Twenty-seven years of primary salivary gland carcinoma in Wales: an analysis of histological subtype and associated risk factors.

OBJECTIVE: Risk factors for salivary gland carcinoma are poorly understood. Although links between background radiation, smoking and obesity have been previously suggested, no studies have so far established any significant results. This study aimed to establish correlations between common environmental and lifestyle risk factors and different subtypes of salivary gland carcinoma. METHOD: A study of population data in Wales spanning 27 years was conducted; 2 national databases were used to identify 356 cases of primary salivary gland carcinoma over this period. Histological subtype of cancer and geographical location of each case was recorded. Public health data was used to establish radon levels, smoking, obesity and activity levels of populations in each geographical location. A population matched multivariate analysis of variance analysis was performed using histological subtype and risk factor data for each geographical location. RESULTS: A significantly higher incidence of mucoepidermoid cancer in populations with higher background radon levels (p = 0.006), epithelial-myoepithelial cancer in populations with higher smoking levels (p = 0.029) and adenoid cystic cancer in populations with higher obesity levels (p = 0.028) was found. CONCLUSION: To the authors' knowledge, this is the first study to establish significant links between background radiation, smoking and obesity with different subtypes of salivary gland carcinoma.

Appendicitis in the COVID-19 era: a modern challenge for experienced hands.

INTRODUCTION: The first wave of COVID-19 was accompanied by global uncertainty. Delayed presentation of patients to hospitals ensued, with surgical pathologies no exception. This study aimed to assess whether delayed presentations resulted in more complex appendicectomies during the first wave of COVID-19. METHODS: Operation notes for all presentations of appendicitis (n=216) within a single health board (three hospitals) during two three-month periods (control period (pre-COVID) vs COVID pandemic) were analysed, and the severity of appendicitis was recorded as per the American Association for the Surgery of Trauma (AAST) grading system. RESULTS: Presentations of appendicitis were delayed during the COVID period with a median duration of symptoms prior to hospital attendance of two days versus one day (p=0.003) with individuals presenting with higher median white cell count than during the control period (14.9 vs 13.3, p=0.031). Use of preoperative CT scanning (OR 3.013, 95% CI 1.694-5.358, p<0.001) increased significantly. More complex appendicectomies (AAST grade >1) were performed (OR 2.102, 95% CI 1.155-3.826, p=0.015) with a greater consultant presence during operations (OR 4.740, 95% CI 2.523-8.903, p<0.001). Despite the greater AAST scores recorded during the COVID period, no increase in postoperative complications was observed (OR 1.145, 95% CI 0.404-3.244, p=0.798). CONCLUSIONS: Delayed presentations during the COVID-19 pandemic were associated with more complex cases of appendicitis. Important lessons can be learnt from the changes in practice employed as a result of this global pandemic.

Challenge of forecasting demand of medical resources and supplies during a pandemic: A comparative evaluation of three surge calculators for COVID-19.

Ever since the World Health Organization (WHO) declared the new coronavirus disease 2019 (COVID-19) as a pandemic, there has been a public health debate concerning medical resources and supplies including hospital beds, intensive care units (ICU), ventilators and protective personal equipment (PPE). Forecasting COVID-19 dissemination has played a key role in informing healthcare professionals and governments on how to manage overburdened healthcare systems. However, forecasting during the pandemic remained challenging and sometimes highly controversial. Here, we highlight this challenge by performing a comparative evaluation for the estimations obtained from three COVID-19 surge calculators under different social distancing approaches, taking Lebanon as a case study. Despite discrepancies in estimations, the three surge calculators used herein agree that there will be a relative shortage in the capacity of medical resources and a significant surge in PPE demand if the social distancing policy is removed. Our results underscore the importance of implementing containment interventions including social distancing in alleviating the demand for medical care during the COVID-19 pandemic in the absence of any medication or vaccine. The paper also highlights the value of employing several models in surge planning.

MRI quantification of diffusion and perfusion in bone marrow by intravoxel incoherent motion (IVIM) and non-negative least square (NNLS) analysis.

