“Atrial Fibrillation and Premature Ventricular Complexes” – is there a unifying diagnosis?

Introduction: Cardiac resynchronization therapy (CRT) with multipoint left ventricular (LV) pacing (MultiPoint™ Pacing, MPP) has been shown to improve CRT response, although MPP response using automated pacing vector programming has not been demonstrated in the Middle East. Objective: Compare the impact of MPP to conventional biventricular pacing (BiV) using echocardiographic and clinical changes at 6 months post-implant. Methods: This prospective, randomized study was conducted at 13 Middle Eastern centers. After de novo CRT-D implant (Abbott Unify Quadra MP™ or Quadra Assura MP™) with quadripolar LV lead (Abbott Quartet™), patients were randomized to either BiV or MPP therapy. In BiV patients, the LV pacing vector was selected per standard practice; in MPP patients, the two LV pacing vectors were selected automatically using VectSelect. CRT response was defined at 6 months post-implant by a reduction in LV end-systolic volume (ESV) ≥15%. Results: One-hundred and forty-two patients (61 years old, 68% male, NYHA class II/III/IV 19%/75%/6%, 33% ischemic, 57% hypertension, 52% diabetes, 158 ms QRS, 25.8% ejection fraction [EF]) were randomized to either BiV (N=69) or MPP (N=73). After 6 months, MPP vs. BiV patients experienced greater ESV reduction (25.0% vs. 15.3%, P=0.08), greater EF elevation (11.9% vs. 8.6%, P=0.36), significantly greater ESV response rate (68.5% vs. 50.7%, P=0.04), and significantly greater NYHA class improvement rate (80.8% vs. 60.3%, P=0.01). Conclusions: With MPP and automatic LV vector selection, more CRT patients in the Middle East experienced reverse remodeling and clinical improvement relative to conventional BiV pacing.

Low-field nuclear magnetic resonance (NMR) relaxometry is an attractive approach for point-of-care testing medical diagnosis, industrial food science, and in situ oil-gas exploration. However, one of the problems is the inherently long relaxation time of the (liquid) sample (and hence low signal-to-noise ratio) which causes unnecessarily long repetition time. In this work, a new methodology is presented for a rapid and accurate object classification using NMR relaxometry with the aid of machine learning techniques. It is demonstrated that the sensitivity and specificity of the classification are substantially improved with a higher order of (pseudo)-dimensionality (e.g., 2D or multidimensional). This new methodology (the so-called Clustering NMR) may be extremely useful for rapid and accurate object classification (in less than a minute) using the low-field NMR.

Background: Whether there is also a correlation between viral shedding duration and the clinical course of illness in COVID-19 has not yet been determined. Methods: In this retrospective study, we included 239 adult inpatients (all ≥18 years old) with laboratory-confirmed COVID-19 from the Wuhan Tongji Hospital (Wuhan, China). Results: Of the subset of 239 patients included in this study, 33 patients died due to COVID-19 and 45 patients demonstrated clinical progression to critical illness. Patients with a long duration of viral RNA shedding as compared to short duration of viral RNA shedding also had significantly lower mortality rates ((9.5% vs. 18.6%, P= 0.04) and a lower rate of progression to critical illness (16.7% vs. 21.2%, P= 0.37). Viral RNA shedding is an independent risk factor for mortality within 28 days of observation (OR 0.94, 95% CI: 0.88-0.99, P= 0.025, by multivariable regression analyses) and increased duration of viral shedding is correlated with a significant survival advantage (P =0.047) and lower risk of progression to critical illness (P =0.029, by Kaplan-Meier analyses). Conclusions: Prolonged viral RNA shedding duration is associated with improved patient prognosis and reduces the risk of progression to critical illness in this subset of COVID-19 patients. Further clinical studies are necessary to determine if a longer duration of viral RNA shedding with COVID-19 is predictive of an overall better patient prognosis and outcome.

