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prove the differentiation of benign and malignant biliary strictures.Colorectal cancers (CRCs) remain one of the most common and challenging neoplasia in the Western world. The response rate of immunotherapeutic treatment approaches in a subset of advanced CRCs is remarkable and has sustainably changed treatment regimens. Unfortunately, currently available immunotherapeutics only displayed significant antitumoral activity – in terms of progression free survival (PFS) and objective response rate (ORR) – in microsatellite instability-high (MSI-H)/DNA mismatch repair deficient (dMMR) CRCs. Subsequently, these remarkable results had led to the US Food and Drug Administration’s approval of both immune checkpoint inhibitors (ICIs) pembrolizumab and nivolumab in the treatment of advanced MSI-H/dMMR CRCs. However, in microsatellite stable (MSS)/DNA mismatch repair proficient (pMMR) CRCs, ICIs have clearly failed to meet their expectations and are therefore not considered effective. As the vast majority of CRCs display a molecular MSS/pMMR profile, current treatment approaches endeavor to improve tumor immunogenicity that consecutively leads to increased proinflammatory cytokine levels as well as tumor infiltrating T-cells, which in turn may be targeted by various immunotherapeutic agents. Therefore, ongoing studies are investigating novel synergistic therapy modalities and approaches to overcome a “cold” to “hot” tumor conversion in MSS/pMMR CRCs. In this review, we summarize the efficacy and possible immune-related adverse events as well as novel therapeutic approaches of ICIs in the treatment of MSI-H/dMMR and MSS/pMMR CRCs.

Proton-pump inhibitors (PPI) are among the most prescribed drugs worldwide, and a large body of evidence raises concerns about their inappropriate use. Previous estimates of inappropriate use varied due to different definitions and study populations.

We aimed to measure the population-based incidence and time trends of PPI and potentially inappropriate PPI prescriptions (PIPPI) with a novel method, continuously assessing excessive cumulative doses based on clinical practice guidelines. We also assessed association of patient characteristics with PPI prescriptions and PIPPI.

This was an observational study based on a large insurance claims database of persons aged >18 years with continuous claims records of ⩾12 months. The observation period was January 2012 to December 2017. We assessed the incidence and time trends of PPI prescriptions and PIPPI based on doses prescribed, defining ⩾11.5 g of pantoprazole dose equivalents during any consecutive 365 days (average daily dose >31 mg) as inappropriateguideline recommendations could reduce polypharmacy and improve patient safety.In the Covid-19 pandemic, being older means being in a special focus Probabilities for severe infections and mortality rise with increasing age and protective measures for this population group have been increased. This was accompanied by public discourse that portrayed older adults stereotypically as vulnerable and frail but also highlighted the hardships younger people have to endure to protect them. Given the possibly detrimental effects of ageism on individuals and societies, we were interested in older adults’ perception of ageism in the Corona-crisis and its relation to their health and well-being. Furthermore, we were interested in subjective aging variables as moderators in the ageism-health relationship. In June 2020, N = 611 independently living people aged 60 + from the Grand Duchy of Luxembourg were recruited via a survey research institute and interviewed online or by phone. They reported on perceived ageism in different contexts, their life satisfaction, subjective health, subjective age and self-perceptions of aging. Depending on context, ageism was perceived by around 20% of participants, and overall negatively related to subjective health and life satisfaction after the onset of the pandemic. Moderated hierarchical regressions showed that a younger subjective age buffered the negative effect of ageism on subjective health, while perceiving aging as social loss increased its effect on life satisfaction. We discuss the importance of addressing and reducing ageism (not only) in times of crisis and the consequences for individuals and societies.The native people of the Himalayan region use an indigenously designed watermill locally called as ‘Gharat’. The ‘Gharat’ is made from the natural resources that are easily available in the area and operates through the water force coming from glaciers, perennial streams and rivulets. Thus, it is an environment friendly source of livelihood for the ‘Gharatis’ (the owner of Gharat). In the present communication, an effort was made to document the status of Gharats in the high-altitude Himalayan regions of Pangi and Tissa of district Chamba. Field surveys were conducted in a total of twenty remote villages of Pangi and Tissa regions (ten in each site). Information was collected on pre-designed semi-structured questionnaires from local people that primarily consisted of Gharatis, elderly informants and the inhabitants living in the vicinity of Gharats. All possible reasons responsible for the increase and reduction in the number of Gharats in the study areas were also documented by interviewing the informants. The study revealed that in the Pangi region number of Gharats have increased and are in good condition whereas there is a drastic decline in the number of Gharats in Tissa. The informants in Pangi gave maximum responses favouring motivational factors while in Tissa maximum responses were obtained for demotivational factors. click here Based on these responses, we prioritized the corrective measures for improving the efficiency of Gharats and restoration of this age-old indigenous and environment friendly technology. This will surely enhance livelihood security of the inhabitants besides optimum utilization of the natural resources in the Himalayan region.

The online version contains supplementary material available at 10.1007/s10668-021-01455-4.

The online version contains supplementary material available at 10.1007/s10668-021-01455-4.