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Antibodies are a key element of the immune response. They can bind their molecular targets with exquisite sensitivity and specificity, providing protection against a multitude of pathogens. They have long been understood to be markers of a successful response to vaccination, and are now widely manufactured as highly specific and robust immunotherapeutic agents. Less well understood are the polyreactive antibodies, found in serum, which are able to bind more than one target molecule. selleck compound Here, we highlight new research into these naturally occurring polyreactive antibodies, which demonstrates their importance for protection against Streptococcus pneumoniae, a common cause of airway infection.Acute iron toxicity in adults is rare, usually occurring due to intentional ingestion in suicide attempts. Few cases of the clinical and autopsy findings in acute iron toxicity have previously been reported in the literature. Ingestion of large amounts of iron salts can lead to hemorrhagic shock, multi-system organ failure, coagulopathy, and death. We present the case of a 25-year-old man who reportedly ingested a large quantity of iron tablets along with ethanol in a suicide attempt and subsequently died approximately 65.5 h later. His clinical course and laboratory findings demonstrated hepatic and renal compromise with markedly elevated serum iron levels. At autopsy, iron encrustations were present over the gastric rugae. Superficial deposits of stainable iron were present overlying areas of mucosal necrosis with underlying submucosal fibrin thrombi. No significant stainable iron was present in the liver. Literature review revealed that the clinical course and laboratory testing of severe acute iron overdose is fairly non-specific. The length and type of treatment may alter the clinical course and laboratory results. Peak serum iron levels may be helpful in differentiating acute toxicity from chronic iron overload states. Gross findings of gastric iron encrustation are specific for acute ingestion when present.

Mechanical ventilation is a potentially painful and discomforting intervention that is widely used in neonatal intensive care. Newborn infants demonstrate increased sensitivity to pain, which may affect clinical and neurodevelopmental outcomes. The use of drugs that reduce pain might be important in improving survival and neurodevelopmental outcomes.

To determine the benefits and harms of opioid analgesics for neonates (term or preterm) receiving mechanical ventilation compared to placebo or no drug, other opioids, or other analgesics or sedatives.

We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 9), in the Cochrane Library; MEDLINE via PubMed (1966 to 29 September 2020); Embase (1980 to 29September 2020); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 29 September 2020). We searched clinical trials databases, conference proceedings, and the reference lists of retrieved articlet allow any conclusions. In the absence of firm evidence to support a routine policy, opioids should be used selectively - based on clinical judgement and evaluation of pain indicators - although pain measurement in newborns has limitations.

There is a paucity of research available regarding the epidemiology of patients attending dermatology outpatient services in Australia. Our objective was to analyse who was attending public dermatology outpatient clinics in a Northern Territory tertiary hospital, with a particular focus on Indigenous and rural patients.

This is a retrospective cohort study of patients who attended dermatology outpatient clinics between 1 January 2016 and 31 December 2016. Outcome measures included patient demographics (age, gender, ethnicity and postcode) and referrer details.

Over the 12month study period, 923 appointments were scheduled for 500 patients. Of the appointments scheduled, 667 were attended. Twelve per cent of patients were Indigenous, and of the total appointment attendances, 10% were by Indigenous patients. Of the 923 appointments, 28% were not attended, with a higher non-attendance rate for Indigenous patients at 36%. The majority of patients seen were adults, for both groups, but a larger proportion of Indigenous children were seen. Nine per cent of patients with a recorded address were from a remote region.

Dermatology outpatient services are likely under-utilised by Indigenous, and remote patients. If we are to improve skin health in Australia, barriers such as limited access to dermatological services in remote regions must be addressed.

Dermatology outpatient services are likely under-utilised by Indigenous, and remote patients. If we are to improve skin health in Australia, barriers such as limited access to dermatological services in remote regions must be addressed.

There is limited evidence supporting the use of alternative treatments for patients with nonstable vitiligo.

This study aimed to review the effects of oral mini-pulse (OMP) therapy in the management of nonsegmental vitiligo.

The following databases were searched between inception and May 2020 for relevant studies Scopus, Web of Science, MEDLINE, and Embase. All randomized controlled trials that compared OMP therapy with any other active treatment or placebo for nonstable vitiligo were included. The Cochrane's risk of bias tool was used to evaluate the risk of bias (ROB) in selected studies, and the overall quality of evidence of each outcome was assessed using the Grading Recommendations, Assessment, Development, and Evaluations (GRADE) system.

