other practical teaching aids like bones, specimens, embryology models, microscopic slides etc. is challenging. This approach misses the feel and human visual impacts. Potential educational disruption is felt currently and will be experienced even after the pandemic is over due to scarcity of cadavers. As the body donor may be carrier or died of Covid-19 and there is no proven screening to rule out this infection in donor, so the acceptance of body donations is not advisable for the safety of medical students and health care workers. To conclude, anatomy education is cadaverless currently due to Covid-19 lockdown and it is prophesied that after the pandemic, real cadavers will be replaced by virtual cadavers because of paucity of cadavers. Research in the field of anatomy will also be adversely affected.

Low-Voltage Domain-Wall LiNbO3 Memristors.

Application of conducting ferroelectric domain walls (DWs) as functional elements may facilitate development of conceptually new resistive switching devices. In a conventional approach, several orders of magnitude change in resistance can be achieved by controlling the DW density using supercoercive voltage. However, a deleterious characteristic of this approach is high-energy cost of polarization reversal due to high leakage current. Here, we demonstrate a new approach based on tuning the conductivity of DWs themselves rather than on domain rearrangement. Using LiNbO3 capacitors with graphene, we show that resistance of a device set to a polydomain state can be continuously tuned by application of subcoercive voltage. The tuning mechanism is based on the reversible transition between the conducting and insulating states of DWs. The developed approach allows an energy-efficient control of resistance without the need for domain structure modification. The developed memristive devices are promising for multilevel memories and neuromorphic computing applications.

DNA DSB Repair Dynamics following Irradiation with Laser-Driven Protons at Ultra-High Dose Rates.

Protontherapy has emerged as more effective in the treatment of certain tumors than photon based therapies. However, significant capital and operational costs make protontherapy less accessible. This has stimulated interest in alternative proton delivery approaches, and in this context the use of laser-based technologies for the generation of ultra-high dose rate ion beams has been proposed as a prospective route. A better understanding of the radiobiological effects at ultra-high dose-rates is important for any future clinical adoption of this technology. In this study, we irradiated human skin fibroblasts-AG01522B cells with laser-accelerated protons at a dose rate of 109 Gy/s, generated using the Gemini laser system at the Rutherford Appleton Laboratory, UK. We studied DNA double strand break (DSB) repair kinetics using the p53 binding protein-1(53BP1) foci formation assay and observed a close similarity in the 53BP1 foci repair kinetics in the cells irradiated with 225 kVp X-rays and ultra- high dose rate protons for the initial time points. At the microdosimetric scale, foci per cell per track values showed a good correlation between the laser and cyclotron-accelerated protons indicating similarity in the DNA DSB induction and repair, independent of the time duration over which the dose was delivered.

Prevalence of Extended Spectrum Beta-Lactamase Producing Klebsiella Pneumoniae Isolated From Urinary Tract Infected Patients.

BACKGROUND: Klebsiella pneumoniae, one of the bacterial agents associated with urinary tract infection has been often implicated as a major extended spectrum beta-lactamase (ESBL) producer in last few decades. This study was designed to assess the prevalence of ESBL producing Klebsiella pneumoniae in urinary isolates at a tertiary care hospital in Kathmandu, Nepal, from July to December 2014. METHODS: One thousand nine hundred eighty six mid-stream urine specimens were collected aseptically from the clinically suspected patients of urinary tract infections attending Capital Hospital and Research Center, Kathmandu. The samples were processed following standard guidelines as recommended by American Society for Microbiology (ASM) and the isolates including Klebsiella spp. were identified using the specific biochemical and sugar fermentation tests recommended by ASM. Antibiotic sensitivity testing was done by modified Kirby-Bauer disk diffusion method and interpreted following Clinical and Laboratory Standards Institute (CLSI) guidelines. Klebsiella pneumoniae isolates showing resistance upon initial screening with ceftriaxone (30 µg) disc were then confirmed for ESBL production by phenotypic confirmatory disc diffusion test (PCDDT) using ceftazidime (30 µg) and ceftazidime + clavulanic acid (30 µg + 10µg) and cefotaxime (30 µg) and cefotaxime + clavulanic acid (30 µg +10µg) disc as per CLSI guidelines. RESULTS: Out of a total 1986 specimens investigated, Escherichia coli was isolated in 309 (83.9%) and Klebsiella pneumoniae in 38 (10.3%) cases. Initial screening with ceftriaxone disc revealed 18 isolates of Klebsiella pneumoniae to be resistant. Further testing by PCDDT method confirmed 7 (18.4%) Klebsiella pneumoniae isolates to be ESBL producers. CONCLUSIONS: Compared to some earlier studies done in Nepal, higher prevalence of ESBL-producing Klebsiella pneumoniae was observed warranting a national surveillance for routine monitoring of ESBL producing Klebsiella pneumoniae isolates.

