Background Adverse drug reactions (ADRs) constitute major clinical burden of public health concern. Intensive adverse drug reactions monitoring in hospitals, though advocated are rare. Aims Intensive monitoring of medical patients for ADRs to assess incidence, risk factors and fatality of ADRs leading to hospital admission or occurring in the hospital. Research design and methods Prospective cohort study on 1280 adult patients admitted to the six medical wards of a tertiary institution over a 12-month period. Patients were assessed for ADRs during and throughout admission. Causality assessment and preventability of ADRs were assessed. Results Sixty-seven (5.2%) patients had ADRs, which was the cause of admission in 46 (3.6%), and majority 61(91%) of the ADRs were preventable. NSAIDs, 14 (20.3%), antidiabetics, 12 (17.4%) and antibacterial, 11 (15.8%) were the most suspected drugs. Gastrointestinal tract (37%), CNS (30.2%), and skin (24.7%) were the most affected organ/systems, while upper GI bleeding and hypoglycaemia were the most observed ADRs. ADRs led to deaths in 7(10.4%) patients, with overall case fatality rate of 0.5%. Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis 3/7(42.9%) had the highest fatality rate. Risk factors, relative risk, 95% confidence interval for ADRs were alcohol intake, 1.7 (1.04, 2.80) and duration of hospital stay, 2.0 (1.16, 3.26). Conclusions Preventable ADRs are common and important cause of hospitalization and inpatients’ morbidity and mortality among medical patients in Nigeria. Upper GI bleeding and hypoglycaemia, resulting from NSAIDs and antidiabetic drugs were the most observed ADRs. Strategic planning for intensive follow up of ADRs in Nigeria is advocated.

The novel coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has posed a serious threat to global public health. Respiratory failure followed by cardiovascular complications with wide-spread endothelial dysfunction and inflammation is rapidly emerging as a key threat in COVID-19. ACE-2 receptors are the cell-entry gate for SARS-CoV-2. Valproic Acid (VPA) is a proposed potential drug to treat COVID-19 but its mechanism of action is not well understood. We demonstrate that VPA-treatment significantly reduced ACE-2 expression in endothelial cells. VPA-treatment significantly reduced the expression of inflammatory cytokines IL-6 along with the endothelial activation marker ICAM-1. We provide evidence and discuss the plausible mechanism in detail for VPA use to prevent and treat COVID-19 in a personalized manner. Our study is expected to entice the scientific and clinical society to investigate VPA as a potential therapeutic option against COVID-19.

A document by Xiaomei Peng. Click on the document to view its contents.

Aim: To evaluate the pathogenesis, risk factors, diagnosis and management strategies in pregnant women suspected or confirmed with COVID-19 infection. Methods: A literature review of published articles was carried out using keywords of corona virus (and its root derivatives), pregnancy, vertical transmission and childbirth in Medline, Cochrane, CINAHL, Clinicaltrials.gov and Web of Sciences. Clinical articles including case-control, case reports, case series and reviews published between 2019 and 2020, in English language were included. Editorials and Letter to Editors were not included. Two independent authors reviewed title and abstract of the articles and another set of two independent authors screened full text. A total of 22 articles were shortlisted for addition into the final manuscript Results: A total of 403 pregnancies were considered in the study with most of the patients in the third trimester of pregnancy. There was no maternal mortality reported in the literature, however 1.49% fetal mortality has been reported. Conclusion: The ideal management revolves around, rapid detection, prompt diagnosis and effective isolation.

A 2-year-old girl with TCF3-ZNF384 re-arranged standard-risk B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) showed an apparent lineage-switch to predominantly myeloid blasts following 7-days of corticosteroid therapy. ZNF384-re-arranged leukemias are increasingly recognized to present either as mixed-phenotype acute leukemia or as BCP-ALL with pro-B immunophenotype. Lineage switch is a rare phenomenon described at relapse or following CAR-T-cell therapy previously mostly in KMT2A re-arranged leukemias; and now, also in ZNF384-rearranged patients. It is previously unreported in any patient after pre-phase corticosteroid therapy. Hematologists should be aware of this distinct emerging entity among leukemias with multi-lineage differentiation potential.

