Clotrimazole is a broad‐spectrum antimycotic drug mainly used for the treatment of Candida albicans and other fungal infections. A synthetic, azole antimycotic, clotrimazole is widely used as a ...topical treatment for tinea pedis (athlete's foot), as well as vulvovaginal and oropharyngeal candidiasis. It displays fungistatic antimycotic activity by targeting the biosynthesis of ergosterol, thereby inhibiting fungal growth. As well as its antimycotic activity, clotrimazole has become a drug of interest against several other diseases such as sickle cell disease, malaria and some cancers. It has also been combined with other molecules, such as the metals, to produce clotrimazole complexes that show improved pharmacological efficacy. Moreover, several new, modified‐release pharmaceutical formulations are also undergoing development. Clotrimazole is a very well‐tolerated product with few side effects, although there is some drug resistance appearing among immunocompromised patients. Here, we review the pharmaceutical chemistry, application and pharmacology of clotrimazole and discuss future prospects for its further development as a chemotherapeutic agent.
Diabetic nephropathy affects 30–40% of people with diabetes, and is the leading cause of end‐stage kidney disease. The current treatment paradigm relies on early detection, glycaemic control and ...tight blood pressure management with preferential use of renin‐angiotensin system blockade. This strategy has transformed outcomes in diabetic kidney disease over the last 20 years. Over the last two decades we have also witnessed significant advances in the understanding of the pathophysiology of diabetic nephropathy; however, despite this new knowledge, we have yet to develop new treatments of proven efficacy. Whilst a continued emphasis on preclinical and clinical research is clearly needed, clinicians treating people with diabetes should not forget that, in the short term, the greatest gains are likely to be realised by more consistent deployment of existing therapies.
In vitro and retrospective clinical studies suggest an association between anaesthetic technique during primary breast cancer surgery and cancer outcome. Apoptosis is an important step in the ...mechanism of breast cancer metastasis, but whether it is influenced by anaesthetic technique is unknown. Using serum from breast cancer surgery patients randomized to receive distinct anaesthetic techniques, we investigated its effect on apoptosis in oestrogen receptor (ER)-negative breast cancer cells in vitro.
Women with biopsy-proven breast cancer were randomized to receive either propofol general anaesthesia with paravertebral analgesia (PPA) or standard sevoflurane general anaesthesia with opioid analgesia (SGA) in an ongoing, prospective clinical trial (NCT 00418457). Serum from a randomly selected subset of these patients (10 PPA and 10 SGA) who had donated 20 ml venous blood immediately before anaesthetic induction and at 1 h after operation was exposed to ER-negative MDA-MB-231 cells. Apoptosis was measured using ApoLive-Glo Multiplex Assay™.
Exposure of MDA-MB-231 cells to postoperative serum of PPA patients resulted in higher luminescence ratio (apoptosis) than SGA patients, median (25–75%), 0.40 (0.35–0.43) compared with 0.22 (0.21–0.30), respectively (P=0.001). The luminescence ratio of postoperative serum from SGA was reduced compared with preoperative SGA 0.22 (0.21–0.30) compared with 0.3 (0.25–0.35) (P=0.045).
Serum from patients given sevoflurane anaesthesia and opioids for primary breast cancer surgery reduces apoptosis in ER-negative breast cancer cells to a greater extent than serum from patients given propofol–paravertebral anaesthesia. Anaesthetic technique might affect the serum milieu in a manner that impacts cancer cell apoptosis, and thereby tumour metastasis.
Although disasters are a major cause of mental health problems and typically affect large numbers of people and communities, little is known about how social structures affect mental health after a ...disaster. The authors assessed the extent to which mental health outcomes after disaster are associated with social network structures.
In a community-based cohort study of survivors of a major bushfire disaster, participants (N=558) were assessed for probable posttraumatic stress disorder (PTSD) and probable depression. Social networks were assessed by asking participants to nominate people with whom they felt personally close. These nominations were used to construct a social network map that showed each participant's ties to other participants they nominated and also to other participants who nominated them. This map was then analyzed for prevailing patterns of mental health outcomes.
