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.

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.

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.

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.

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.

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.

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.

Achieving Millennium Development Goals 4 and 5 in Nepal.

The under 5 child mortality rate in Nepal is on track to achieve the target of 54 per 1000 live births by 2015 compared with 158 per 1000 live births in 1991. The maternal mortality rate also looks set to drop to its target of 134 per 100,000 live births by 2015 from 539 per 100,000 live births in 1991. A 3-year interim plan (2008-11) was established to provide free basic health care for all citizens and the safe delivery incentive programme has proved to help progression towards achieving Millennium Development Goals 4 and 5. The development of a policy targeting women, children and vulnerable populations in hard to reach places is a key feature. The principle of a primary healthcare approach is applied in the development and implementation of strategy plans and programmes. The focus is on ensuring that there are functioning facilities for essential obstetric care at health facilities and provision of trained personnel at delivery.

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.

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.

GrpL, a Grb2-related adaptor protein, interacts with SLP-76 to regulate nuclear factor of activated T cell activation.

Propagation of signals from the T cell antigen receptor (TCR) involves a number of adaptor molecules. SH2 domain-containing protein 76 (SLP-76) interacts with the guanine nucleotide exchange factor Vav to activate the nuclear factor of activated cells (NF-AT), and its expression is required for normal T cell development. We report the cloning and characterization of a novel Grb2-like adaptor molecule designated as Grb2-related protein of the lymphoid system (GrpL). Expression of GrpL is restricted to hematopoietic tissues, and it is distinguished from Grb2 by having a proline-rich region. GrpL can be coimmunoprecipitated with SLP-76 but not with Sos1 or Sos2 from Jurkat cell lysates. In contrast, Grb2 can be coimmunoprecipitated with Sos1 and Sos2 but not with SLP-76. Moreover, tyrosine-phosphorylated LAT/pp36/38 in detergent lysates prepared from anti-CD3 stimulated T cells associated with Grb2 but not GrpL. These data reveal the presence of distinct complexes involving GrpL and Grb2 in T cells. A functional role of the GrpL-SLP-76 complex is suggested by the ability of GrpL to act alone or in concert with SLP-76 to augment NF-AT activation in Jurkat T cells.

Atypical sarcoidosis masquerading as neutropenia.

Sarcoidosis is a systemic granulomatous disease of unknown etiology. Gastrointestinal involvement in sarcoidosis is rare and so are its hematological manifestations. We report an unusual case of sarcoidosis with isolated gastric involvement and concomitant B12 and iron deficiency, leucopenia and severe neutropenia. The diagnosis of GI tract sarcoidosis is difficult and other causes of GI tract granulomas should be excluded. Patients can have unusual manifestations like B12 deficiency and one should be aware of this possibility. Careful follow-up and frequent reevaluation of the patient may be a sound strategy in equivocal cases with unusual presentation.

Supply chain dynamics in healthcare services.

PURPOSE: The purpose of this paper is to analyse health service supply chain systems. A great deal of literature is available on supply chain management in finished goods inventory situations; however, little research exists on managing service capacity when finished goods inventories are absent. DESIGN/METHODOLOGY/APPROACH: System dynamics models for a typical service-oriented supply chain such as healthcare processes are developed, wherein three service stages are presented sequentially. FINDINGS: Just like supply chains with finished goods inventory, healthcare service supply chains also show dynamic behaviour. Comparing options, service reduction, and capacity adjustment delays showed that reducing capacity adjustment and service delays gives better results. RESEARCH LIMITATIONS/IMPLICATIONS: The study is confined to health service-oriented supply chains. Further work includes extending the study to service-oriented supply chains with parallel processing, i.e. having more than one stage to perform a similar operation and also to study the behaviour in service-oriented supply chains that have re-entrant orders and applications. Specific case studies can also be developed to reveal factors relevant to particular service-oriented supply chains. PRACTICAL IMPLICATIONS: The paper explains the bullwhip effect in healthcare service-oriented supply chains. Reducing stages and capacity adjustment are strategic options for service-oriented supply chains. ORIGINALITY/VALUE: The paper throws light on policy options for managing healthcare service-oriented supply chain dynamics.

Dominance of Methanomicrobium phylotype in methanogen population present in Murrah buffaloes (Bubalus bubalis).