Iatrogenic acute aortic dissection during percutaneous coronary intervention is an extremely rare but potentially life-threatening complication occurring in less than < 0,02% of the procedures. We report the cases of 3 patients with aortic dissection during percutaneous coronary intervention successfully treated with an emergent ascending aorta replacement. The main goal is the closing of the intimal tear as fast as possible damage either with a percutaneous system (i.e. a proximal stent) or with an open heart open surgery to prevent the extension of the dissection and neurological. A conservative strategy should be pursuit only in small localized sinus dissections.

Commentary: Animal free applications in the development of cell-based therapies

Catheter ablation is a widely accepted therapy for atrial fibrillation (AF), of which stroke is a major complication. A stroke after catheter ablation has been reported in numerous studies not only in the acute phase but also in the chronic phase. A 66-year-old man with drug refractory paroxysmal AF underwent catheter ablation. Fourteen months later, the patient was diagnosed with cerebral infarction. Transesophageal echocardiography detected an ovoid mass on the anterior aspect of the right superior pulmonary vein atrium, where the previous ablation was performed. We report a very rare case of left atrial thrombus formation required surgical treatment 14 months after cryoballoon ablation.Careful follow up with multimodalities is necessary for the detection and diagnosis of chronic phrase thrombus formation.

Alternatives to traditional aortic valve replacement now form part of the valve surgeon's armamentarium. Sutureless valves offer decreased bypass and crossclamp times, excellent maneuverability, and promising outcomes. We present a case of a sutureless aortic valve replacement for a late failed David procedure, complicated by post-operative development of severe paravalvular regurgitation. We attempted off-label balloon post-dilation to improve expansion of the valve, however paravalvular regurgitation persisted. The patient underwent subsequent aortic valve replacement using a mechanical valve and experienced no further paravalvular leak.

Background and Purpose: COPD is one of the most common respiratory diseases worldwide with high comorbidities as major depressive disorder(MDD). Cigarette smoking(CS) is the most major risk factor and smokers tend to be more easy to get COPD and MDD, the mechanisms still remained poorly defined. Experimental Approach: The gene expression microarray analyzed between COPD lung tissues and MDD brain tissues were conducted and enriching GO and KEGG pathways analysis in R. CS exposure induced COPD animal model in mice was established and followed the expression of hub-bottleneck genes. Key Results: Based on microarray analysis, found some DEGs plays a prominent role in COPD and MDD, such as Casitas B-lineage Lymphoma Proto-OncogeneB (CBLB) is involved in the regulation of immune response. Myocyte enhancer factor 2C (MEF2C) have been associated with severe cognitive disability, stereotypic movements and cerebral malformation. Mitogen-activated protein kinase 7 (MAPK7) was involved in various cellular processes. Furthermore, animal studies showed that mice exposure to CS whose airway inflammation increased and inflammatory cells rise in bronchoalveolar lavage fluid accompanied with markedly declined lung function. In addition, CBLB and MAPK7 with abnormal expression in the brain tissue. Even more important, mice exposure to CS whose brain was seriously injured and the nerve cells morphological have changed, CBLB deficiency increased the GM-CSF signal pathway related inflammatory reactions in brain tissue. Conclusion and Implications: In conclusion, CS causes COPD accompanied with early acute brain injury, GM-CSF and MAPK7 signal pathway may be involved in it. To some extent, the study revealing that inflammatory response accompany with the earliest acute brain injury is the pathological basis of COPD complicating MDD

Many articles have reported that cancer patients are more susceptible to COVID-19 pneumonia and cancer patients with COVID-19 seem to be more often tend to develop severe events. In these studies of infected cancer patients, factors associated with a higher risk of developing severe events included age, baseline fragility, and anti-tumor treatment. However, specific reasons regarding why infected patients with cancer have a higher probability of severe events compared to non-cancer infected patients remain unclear. Thus, we sought to study one particular factor to determine a potential associative effect: differences in Computed tomography (CT) findings. In our study,we found that cancer patients represent a special population which multiple lobes of the lungs were more susceptible to infection by the SARS-CoV-2, and thus were more likely to be transferred from mild illness to severe, should be deserved more intensive attention during the SARS-CoV-2 pandemic.