West Dongting Lake (WD) receives water from local rivers, the Yuan and Lishui Rivers, within the lake basin and is recharged by the Yangtze River outside the basin through three outfalls. Thus, water pollution control is more complicated in WD than in lakes disconnected from the Yangtze River. Here, major ion tracing which was a method rarely applied in the river-lake system was used to characterize the contribution of water and total nitrogen (TN) from the inflow rivers to WD, and 9 sampling sites in WD and its inflow rivers were investigated in December 2016 (the dry season, DS), April 2017 (the normal season, NS) and August 2017 (the wet season, WS). Na+ and Cl－ were suitable tracer ions used in the ion tracing model to estimate the water and TN contributions from inflow rivers to WD. Results showed that the water and TN in WD who presented river and lacustrine phases were mainly contributed by local rivers rather than the three outfalls, in which the contribution of Yuan River was larger than that of Lishui River. However, the contribution rates of water and TN of the three outfalls to WD during WS reached above 20% and 30% respectively, indicating that the contribution of the three outfalls could not be ignored, in which the contributions of water and TN from Songzi outfall were higher than those from Taiping and Ouchi outfalls. Therefore, we suggest that the relevant departments should identify key river management targets during different water periods, implement refined management over water pollution in WD, and prioritize the pollutant input of Yuran River and Songzi outfall (especially during WS).

We present, by using previous results on extended Petri Nets, the relations of various hydrological dynamical systems ($\mathtt{HDSys}$) derived from the water budget ($\mathtt{DynWB}$). Once $\mathtt{DynWB}$ has been implemented, there exist a consistent way to get the equations for backward travel time distributions ($\mathtt{DynTT}$), for the forward response time distribution ($\mathtt{DynRTD}$) and for the concentration for a solute or a tracer ($\mathtt{DynC}$). We show that the $\mathtt{DynWB}$ has a correspondence one to many with the $\mathtt{DynTT}$. In fact to any one of the $\mathtt{DynWB}$ equation correspond as many equation as the input precipitation events times. The $\mathtt{DynTT}$ is related to $\mathtt{DynRTD}$ by the Niemi’s relationship and, in presence of multiple, $n$ outputs, by the specification of $n-1$ partition functions, which determine which fraction of water volume, injected in the control volume at a specific time $t_{in}$, goes asymptotically into a specific output. The $\mathtt{DynC}$, given $\mathtt{DynTT}$, depends further on the solute/tracer concentration in inputs. The paper clarifies the complicate set of relations above by using an example from literature. Upon the introduction of the appropriate information, it is also shown how these ($\mathtt{HDSys}$) can be solved simultaneously without duplicating calculations. It is also shown that these systems can be solved exactly, under the hypothesis of uniform mixing of water ages inside each reservoir within the system.

A document by Bruno de Paula. Click on the document to view its contents.

COVID-19 has undergone rapid spread worldwide, with the number of infected patients and death events being increased at exponential rates, and thus considered an epidemic disaster. However, SARS-CoV-2 has reduced case-fatality rate and enhanced transmission capacity that favor its propagation and make it evolutionarily more advanced than the other coronaviruses. Further, SARS-CoV-2 preserves virulence to certain patients while keeping some patients symptom-free. It is hypothesized here that SARS-CoV-2 functions as a natural selection pressure for human evolution. That is, COVID-19 is an epidemic disaster at the individual level but may be evolutionarily beneficial for the human at the population level, and survived individuals from SARS-CoV-2 infection may be more tolerable to redox pressure and not suffer anymore from diseases such as hypertension if without external intervention.

During the later stages of seed maturation, two key adaptive traits are acquired that contribute to seed lifespan and dispersal, longevity and dormancy. The seed-specific heat shock transcription factor A9 is an important hub gene in the transcriptional network of late seed maturation. Here we demonstrate that HSFA9 plays a role in thermotolerance rather than in ex situ seed conservation. Storage of hsfa9 seeds of Medicago truncatula and Arabidopsis had comparable lifespan at moderate storage relative humidity (RH), whereas at high RH, hsfa9 seeds lost their viability much faster than wild type seeds. Furthermore, we show that in M. truncatula, Mthsfa9 seeds acquired more dormancy during late maturation than wild type. Transient expression of MtHSFA9 in hairy roots and transcriptome analysis of Mthsfa9 Tnt1 insertion mutants identified a deregulation of genes involved in ABA biosynthesis, catabolism and signalling. Consistent with these results, Mthsfa9 seeds exhibited increased ABA levels and higher sensitivity to ABA. These data suggest that in legumes, HSFA9 acts as a negative regulator of the depth of seed dormancy during seed development via the modulation of hormonal balance.

