Psoriasis and family history of psoriasis may not affect disease severity of rheumatoid arthritis.

The incidence of psoriasis in patients with rheumatoid arthritis (RA) is higher than in the general population. In addition, psoriasis may negatively affect the severity of rheumatological diseases in patients with autoinflammatory or autoimmune diseases. In this study, we evaluated the effect of psoriasis or a family history of psoriasis on the characteristics of RA. This is a cross-sectional study. We included 737 RA patients who met the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) RA Classification Criteria, but did not meet the CASPAR psoriatic arthritis criteria. Subsequently, we compared disease activity, the need for biologic therapy, the number of conventional synthetic disease-modifying anti-rheumatic drugs taken, the frequency of erosive disease and extra-articular involvement, glucocorticoid doses and the Stanford Health Assessment Questionnaire scores between patients with and without a history of psoriasis, and patients with and without a family history of psoriasis. Thirteen (1.8%) patients had psoriasis, while 58 (7.9%) had a family history of psoriasis in first- or seconddegree relatives. All outcome parameters were found to be similar between the groups. We show that concomitant psoriasis has no effect on the evaluated disease characteristics of RA.

SARS-CoV-2 spike protein predicted to form complexes with host receptor protein orthologues from a broad range of mammals.

SARS-CoV-2 has a zoonotic origin and was transmitted to humans via an undetermined intermediate host, leading to infections in humans and other mammals. To enter host cells, the viral spike protein (S-protein) binds to its receptor, ACE2, and is then processed by TMPRSS2. Whilst receptor binding contributes to the viral host range, S-protein:ACE2 complexes from other animals have not been investigated widely. To predict infection risks, we modelled S-protein:ACE2 complexes from 215 vertebrate species, calculated changes in the energy of the complex caused by mutations in each species, relative to human ACE2, and correlated these changes with COVID-19 infection data. We also analysed structural interactions to better understand the key residues contributing to affinity. We predict that mutations are more detrimental in ACE2 than TMPRSS2. Finally, we demonstrate phylogenetically that human SARS-CoV-2 strains have been isolated in animals. Our results suggest that SARS-CoV-2 can infect a broad range of mammals, but few fish, birds or reptiles. Susceptible animals could serve as reservoirs of the virus, necessitating careful ongoing animal management and surveillance.

Baseline electrolyte abnormalities would be related to poor prognosis in hospitalized coronavirus disease 2019 patients.

Electrolyte abnormalities are not uncommon in coronavirus disease 2019 (COVID-19). Several studies have suggested that various electrolyte imbalances seem to have an impact on disease prognosis. However, no study has primarily focused on the effect of baseline electrolyte abnormalities on disease outcome. In this study, we assessed the validity of the hypothesis that baseline electrolyte imbalances may be related to unfavourable outcomes in hospitalized COVID-19 patients. Design of the study was retrospective and observational. We included 408 hospitalized individuals with COVID-19 over 18 years old. Baseline levels of sodium, potassium, calcium and chloride were assessed and the effects of abnormalities in these electrolytes on requirement for intensive care unit and mechanical ventilation, hospitalization duration and treatment outcome were evaluated. Patients were clustered based on electrolyte levels and clusters were compared according to outcome variables. Frequency of other severe disease indices was compared between the clusters. Lastly, we evaluated the independent factors related to COVID-19-associated deaths with multivariate analyses. In all, 228 (55.8%) of the patients had at least one electrolyte imbalance at baseline. Hyponatraemia was the most frequent electrolyte abnormality. Patients with hyponatraemia, hypochloraemia or hypocalcaemia had, respectively, more frequent requirement for intensive care unit and mechanical ventilation, higher mortality rate and longer hospitalization. The clusters associated with electrolyte abnormalities had unfavourable outcomes. Also, Clinical and laboratory features associated with severe disease were detected more often in those clusters. Hyponatraemia was an independent factor related to death from COVID-19 (OR 10.33; 95% CI 1.62-65.62; p 0.01). Furthermore, baseline electrolyte imbalances, primarily hyponatraemia, were related to poor prognosis in COVID-19 and baseline electrolyte assessment would be beneficial for evaluating the risk of severe COVID-19.

Assessment of atrial fibrillation and ventricular arrhythmia risk in patients with asthma by P wave/corrected QT interval dispersion.

