Key points 1. This is the first report of adult primary herpetic oropharyngitis in the view point of the differences between the two types of herpes simplex virus (HSV). 2. 41 (25 type 1 and 16 type 2) HSV specific antigen positive cases among 68 immunoserologically confirmed adult HSV primary infection cases were investigated. 3. Significantly low incidence of oral lesions and high incidence of nausea were seen in HSV type 2 oropharyngitis cases, that might mean particular correlation vagus nerve and HSV type 2. 4. Significantly increased white blood cell count and high C-reacative protein value were seen in oropharyngitis by HSV type 2. 5. HSV type 2 possibly cause more severe symptoms and higher inflammatory reactions than type 1, without oral lesions.

Keypoints: • Implementing a one-stop Transnasal oesophagoscopy (TNO) service will benefit patients, clinicians as well as the NHS Trusts. • TNO is safe, well-tolerated and improves diagnostic and therapeutic precision in the upper aerodigestive tract and oesophagus. • The one-stop TNO service has clear financial benefits. • The one-stop TNO service is a streamlined pathway which improves patient care and experience. • Both the clinical and financial risk of introducing the service is low.

Theory predicts that threatened species living in small populations will experience high levels of inbreeding that will increase their negative genetic load but recent work suggests that the impact of load may be minimized by purging resulting from long term population bottlenecks. Empirical studies that examine this idea using genome-wide estimates of inbreeding and genetic load in threatened species are limited. Here we use genome resequencing data to compare levels of inbreeding, levels of genetic load and population history in threatened Eastern massasauga rattlesnakes (Sistrurus catenatus) which exist in small isolated populations and closely-related yet outbred Western massasauga rattlesnakes (S. tergeminus). In terms of inbreeding, S. catenatus genomes had a greater number of ROHs of varying sizes indicating sustained inbreeding through repeated bottlenecks when compared to S. tergeminus. At the species level, outbred S. tergeminus had higher genome-wide levels of genetic load in the form of greater numbers of derived deleterious mutations compared to S. catenatus presumably due to long-term purging of deleterious mutations in S. catenatus. In contrast, mutations that escaped the “drift sieve” and were polymorphic within S. catenatus populations were more abundant and more often found in homozygote genotypes than in S. tergeminus suggesting a reduced efficiency of purifying selection in smaller S. catenatus populations. Our results support an emerging idea that the historical demography of a threatened species has a significant impact on the type of genetic load present which impacts implementation of conservation actions such as genetic rescue.

A document by Mina Kelleni. Click on the document to view its contents.

A document by Mina Kelleni. Click on the document to view its contents.

A document by Mina Kelleni. Click on the document to view its contents.

Aspirin has been recently suggested to be independently associated with reduced risk of mechanical ventilation, ICU admission and in-hospital mortality of COVID-19. However, we claim that the molecular interpretation of these important results was not scientifically valid, and we provide our academic interpretation that is also basing on our real-life practice using non-steroidal anti-inflammatory drugs in management of COVID-19 and we suggest that inhibition of COX-1 and/or COX-2 enzymes might play a lifesaving role in COVID-19 management, and we further discuss the potential of aspirin triggered lipoxins and resolivns in the same context.

IntroductionMediators of immunity and inflammation are playing a crucial role in COVID-19 pathogenesis and complications as demonstrated by several genetic and clinical studies. Moreover, a weak, irregular, or inhibited early interferon response to SARS CoV-2 infection was shown to trigger an exaggerated inflammatory response leading to the COVID-19 associated mortality. Thus, repurposing of drugs that possess anti-inflammatory and/or immune-modulatory effects for COVID-19 is considered a rational approach.Areas coveredWe present a concise analysis and interpretations of selected studies that correlated COVID-19 with dysregulated interferon and inflammatory responses while reflecting on our academic and real-life experience using non-steroidal anti-inflammatory drugs, nitazoxanide and azithromycin for management of COVID-19. Moreover, we interpret the recent results that suggested a potential survival benefit of low dose aspirin and colchicine when used for COVID-19.Expert opinionNitazoxanide/azithromycin combination has been first hypothesized by the author and practiced by him and several researchers to benefit COVID-19 patients due to a potential ability to augment the natural interferon response as well as their positive immunomodulatory effects on several cytokines. Furthermore, NSAIDs, that were unfortunately almost globally avoided early in the COVID-19 era and still avoided in many developing ones or at best of second choice in the developed ones, have been early postulated and clinically practiced by the author to prevent or ameliorate COVID-19 complications and mortality due to their ability to prevent, constrain or reverse COVID-19 associated dysregulated immune and hyper-inflammatory responses through mitigating the formation of several inflammatory cytokines and pathways including the interleukin-6 amplifier and its NF-kB component, as well as modulation of a described monocytic immunological dysrhythmia, which is also known to trigger the COVID-19 cytokine storm. Finally, we repeat our previous call to adopt our observational study that used these drugs in sufficiently powered double blind randomized clinical trials as COVID-19 potential safe and economic cure might be available and unfortunately repeatedly ignored for one year.