Four studies met our selection criteria. All of them were conducted in India and included 246 patients. OMP therapy included betamethasone or dexamethasone. The duration of treatment was 6months in all studies. Up to 32% of patients achieved a repigmentation rate of >75% when OMP therapy was administered as monotherapy. No difference was observed between OMP therapy and other treatments in arresting the disease, and weight gain was the most frequent adverse effect. The overall ROB in all included studies was relatively high because of the randomization process, outcome measurement and informed selection of outcomes.

Based on the findings of these studies, OMP therapy did not demonstrate additional value compared with other treatments. Hence, there is an urgent need to conduct high-quality clinical trials to evaluate this therapy.

Based on the findings of these studies, OMP therapy did not demonstrate additional value compared with other treatments. Hence, there is an urgent need to conduct high-quality clinical trials to evaluate this therapy.

Alternative metrics are emerging scores to assess the impact of research beyond the academic environment.

To analyse whether a correlation exists between manuscript characteristics and alternative citation metrics.

This bibliometric analysis included original articles published in the five journals with the highest impact factors during 2019. We extracted the following characteristics from each record journal, publication month, title, number of authors, type of institution, type of publication, research topic, number of references, financial support, free/open access status and literature citations. The main measure was the identification of variables of higher social attention (measured by the Altmetric Attention Score ≥25) using binary logistic regression. Model performance was assessed by the change in the area under the curve (AUC).

A total of 840 manuscripts were included. The Altmetric scores across all five journals ranged from 0 to 465 (mean 12.51±33.7; median 3). The most prevalent topic was skin cancer, and the study design was clinical science. The scientific journal (P<0.001), the presence of conflicts of interest (OR 2.2 [95%CI 1.3-3.7]; P=0.002) and open access status OR 3.2 [95%CI 1.6-6.7]; P=0.002) were found as independent predictors of high Altmetric scores.

Our study suggests an article´s social recognition may be dependent on some manuscript characteristics, thus providing useful information on the dissemination of dermatology research to the general public.

Our study suggests an article´s social recognition may be dependent on some manuscript characteristics, thus providing useful information on the dissemination of dermatology research to the general public.High-grade cervical intraepithelial neoplasia (CIN2 and CIN3) represents a heterogeneous disease with varying cancer progression risks. Biomarkers indicative for a productive human papillomavirus (HPV) infection (HPV E4) and a transforming HPV infection (p16ink4a , Ki-67 and host-cell DNA methylation) could provide guidance for clinical management in women with high-grade CIN. This study evaluates the cumulative score of immunohistochemical expression of p16ink4a (Scores 0-3) and Ki-67 (Scores 0-3), referred to as the "immunoscore" (IS), in 262 CIN2 and 235 CIN3 lesions derived from five European cohorts in relation to immunohistochemical HPV E4 expression and FAM19A4/miR124-2 methylation in the corresponding cervical scrape. The immunoscore classification resulted in 30 lesions within IS group 0-2 (6.0%), 151 lesions within IS group 3-4 (30.4%) and 316 lesions within IS group 5-6 (63.6%). E4 expression decreased significantly from CIN2 to CIN3 (P less then  .001) and with increasing immunoscore group (Ptrend less then  .001). Methylation positivity increased significantly from CIN2 to CIN3 (P less then  .001) and with increasing immunoscore group (Ptrend less then  .001). E4 expression was present in 9.8% of CIN3 (23/235) and in 12.0% of IS group 5-6 (38/316). Notably, in a minority (43/497, 8.7%) of high-grade lesions, characteristics of both transforming HPV infection (DNA hypermethylation) and productive HPV infection (E4 expression) were found simultaneously. Next, we stratified all high-grade CIN lesions, based on the presumed cancer progression risk of the biomarkers used, into biomarker profiles. These biomarker profiles, including immunoscore and methylation status, could help the clinician in the decision for immediate treatment or a "wait and see" policy to reduce overtreatment of high-grade CIN lesions.Type I IFNs are so-named because they interfere with viral infection in vertebrate cells. The study of cellular responses to type I IFNs led to the discovery of the JAK-STAT signaling pathway, which also governs the response to other cytokine families. We review here the outcome of viral infections in mice and humans with engineered and inborn deficiencies, respectively, of (i) IFNAR1 or IFNAR2, selectively disrupting responses to type I IFNs, (ii) STAT1, STAT2, and IRF9, also impairing cellular responses to type II (for STAT1) and/or III (for STAT1, STAT2, IRF9) IFNs, and (iii) JAK1 and TYK2, also impairing cellular responses to cytokines other than IFNs. A picture is emerging of greater redundancy of human type I IFNs for protective immunity to viruses in natural conditions than was initially anticipated. Mouse type I IFNs are essential for protection against a broad range of viruses in experimental conditions. These findings suggest that various type I IFN-independent mechanisms of human cell-intrinsic immunity to viruses have yet to be discovered.

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