Abstract Background In December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, Hubei, China. Finding markers that predict the prognosis of patients with severe COVID-19 are of great value. Methods In this single-center，retrospective study, 157 patients with severe COVID-19 were recruited from a consecutive series. After screening, a total of 105 patients were included in this study. All-cause death was the primary endpoint. All patients were followed up from admission till discharge or death. Results The dominant symptoms observed in the study included fever on admission, cough, fatigue and shortness of breath. The most frequent comorbidities were hypertension and diabetes. Compared with patients with higher CD4+T cells level, patients with lower CD4+T cells level were older and were more frequently male. In terms of laboratory findings, lymphocyte percentage, lymphocyte absolute value, CD3+T cell count, CD4+T cell count, CD8+T cell count were significantly lower in low group than in high group. The case in-hospital death rate was significant higher in patients with lower CD4+T level than in those with higher CD4+T level. After adjusting for potential confounding factors, CD4+T cells count below normal values showed independent prognostic value for all-cause in-hospital death in patients with severe COVID-19. Conclusions In patients with severe COVID-19, lower CD4+T cells count are independently associated with an increased rate of in-hospital death.

To the Editor:Antigen binding to a receptor initiates a cascade of intracellular signaling pathways and efficiently mounts an adaptive immune response in a given tissue microenvironment. Immunoreceptor engagement activates cytoplasmic protein tyrosine kinases such as SRC proto-oncogene (SRC), LYN proto-oncogene (LYN), and spleen associated tyrosine kinase. These kinases phosphorylate the immunoreceptor tyrosine-based activation motif (ITAM) and activate downstream immune effector functions through their interaction with the cytoplasmic tail. However, excessive activation can result in immune-mediated tissue damage. The cytoplasmic tail of programmed cell death-1 (PD-1) harbors an immunoreceptor tyrosine-based inhibitory motif (ITIM) and an immunoreceptor tyrosine-based switch motif (ITSM).1 Like ITAM, these highly conserved motifs are phosphorylated upon immunoreceptor engagement2 and interact with protein tyrosine phosphatase non-receptor type 6 or protein tyrosine phosphatase non-receptor type 11 (SHP-2). It is known that PD-1 interacts with SHP-2 and regulates antigen receptor signaling pathways through the cytoplasmic tail.3, 4The mast cell (MC) is not only a key component of innate immunity but also serves as a critical effector in the adaptive immune response. Analogous to the T/B cell receptor signaling pathways, the high-affinity immunoglobin E receptor (FcεRI) signaling pathway involves ITAM phosphorylation, which in turn results in degranulation and the release of mediators/enzymes. Conversely, the ITIM/ITSM phosphorylation event negatively regulates the MC effector function.5Although it was recently shown that the ligation of PD-1 on MCs induces peripheral tolerance,6 there has been a paucity of direct evidence showing the inhibitory role of PD-1 on MC effector function in vivo . To this end, we employed the IgE-mediated passive anaphylaxis model. We compared the consequences of total PD-1 absence with PD-1 receptor blockade7 and delineated the requirement of the cytoplasmic tail for the regulation of FcεRI signaling.In contrast to the findings for MC-specific deletion of SHP-2,8 cutaneous, or peritoneal MC populations in PD-1 knockout (PD-1KO) mice were not altered significantly (Fig. S1a, b). This discrepancy suggests that PD-1 is dispensable for the development of the tissue MC lineage on the KIT proto-oncogene/SHP-2 axis.8 Regarding the passive systemic anaphylaxis, PD-1KO mice exhibited a significantly increased drop in body temperature compared with wild-type (WT) mice (Fig. 1a). Likewise, in the late-phase passive cutaneous anaphylaxis, PD-1KO mice showed a significantly enhanced ear swelling compared with WT mice (Fig. 1b). However, a monoclonal antibody (mAb)-mediated PD-1 receptor blockade did not exacerbate the anaphylactic response (Fig. 1c, d, and Fig. 2).Monoclonal antibodies targeting the PD-1/programmed death-ligand 1 (PD-L1) pathway or cytotoxic T-lymphocyte antigen 4 have revolutionized the medical oncology. Nonetheless, such a therapeutic approach inherently runs the risk of evoking immune-related adverse events (irAEs).9 Previously, we have shown that either genetic deletion of PD-1 or mAb-mediated PD-1 receptor blockade exacerbates allergic contact dermatitis, and we inferred that the PD-1/PD-L1 pathway is a critical regulator of cutaneous irAE (C-irAE).7 In contrast to the cell-mediated cutaneous immune response, we found that the augmented IgE humoral immune response required the total absence of PD-1, but immunoreceptor engagement was dispensable. This discrepancy may be analogous to the fact that the cytoplasmic PD-1 tail can interact with the SHP-2 phosphatase upon T cell receptor ligation, even in the absence of PD-1 receptor engagement.2 These lines of evidence and our results further suggest that PD-1 evolved to regulate the adaptive immune response at the effector phase7 along with other inhibitory immunoreceptors. Our results may also correlate with clinical observations. Although the urticarial rash is the most common form of C-irAE, anaphylaxis, the systemic counterpart of urticaria has never been reported in this context. Therefore, our results could be an important guide for the medical oncology practice in that aggravated IgE-mediated anaphylaxis is due to the total absence of PD-1, but not receptor engagement.