Depression risk was higher for participants who reported fewer social connections, were connected to other depressed people, or were connected to people who had left their community. PTSD risk was higher if fewer people reported being connected with the participant, if those who felt close to the participant had higher levels of property loss, or if the participant was linked to others who were themselves not interconnected. Interestingly, being connected to other people who in turn were reciprocally close to each other was associated with a lower risk of PTSD.
These findings provide the first evidence of disorder-specific patterns in relation to one's social connections after disaster. Depression appears to co-occur in linked individuals, whereas PTSD risk is increased with social fragmentation. These patterns underscore the need to adopt a sociocentric perspective of postdisaster mental health in order to better understand the potential for societal interventions in the wake of disaster.
Retrospective analyses suggest anaesthetic-analgesics technique during cancer surgery may affect recurrence/metastasis. This could involve direct effects of anaesthetic-analgesic drugs on cancer ...cells. While μ-opioid receptor over-expression in lung tumours is associated with greater metastasis, other anaesthetic-analgesic receptor targets in cancer recurrence/metastasis remain unexplored. Therefore, we evaluated the association between genetic expression of anaesthetic-analgesic receptor targets and recurrence/metastasis, using a repository of breast cancer gene expression and matching clinical data.
A list of 23 genes encoding for the most prominent anaesthetic-analgesic receptor targets was compiled. This was processed through BreastMark- an algorithm integrating gene expression data from ~17,000 samples and clinical data from >4,500 breast cancer samples. Gene expression data was dichotomized using disease-free survival (survival without recurrence) and distant disease-free survival (survival without metastasis) as end points. Hazard ratios were calculated by Cox-regression analysis. Enrichment for prognostic markers was determined by randomly choosing 23-member gene lists from all available genes, calculating how often >5 significant markers were observed and adjusting p-values for multiple testing. This was repeated 10,000 times and an empirical p-value calculated.
Of 23 selected genes, 9 were significantly associated with altered rates of metastasis and 4 with recurrence on univariate analysis. Adjusting for multiple testing, 5 of these 9 genes remained significantly associated with metastasis, non with recurrence. This ratio of genes (5/23) was not significantly enriched for markers of metastasis (p = 0.07).
Several anaesthetic-analgesic receptor genes were associated with metastatic spread in breast cancer. Overall there was no significant enrichment in prognostic markers of metastasis, although a trend was observed.
Social disruption caused by natural disasters often interrupts educational opportunities for children. However, little is known about children's learning in the following years. This study examined ...change in academic scores for children variably exposed to a major bushfire in Australia. Comparisons were made between children attending high, medium, and low disaster-affected primary schools 2-4 years after the disaster (n = 24,642; 9-12 years). The results showed that in reading and numeracy expected gains from Year 3 to Year 5 scores were reduced in schools with higher levels of bushfire impact. The findings highlight the extended period of academic impact and identify important opportunities for intervention in the education system to enable children to achieve their academic potential. Author abstract
Although much research has focused on the influence of second language (L2) proficiency on L2 use and on outcomes of intercultural adaptation, these two strands have remained largely separate. This ...study examines the impact of willingness to communicate in the L2 (L2 WTC) on the daily hassles and stress of international students, with the aim of demonstrating a conceptual overlap of the L2 WTC model with theories of stress and cross-cultural adaptation that focus on a transactional person-environment fit. Participants included 104 Chinese-speaking students attending a British university. Structural equation modeling supported a model in which L2 WTC played a significant role in the experience of daily hassles related to communication difficulties, social isolation, and time and financial constraints. A second, similar model is also advanced in which communication difficulties, in particular, are afforded a unique role. Results support the appropriateness of locating L2 WTC within a general transactional framework of cross-cultural adaptation.