AIMS: To study the diversity of rumen methanogens in Murrah buffaloes (Bubalus bubalis) from North India by using 16S rRNA gene libraries obtained from the pooled rumen content from four animals and using suitable software analysis. METHODS AND RESULTS: Genomic DNA was isolated and PCR was set up by using specific primers. Amplified product was cloned into a suitable vector and the positive clones were selected on the basis of blue-white screening and sequenced. The resulting nucleotide sequences were arranged in the phylogenetic tree. A total of 108 clones were examined, revealing 17 different 16S rRNA gene sequences or phylotypes. Of the 17 phylotypes, 15 (102 of 108 clones) belonged to the genus Methanomicrobium, indicating that the genus Methanomicrobium is the most dominant component of methanogen populations in Murrah buffaloes (Bubalus bubalis) from North India. The largest group of clones (102 clones) was more than 98% similar to Methanomicrobium mobile. BLAST analysis of the rumen contents from individual animals also revealed 17 different phylotypes with a range of 3-10 phylotypes per animal. CONCLUSION: Methanomicrobium phylotype is the most dominant phylotype of methanogens present in Murrah buffaloes (Bubalus bubalis). SIGNIFICANCE AND IMPACT OF THE STUDY: Effective strategies can be made to inhibit the growth of Methanomicrobium phylotype to reduce the methane emission from rumen contents and thus help in preventing global warming.

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.

Induction of spindle cell morphology in human vascular endothelial cells by human herpesvirus 8-encoded viral FLICE inhibitory protein K13.

Human herpesvirus 8 (HHV8), also known as Kaposi's sarcoma-associated herpesvirus, is linked to the development of Kaposi's sarcoma, a disease characterized by the presence of distinctive proliferating spindle-like cells. Although HHV8 can induce spindle cell transformation of vascular endothelial cells in vitro, the viral gene(s) responsible for this phenotype remain to be identified. We demonstrate that expression of HHV8-encoded viral Fas-associated death domain protein-like IL-1beta-converting enzyme inhibitory protein K13 is sufficient to induce spindle cell phenotype in human umbilical vein endothelial cells (HUVEC), which is associated with the activation of the nuclear factor-kappaB (NF-kappaB) pathway and can be blocked by Bay-11-7082, a specific inhibitor of this pathway. K13 induces the expression of several genes known to be upregulated in HHV8-transformed vascular endothelial cells, such as interleukin (IL)-6, IL-8, CXC ligand 3 (CXCL3), orphan G protein coupled receptor (RDC1), cyclooxygenase-2 (COX-2) and dual-specificity phosphatase 5 (DUSP5). Furthermore, similar to K13, HHV8-induced spindle cell transformation of HUVEC is associated with NF-kappaB activation and can be blocked by Bay-11-7082. Thus, ectopic expression of a single latent gene of HHV8 is sufficient for the acquisition of spindle cell phenotype by vascular endothelial cells and NF-kappaB activation plays an essential role in this process.

Induction of IL-8 expression by human herpesvirus 8 encoded vFLIP K13 via NF-kappaB activation.

Human herpesvirus 8 (HHV-8) encodes a viral FLICE inhibitory protein (vFLIP), called K13, with homology to the prodomain of caspase 8. K13 has been postulated to protect virally infected cells against death receptor-induced apoptosis. We report that K13 leads to constitutive upregulation of IL-8 secretion by transcriptional upregulation of its promoter. K13-induced IL-8 promoter activation is dependent on an intact NF-kappaB-binding site and is associated with increased binding of classical NF-kappaB pathway subunits p65, c-Rel and p50, respectively. IL-8 production is defective in K13 mutants defective in classical NF-kappaB activation and is blocked by genetic and pharmacological inhibitors of this pathway. In contrast, K13 failed to activate the JNK/AP-1 pathway and deletion of AP-1-binding site in the IL-8 promoter or use of a specific JNK inhibitor had only a partial effect on K13-induced IL-8 promoter activation. Collectively, above results demonstrate that K13 is a major mediator of IL-8 production and therapeutic agents targeting K13-induced NF-kappaB pathway may have a role in the treatment of conditions in which HHV-8-induced IL-8 production plays a pathogenic role.