ACE2 polymorphisms have been previously linked to increased susceptibility to multiple diseases and are currently linked to SARS CoV-2 susceptibility and complications. Notably, ACE2 transcribed or regulated proteins include the activity of metaloproteinsase-2 and apelin-13 and 36, might be linked to abnormal immune responses and complications. Potential genetic or serological tests might be developed to detect the higher vulnerable groups to SARS CoV-2 complications and/or mortality. Moreover, we postulate that diabetic and obese patients suffer from exhausted and/or abnormally functioning apelinergic peptides that predispose them to a higher severe COVID-19 risk. Finally, infusion of apelin-13 to treat selected critical cases of COVID-19, especially those complaining of refractory advanced heart failure, might be considered for clinical trials. 

We have previously suggested numerous immunomodulatory and anti-inflammatory benefits when NSAIDs are administered to manage COVID-19 and in this commentary, we add other potential benefits related to SARS CoV-2 ORF proteins dependent activation of caspases with subsequent mitochondrial dysfunction, endoplasmic reticulum stress and necroptosis that were described with complicated COVID-19 as NSAIDs are known to be caspase inhibitors. Moreover, NSAIDs might independently inhibit other COVID-19 associated downstream pathological signaling mechanisms. We also postulate that CARD-14, a caspase recruitment domain-containing protein, polymorphisms might play a role in development of severe and critical COVID-19. We believe that it is very unfortunate that for more than one year of relentless struggle, our recommendation to adopt NSAIDs as first choice COVID-19 therapy has not adopted while lives are lost are succumbed every day.

In the first version, I have made a mistake SARS COV-2 Vaccines have not shared in development of the original SARS CoV-2 B.1.617 variants in India (yet they might have shared in the evolution of the more virulent delta plus variant). I have updated the manuscript, thanks to Authorea, and in the updated versions Remdesivir, Favipiravir and Dexamethasone are suggested as potential crucial causes that led to B.1.617 variants in India and elsewhere. Moreover, SARS CoV-2 mass vaccination programs and the unfortunately anticipated Molnupiravir are suggested to share in evolution of potentially more virulent variants e.g. delta plus and the catastrophic Indian surge of mortality is also anticipated to be repeated elsewhere unless some prompt interventions are considered.

Nucleic acid based - mRNA based and adenovirus vectored - vaccines, were first ever or first commercially ever approved for the public, respectively. However, these newly emergency approved types possess a potential risk to induce auto-immune diseases e.g., thrombocytopenia, myocarditis and immune induced thrombosis and thromboembolism that might be fatal and could reason for some of the post vaccination sudden death reports. Moreover, all SARS CoV-2 types of vaccines, depending on the spike protein immunogenicity, especially the conventional inactivated ones might increase the likelihood of COVID-19 severity upon re-infection through antibody dependent enhancement which might reason for the recently described abundance of hospital admissions within seven days of vaccination and might also reason for some of the serious adverse effects encountered with administration of convalescent plasma to COVID-19 patients as well as they might share in development of some lethal SARS CoV-2 variants. Importantly, we suggest that SARS CoV-2 mass vaccination campaigns were the worst ever decision made and that making these COVID-19 vaccines compulsory or administering them to children or pregnant participants might be considered as a crime against humanity to the extent that no prior companies- governmental agreements would ever secure impunity. Finally, a full informed personalized risk benefit ratio especially for some described high-risk groups must be secured while suggesting that the subunit vaccines are the least hazardous ones.

