Knock down of spinal NMDA receptors reduces NMDA and formalin evoked behaviors in rat

Chronic pain remains a major health problem afflicting an estimated 70% of patients with advanced cancer and inflammatory disorders, and up to 94% of patients with spinal cord injuries. Although progress has been made in the pharmacotherapy of chronic pain management, such as usage of adjuvant drugs and more effective methods of drug delivery, the mainstay of clinical pain management still depends on opiates. NMDA receptor activation, at the level of the spinal cord has been shown to play an important role in the facilitation of nociception (pain) in several animal models. Unfortunately, potent NMDA receptor antagonists, such as MK-801 and APV, have toxic properties and low safety margins that preclude their clinical use. We present evidence which indicates that the use of antisense oligonucleotides targeted to the NMDA-R1 receptor subunit (AS-NMDA-R1), but not sense, abolishes NMDA and formalin induced behaviors. Moreover, we demonstrate that spinal administration of AS-NMDA-R1 results in the abolition of staining for immunoreactive NMDA-R1 in the spinal cord. These data provide novel evidence supporting the feasibility of the use of gene therapy approaches in the management of neuropathic pain.     

Trans-scleral cyclophotocoagulation: a tale of two probes

To compare the histological effects of trans-scleral cyclophotocoagulation (TCP) performed with two different probes, the G-probe (IRIDEX Medical Instruments, Mountain View, CA, USA) and the Ciliprobe (Katalyst Surgical, Chesterfield, MO, USA). TCP was performed on two human cadaver eyes from the same corpse. The vertical meridian was marked and opposite sides were treated using either the G-probe or Ciliprobe. The first eye was treated with each probe at 2000ms/2000 mW and the second eye at 3000ms/1500 mW. Histological examination revealed separation and loss of the non-pigmented ciliary epithelium as well as vacuolization in all sections for both probes and settings. Changes to the non-pigmented ciliary epithelium treated at 3000ms/1500 mW were similar between the two probes. A slightly more complete separation of the non-pigmented epithelium was noted on the Ciliprobe treated sections as compared to the G-probe treated sections in the eye treated at 2000ms/2000 mW. Therefore, in human cadaver eyes, both the G-probe and Ciliprobe produced separation, vacuolization, and loss of the non-pigmented ciliary epithelium at two different, clinically utilized settings.     

Overview of Thoracic Oncology Trials in Cooperative Groups Around the Globe

Survival rates of patients with either early and advanced stage non–small-cell lung cancer (NSCLC) have improved with newer systemic therapy and radiation techniques, including combination regimens, targeted therapies, and immunotherapies. The cancer cooperative groups have historically played a critical role in the advancement of NSCLC therapy. Annually, representatives from cooperative groups worldwide convene at the International Lung Cancer Congress (ILCC). In summer 2015, the ILCC reached its 16th anniversary. This article highlights the NSCLC studies presented by participating groups in 2015.     

Identification of HPV16's E6 gene in suspected cases of cervical lesions and docking Study of its L1 protein with active components of Echinacea purpurae

BackgroundHPV 16 is the primary etiologic agent of cervical cancer and the presence of L1 and E6 oncoproteins are largely responsible for its virulence. It was the objective of this study to identify HPV16 isolates from suspected cases of cervical cancer at Specialist Hospital Sokoto and Sir Yahaya Memorail Hospiatal Birnin Kebbi, Nigeria and also to identify potent HPV16''s L1 protein inhibitor using in silico analysis.MethodsA total of 144 cervical samples consisting of 21 low grade squamous intraepithelial lesion, 6 high grade lesion and 117 negative pap smears were collected. The samples were subjected for molecular detection using PCR targeting E6 gene of the virus. Data generated for the molecular prevalence was statistically analyzed using Chi-square method. AutoDock Vina was used to carry out the molecular docking between 2hr5 and Chicoric acid, curcumin and Echinacoside.ResultsOut of the 144 samples, 24 samples were positive for the PCR representing 16.9% molecular prevalence rate. There is statistically significant association between cyto-diagnoses and presence of HPV16 (P < 0.05). Docking analysis showed that the Chicoric acid components of Echinacea purpurae have strong binding affinity (-8.7 kcal/mol) to the L1 protein of the HPV.ConclusionThis study provides data on HPV 16 epidemiology in northern Nigeria, and also provides novel evidence for consideration on certain interacting residues, when synthesizing Anti-HPV compounds in the wet lab.     

Indirect Protection from Vaccinating Children against Influenza A Virus Infection in Households

Influenza vaccination is an important intervention to prevent influenza virus infection. Our previous analysis suggested that indirect protection is limited in an influenza B epidemic in Hong Kong. We further analyzed six influenza A epidemics to determine such potential. We applied a statistical model to estimate household transmission dynamics in the 3 influenza A(H3N2) and 3 pandemic influenza A(H1N1) epidemics. Then, we estimated the reduction in infection risk among unvaccinated household members when all children in households are vaccinated, with different assumptions on vaccine efficacy (VE). In the optimal scenario that VE was 70%, the reduction to the total probability of infection was only marginal, with relative probabilities ranged from 0.91–0.94 when all children in households were vaccinated because community was by far the main source of infection during the six epidemics in our study. The proportion of cases attributed to household transmission was 10% (95% CrI: 7%, 13%). Individual influenza vaccination is important even when other household members are vaccinated, given the degree of indirect protection is small.     

