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BackgroundDepression and anxiety are prevalent in youth populations and typically emerge during adolescence. Repetitive negative thinking (RNT) is a putative transdiagnostic mechanism with consistent associations with depression and anxiety. Targeting transdiagnostic processes like RNT for youth depression and anxiety may offer more targeted, personalised and effective treatment.MethodsA meta-analysis was conducted to examine the effect of psychological treatments on RNT, depression and anxiety symptoms in young people with depression or anxiety, and a meta-regression to examine relationships between outcomes.ResultsTwenty-eight randomised controlled trials examining 17 different psychological interventions were included. Effect sizes were small to moderate across all outcomes (Hedge's g depression = −0.47, CI −0.77 to −0.17; anxiety = −0.42, CI −0.65 to −0.20; RNT = −0.45, CI −0.67 to −0.23). RNT-focused and non-RNT focused approaches had comparable effects; however, those focusing on modifying the process of RNT had significantly larger effects on RNT than those focusing on modifying negative thought content. Meta-regression revealed a significant relationship between RNT and depression outcomes only across all intervention types and with both depression and anxiety for RNT focused interventions only.ConclusionConsistent with findings in adults, this review provides evidence that reducing RNT with psychological treatment is associated with improvements in depression and anxiety in youth. Targeting RNT specifically may not lead to better outcomes compared to general approaches; however, focusing on modifying the process of RNT may be more effective than targeting content. Further research is needed to determine causal pathways.

The concept of polypharmacy in the type 2 diabetic patient is both historic and redundant. A combination of three or more medications usually at doses which are less than those utilized for monotherapy is efficacious not only in the therapy of hyperglycemia but also in the therapy of the comorbidities of hypertension and hyperlipidemia. In addition, multiple medications are now accepted as being necessary to reduce albuminuria and decelerate the decline in renal function in the patient with diabetic nephropathy.

Host genetic variation can shape the diversity and composition of associated microbiomes, which may reciprocally influence host traits and performance. While the genetic basis of phenotypic diversity of plant populations in nature has been studied, comparatively little research has investigated the genetics of host effects on their associated microbiomes. Switchgrass (Panicum virgatum) is a highly outcrossing, perennial, grass species with substantial locally adaptive diversity across its native North American range. Here, we compared 383 switchgrass accessions in a common garden to determine the host genotypic influence on rhizosphere bacterial composition. We hypothesized that the composition and diversity of rhizosphere bacterial assemblages would differentiate due to genotypic differences between hosts (potentially due to root phenotypes and associated life history variation). We observed higher alpha diversity of bacteria associated with upland ecotypes and tetraploids, compared to lowland ecotypes and octoploids, respectively. Alpha diversity correlated negatively with flowering time and plant height, indicating that bacterial composition varies along switchgrass life history axes. Narrow-sense heritability (h2) of the relative abundance of twenty-one core bacterial families was observed. Overall compositional differences among tetraploids, due to genetic variation, supports wide-spread genotypic influence on the rhizosphere microbiome. Lastly, a genome-wide association study identified 1,861 single-nucleotide polymorphisms associated with 110 families and genes containing them related to potential regulatory functions. Our findings suggest that switchgrass genomic and life-history variation influences bacterial composition in the rhizosphere, potentially due to host adaptation to local environments.

Metformin blocks the absorption of vitamin B12 through a mechanism that has not been established but could be because of interference with the calcium-dependent binding of the intrinsic factor vitamin B12 complex to the cubam receptor in the terminal ileum. The subsequent deficiency of vitamin B12 may cause or accelerate distal symmetrical and autonomic neuropathy in the patient with diabetes. Several observational studies and meta-analyses have reported a significant association between metformin utilization and vitamin B12 deficiency. Prospective studies have shown that not only do metformin utilizers have lower vitamin B12 levels but they also have higher frequencies of distal symmetrical polyneuropathy and autonomic neuropathy (including cardiac denervation, which is associated with increased incidences of cardiac arrhythmias, cardiac events and mortality). Therefore, periodic monitoring of vitamin B12 is recommended in all patients who utilize metformin, particularly if metformin has been used for over 5 years at which stage hepatic stores of vitamin B12 would probably be depleted. Factors that accelerate the loss of hepatic vitamin B12 stores are proton pump inhibitors, bariatric surgery, being elderly and having an increased turnover of red blood cells. If serum vitamin B12 levels are borderline, measurement of methylmalonic acid and homocysteine levels can detect vitamin B12 deficiency at its earliest stage. Therapies include prophylactic calcium and vitamin B12 supplements, metformin withdrawal, replenishing vitamin B12 stores with intramuscular or oral vitamin B12 therapy and regular monitoring of vitamin B12 levels and vitamin B12 supplements if metformin continues to be utilized. With adequate vitamin B12 replacement, while symptoms of neuropathy may or may not improve, objective findings of neuropathy stabilize but do not improve.

