Notes

Efficient genome editing using endogenous U6 snRNA promoter-driven CRISPR/Cas9 sgRNA within Sclerotinia sclerotiorum.
Such an approach could help support young people's future life chances and break the vicious cycle between mental illness and poverty that spirals many young people into both socioeconomic and mental health disadvantage.
The effect of the COVID-19 pandemic on HIV outcomes in low-income and middle-income countries is poorly described. Ro-3306 in vivo We aimed to measure the impact of the 2020 national COVID-19 lockdown on HIV testing and treatment in KwaZulu-Natal, South Africa, where 1·7 million people are living with HIV.

In this interrupted time series analysis, we analysed anonymised programmatic data from 65 primary care clinics in KwaZulu-Natal province, South Africa. We included data from people testing for HIV, initiating antiretroviral therapy (ART), and collecting ART at participating clinics during the study period, with no age restrictions. We used descriptive statistics to summarise demographic and clinical data, and present crude summaries of the main outcomes of numbers of HIV tests per month, ART initiations per week, and ART collection visits per week, before and after the national lockdown that began on March 27, 2020. We used Poisson segmented regression models to estimate the immediate impact of the lockdown on these on 18 519 visits per week before lockdown [IQR 17 074-19 922] vs 17 863 visits per week after lockdown [17 509-18 995]; estimated effect in the first week of lockdown IRR 0·932, 95% CI 0·794-1·093). As restrictions eased, HIV testing and ART initiations gradually improved towards pre-lockdown levels (slope change 1·183/month, 95% CI 1·113-1·256 for HIV testing; 1·156/month, 1·085-1·230 for ART initiations).

ART provision was generally maintained during the 2020 COVID-19 lockdown, but HIV testing and ART initiations were heavily impacted. Strategies to increase testing and treatment initiation should be implemented.

Wellcome Trust, Africa Oxford Initiative.
Wellcome Trust, Africa Oxford Initiative.
The prevalence of diabetes has increased in the UK and other high-income countries alongside a substantial decline in cardiovascular mortality. Yet data are scarce on how these trends have changed the causes of death in people with diabetes who have traditionally died primarily of vascular causes. We estimated how all-cause mortality and cause-specific mortality in people with diabetes have changed over time, how the composition of the mortality burden has changed, and how this composition compared with that of the non-diabetes population.

In this epidemiological analysis of primary care records, we identified 313 907 individuals with diabetes in the Clinical Practice Research Datalink, a well described primary care database, between 2001 to 2018, and linked these data to UK Office for National Statistics mortality data. We assembled serial cross sections with longitudinal follow-up to generate a mixed prevalence and incidence study population of patients with diabetes. We used discretised Poisson regressncers as the leading contributor to death rates in individuals with diagnosed diabetes and to the gap in death rates between those with and without diabetes.

The decline in vascular death rates has been accompanied by a diversification of causes in individuals with diagnosed diabetes and a transition from vascular diseases to cancers as the leading contributor to diabetes-related death. Clinical and preventative approaches must reflect this trend to reduce the excess mortality risk in individuals with diabetes.

Wellcome Trust.
Wellcome Trust.
Around 15% of cerebral ischemias are caused by lesions of the extracranial carotid artery. The goal of this guideline is to provide evidence- and consensus-based recommendations for the management of patients with extracranial carotid stenoses throughout Germany and Austria.

A systematic literature search (1990-2019) and methodical assessment of existing guidelines and systematic reviews; consensus-based answers to 37 key questions with evidence-based recommendations.

The prevalence of extracranial carotid artery stenoses is around 4% overall, higher from the age of 65 years. The most important examination modality is duplex sonography. Randomized trials have shown that carotid endarterectomy (CEA) significantly reduces the 5-year risk of stroke in patients with 60-99 % asymptomatic stenoses (absolute risk reduction [ARR] 4.1% over 5 years, number needed to treat [NNT] 24) or 50-99% symptomatic stenoses (50-69% ARR 4.6 % over 5 years, NNT 22; 70-99% 15.9 % over 5 years, NNT 6). With the aid of intensiveindividualized treatment, whether conservative, surgical, or endovascular.
There are many ways in which computer-assisted orthopedic and trauma surgery (CAOS) procedures can help surgeons to plan and execute an intervention.

This study is based on data derived from a selective search of the literature in the PubMed database, supported by a Google Scholar search.

For most applications the evidence is weak. In no sector did the use of computer-assisted surgery yield any relevant clinical or functional improvement. In trauma surgery, 3D-navigated sacroiliac screw fixation has become clinically established for the treatment of pelvic fractures. One randomized controlled trial showed a reduction in the rate of screw misplacement 0% with 3D navigation versus 20.4% with the conventional procedure und 16.6% with 2D navigation. Moreover, navigation-assisted pedicle screw stabilization lowers the misplacement rate. In joint replacements, the long-term results showed no difference in respect of clinical/functional scores, the time for which the implant remained in place, or aseptic loosening.

Computer-assisted procedures can improve the precision of certain surgical interventions. Particularly in joint replacement and spinal surgery, the research is moving away from navigation in the direction of robotic procedures. Future studies should place greater emphasis on clinical and functional results.
Computer-assisted procedures can improve the precision of certain surgical interventions. Particularly in joint replacement and spinal surgery, the research is moving away from navigation in the direction of robotic procedures. Future studies should place greater emphasis on clinical and functional results.
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