Summary. Objectives: After corrective for scoliosis, postoperative pulmonary complications lead to increases in morbidity, length of hospital stay and mortality. This study aimed to identify associations with such respiratory complications. Methods: This retrospective cohort study included all children aged ≤17 years who underwent spinal surgery for scoliosis between January 2009 and January 2012 at a quaternary paediatric hospital. Factors associated with severely compromised pulmonary function (SCPF) were established and correlations with the occurrence of postoperative pulmonary complications and length of hospital stay (LOS) were identified. Rresults: Altogether, 133 children had corrective surgery for scoliosis, aged 12.7 (range 2-17) years at operation. Scoliosis causes were identified as: idiopathic (39.8%), neuromuscular disease (32.2%), syndrome (15.7%) and congenital (12%). Correlates with SCPF (FVC<40% predicted, n=10) included markers of sleep hypoventilation, including serum bicarbonate ≥29 mmol/L, morning pCO2 >50 mmHg (P=0.003), and overnight, episodic CO2 retention of >7 mmHg, thus an additional 8 children with SCPF were identified. Post-operative pulmonary complications were seen in 24 children (18%) and their occurrence correlated with higher Cobb angle (>90°), lower pulmonary function (FVC), higher serum bicarbonate and underlying neuromuscular disease. Amongst 18 children with SCPF, regular use of NIV pre-operatively was associated with reduced rate of post-operative pulmonary complications (P =0.02) and reduced LOS by 6.4 days (P =0.01). Conclusion: Nocturnal hypoventilation identifies children with SCPF. Use of NIV in children with SCPF was linked to fewer post-operative pulmonary complications and reduced duration of hospital stay. Keywords: Ventilation ; Pulmonary complications ; Scoliosis ; Polysomnography.