Electrochemical ammonia synthesis is being actively studied as a low temperature, low pressure alternative to the Haber-Bosch process. This work studied iridium as the electrochemical catalyst, following a previous study of adsorption characteristics on platinum. The characteristics studied include bond energies, bond lengths, spin densities, and free and adsorbed vibrational frequencies for the molecules N2, N, NH, NH2, and NH3. Overall, these descriptive characteristics explore the use of dispersion-corrected Density Functional Theory methods that can model N2 adsorption – the key reactant for electrochemical ammonia synthesis via transition metal catalysis. Specifically, three methods were tested: hybrid B3LYP, a dispersion-corrected form B3LYP-D3, and semi-empirical B97-D3. The latter semi-empirical method was explored to increase the accuracy obtained in vibrational analysis as well as reduce computational time. Two lattice surfaces, (111) and (100), were compared. The adsorption energies are stronger on (100) and follow the trend EB3LYP > EB3LYP-D3 > EB97-D3 on both surfaces.

Pan evaporation is an important indicator of atmospheric evaporative demand, and its long-term variation is of much concern in studies of climate change. Estimation of evaporation is also important for water budgeting and yet is difficult to quantify because of the combined effects of four meteorological variables: net radiation, wind speed, atmospheric humidity, and air temperature. This work considered the temporal trends of pan evaporation and the meteorological variables that affect them for a station located in Roorkee (India). In this study, observed meteorological data at NIH observatory for the period from 1987 to 2018 was used for trend analysis of the data (rainfall, relative humidity, maximum temperature, minimum temperature, average temperature, wind speed and pan evaporation). Evaporation was also estimated using Penman method, Meyer method and other empirical equations, and compared with the observed evaporation values. Anomalies in the time series of meteorological variables were computed to find out the magnitude of rise or fall in the series. Pettitt-Mann-Whitney (PMW) test for detection of shift in the time series has been carried out, and the trend and shift in meteorological data is correlated with the same in evaporation. Based on this research, a number of conclusions are drawn: (1) minimum temperature and relative humidity have been increasing whereas maximum temperature and wind speed have been decreasing during the period 1987-2018, (2) pan evaporation series has not shown any significant trend, except during post-monsoon when it decreased, (3) significant change points (shifts) in the time series of temperature, relative humidity and wind speed may attribute the influence of fast urbanization and enhanced anthropogenic activities in Roorkee town after creation of Uttarakhand as a separate State in the year 2000.

The internal disorder of the two-dimensional confined hydrogenic atom is numerically studied in terms of the confinement radius for the 1_s_, 2_s_, 2_p_ and 3_d_ quantum states by means of the statistical Crámer-Rao complexity measure. First, the confinement dependence of the variance and the Fisher information of the position and momentum spreading of its electron distribution are computed and discussed. Then, the Crámer-Rao complexity measure (which quantifies the combined balance of the charge concentration around the mean value and the gradient content of the electron distribution) is investigated in position and momentum spaces. We found that confinement does disentangle complexity of the system for all quantum states by means of this two component measure.

Purpose: The COVID-19 pandemic has presented an international health crisis of a scope not seen in our lifetime. While much attention has been paid to health workers in critical care and acute areas, nurses working outside of hospitals are also significantly affected. This study sought to investigate the experience of nurses working in Australian primary health care during the COVID-19 pandemic. In particular, it sought to understand the implications on their employment status, role and access to personal protective equipment.Design and Method: Nurses employed in primary health care across Australia were invited to participate in a cross-sectional online survey through social media and professional organisations. The survey tool was comprised of demographics, questions about the nurses’ employment and work role and access to personal protective equipment.Findings: Of the 637 responses received, nearly half (43.7%) reported a decrease in hours, threatened or actual loss of employment. While most respondents felt that they had sufficient knowledge about COVID-19, they expressed concern about work-related risks to themselves and their family. Most respondents described never or only sometimes having sufficient personal protective equipment in their workplace. Just over half of respondents (54.8%) felt well supported by their employer. A third of respondents (34%) perceived that care provided in their workplace was significantly or slightly worse than before the pandemic.Conclusions: This is the first study of primary health care nurses experiences during the COVID-19 pandemic. The study findings have highlighted a concerning level of insecurity around primary health care nursing employment, as well as issues with the availability of personal protective equipment for these nurses. The perception that the pandemic has resulted in reduced quality of care needs further exploration to ensure that those with chronic conditions are supported to maintain and promote health.Clinical Relevance: Understanding the implications of COVID-19 on the primary health care nursing workforce is vital to ensure staff retention and care quality. Ensuring that the community remain healthy and supported at home is vital to both reduce the burden on the health system and reduce secondary mortality.