OBJECT: To assess the feasibility of measuring diffusion and perfusion fraction in vertebral bone marrow using the intravoxel incoherent motion (IVIM) approach and to compare two fitting methods, i.e., the non-negative least squares (NNLS) algorithm and the more commonly used Levenberg-Marquardt (LM) non-linear least squares algorithm, for the analysis of IVIM data. MATERIALS AND METHODS: MRI experiments were performed on fifteen healthy volunteers, with a diffusion-weighted echo-planar imaging (EPI) sequence at five different b-values (0, 50, 100, 200, 600 s/mm2), in combination with an STIR module to suppress the lipid signal. Diffusion signal decays in the first lumbar vertebra (L1) were fitted to a bi-exponential function using the LM algorithm and further analyzed with the NNLS algorithm to calculate the values of the apparent diffusion coefficient (ADC), pseudo-diffusion coefficient (D*) and perfusion fraction. RESULTS: The NNLS analysis revealed two diffusion components only in seven out of fifteen volunteers, with ADC=0.60±0.09 (10(-3) mm(2)/s), D*=28±9 (10(-3) mm2/s) and perfusion fraction=14%±6%. The values obtained by the LM bi-exponential fit were: ADC=0.45±0.27 (10(-3) mm2/s), D*=63±145 (10(-3) mm2/s) and perfusion fraction=27%±17%. Furthermore, the LM algorithm yielded values of perfusion fraction in cases where the decay was not bi-exponential, as assessed by NNLS analysis. CONCLUSION: The IVIM approach allows for measuring diffusion and perfusion fraction in vertebral bone marrow; its reliability can be improved by using the NNLS, which identifies the diffusion decays that display a bi-exponential behavior.

The mitogen-activated protein kinase (MAPK)-activated protein kinases MK2 and MK3 cooperate in stimulation of tumor necrosis factor biosynthesis and stabilization of p38 MAPK.

MK2 and MK3 represent protein kinases downstream of p38 mitogen-activated protein kinase (MAPK). Deletion of the MK2 gene in mice resulted in an impaired inflammatory response although MK3, which displays extensive structural similarities and identical functional properties in vitro, is still present. Here, we analyze tumor necrosis factor (TNF) production and expression of p38 MAPK and tristetraprolin (TTP) in MK3-deficient mice and demonstrate that there are no significant differences with wild-type animals. We show that in vivo MK2 and MK3 are expressed and activated in parallel. However, the level of activity of MK2 is always significantly higher than that of MK3. Accordingly, we hypothesized that MK3 could have significant effects only in an MK2-free background and generated MK2/MK3 double-knockout mice. Unexpectedly, these mice are viable and show no obvious defects due to loss of compensation between MK2 and MK3. However, there is a further reduction of TNF production and expression of p38 and TTP in double-knockout mice compared to MK2-deficient mice. This finding, together with the observation that ectopically expressed MK3 can rescue MK2 deficiency similarly to MK2, indicates that both kinases share the same physiological function in vivo but are expressed to different levels.

The double-stranded RNA-binding protein X1rbpa promotes RNA strand annealing.

RNA-annealing activity is a common feature of several RNA-binding proteins. The Xenopus RNA-binding protein X1rbpa is composed of three tandemly arranged double-stranded RNA-binding domains (dsRBDs) but lacks any other catalytic or functional domains, therefore making the assessment of biological functions of this protein rather difficult. Here we show that full-length X1rbpa but also isolated dsRBDs from this protein can facilitate RNA strand annealing. RNA annealing can be efficiently inhibited by heparin. However, dsRBDs with a neutral pI still promote strand annealing, suggesting that charged residues within the dsRBD are important for strand annealing. Additionally, mutant versions of the dsRBD, unable to bind dsRNA in northwestern assays, were tested. Of these, some show RNA-annealing activity while others fail to do so, indicating that RNA annealing and dsRNA binding are separable functions. Our data, together with the previously reported association of the protein with most cellular RNAs, suggests an RNA chaperone-like function of X1rbpa.