A graph is called a partial cube if it can be embedded into a hypercube isometrically. In this paper, we study a class of Cayley graphs —Cayley graphs generated by transpositions and show that a Cayley graph Γ generated by transpositions is a partial cube if and only if Γ is a bubble sort graph. This result enhances a result of Alahmadi et al. [Math. Meth. Appl. Sci. 39 (2016), 4856–4865]: BSn is a partial cube. As a corrollary, we give the analytical expressions of the Wiener indices of bubble sort graphs.

African Swine Fever Virus (ASFV) causes a deadly disease of pigs which spread through southeast Asia in 2019. We investigated one of the first outbreaks of ASFV in Lao Peoples Democratic Republic amongst smallholder villages of Thapangtong District, Savannakhet Province. In this study, two ASFV affected villages were compared to two unaffected villages. Evidence of ASFV-like clinical signs appeared in pig herds as early as May 2019, with median epidemic days on 1 and 18 June in the two villages, respectively. Using participatory epidemiology mapping techniques, we found statistically significant spatial clustering in both outbreaks (P < 0.001). Villagers reported known risk factors for ASFV transmission − such as free-ranging management systems and wild boar access − in all four villages. The villagers reported increased pig trader activity from Vietnam before the outbreaks; however, the survey did not determine a single outbreak source. The outbreak caused substantial household financial losses with an average of 9 pigs lost to the disease, and Monte Carlo analysis estimated this to be USD 215 per household. ASFV poses a significant threat to food and financial security in smallholder communities such as Thapangtong, where 40.6% of the district’s population are affected by poverty. This study shows ASFV management in the region will require increased local government resources, knowledge of informal trader activity and wild boar monitoring alongside education and support to address intra-village risk factors such as free-ranging, incorrect waste disposal and swill feeding.

A document by Jon Lomasney. Click on the document to view its contents.

Obturator hernia is a rare condition. It is more commun in women than men owing to their greater width of the pelvis and larger obturator canal. We report 2 cases of strangulated obturator hernia, which were preoperatively diagnosed, in 2 female patients without previous history of abdominal surgery.

Isolated cecal necrosis is a rare variant of ischemic colitis which typically simulates the presentation of acute appendicitis. The elderly population is the most affected. We report 2 cases of isolated caecal necrosis, which were preoperatively diagnosed, in 2 female patients with a history of hypertension and renal failure.

Disclosed: quasiparticle properties and dynamics in real and momentum spaceUrsula Wurstbauer

Nicotine is best known for its troublesome role in tobacco addiction. However, in small doses, it is actually quite a potent and safe stimulant. Based on significant reports about a positive role of nicotine on narcoleptic seizures, we searched the medical literature for signals to better understand the opportunities and risks of medical nicotine use in patients with any severe form of narcolepsy.

Introduction: COVID-19 management still lacks a protocol of proven efficacy and we present a novel COVID-19 immunomodulatory protocol basing on our early pioneering article that justified repurposing nitazoxanide/azithromycin combination for early COVID-19 which was followed by two articles to justify addition of non-steroidal anti-inflammatory drugs to nitazoxanide/azithromycin as well as by our recent article that illustrates the potential immunomodulatory mechanisms by which all the drugs used in this manuscript might benefit COVID-19 patients.Methods: We present a case series of 38 confirmed and highly suspected COVID-19 consented native Arabic speaking patients, including 12 confirmed by PCR, and the others diagnosed by other measures who were managed by telemedicine. The patients included 15 adult males including an immunocompromised patient, 16 adult females including one lactating, 3 pregnant patients including one confirmed by PCR as well as 4 children. All patients have received a short 5-day-regimen of NSAIDs / nitazoxanide/ azithromycin +/- cefoperazone either in full or in part. The primary endpoint of this protocol was a full relief of all serious COVID-19 clinical manifestations. Results: The primary endpoint was fully achieved within two weeks. Most of the patients who were treated early, have fully recovered during its described five days; the leucocytic/lymphocytic count was significantly improved for those with prior leucopenia or leucocytosis/lymphopenia. Neither significant adverse effects, nor post/para COVID syndrome was reported. Conclusions: a novel 5-day-protocol to safely and effectively cure COVID-19 using repurposed immunomodulatory safe and inexpensive FDA approved drugs is illustrated and we recommend performing sufficiently powered double-blind randomized clinical trials.