OBJECTIVE: Although the relationship between obesity-asthma, obesity-atrial fibrillation (AF) and obesity-sudden cardiac death is clearly known, the risk of AF and ventricular arrhythmia has not been clearly determined in asthmatic patients. The aim of this study was to investigate whether AF, ventricular arrhythmia, and sudden cardiac death risk were increased in asthmatic patients using P wave dispersion (PWD) and corrected QT interval dispersion (CQTD). PATIENTS AND METHODS: The study was designed as a cross-sectional study. A total of 164 participants (88 patients with asthma and 76 healthy volunteers) were enrolled into the study. PWD and CQTD were measured and recorded in both groups. The statistical difference between the two groups was examined. RESULTS: PWD was higher in the asthma patients than in control subjects (31.53 ± 3.18 vs. 30.33 ± 3.53, p = 0.023). However, there was no statistically difference between the groups in terms of CQTD measurement (43.9 ± 1.84 vs. 43.63 ± 2.06, p = 0.385). In comparison between control group and asthma subgroups (mild, moderate and severe), there was a statistically significant difference among these four groups in terms of PWD (p = 0.017). Subgroup analyses showed that this difference was mainly due to patients with severe asthma. CONCLUSIONS: PWD value was elevated in asthmatic compared to the control group. The CQTD was not statistically significant between the groups. These results indicate that the risk of developing AF in asthmatic patients might be higher than in the normal population. Ventricular arrhythmia and sudden cardiac death risk may not be high in asthmatic patients.

Primary abdominal wall actinomycosis.

PURPOSE: Actinomycosis is a progressive, chronic, granulomatous and suppurative disease caused by different types of actinomyces. Instead of chronic suppurative disease, sinus formation can also be seen. Cervicofascial, abdominal and thoracal involvement can occur. Abdominal wall actinomycosis is an infrequent clinical form. Isolated anterior wall actinomycosis is a very rare form of the disease. METHODS: This is an interventional case report. RESULTS: A 62-year-old female patient with abdominal mass was referred to hospital. She had diabetes mellitus. On the examination she had abdominal tenderness. The computerized tomography revealed an irregular density sized 6.5 × 5 × 3.5 cm in the umbilical area. Surgical debridement and incisional biopsy performed. The diagnosis is confirmed by histopathological examination. The patient received parenteral crystalline penicillin treatment and recovered. CONCLUSION: Physicians should consider abdominal wall actinomycosis in the cases of abdominal masses especially in immunosuppressive patients.

Anti-cyclic citrullinated peptide antibodies in patients with sarcoidosis.

INTRODUCTION: Anti-cyclic citrullinated peptide (anti-CCP) antibodies have a high predictive value in rheumatoid arthritis (RA) patients and are associated with disease severity. Sarcoidosis is a chronic inflammatory disease characterized by non-calcified granuloma formations. AIM: To determining the prevalence of anti-CCP antibodies in patients with sarcoidosis, and identifying a possible correlation with clinical and laboratory findings. MATERIALS AND METHODS: Forty-two patients presenting to the rheumatology polyclinic and diagnosed with sarcoidosis as a result of the examinations made, 45 RA patients and 45 healthy subjects were included in the study. Demographic, clinical, serological and radiological data of all patients were recorded. Anti-CCP antibodies were evaluated by using a second-generation ELISA method. Rheumatoid factor (RF) IgM was determined with the nephelometry method. RESULTS: Forty-two patients (10 males) were included in the study. Mean patient age was 45.2 years (20-70 years) and mean duration of disease was 3.5 years. Two sarcoidosis patients (4.7%) and 38(84.4%) RA patients were found to be positive for anti-CCP antibodies while the antibody wasn't detected in any healthy subject. The two sarcoidosis patients found positive for anti-CCP were also diagnosed with rheumatoid arthritis. RF positivity was detected in 7 sarcoidosis patients (16.6%) and in only one subject in the control group. CONCLUSION: The prevalence of anti-CCP antibodies in patients with sarcoidosis was found to be significantly lower than RA patients and similar with the healthy control group. This result shows that anti-CCP antibodies don't have an important role in the pathogenesis of sarcoidosis, but could be important in revealing the overlap syndromes of sarcoidosis-RA.

Role of chemoradiotherapy in the adjuvant and neoadjuvant settings for resectable pancreatic cancer.

