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71.
72.

Background

Many studies on resilience have shown that people can succeed in preserving mental health after a traumatic event. Less is known about whether and how people can preserve subjective wellbeing in the presence of psychopathology. We examined to what extent psychopathology can co-exist with acceptable levels of subjective wellbeing and which personal strengths and resources moderate the association between psychopathology and wellbeing.

Methods

Questionnaire data on wellbeing (Manchester Short Assessment of Quality of Life/Happiness Index), psychological symptoms (Depression Anxiety Stress Scales), and personal strengths and resources (humor, Humor Style questionnaire; empathy, Empathy Quotient questionnaire; social company; religion; daytime activities, Living situation questionnaire) were collected in a population-based internet study (HowNutsAreTheDutch; N = 12,503). Data of the subset of participants who completed the above questionnaires (n = 2411) were used for the present study. Regression analyses were performed to predict wellbeing from symptoms, resources, and their interactions.

Results

Satisfactory levels of wellbeing (happiness score 6 or higher) were found in a substantial proportion of the participants with psychological symptoms (58% and 30% of those with moderate and severe symptom levels, respectively). The association between symptoms and wellbeing was large and negative (-0.67, P < .001), but less so in persons with high levels of self-defeating humor and in those with a partner and/or pet. Several of the personal strengths and resources had a positive main effect on wellbeing, especially self-enhancing humor, having a partner, and daytime activities.

Conclusions

Cultivating personal strengths and resources, like humor, social/animal company, and daily occupations, may help people preserve acceptable levels of wellbeing despite the presence of symptoms of depression, anxiety, and stress.  相似文献   
73.
74.

Background

The presence of poor quality medicines in the market is a global threat on public health, especially in developing countries. Therefore, we assessed the quality of two commonly used anthelminthic drugs [mebendazole (MEB) and albendazole (ALB)] and one antiprotozoal drug [tinidazole (TNZ)] in Ethiopia.

Methods/Principal Findings

A multilevel stratified random sampling, with as strata the different levels of supply chain system in Ethiopia, geographic areas and government/privately owned medicines outlets, was used to collect the drug samples using mystery shoppers. The three drugs (106 samples) were collected from 38 drug outlets (government/privately owned) in 7 major cities in Ethiopia between January and March 2012. All samples underwent visual and physical inspection for labeling and packaging before physico-chemical quality testing and evaluated based on individual monographs in Pharmacopoeias for identification, assay/content, dosage uniformity, dissolution, disintegration and friability. In addition, quality risk was analyzed using failure mode effect analysis (FMEA) and a risk priority number (RPN) was assigned to each quality attribute. A clinically rationalized desirability function was applied in quantification of the overall quality of each medicine. Overall, 45.3% (48/106) of the tested samples were substandard, i.e. not meeting the pharmacopoeial quality specifications claimed by their manufacturers. Assay was the quality attribute most often out-of-specification, with 29.2% (31/106) failure of the total samples. The highest failure was observed for MEB (19/42, 45.2%), followed by TNZ (10/39, 25.6%) and ALB (2/25, 8.0%). The risk analysis showed that assay (RPN = 512) is the most critical quality attribute, followed by dissolution (RPN = 336). Based on Derringer''s desirability function, samples were classified into excellent (14/106,13%), good (24/106, 23%), acceptable (38/106, 36%%), low (29/106, 27%) and bad (1/106,1%) quality.