Immunomodulatory drugs target IKZF1-IRF4-MYC axis in primary effusion lymphoma in a cereblon-dependent manner and display synergistic cytotoxicity with BRD4 inhibitors.

Primary effusion lymphoma (PEL) is an aggressive type of non-Hodgkin lymphoma localized predominantly in body cavities. Kaposi's sarcoma-associated herpes virus (KSHV) is the causative agent of PEL. PEL is an incurable malignancy and has extremely poor prognosis when treated with conventional chemotherapy. Immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide are Food and Drug Administration-approved drugs for the treatment of various ailments. IMiDs display pronounced antiproliferative effect against majority of PEL cell lines within their clinically achievable concentrations, by arresting cells at G0/G1 phase of cell cycle and without any induction of KSHV lytic cycle reactivation. Although microarray examination of PEL cells treated with lenalidomide revealed activation of interferon (IFN) signaling, blocking the IFN pathway did not block the anti-PEL activity of IMiDs. The anti-PEL effects of IMiDs involved cereblon-dependent suppression of IRF4 and rapid degradation of IKZF1, but not IKZF3. Small hairpin RNA-mediated knockdown of MYC enhanced the cytotoxicity of IMiDs. Bromodomain (BRD) and extra-terminal domain (BET) proteins are epigenetic readers, which perform a vital role in chromatin remodeling and transcriptional regulation. BRD4, a widely expressed transcriptional coactivator, belongs to the BET family of proteins, which has been shown to co-occupy the super enhancers associated with MYC. Specific BRD4 inhibitors were developed, which suppress MYC transcriptionally. Lenalidomide displayed synergistic cytotoxicity with several structurally distinct BRD4 inhibitors (JQ-1, IBET151 and PFI-1). Furthermore, combined administration of lenalidomide and BRD4 inhibitor JQ-1 significantly increased the survival of PEL bearing NOD-SCID mice in an orthotopic xenograft model as compared with either agent alone. These results provide compelling evidence for clinical testing of IMiDs alone and in combination with BRD4 inhibitors for PEL.

Primary hepatic angiosarcoma.

Primary hepatic angiosarcoma is a rare, aggressive tumor; composed of spindle or pleomorphic cells that line, or grow into, the lumina of pre-existing vascular spaces like sinusoids and terminal hepatic venules; with only about 200 cases diagnosed annually worldwide but it is the most common primary malignant mesenchymal tumor of the liver in adults and accounts for 2% of all primary hepatic malignancies. HAS occurs in association with known chemical carcinogens, but 75% of the tumors have no known etiology. Patients present with vague symptoms like abdominal pain, weight loss, fatigue or an abdominal mass. Hepatic angiosarcoma is usually multicentric and involves both lobes, entire liver may also found to be involved. CD31 is the most reliable marker. These tumors lack specific features on imaging, so, pathological diagnosis is necessary. There are no established treatment guidelines because of low frequency and aggressive nature of tumor, chemotherapy is only palliative, liver resection is indicated for solitary mass and liver transplant is contraindicated. The aim of this article is to comprehensively review all the available literature and to present detailed information and an update on primary hepatic angiosarcoma.

Protective effect of proteins derived from Calotropis procera latex against acute inflammation in rat.

The non-dialysable proteins present in the latex of plant Calotropis procera possess anti-inflammatory and analgesic properties. The aim of this study was to evaluate the effect of latex proteins (LP) on the level of inflammatory mediators, oxidative stress markers and tissue histology in the rat model of carrageenan-induced acute inflammation. This study also aimed at evaluating the anti-inflammatory efficacy of LP against different mediators and comparing it with their respective antagonists. Paw inflammation was induced by subplantar injection of carrageenan, and the effect of LP was evaluated on oedema volume, level of TNF-α, PGE(2), myeloperoxidase, nitric oxide, reduced glutathione, thiobarbituric acid-reactive substances and tissue histology at the time of peak inflammation. Paw inflammation was also induced by histamine, serotonin, bradykinin and PGE(2), and the inhibitory effect of LP against these mediators was compared with their respective antagonists at the time of peak effect. Treatment with LP produced a dose-dependent inhibition of oedema formation, and its anti-inflammatory effect against carrageenan-induced paw inflammation was accompanied by reduction in the levels of inflammatory mediators, oxidative stress markers and normalization of tissue architecture. LP also produced a dose-dependent inhibition of oedema formation induced by different inflammatory mediators, and its efficacy was comparable to their respective antagonists and more pronounced than that of diclofenac. Thus, our study shows that LP has a potential to be used for the treatment of various inflammatory conditions where the role of these mediators is well established.