Pancreatic cancer is the 10th most commonly diagnosed malignancy in the USA and the fourth most common cause of cancer-related death. Worldwide, the mortality incidence ratio approaches 98%. Although only 15-20% of patients present with resectable disease, there is international consensus that complete surgical resection (R0, i.e. grossly and microscopically negative margins) is a vital part of any curative treatment paradigm. Despite advances in surgical technique, peri-operative care, chemotherapy and radiation delivery techniques over the past two decades, 5 year overall survival rates for resected pancreatic cancer with modern therapies remain around 20-25%. There is level I evidence for adjuvant chemotherapy in fully resected pancreatic cancer, but randomised trials examining the role of adjuvant chemoradiotherapy to date do not provide clear support for radiation therapy in this setting. In addition, efforts to increase the proportion of long-term survivors have recently centred on increasing the resectability of locoregional disease by incorporating neoadjuvant treatment before definitive surgery. Post-hoc analysis of randomised data as well as retrospective reviews have shown that there are several independent prognostic factors that may have considerable impact on survival outcomes, complicating interpretation and comparison of historical data. There is considerable interest in adjuvant and neoadjuvant therapy, but there is significant controversy as to whether radiation is of value, especially in the adjuvant context. Herein, we explore the sources of those controversies.

Increased epicardial fat tissue is a marker of subclinical atherosclerosis in patients with psoriasis.

BACKGROUND: Carotid intima-media thickness (CIMT) is a potential indicator of subclinical atherosclerosis in patients with psoriasis. Epicardial fat thickness (EFT) is proposed as a new cardiometabolic risk factor. OBJECTIVE: To evaluate the association between EFT and CIMT in patients with psoriasis. METHODS: This was a cross-sectional and observational study; 65 patients with psoriasis and 50 age- and sex- matched control subjects were included. Data about echocardiographic EFT, CIMT, anthropometric measurements and metabolic profile were obtained. RESULTS: The EFT and CIMT were significantly increased (7.3 ± 0.5 vs. 6.5 ± 0.5 mm, P < 0.01; 0.74 ± 0.11 vs. 0.60 ± 0.07 mm, P < 0.01, respectively) in patients with psoriasis compared with the controls. EFT was significantly correlated with CIMT (r = 0.69, P < 0.01). In a multiple linear regression model in which EFT was independently associated with psoriasis (ß = 0.45, P < 0.01), age (ß = 0.33, P = 0.01), CIMT (ß = 0.50, P < 0.01), body mass index (ß = 0.25, P = 0.01), high-sensitivity C-reactive protein (ß = 0.32, P < 0.01) and duration of disease (ß = 0.34, P = 0.03). CONCLUSIONS: We demonstrated that EFT and CIMT are increased in patients with psoriasis, and that echocardiographic EFT is closely correlated with CIMT in patients with psoriasis. The echocardiographic assessment of EFT may have the potential to be a simple marker of subclinical atherosclerosis and increased cardiovascular risk in patients with psoriasis.

GADD34 induces cell death through inactivation of Akt following traumatic brain injury.

Neuronal cell death contributes significantly to the pathology of traumatic brain injury (TBI) irrespective of the mode or severity of the injury. Activation of a pro-survival protein, Akt, is known to be regulated by an E3 ligase TRAF6 through a process of ubiquitination-coupled phosphorylation at its T308 residue. Here we show that upregulation of a pro-apototic protein, GADD34, attenuates TRAF6-mediated Akt activation in a controlled cortical impact model of TBI in mice. TBI induces the expression of GADD34 by stimulating binding of a stress inducible transcription factor, ATF4, to the GADD34 promoter. GADD34 then binds with TRAF6 and prevents its interaction with Akt. This event leads to retention of Akt in the cytosol and prevents phosphorylation at the T308 position. Finally, in vivo depletion of GADD34 using a lentiviral knockdown approach leads to a rescue of Akt activation and markedly attenuates TBI-induced cell death.

Effectiveness of a multidimensional approach for prevention of ventilator-associated pneumonia in 21 adult intensive-care units from 10 cities in India: findings of the International Nosocomial Infection Control Consortium (INICC).