Letter to the Editor, BJOG Exchange

Speculations on the connection of α-Gal allergy to Coronary Artery Disease.Pitsios Constantinos1,2, Dimitriou Anastasia2, Vassilopoulou Emilia3.1. Medical School, University of Cyprus, Nicosia, Cyprus2. Allergy Private Practice Network, Athens, Greece3. International Hellenic University, Department of Nutritional Sciences and Dietetics, Thessaloniki, GreeceAuthors have no conflict of interest to declareCorresponding author :Constantinos PitsiosMedical School, University of CyprusPanepistimiou 1, 2109 AglantziaNicosia, CyprusTel; +30 6974348638Email; pitsios.constantinos@ucy.ac.cyStatement:Authors have no conflict of interestPitsios C, was the main author and clinical supervisor.Dimitriou A; drdimiana@gmail.com , was the clinician of the cases reported and reviewed the paper.Vassilopoulou E; vassilopoulouemilia@gmail.com , has contributed as author to the diet suggestions and as reviewer.Text word count; 866To the Editor,In 2009, we reported a case-report of generalized allergic reaction during the performance of allergy tests to red meat products [1]. It was the case of a 59-year-old male, with a 10-year-long anamnesis of several anaphylactic episodes (urticaria-angioedema and asthma attacks) 2 hours after the consumption of mammalian meats. He was tolerating dairies and avian meat. His medical history was including seborrheic dermatitis, gastric ulcer, coronary artery disease (CAD) and symptoms of exercise-induced bronchospasm [1]. Since all reactions were reported to happen after the ingestion of well-cooked meat we concluded that the culprit allergen was heat-stabile, without being able to specify it.Two more cases of allergy to red meat, males, 68-year-old (yo) and 52yo respectively, were referred to us last year, both confirmed with skin prick tests. The 68yo patient reported tolerating small quantities of cold cuts. They both had anamnesis of CAD. At that time, CAD had been recently described as comorbidity to mammalian meat allergy and α-Gal allergen was inculpated [2]. Patients’ sensitization to α-Gal was later confirmed with specific IgE test (sIgE) against this allergen. We tried to contact the first case of meat allergy in order to prescribe the same test, but unfortunately we were informed that he had passed away due to myocardial infarction.In the 2010s, tick bites were recognized as the main “sensitizer” to α-Gal, causing cross-allergic reactions to mammalian meat [3]. Our patients are located in the rural area of the island of Euboea, Greece, engaged in outdoor activities and tick bites seem the most reasonable explanation of their sensitization. Three genera of IxodidaeFamily are the main ticks parasitizing humans in Greece;Rhipicephalus , Ixodes and Hyalomma [4]. Although not all tick bites cause IgE-sensitization to α-Gal, the above mentioned do [3, 5].Alpha-Gal has been recognized as the culprit allergen for severe and fatal anaphylaxis to the mAb cetuximab, while case-reports have been published also for drugs like heparin, vaccines and anti-venom [3]. Although parenteral administration can cause immediate allergy, food allergy due to α-Gal is commonly expressed with a delay in symptom onset and is dose-unrelated, features also noticed in our cases [6]. The pathophysiological mechanism differs when α-Gal is administeredvia the parenteral route than intake via the gastrointestinal system. α-Gal parenteral administration (i.g injection of cetuximab) triggers an acute IgE-mediated reaction, while a delayed allergy is observed when it enters through the digestive system.The pathophysiological background of the ‘digestive’ delay has been elucidated by an in vitro study, analyzing the transport of α-Gal through the intestinal epithelium [7]. It was found that only the lipid-bound α-Gal is able to cross the intestinal epithelium, while protein-bound α-Gal was not detected in the basolateral media of enterocytes [7]. Alpha-Gal contained in glycolipids is digested, absorbed and enters the blood stream by the thoracic duct after hours, explaining the late-onset of allergic symptoms [3, 7]. Furthermore in α-Gal allergic patients, dairies may cause delayed onset of gastrointestinal symptoms over 2 hours [8].There is a strong epidemiological connection between CAD and “α-Gal syndrome”, a term used to describe different clinical allergies due to this allergen [9]. This relationship has been confirmed by a study using intravascular ultrasound imaging in subjects undergoing cardiac catheterization [2]. A mechanistic model has been proposed to clarify this connection, describing the delivery of α-Gal epitopes -connected to lipid particles- to mast cells within atherosclerotic plaques [9].Due to the intraindividual tolerability to the culprit allergen, patients with α-Gal allergy exclude or reduce mammalian meat from their diet, but often consume tolerable quantities of products containing α-Gal. This can induce local mast cell degranulation leading to chronic mast cell activation and pro-inflammatory events contributing to the chronic inflammatory procedures of CAD pathogenesis [9]. Our objection is that if mast cells play a pivotal role to this inflammation, red meat ingestion would cause a massive mast cell degranulation in atherosclerotic plaques so angina would be a common symptom of the delayed-type allergic reactions to red meat, resembling to Kounis Syndrome.The hypothesis that small tolerable quantities cause the ongoing coronary inflammation via local mast cell degranulation is an emerging concern for us. Based on the knowledge that participation of chylomicrons and inflammation are common parameters of CAD and α-Gal sensitization, their exact immunological connection remains to be clarified. Can α-Gal molecules generate the inflammation, as plaque’s component, maybe through a process of immune-complexes? Are they inducing transdifferentiation of vascular smooth muscle cells to macrophages or local proliferation of monocytes and formation of foam cells?Immunological pathophysiology of CAD is still unclear, while on the other hand epidemiological data seem definite and alarming. In order to avoid worsening of CAD by accumulation of lipoproteins containing α-Gal, we recommend the strict avoidance of all α-gal containing food, regardless the tolerance-level of each patient. Thus, dairies, gelatin and mammalian meat products should be avoided.Should a patient with CAD be tested for α-Gal? Screening in vivoand in vitro tests have been established as prevention in the field of Cardiology. The impact of α-Gal should further be investigated and compared between areas with high prevalence of sensitization due to tick bites and tick bites free. Metabolomic profiling of such patients will clarify the future of α-Gal allergy.