Based on a coarsening strategy of adjacency matrix, a new algebraic prolongation operator is developed for standard V-cycle multigrid method to accelerate the whole process. An efficient algebraic multigrid (EAMG) method is proposed for solving large-scale linear systems, arising from finite element (FE) discretization of second order elliptic boundary value problems. Numerical experiments on polygonal domains are conducted to demonstrate the EAMG computation is more efficient than standard method.

The safety of transesophageal echocardiography (TEE) probes has been documented in pediatric patients (neonates, infants, and small children even < 2.5 Kg). The overall safety profile of TEE probe is quite favourable with a reported incidence of complications is about 1-3%. However, insertion of the TEE probe can induce vagal and sympathetic reflexes such as hypertension or hypotension, non-sustained ventricular and supraventricular tachyarrhythmias or bradyarrhythmias [3rd degree heart block], and even angina and myocardial infarction. We hereby document a repeated and fatal intraoperative VF precipitated by TEE probe in a 2-year-old, 10 kg paediatric patient diagnosed with ostium secundum atrial septal defect (OS-ASD), supravalvular pulmonary stenosis (PS) and severe right ventricular (RV) dysfunction.

Water resource management in ungauged catchments is complex due to the uncertainties around the hydrological parameters that dominate the streamflow behaviour. These parameters are usually defined by regionalization approaches in which hydrological response patterns are transferred from gauged to ungauged basins. Regression-based methods using physical properties derived from cartographic data sources are widely used. The current remote sensing techniques offer us new standpoints in regionalisation processing since the hydrological response depends on the physical attributes related to the spectral responses of the territory. Moreover, machine learning approaches have not been specifically applied to the regionalization of hydrologic parameters. This work studies the capability of a catchment’s spectral response based on Sentinel-1 and Sentinel-2 data to address a regression-based regionalization of hydrological parameters using a machine learning approach. Hydrological modelling was conducted by the HBV-light model. We tested the random forest algorithm in several regionalization scenarios: the new approach using the catchments’ spectral signature, the traditional method using physical properties and a fusion of them. The calibration results were excellent (median KGE = 0.83), and the regionalized parameters obtained with the random forest algorithm achieved good performance in which the three scenarios showed almost the same goodness of fit (median KGE = 0.45 to 0.50). We found that the effectiveness depends on the climatic environment and that predictions in humid catchments exhibited better performance than those in the driest catchments. The physical approach (median KGE= 0.71) exhibited better performance than the spectral approach (median KGE= 0.64) in humid catchments, whereas spectral regionalization (median KGE= 0.33) outperformed the physical scenario in the driest catchments (median KGE= 0.25). Herein, our results confirm that regionalization is still challenging in Mediterranean climate variants where the new spectral approach showed promising results and time series of satellite data could improve seasonal regionalization methodologies.

Abstract: 2-O-α-D-Glucopyranosyl-L-ascorbic acid (AA-2G) is an important industrial derivative of L-ascorbic acid (AA), which has the distinct advantages of non-reducibility, antioxidation, and reproducible decomposition into L-ascorbic acid and glucose. Enzymatic synthesis is a preferred method for AA-2G production over alternative chemical synthesis owing to the regioselective glycosylation reaction. α-Glucosidase, an enzyme classed into O- glycoside hydrolases, may be used in glycosylation reactions to synthesize AA-2G. Here, one α-glucosidase from Oryza sativa (rAGL) was recombinantly produced in Pichia pastoris GS115 and used for biosynthesis of AA-2G with few intermediates and byproducts. The extracellular rAGL reached 9.11 U/mL after fed-batch cultivation for 102 h in a 5-L fermenter. The specific activity of purified rAGL is 49.83 U/mg at 37 °C and pH 4.0. The optimal temperature of rAGL was 65 °C, and it was stable below 55 °C. rAGL was active over the range of pH 3.0–7.0, with the maximal activity at pH 4.0. Under the condition of 37 °C , pH 4.0, equimolar maltose and AA·Na, 8.7±0.4 g/L of AA-2G was synthesized by rAGL. These studies lay the basis for the industrial application of recombinant α-glucosidase. Keywords: α-Glucosidase; Oryza sativa; 2-O-α-D-glucopyranosyl-L-ascorbic acid; Transglycosylation; Pichia pastoris