Sequence-based identification and detection technologies have revolutionized plant disease diagnostics in the last few decades, opening the door to highly selective and specific diagnostic assays. However, diagnostic assay development and validation remain hindered by many factors that would be ameliorated by research prioritization and coordination. Massive amounts of sequence data, in the forms of evolutionarily informative markers and now whole genomes, are available yet not easily accessible or properly organized to guide efficient assay development and deployment. For many key pathogen groups, particularly those that are not easily culturable, data are scant. Identification of pathogen-specific sequences in microbial genomes, the ultimate diagnostic markers, requires massive data processing and is slowed by a lack of quality data curation pipelines that efficiently translate data into problem solving. New technologies have the potential to enable detection at extremely low titers, but many of these have not yet found their way into diagnostic labs, much less the field. Here, we review the current status of diagnostics readiness in select groups of pathogens and pathosystems and define research priorities to fill knowledge and resource gaps to support scientists engaged in diagnostics. These priorities include improved coordination of data generation and curation and validation of new technologies, such as LAMP, MiFi, RPA, and CRISPR-Cas, to accelerate the implementation of more specific and sensitive assays. Finally, novel approaches, such as detection of volatile profiles and microbiome analyses, have the potential to complement pathogen diagnostics focusing on specific pathogens. [Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2023.

Wastewater Based Epidemiology (WBE) has become an integral part of the public health effort to track the levels of SARS-CoV-2 within communities. Detection of SARS-CoV-2 in wastewater can be challenging due to relatively low levels of virus within the sample. The wastewater matrix is also comprised of commercial and domestically derived contaminants, as well as RNases, all of which can adversely affect RT-qPCR analysis. To improve SARS-CoV-2 detection within wastewater samples we investigated both the effect of template dilution (as a means to reduce RT-qPCR inhibition) and sample stabilisation via addition of DNA/RNA Shield™ and/or RNA Later™ (to prevent RNA degradation via RNases) as a means to improve viral fragment detection. Using both methodologies a significant improvement in SARS-CoV-2 detection from wastewater samples was observed. No adverse effects of stabilising agent addition on downstream Next Generation Sequencing workflows were detected.

Palliative care has been defined as ‘the active holistic care of individuals across all ages with serious health-related suffering due to severe illness, and especially of those near the end of life’. Unfortunately, palliative care and especially paediatric palliative care remain a neglected area of medicine and are widely misunderstood, with few healthcare providers having any formal training in South Africa. To relieve health-related suffering, healthcare providers must understand that the field is not limited to end-of-life care for the terminally ill, and holistic care (physical, emotional, social and spiritual) should commence at the time of diagnosis of a serious illness. It is imperative that all healthcare providers develop the knowledge and skills to provide this essential care across all levels of care and disciplines. The article aims to raise awareness and show how to practically implement palliative care through case studies.

In grapevine, metabolic activity of absorptive roots changes rapidly as roots age, but it is unclear if nearby microbial assemblages shift as well. Here, we investigated whether first-order root age impacts bacterial and fungal variation adjacent to the root surface, and if root age should be integrated into future studies on root functional traits and associated microbes. We hypothesized that microbial diversity and composition would differ between young (≤ 11 days old) and old (11.5 – 40 days old) first-order roots due to expected differences in metabolism over root lifespan (i.e., higher metabolism in young roots). Overall, we found that microbial composition was distinct between young and old absorptive roots, with stronger evidence at the phylum and ASV taxonomic levels for fungi (p = 0.003 and p = 0.038, respectively) than bacteria (p = 0.082 and p = 0.129, respectively). Furthermore, we identified differentially abundant fungal and bacterial ASVs in young and old roots that related to expected differences in root function, including instances of microbes previously described as copiotrophs more abundant adjacent to young roots and microbes described as oligotrophs and saprotrophs more abundant adjacent to old roots. In contrast to the distinct shifts in microbial composition, there was little evidence of shifts in alpha diversity (i.e., observed ASVs and Shannon diversity) between young and old roots. Our study suggests that future work on the impacts of root functional traits on localized microbial composition may improve results interpretation and reduce some variation by accounting for root age at sampling.

Castrate-resistant prostate cancer (CRPC) and neuroendocrine carcinoma of the prostate are invariably fatal diseases for which only palliative therapies exist. As part of a prostate tumor sequencing program, a patient tumor was analyzed using Illumina genome sequencing and a matched renal capsule tumor xenograft was generated. Both tumor and xenograft had a homozygous 9p21 deletion spanning the MTAP, CDKN2, and ARF genes. It is rare for this deletion to occur in primary prostate tumors, yet approximately 10% express decreased levels of methylthioadenosine phosphorylase (MTAP) mRNA. Decreased MTAP expression is a prognosticator for poor outcome. Moreover, it seems that this deletion is more common in CRPC than in primary prostate cancer. We show for the first time that treatment with methylthioadenosine and high dose 6-thioguanine causes marked inhibition of a patient-derived neuroendocrine xenograft growth while protecting the host from 6-thioguanine toxicity. This therapeutic approach can be applied to other MTAP-deficient human cancers as deletion or hypermethylation of the MTAP gene occurs in a broad spectrum of tumors at high frequency. The combination of genome sequencing and patient-derived xenografts can identify candidate therapeutic agents and evaluate them for personalized oncology. Mol Cancer Ther; 11(3); 775–83. ©2012 AACR.

Fig.S15 POU3F2 and SMARCA5 are positively correlated with each other in GBM cohorts

Table S4. Multivariable analyses of clinic-pathologic parameters with MGMT methylation status in patient with GBM

Supplementary Materials