Internal mammary harvesting: the long-lasting history and harvesting techniquesRunning Head: Internal mammary artery

KEY POINTSSARS-CoV-2 disease (COVID-19) is a major challenge for healthcare systems and physicians and may impact young otolaryngologists’ training and clinical practice.The COVID-19 outbreak negatively influenced otolaryngologists’ clinical activity and training in Italy.Interventions to evaluate and address residents’ training gaps are needed.Online lectures represent a promising strategy to cope with the current situation while laying the foundations of a structured high-quality national teaching curriculum.A lack of training on the use of personal protective equipment, oxygen ventilation systems and COVID-19 therapies has been highlighted.INTRODUCTIONSince February 21, 2020 Italy has been witnessing a massive COVID-19 outbreak and Italian hospitals have been rapidly overcrowded with COVID-19 patients. In keeping with current recommendations of the Italian Ministry of Health, all non-urgent surgeries have been postponed1 with a major shift of resources towards pandemic management, profoundly affecting the training of Otorhinolaryngology (ENT) residents2. Currently, residency programs face the challenge of establishing the effects of the disruption of training on procedural skills and competency development in order to effectively address training gaps. Moreover, since current information indicates that roughly 10% of Italian cases have been among health-care workers, the impact of the disease on trainees deserves to be evaluated.A nationwide survey has therefore been conducted to assess the impact of COVID-19 on ENT residency programs and gain information that could be employed to implement compensative strategies to maintain high-quality standards of training.MATERIALS AND METHODS

Background: The ultimate goal of mitral valve surgery in younger women is to extend life expectancy and improve quality of life. Mitral valve replacement prosthesis in the middle-aged women is a difficult choice between the lifelong anticoagulation of a mechanical prosthesis versus a limited long-term durability of the bioprosthesis. The current trend towards reducing the women age for selection of the mitral bioprosthesis over a mechanical prosthesis lead to a dilemma for younger women decision making.1,2 The aim of this study is to compare the clinical out-comes after mitral valve bioprosthesis versus mechanical prosthesis in younger women population when mitral valves repair not feasible or unsuitable. Methods: A single-centre prospective non randomized registration of all women patients undergoing Mitral Valve Replacement at our center from January 2010 to February 2020 established. Results: Between January 2010 and February 2020, 355 female patients underwent mitral valve replacement at our center, 174 female patients of them had mitral valve replacement with mitral bioprosthesis (Mb) and 181 female patients of them had mitral valve replacement with mitral mechanical (Mm) prosthesis. Our study proved that the use of anticoagulation among the Mm young women associated with a remarkable risk of postoperative bleeding, abortion and increase frequency of the pregnancy related complication of the anticoagulation (p=< 0.0001), moreover, there is a considerable survival benefits for younger women patients received Mb(p= 0.0001). Conclusions: These data confirm that the impulse for the use of mitral bioprosthesis for young women population has been great with an astonishing survival benefits.