We report on the effect of the International Nosocomial Infection Control Consortium's (INICC) multidimensional approach for the reduction of ventilator-associated pneumonia (VAP) in adult patients hospitalized in 21 intensive-care units (ICUs), from 14 hospitals in 10 Indian cities. A quasi-experimental study was conducted, which was divided into baseline and intervention periods. During baseline, prospective surveillance of VAP was performed applying the Centers for Disease Control and Prevention/National Healthcare Safety Network definitions and INICC methods. During intervention, our approach in each ICU included a bundle of interventions, education, outcome and process surveillance, and feedback of VAP rates and performance. Crude stratified rates were calculated, and by using random-effects Poisson regression to allow for clustering by ICU, the incidence rate ratio for each time period compared with the 3-month baseline was determined. The VAP rate was 17.43/1000 mechanical ventilator days during baseline, and 10.81 for intervention, showing a 38% VAP rate reduction (relative risk 0.62, 95% confidence interval 0.5-0.78, P = 0.0001).

Single-stage repair of adult aortic coarctation and concomitant coronary artery disease: an unusual surgical approach through median sternotomy.

Surgical repair of postductal aortic coarctation associated with severe coronary artery disease is in most cases a difficult decision to make. As staged procedures are associated with a higher rate of morbidity and mortality, simultaneous operative management of both pathologies is desirable. We describe a case of a 51-year-old man who was referred to our department for surgical treatment of postductal aortic coarctation and concomitant coronary artery disease, which we managed with single-stage surgery through median sternotomy.

Nebivolol therapy improves QTc and QTcd parameters in heart failure patients.

AIM: It has previously been shown that ß-blocker therapy reduces QT dynamics in heart failure patients. The aim of this study was to demonstrate this improvement with the third-generation ß-blocker, nebivolol. METHODS: A total of 72 heart failure patients with systolic dysfunction were included in the study. Corrected QT (QTc) and QT dispersion (QTcd) were measured manually by two independent observers at baseline and after nebivolol use (5 mg/day) in the first and third months of follow up. RESULTS: Both QTc and QTcd were found to be significantly reduced in the first (455.3 ± 26.7 vs 441.2 ± 25.7 ms, p < 0.001 for QTc, and 65.6 ± 5.3 vs 58.2 ± 5.6 ms, p = 0.001 for QTcd) and third months (455.3 ± 26.7 vs 436.0 ± 28.7 ms, p < 0.001 for QTc, and 65.6 ± 5.3 vs 56.0 ± 6.2 ms, p < 0.001 for QTcd) compared with baseline values. CONCLUSION: Nebivolol was associated with improved QT dynamics in heart failure patients with systolic dysfunction.

The prevalence of the metabolic syndrome and its impact on the left ventricular systolic function in the patients with non-diabetic first ST elevation myocardial infarction.

OBJECTIVE: Metabolic syndrome (MS) is common among the patients with myocardial infarction. The degree of the left ventricular systolic dysfunction is shown to be associated with poor prognosis after myocardial infarction. The aim of this study was to evaluate the prevalence of MS and its impact on the left ventricular systolic function in non-diabetic patients suffering first ST elevation myocardial infarction (STEMI). MATERIAL AND METHODS: This study was conducted prospectively in three centers. We included patients presenting with non-diabetic first acute STEMI. The systolic functions of the left ventricle were assessed through the ejection fraction, the wall motion score index (WMSI) and tissue Doppler myocardial S wave velocities. The diagnosis of MS was done based on the Adult Treatment Panel III clinical definition of the MS. RESULTS: Among the 240 patients, 90 patients (37.5%) had MS but 150 patients (62.5%) were free of the MS. The patients in the MS group were older and the prevalence was higher among the females. Mean myocardial S wave velocities were significantly lower in the patients with the MS in comparison to the patients without the MS (6.70 +/- 1.68 vs. 7.39 +/- 1.64; p < 0.01). LVEF and WMSI were similar in two groups. CONCLUSIONS: MS was highly common in nondiabetic patients with acute STEMI and left ventricular systolic function were more severely impaired in these patients. Our observations suggest that more severely impaired left ventricular systolic function after acute STEMI may contribute to the higher morbidity and mortality seen in the patients with MS after acute STEMI.

Multiple thromboses at multiple sites. A known hereditary disease emerging late but suddenly and extensively.

Hyperhomocysteinemia is a significant independent, usually heritable, prothrombotic risk factor for atherothrombotic cardiovascular, cerebrovascular, and peripheral vascular disease. We report a 42-year-old woman who had multiple embolic events.

Assessment of the relationship between coronary artery ectasia and erectile function score.