Conclusions/Significance

This study evidenced that there is a relatively high prevalence of poor quality MEB, ALB and TNZ in Ethiopia: up to 45% if pharmacopoeial acceptance criteria are used in the traditional, dichotomous approach, and 28% if the new risk-based desirability approach was applied. The study identified assay as the most critical quality attributes. The country of origin was the most significant factor determining poor quality status of the investigated medicines in Ethiopia.  相似文献   
75.
Finding new, effective antibiotics is a challenging research area driven by novel approaches required to tackle unconventional targets. In this review we focus on the bacterial protein secretion pathway as a target for eliminating or disarming pathogens. We discuss the latest developments in targeting the Sec-pathway for novel antibiotics focusing on two key components: SecA, the ATP-driven motor protein responsible for driving preproteins across the cytoplasmic membrane and the Type I signal peptidase that is responsible for the removal of the signal peptide allowing the release of the mature protein from the membrane. We take a bird's-eye view of other potential targets in the Sec-pathway as well as other Sec-dependent or Sec-independent protein secretion pathways as targets for the development of novel antibiotics. This article is part of a Special Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey.  相似文献   
76.
Bioactive peptides have great pharmaceutical potential as nutraceuticals, diagnostics, and therapeutic drugs in several clinical areas. Thus, the search for novel lead peptides with a biological function has attracted renewed interest. Crude peptide material (i.e., ~70% purity) of INSL6[151–161] (NH2-FRSLFWGNHSQ-COOH) was found to trigger a contractile response in guinea pig ileum longitudinal smooth muscle preparations using tissue–organ baths. However, the purified peptide (i.e., ?95% purity) had no effect on this model. Further investigation with crude materials from other suppliers, with purities ranging between 50% and 80%, indicated that the crude products gave a false-positive functional tissue–organ bath conclusion. These observations question the functionality conclusions when using crude-purity peptide materials; during the initial research or discovery phase, peptide quality is generally neglected, possibly leading to misinterpretation of biological results due to by-products from peptide synthesis and, thus, wrong fail/pass decisions. Therefore, we strongly recommend appropriate quality control testing before using any peptides for initial biomedical research or discovery purposes.  相似文献   
77.
We manufactured a novel type of lipid‐coated superparamagnetic nanoparticles that allow for a rapid isolation of plasma membranes (PMs), enabling high‐resolution proteomic, glycomic and lipidomic analyses of the cell surface. We used this technology to characterize the effects of presenilin knockout on the PM composition of mouse embryonic fibroblasts. We found that many proteins are selectively downregulated at the cell surface of presenilin knockout cells concomitant with lowered surface levels of cholesterol and certain sphingomyelin species, indicating defects in specific endosomal transport routes to and/or from the cell surface. Snapshots of N‐glycoproteomics and cell surface glycan profiling further underscored the power and versatility of this novel methodology. Since PM proteins provide many pathologically relevant biomarkers representing two‐thirds of the currently used drug targets, this novel technology has great potential for biomedical and pharmaceutical applications.  相似文献   
78.
Several risk factors for colorectal cancer (CRC) have been identified. If individuals with risk factors are more likely to harbor cancer or it precursors screening programs should be targeted toward this population. We evaluated the predictive value of colorectal cancer risk factors for the detection of advanced colorectal adenoma in a population based CRC colonoscopy screening program. Data were collected in a multicenter trial conducted in the Netherlands, in which 6600 asymptomatic men and women between 50 and 75 years were randomly selected from a population registry. They were invited to undergo a screening colonoscopy. Based on a review of the literature CRC risk factors were selected. Information on risk factors was obtained from screening attendees through a questionnaire. For each CRC risk factor, we estimated its odds ratio (OR) relative to the presence of advanced neoplasia as detected at colonoscopy. Of the 1426 screening participants who underwent a colonoscopy, 1236 (86%) completed the risk questionnaire. 110 participants (8.9%) had advanced neoplasia. The following risk factors were significantly associated with advanced neoplasia detected by colonoscopy: age (OR: 1.06 per year; 95% CI: 1.03–1.10), calcium intake (OR: 0.99 per mg; 95% CI: 0.99–1.00), positive CRC family history (OR: 1.55 per first degree family member; 95%CI: 1.11–2.16) and smoking (OR: 1.75; 95%CI: 1.09–2.82). Elderly screening participants, participants with lower calcium intake, a CRC family history, and smokers are at increased risk of harboring detectable advanced colorectal neoplasia at screening colonoscopy.  相似文献   
79.
Abstract

The cytotoxicity of Gemcitabine (dFdC) was 10 (ovarian cancer) to > 10,000 (colon cancer) fold higher in monolayer compared to three-dimensional multilayer cell cultures. This selectivity was related to marked differences in dFdC activation and effects on ribonucleotides.  相似文献   
80.
Much of the debate about reciprocity in humans and other primates hinges on proximate mechanisms, or more precisely, the contingency of one service on another. While there is good evidence for long-term statistical contingencies of services given and received in primates, results for short-term behavioral contingencies are mixed. Indeed, as we show here controlled experiments using artificial tasks and explicit turn-taking were unlikely to find short-term effects. We therefore used more naturalistic experiments to test for short-term contingencies of grooming on food sharing and vice versa in one group of chimpanzees and two groups of bonobos. Overall, we found significant effects of grooming on food sharing and vice versa, however, in the chimpanzees these effects disappeared when controlling for long-term characteristics of the dyad including services exchanged over the whole study period. In the bonobos, short-term contingencies remained significant which was likely a consequence of considerable tension surrounding monopolizable food resulting in higher rates of grooming and other affiliative behaviors around sharing sessions. These results are consistent with the fact that previous evidence for short-term contingency often involved grooming and that long-term contingency is more commonly observed in primates. We propose that long-term contingency is proximately regulated by a ‘relationship score’ computed through a tally of past interactions which tend to outweigh recent single events. We therefore suggest that future research into the proximate mechanisms of reciprocity should trace the development of such a score by focusing on newly formed dyads with no history of interactions.  相似文献   
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