Many organisms show signs of deterioration with age, both in terms of survival and reproduction. Theory suggests that variation in such senescence patterns can be driven by resource availability or reproductive history. To test this prediction, we experimentally manipulated nutritional stress and age at first reproduction to investigate senescence in tsetse flies (Glossina). Across all treatments, offspring weight and survival followed a concave curve with mother age. Nutritionally stressed females had accelerated survival senescence, higher probability of abortion and produced smaller offspring. Despite this, there was no evidence of accelerated reproductive senescence in nutritionally stressed females and no evidence of a delay in senescence in females mated later. Offspring quality may be prioritised over somatic maintenance. Younger females who were nutritionally stressed produced offspring with the lowest starvation tolerance. As tsetse are vectors of trypanosomes, our results may have implications for population dynamics and trypanosome transmission in times of stress.

In the midst of modernization of human lifestyle with the profound effect of sophisticated technologies, pathogens in parallel have also evolved gradually to stay masked and smuggled their ways into our lives. Of different pathogens, zoonotic microbes are the most challenging to control, attributed to faulty surveillance systems to monitor the emergence of any pathogens at the human-animal interface. Amongst different infectious diseases in bovines, mastitis is a prototypic emerging and reemerging disease caused by pathogenic microbes that have overcome a series of hierarchical barriers resulting in zoonotic transmission. Although it has been annoyingly persistent since ancient times, it has never been a focus for desperate measures. However, the most critical is the chronic asymptomatic subclinical mastitis that results in cut-by-cut torture to not only the animals but also to the global economy. Despite the rapid technological advancement, identification of mastitis in subclinical form at the local community level is still improbable, leading to a high chance of the pathogenic and antimicrobial spillover. Understanding the complex sociological and ecological factors influencing disease transmission risks and pathogen containment remains unelucidated. Multiple factors are essential for the successful detection and containment of pathogens that have prompted the initiation of the “One Health” approach. Nevertheless, there is a lack of collaborative approach between the local and global strategists to suggest and implement checkpoints at different horizons to control mastitis. Here, we review the evolution of these pathogens in the reservoir host, their zoonotic potential and the pros and cons of current management strategies. We also address the extent of success in implementing a concerted approach like “One Health One Welfare,” which calls for interdisciplinary collaboration between professionals in human, animal and environmental health along with multi-omics to keep the pathogens at bay.

Rationale, aims and objectives Public health systems are under pressure to meet increasing demand for health care in environments of increasing financial resource constraint. There is therefore a need to maximise health outcomes given limited public healthcare expenditure. This paper aims to establish the extent of literature and approaches to efficiency improvement in public health systems of developed countries. Methods The Rapid Evidence Assessment model was used to address the review question. Two database searches returned a result of 3,526 unique titles, which were individually screened for potential relevance. 144 titles were selected for full review to determine relevance. 73 papers were included in the final review. Results Data on country, study design, key findings and links to efficiency improvement were extracted and synthesized. Synthesis of findings revealed that the literature on this topic is disparate and non-cohesive. A range of isolated approaches were described, and no evidence or consensus on a single best-practice approach to efficiency improvement was identified. Conclusions Combining the factors identified in this review has the potential to inform a framework for supporting efficiency improvement in public health systems. By considering these factors central health system management bodies can support efficiency improvement to deliver both financial and health services benefits.