Inhibition of triple-negative and Herceptin-resistant breast cancer cell proliferation and migration by Annexin A2 antibodies.

BACKGROUND: Annexin A2 (AnxA2), a calcium-dependent phospholipid binding protein, is abundantly present at the surface of triple-negative and Herceptin-resistant breast cancer cells. Interactions between cell-surface AnxA2 and tyrosine kinase receptors have an important role in the tumour microenvironment and act together to enhance tumour growth. The mechanism supporting this role is still unknown. METHODS: The membrane function of AnxA2 was blocked by incubating cells with anti-AnxA2 antibodies. Western blotting, immunoprecipitation, immunofluorescence, 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT), flow cytometry, Clonogenic, and wound-healing assays were performed in this study. RESULTS: We demonstrate that AnxA2 interacts with epidermal growth factor receptor (EGFR) at the cell surface and has an important role in cancer cell proliferation and migration by modulating EGFR functions. Blocking AnxA2 function at the cell surface by anti-AnxA2 antibody suppressed the EGF-induced EGFR tyrosine phosphorylation and internalisation by blocking its homodimerisation. Furthermore, addition of AnxA2 antibody significantly inhibited the EGFR-dependent PI3K-AKT and Raf-MEK-ERK downstream pathways under both EGF-induced and basal growth conditions, resulting in lower cell proliferation and migration. CONCLUSIONS: These findings suggest that cell-surface AnxA2 has an important regulatory role in EGFR-mediated oncogenic processes by keeping EGFR signalling events in an activated state. Therefore, AnxA2 could potentially be used as a therapeutic target in triple-negative and Herceptin-resistant breast cancers.

Targeting Myc in KSHV-associated primary effusion lymphoma with BET bromodomain inhibitors.

Primary effusion lymphoma (PEL) is an aggressive form of non-Hodgkin's B-cell lymphoma associated with infection by Kaposi's sarcoma-associated herpes virus (KSHV). (+)-JQ1 and I-BET151 are two recently described novel small-molecule inhibitors of BET bromodomain chromatin-associated proteins that have shown impressive preclinical activity in cancers in which MYC is overexpressed at the transcriptional level due to chromosomal translocations that bring the MYC gene under the control of a super-enhancer. PEL cells, in contrast, lack structural alterations in the MYC gene, but have deregulated Myc protein due to the activity of KSHV-encoded latent proteins. We report that PEL cell lines are highly sensitive to bromodomain and extra-terminal (BET) bromodomain inhibitors-induced growth inhibition and undergo G0/G1 cell-cycle arrest, apoptosis and cellular senescence, but without the induction of lytic reactivation, upon treatment with these drugs. Treatment of PEL cell lines with BET inhibitors suppressed the expression of MYC and resulted in a genome-wide perturbation of MYC-dependent genes. Silencing of BRD4 and MYC expression blocked cell proliferation and cell-cycle progression, while ectopic expression of MYC from a retroviral promoter rescued cells from (+)-JQ1-induced growth arrest. In a xenograft model of PEL, (+)-JQ1 significantly reduced tumor growth and improved survival. Taken collectively, our results demonstrate that the utility of BET inhibitors may not be limited to cancers in which genomic alterations result in extremely high expression of MYC and they may have equal or perhaps greater activity against cancers in which the MYC genomic locus is structurally intact and c-Myc protein is deregulated at the post-translational level and is only modestly overexpressed.

Major non-ABO incompatibility caused by anti-Jk(a) in a patient before allogeneic hematopoietic stem cell transplantation.

A 49-year-old white man with blood group AB, D+ was found to have alloanti-Jk(a) and -K when he developed a delayed hemolytic transfusion reaction before allogeneic hematopoietic stem cell transplant (HSCT). Given that his stem cell donor was blood group O, D+, Jk(a+), K-, rituximab was added to his conditioning regimen of fludarabine and melphalan to prevent hemolysis of engrafting Jk(a+) donor red blood cells. The patient proceeded to receive a peripheral blood stem cell transplant from a matched unrelated donor with no adverse events. To our knowledge, this is the first case of successful management of major non-ABO incompatibility caused by anti-Jk(a) in a patient receiving an allogeneic HSCT reported in the literature.