The relation between coronary artery ectasia (CAE) and erectile dysfunction (ED) has not been studied so far. Hence, we decided to investigate the erectile function score in patients with CAE. We investigated the international index of erectile function (IIEF)-5 score in 34 men with CAE, 38 men with coronary artery disease (CAD), and 30 male controls with normal coronary arteries whose mean ages were 53.2 ± 5.6, 51.4 ± 7.8, and 49.6 ± 8.6 years, respectively. Erectile function was evaluated by the five-item version of the IIEF-5. Each question is scored from 0 to 5. CAE was defined as being without any stenotic lesions with a visual assessment of the coronary arteries showing a luminal dilatation 1.5-fold or more of the adjacent normal coronary segments. IIEF-5 scores in CAE group were found statistically significantly lower than the control group (P<0.001). There were no statistically significant differences in IIEF-5 scores between CAE and CAD groups (P=0.13). We have shown for the first time that patients with CAE have lower IIEF-5 scores compared with controls with normal coronary angiograms. Many studies reported that endothelial dysfunction in patients with CAE was more dominant than those with CAD. This study suggests that ED and CAE may be different manifestations of a common underlying vascular pathology and vasculogenic ED is frequently seen in CAE at least as much as in CAD.

Positive supercoiling of mitotic DNA drives decatenation by topoisomerase II in eukaryotes.

DNA topoisomerase II completely removes DNA intertwining, or catenation, between sister chromatids before they are segregated during cell division. How this occurs throughout the genome is poorly understood. We demonstrate that in yeast, centromeric plasmids undergo a dramatic change in their topology as the cells pass through mitosis. This change is characterized by positive supercoiling of the DNA and requires mitotic spindles and the condensin factor Smc2. When mitotic positive supercoiling occurs on decatenated DNA, it is rapidly relaxed by topoisomerase II. However, when positive supercoiling takes place in catenated plasmid, topoisomerase II activity is directed toward decatenation of the molecules before relaxation. Thus, a topological change on DNA drives topoisomerase II to decatenate molecules during mitosis, potentially driving the full decatenation of the genome.

Effects of 8-residue ß sheet breaker peptides on aged Aß40-induced memory impairment and Aß40 expression in rat brain and serum following intraamygdaloid injection.

Amyloidß-protein (Aß) assembly into toxic fibrillar structures is seminal in development of senile plaques, the pathological hallmark of Alzheimer's disease. Blocking this process could have a therapeutic value. ß-sheet breaker peptides (ßSBP) decrease Aß fibrillogenesis and neurotoxicity by preventing or dissolving misfolded Aß aggregates. The present study investigated the effects of ßSBPs on Aß40-related neuropathology, memory impairment in 8-armed radial maze and expression of Aß40 in brain and serum. Aß40 was injected into amygdaloid nucleus followed 8 days later by octapeptideßSBPs 15-22, 16-23 and 17-24. Aß40 was detected not only in amygdala, but also in serum. Aß40 induced cellular changes in amygdala and additionally in hippocampus. Aß40 decreased correct choices, whereas increased errors (both number of arms revisited and total number of revisits) and latency of completing the maze test. The ßSBPs decreased Aß40-induced pathological changes, memory impairment and Aß40 expression in serum. The ßSBP15-22 distinctively decreased the total errors on day 14. The present results show that octapeptide ßSBPs corrected Aß40-induced memory impairment, and support investigation of ßSBPs as a promising treatment of diseases characterized by neurodegeneration and memory impairment such as Alzheimer's disease.

ERP correlates of item recognition memory: effects of age and performance.

Decline in episodic memory is a common feature of healthy aging. Event-related potential (ERP) studies in young adults have consistently reported several modulations thought to index memory retrieval processes, but relatively limited work has explored the impact of aging on them. Further, work with functional imaging has demonstrated differential neural recruitment in elderly subjects depending on their level of cognitive performance which may reflect compensatory or, alternatively, inefficient processing. In the present study we examined the effect of aging and level of performance on both early (FN400, LPC) and later [late frontal effect (LFE)] ERP indices of recognition memory. We found that the FN400 and LPC were absent or attenuated in the older group relative to young adults, but that the LFE was actually increased, analogous to findings in the functional imaging literature. Additionally, the latter effect was most prominent in the poorer performing older participants. These findings suggest that weak memory retrieval supported by earlier ERP modulations, may lead to an enhanced LFE in the service of additional retrieval attempts.