Background: Diagnosis of Severe Acute Respiratory Coranavirus-2 (SARS-CoV-2) infection is currently based on Real-Time PCR (RT-PCR) performed on either nasopharyngeal (NPS) or oropharyngeal (OPS) swabs; saliva specimen collection can be used, too. Diagnostic accuracy of these procedures is suboptimal, and some procedural mistakes may account for it.Methods and results: The video shows how to properly collect secretions from the upper airways for non-serologic diagnosis of COVID-19 by nasopharyngeal swab (NPS), oropharyngeal swab (OPS), and deep saliva collection after throat-cleaning manoeuvre, all performed under videoendoscopic view by a trained ENT examiner.Conclusions: We recommend to perform NPS after elevation of the tip of the nose in order to reduce the risk of contamination from the nasal vestible, and to let it flow over the floor of the nasal cavity in parallel to the hard palate in order to reach the nasopharynx. Then the tip of the swab should be left in place for few seconds, and then rotated in order to achieve the largest absorption of nasopharyngeal secretions. Regards OPS, gentle anterior tongue depression should be used to avoid swab contamination from the oral cavity during collection of secretions from the posterior pharyngeal wall. These procedural tricks would enhance diagnostic reliability.

CLINICAL OUTCOME OF PEDIATRIC EWING SARCOMA AND SIGNIFICANCE OF PATHOLOGICAL NECROSIS AFTER NEOADHUVANT CHEMOTHERAPY: SINGLE INSTITUTIONAL STUDY Authors: Sindhu II, Mehreen A, Wali RM, Abubakar M Affiliation: Shaukat Khanum Memorial Cancer Hospital & Research Center, Lahore. Pakistan Abstract Purpose: Tumor necrosis and histopathological changes in Ewing sarcoma following neoadjuvant chemotherapy are important predictors of disease outcome. The aim of our study is to determine the clinical outcome and significance of pathological necrosis after neoadjuvant chemotherapy as it has not been reported in our country so far. Methods: Data was reviewed after IRB approval from January 2010 to December 2015 were retrospectively reviewed for patients with newly diagnosed Ewing sarcoma on histopathology and less than 20 years of age at the time of diagnosis. Results: A Total of 124 patients were included, in which 89 patients (72%) were non metastatic and 35 patients were metastatic (28%). Histopathology report after doing surgery showed Little or no (Grade 1 ) necrosis seen in 14 patients (11%) and 50-90% (Grade II) necrosis seen in 9 patients (7%), 90-99% (Grade III) necrosis seen in 8 patients (5.5%), and 100% (Grade IV) necrosis in 14 patients (11%). EFS of grade 4 necrosis was 93%, grade-3 71%, grade- 2 22% and grade-1 35%. OS of grade 4 necrosis was 93%, grade -3 75%, grade-2 25 % and grade-1 50%. EFS of Ewing sarcoma patients were 38% and OS was 38%. Conclusion: Tumor necrosis and histopathological changes after surgery has great impact on survival outcome in Ewing Sarcoma.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by severe itching and recurrent eczema-like lesions. Yet, its exact pathological mechanism remains unclear. Objective: The aim of this study was to investigate the role of TRPA1 in the pathogenesis of AD. Methods: The experimental atopic dermatitis (AD)-like skin lesions were established using 2,4-dinitrochlorobenzene (DNCB). Mice were divided into three groups: TRPA1−/− and WT groups were treated with DNCB dissolved in a 3:1 mixture of acetone and olive oil and the negative control group was treated with 3:1 mixture of acetone and olive oil without DNCB. The treatment lasted for 21 days, after which the animals were sacrificed and their blood, ears and dorsal skin tissue samples were collected for analysis. Results: Lower dermatitis score, ear thickness, pruritus score, and epidermal hyperplasia were observed in mice in TRPA1−/− mice compared to the WT group. Besides, lower dermal mast cell infiltration, proinflammatory cytokines, Th2 cytokines and the infiltration of macrophages were observed in the TRPA1−/− mice compared to the WT group. Furthermore, we demonstrated that TRPA1 antagonist HC-030031 could alleviate AD-like symptoms and reduce the degree of epidermal hyperplasia in mice. Conclusions: TRPA1 has a crucial role during the AD pathogenesis in mice, thus could be used as a potential new target for treating patients with chronic skin inflammatory disease.