Psychological models of second language (L2) communication have focused on cognitive, affective, and motivational precursors to L2 communication, while largely neglecting sociostructural factors. One ...way to conceptualize structural variables is in terms of social network reciprocity (mutually acknowledged network ties) and brokerage (social intermediaries). To investigate whether network positions predict willingness to communicate in the second language (L2 WTC), a cohort of English-for-Academic-Purposes students (N = 67) was surveyed about discussion partners within the group. An autologistic actor attribute model was used to examine social network patterns of L2 WTC. As hypothesized, students involved in reciprocal structures reported stronger L2 WTC, as well as those in brokerage positions between larger social clusters. Contrary to initial hypotheses, local forms of brokerage held a negative association with WTC, suggesting the possible role of network closure. Results indicate that communicativeness is supported by tight-knit predictable exchanges, and by being in a position to influence the social diffusion of information.
Objective:
We aimed to map the prevalence and predictors of psychological outcomes in affected communities 3–4 years after the Black Saturday bushfires in the state of Victoria, Australia.
Methods:
...Baseline assessment of a longitudinal cohort study in high-, medium-, and low-affected communities in Victoria. Participants included 1017 residents of high-, medium-, and low-affected fire communities. Participants were surveyed by means of a telephone and web-based interview between December 2011 and January 2013. The survey included measures of fire-related post-traumatic stress disorder (PTSD) and general PTSD from other traumatic events, major depressive episode, alcohol use, and general psychological distress.
Results:
The majority of respondents in the high- (77.3%), medium- (81.3%), and low-affected (84.9%) communities reported no psychological distress on the K6 screening scale. More participants in the high-affected communities (15.6%) reported probable PTSD linked to the bushfires than medium- (7.2%) and low-affected (1.0%) communities (odds ratio (OR): 4.57, 95% confidence interval (CI): 2.61–8.00, p = 0.000). Similar patterns were observed for depression (12.9%, 8.8%, 6.3%, respectively) (OR: 1.83, 95% CI: 1.17–2.85, p = 0.008) and severe psychological distress (9.8%, 5.0%, 4.9%, respectively) (OR: 2.08, 95% CI: 1.23–3.55, p = 0.007). All communities reported elevated rates of heavy drinking (24.7%, 18.7%, 19.6%, respectively); however, these were higher in the high-affected communities (OR: 1.39, 95% CI: 1.01–1.89, p = 0.04). Severe psychological distress was predicted by fear for one’s life in the bushfires, death of someone close to them in the bushfires, and subsequent stressors. One-third of those with severe psychological distress did not receive mental health assistance in the previous month.
Conclusions:
Several years following the Black Saturday bushfires the majority of affected people demonstrated resilience without indications of psychological distress. A significant minority of people in the high-affected communities reported persistent PTSD, depression, and psychological distress, indicating the need for promotion of the use of health and complementary services, community-based initiatives, and family and other informal supports, to target these persistent problems.
Anger is an important dimension of affect and a prominent feature of posttraumatic mental health, but it is commonly overlooked in postdisaster settings. We aimed to examine the distribution and ...implications of significant anger problems in the aftermath of a natural disaster, via analyses of Beyond Bushfires survey data from 736 residents of rural communities 5 years after the 2009 Black Saturday bushfires in Victoria, Australia. Assessments included the five‐item Dimensions of Anger Reaction (DAR‐5) scale along with measures of PTSD, depression, and significant mental illness, and indicators of life satisfaction, suicidality, hostile aggressive behavior, and violence exposure. The results indicated that approximately 10% of respondents from areas highly affected by the bushfires scored above the provisional cutoff criteria for significant anger problems on the DAR‐5, which was a more than 3‐fold increase, OR = 3.26, relative to respondents from areas of low‐to‐moderate bushfire impact. The rates were higher among women, younger participants, and those who were unemployed, and co‐occurred commonly, although not exclusively, with other postdisaster mental health problems. Anger problems were also associated with lower life satisfaction, β = −.31, an 8‐fold increase in suicidal ideation, OR = 8.68, and a nearly 13‐fold increase in hostile aggressive behavior, OR = 12.98. There were associations with anger problems and violence exposure, which were reduced when controlling for covariates, including probable PTSD. The findings provide evidence indicating that anger is a significant issue for postdisaster mental health and should be considered routinely alongside other posttraumatic mental health issues.
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