Interspecies Recombination-Led Speciation of a Novel Geminivirus in Pakistan

Recombination between isolates of different virus species has been known to be one of the sources of speciation. Weeds serve as mixing vessels for begomoviruses, infecting a wide range of economically important plants, thereby facilitating recombination. Chenopodium album is an economically important weed spread worldwide. Here, we present the molecular characterization of a novel recombinant begomovirus identified from C. album in Lahore, Pakistan. The complete DNA- A genome of the virus associated with the leaf distortion occurred in the infected C. album plants was cloned and sequenced. DNA sequence analysis showed that the nucleotide sequence of the virus shared 93% identity with those of the rose leaf curl virus and the duranta leaf curl virus. Interestingly, this newly identified virus is composed of open reading frames (ORFs) from different origins. Phylogenetic networks and complementary recombination detection methods revealed extensive recombination among the sequences. The infectious clone of the newly detected virus was found to be fully infectious in C. album and Nicotiana benthamiana as the viral DNA was successfully reconstituted from systemically infected tissues of inoculated plants, thus fulfilling Koch’s postulates. Our study reveals a new speciation of an emergent ssDNA plant virus associated with C. album through recombination and therefore, proposed the tentative name ‘Chenopodium leaf distortion virus’ (CLDV).     

Monkeypox: A Comprehensive Review

The 2022 multi-country monkeypox outbreak in humans has brought new public health adversity on top of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The disease has spread to 104 countries throughout six continents of the world, with the highest burden in North America and Europe. The etiologic agent, monkeypox virus (MPXV), has been known since 1959 after isolation from infected monkeys, and virulence among humans has been reported since the 1970s, mainly in endemic countries in West and Central Africa. However, the disease has re-emerged in 2022 at an unprecedented pace, with particular concern on its human-to-human transmissibility and community spread in non-endemic regions. As a mitigation effort, healthcare workers, public health policymakers, and the general public worldwide need to be well-informed on this relatively neglected viral disease. Here, we provide a comprehensive and up-to-date overview of monkeypox, including the following aspects: epidemiology, etiology, pathogenesis, clinical features, diagnosis, and management. In addition, the current review discusses the preventive and control measures, the latest vaccine developments, and the future research areas in this re-emerging viral disease that was declared as a public health emergency of international concern.     

A Phase II study of neoadjuvant axitinib for reducing the extent of venous tumour thrombus in clear cell renal cell cancer with venous invasion (NAXIVA)

Background Surgery for renal cell carcinoma (RCC) with venous tumour thrombus (VTT) extension into the renal vein (RV) and/or inferior vena cava (IVC) has high peri-surgical morbidity/mortality. NAXIVA assessed the response of VTT to axitinib, a potent tyrosine kinase inhibitor.Methods NAXIVA was a single-arm, multi-centre, Phase 2 study. In total, 20 patients with resectable clear cell RCC and VTT received upto 8 weeks of pre-surgical axitinib. The primary endpoint was percentage of evaluable patients with VTT improvement by Mayo level on MRI. Secondary endpoints were percentage change in surgical approach and VTT length, response rate (RECISTv1.1) and surgical morbidity.Results In all, 35% (7/20) patients with VTT had a reduction in Mayo level with axitinib: 37.5% (6/16) with IVC VTT and 25% (1/4) with RV-only VTT. No patients had an increase in Mayo level. In total, 75% (15/20) of patients had a reduction in VTT length. Overall, 41.2% (7/17) of patients who underwent surgery had less invasive surgery than originally planned. Non-responders exhibited lower baseline microvessel density (CD31), higher Ki67 and exhausted or regulatory T-cell phenotype.Conclusions NAXIVA provides the first Level II evidence that axitinib downstages VTT in a significant proportion of patients leading to reduction in the extent of surgery.Clinical trial registration {"type":"clinical-trial","attrs":{"text":"NCT03494816","term_id":"NCT03494816"}}NCT03494816.Subject terms: Surgical oncology, Renal cell carcinoma, Predictive markers     

Management of Helicobacter pylori among medical doctors working in Khartoum,Sudan 2019: a cross-sectional study

BackgroundVarious international guidelines have been developed regarding Helicobacter pylori (H. pylori) management, as it is infecting more than half of the world''s population. Sudan''s health system lacks guidelines regarding H. pylori management, leading to a discrepancy in practice. Investigating the current approach could be a step forward in the formulation of a national consensus in the management of H. pylori.MethodsA cross-sectional study was conducted among medical doctors currently working in Khartoum, Sudan. Participants were enrolled from platforms of medical associations through an online questionnaire. The questionnaire was scored out of 25 points, and scoring 13 or above considered a good approach. Data analysis was carried out using Statistical Package for Social Sciences (SPSS).ResultsA total of 358 medical doctors participated in the study. The mean (±SD) score was 12.9(±4.5). Those who were using textbooks, campaigns, symposiums or general medical information to their primary Source of knowledge significantly scored higher. The most selected indication for both diagnosis (76.8%) and treatment (67.6%) was an active peptic ulcer. Stool antigen test (SAT) was the most preferred test (70.7%). The majority of respondents selected triple therapy (82.1%) as a first-line regimen. Only 37.7% confirmed the eradication after four weeks of stopping the treatment. They ensure eradication mainly through SAT (29%).ConclusionA suboptimal approach was noted among medical doctors of Khartoum, Sudan, regarding H. pylori management. Efforts should be invested in forming national guidelines and the implementation of continuous medical education programs.