Background: Chronic rhinosinusitis with and without nasal polyps (CRSwNP/ CRSsNP) is an inflammatory disease affecting the nasal and sinus mucosal lining. Here, to further characterize this heterogeneous disease, we performed an extended endotyping of CRS using the nasal tissue from CRS-patients and a new approach of expression profiling of chemokines related to Th2-type cytokine IL-5. Methods: In this case-control study, we included 66 patients with CRS (CRSwNP n=26; CRSsNP n=40) diagnosed according to the EPOS 2020 criteria. The control group (n=25) consisted of CRS-free patients scheduled for inferior turbinate surgery. The concentration of following chemokines and cytokines was determined in tissue samples obtained during routine surgery from all subjects: TARC/ CCL17, PARC/ CCL18, eotaxin/ CCL11, MCP-3/ CCL7, MIP-1α/ CCL3, IP-10/ CXCL10, ENA-78/ CCL5, and IL-5. The analysis was performed by partition-based clustering. Results: In CRS tissues, the concentration of eotaxin, TARC, total IgE, IL-5, and ECP was significantly higher than in control (p<0.005). The analysis identified seven clusters. Cluster-1 was IL-5- and inflammatory chemokines-negative (11% CRSwNP). Cluster-2 had low IL-5 concentration and elevated MCP-3/CCL7 (100% CRSsNP). Clusters -3 and -4 expressed IP-10/CXCL10 (type-1-dominated), TARC/CCL17 and eotaxin/CCL11 (both type-2-dominated) (CRSwNP 13-31%). Clusters 5-7 had high concentration of IL-5, TARC/ CCL17, PARC/ CCL18, and eotaxin/CCL11 (type-2-dominated), NP 71-100%, asthma 19-50%, N-ERD 29%. Conclusions: Our chemokine expression-based extended analysis identified distinct CRS endotype clusters, possibly impacting future diagnosis, monitoring, and biologics-based treatment of CRS.

Steroids treatment has been studied in influenza, SARS, MERS, COVID-19 and ARDS, but no clear guidelines or recommendations are available regarding the dose and the duration. In this review we summarize the studies available on steroids and influenza, SARS, MERS, COVID-19 and evaluated them according to the steroid dose, duration and beneficial and harmful effects. Steroids were not much useful in influenza infection, but have shown beneficial effects in SARS and COVID-19. Intimidate and high doses for a short duration in SARS is beneficial, especially if used after the viral replication phase. Methyl prednisolone is the preferred steroid compared to hydrocortisone and can be combined with intravenous immunoglobulin, ribavirin, quinolone plus azithromycin. Limited studies are available for COVID-19 and steroids to provide recommendations and steroids use can be harmful in critically ill patients. Delayed viral clearance, secondary bacterial infections, cardiovascular events due to fluid retention, psychosis, diabetes, avascular necrosis and osteoporosis can be side effects of steroid use.

long-range charge transfer organic compounds are remarkable for having very large hyperpolarizabilities and thus improved nonlinear optical (NLO) properties. p-nitroaniline (pNA) is known as a prototypical NLO organic material. The question answered in this work is the NLO properties of pNA will be improved by introducing an extended π-conjugation chain between the phenyl ring and the two NH2/NO2 terminal? By means of sophisticated ab initio/MP2 calculations, new derivatives of pNA with an extended π-conjugation have been designed by introducing –(CH=CH)nNH2 or –(CH=CH)nNO2 (n = 1–5) chain into pNA. The results indicate that introducing such chains results in smaller energy gaps and transition energies, which lead to a significant improvement in the hyperpolarizability (β_0). The novel pNA derivatives exhibit larger β_0 amplitudes up to 4.67 x 104 au, which is 27-fold greater than that of pNA. Moreover, with increasing the β_0 amplitude, the –(CH=CH)nNO2 chain beats the –(CH=CH)nNH2 chain. It is hoped that this study can provide a help for designing higher performance NLO materials based on pNA.