Previous studies have identified that Th17/Treg cells were involved in Graves’ disease (GD). This study aimed at clarifying the association between GD susceptibility and single nucleotide polymorphisms (SNPs) of Th17/Treg cells-related genes, including IL2RA, miR27a, miR182, and FoxO1. A two-stage association study was performed in 650 GD patients and 1300 healthy controls. PCR-RFLP assays, real-time PCR and ELISA were performed. The result demonstrated that significantly increased frequencies of IL2RA/rs3118470 TT genotype (Pc=2.212×10-3) and IL2RA/rs2104286 AA genotype (Pc=1.754×10-5) were observed in GD. Stratification analysis also revealed that rs3118470 TT genotype and rs2104286 AA genotype were associated with Graves’ ophthalmopathy (GO) susceptibility (Pc = 1.848×10-6, Pc = 1.230×10-3, respectively). Functional studies showed that carriers of the rs2104286 AA genotype had lower IL2RA mRNA expression than AG genotype carriers (P=0.021). Cytokine analyses revealed that carriers with the rs3118470 risk genotype had decreased anti-inflammatory cytokine levels (IL-10 and TGF-β1) and increased IL-17 secretion than protective genotype individuals (P < 0.05). For the rs2104286 locus, AA genotype individuals had lower IL-10 levels (P=0.015) and increased IL-17 levels than AG genotype carriers (P =1.467×10-4). In conclusion, our findings suggested that IL2RA/ (rs3118470, rs2104286) were associated with GD and GO susceptibility in Southwest Chinese Han population.

Abstract Objective: Total laryngectomy (TL) is a life-saving procedure for individuals with advanced laryngeal cancer or those suffering from recurrence after initial treatment. The present study aims to evaluate the differences between stapler closure (SC) and manual closure (MC) of the pharynx during TL for patients with laryngeal cancer. Design/Setting: A systematic literature search was performed using the PubMed, Embase and Cochrane Library. The data were analyzed using Comprehensive Meta-Analysis software (Version 3; Biostat, Englewood, NJ). Dichotomous data were calculated by odds ratio (OR) and continuous data were calculated by mean difference (MD) with 95% confidence intervals (CI). Main outcome/Results: A total of 7 studies (535 patients) were included in this meta‐analysis. Pooled analysis showed that the operative time of TL was significantly reduced in the SC group (MD, -63.2; 95% CI, -106.0 to -20.4). Moreover, the SC group had a lower incidence of pharyngocutaneous fistula (OR = 0.38; 95% CI, 0.18-0.83; P = 0.016) and hospital stay (MD, -2.9; 95% CI, -5.6 to -0.1). The incidence of postoperative surgical site infection (OR = 0.41; 95% CI, 0.02-8.73; P = 0.565) was comparable between the two groups. Conclusion: Based on these results, SC may be a useful option for patients who need TL.

Objectives: To distinguish between primary mild COVID-19 patients and the patients with recovery positive virus detection after discharge (recovery positive patients), the clinical characteristics and biochemical indicators were analyzed. Methods: By evaluation of correlations between biochemical indicators and serum ferritin (FE) through univariate and multivariate analyses, we evaluated the differences of FE index and analyzed the effectiveness of the FE* pre-albumin (PA) on discrimination between primary mild and recovery positive COVID-19 patients. The area under curve (AUC) and a predictive nomogram were further employed to evaluate the effectiveness of discrimination. Results: In comparison with recovery positive patients, liver damage-related indicators such as serum FE and PA were significantly lower in primary COVID-19 patients with mild symptoms. Area under the ROC curve values of FE, PA and FE*PA were 0.81, 0.78 and 0.83, respectively. In combination with multivariate analysis and nomogram, FE and FE*PA can be considered as reasonable evaluation systems for predicting primary mild and recovery positive patients. Conclusions: FE*PA was an independent predictive biomarker for distinguishing primary mild and recovery positive COVID-19 cases.

COVID-19 causes significant hypoxia along with an inflammatory milieu, which may lead to secondary myocardial infarction and also atherosclerotic plaque rupture. Here we present a case of COVID-19 presented with ACS followed by PTE and CVA.