In this study, three novel sensitizers with the donor-acceptor-π-spacer-acceptor D-A’-π-A) structure were designed based on the benzothiadiazole (BTD) surrounded by two thiophenes in each side (T4) mono-functionalized by an acid phosphonic (A) T4BTD-A dye by insertion of vinyl and cyanide CN electron-withdrawing moiety in a different position. Their geometrical, electronic and photovoltaic parameters were predicted using density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations, via the functional BHandH in combination with the Poples basis set 6-311G(d) for small atoms and pseudo-potential basis set LANL2DZ for Titanium atom at the chloroform solvent medium via the implicit CPCM model. Results showed that the inclusion of the C=C and the CN moieties exhibits a decrease in the HOMO–LUMO gap, and a redshift in the absorption spectra. The photoelectric conversion efficiency (PCE) for the T4BTD-A dye was estimated to be about 6.57 % under the standard AM 1.5G solar radiation, which is in excellent agreement with its measured value of 6.40 %, suggesting that our calculations scheme is consistent. Moreover, the predicted PCE value after elongation of T4BTD-A by C=C and CN has increased to 7.11 % and (7.82 %, 8.09 %) respectively. Our results revealed that the addition of CN electron-withdrawing moiety enhances the PCE of the studied dyes, while the position of CN moiety has a slight effect on the PCE of the studied dyes. Additionally, our calculation suggests that the CCCN1 and CCCN2 are good candidates as efficient sensitizers for dye-sensitized solar cell DSSCs applications.

OBJECTIVES This study aims to report the outcomes of the combination of preoperative brachytherapy (POBT) followed by a Querleu Morrow Type A hysterectomy as an alternative to upfront surgery for early stage cervical cancer (ESCC) (2018 FIGO IA1-IB2). METHODS A single center retrospective study conducted between 2001 and 2012. After confirming the absence of pelvic node metastasis, all patients with ESCC underwent Low Dose Rate (LDR) POBT followed by Type A hysterectomy. Primary and secondary endpoints were the Disease Free Survival (DFS) and the associated morbidity respectively. RESULTS Out of the 138 patients included, complete response was found in 49.3 % and a residual tumor < 1 cm in 26 %. After a median follow up of 132 months, DFS was 93.5% and 9 recurrences occurred. In univariate analysis, we found that delaying surgery more than 52 days after POBT is associated with a significant decrease in DFS (p = 0.004). Pathological complete response was associated with an increased DFS (p = 0.03). The brachytherapy related rate of late complications was 17.3% (n=24) and the surgery related urinary tract complications rate was 6.5% (n=9), with only 2 patients (1.5%) presented grade 3 complications CONCLUSION The multimodal radio-surgical management of ESCC appears to be a reasonable alternative to upfront open radical hysterectomy particularly in patients with high risk ESCC (< 2cm associated with negative prognostic factors or for tumors measuring between 2 and 4cm). This approach is associated with low complications rate and a reasonable rate of local recurrences.

West Nile virus (WNV) is a vector-borne zoonotic disease maintained in a sylvatic cycle involving mosquito vectors and birds. To detect West Nile virus (WNV) and other flavivirus infections in wild resident and migratory birds, we tested 184 samples from 19 identified species within nine families collected during 2012-2016 from four districts in Bangladesh. We tested serum samples for the immunoglobulin G (IgG) antibody to WNV using competitive Enzyme-Linked Immunosorbent Assay (c-ELISA), whereas tracheal and cloacal swabs subjected to consensus PCR for the detection of the flavivirus RNA. Overall, 11.9% (n=22; 95% CI: 0.07-0.16) samples were seropositive, including 15.9% migratory wild birds and 10.7% resident wild birds. Tufted duck showed 28.5% sero-positivity, whereas crows showed 12.5% sero-positivity. None of the swab samples was positive for flavivirus RNA infection. These study findings suggest that wild birds of Bangladesh may carry WNV. We recommend continued surveillance for early detection and to better understand the epidemiology of WNV and other flavivirus circulation in both birds and mosquitoes in Bangladesh.