Familial multiple myeloma. Two more families

The authors report on two multiple myeloma sibling pairs. In the absence of a known disease-specific marker one can only speculate on an explanation: is it because of inherited errors or is it related to the same environmental exposure, or both? In this study HLA typing and metabolizing enzyme polymorphism studies have been carried out with the aim of finding inherited similarities in the siblings or characteristics that might differ from the average population. Sibling pair 1 shared an HLA haplotype. Sibling pair 2 shared only HLA-B51, DR4, DRw53, DQ3. Sibling 1/1 was GSTT1/GSTM1 null and GSTP1 Ile105Val; sibling 1/2 was a GSTT1/GSTM1 heterozygote and GSTP1 Ile105Val; sibling 2/1 and 2/2 were GSTT1 heterozygotes and shared GSTM1 null/GSTP1 Ile105Ile. The siblings had identical light chain or heavy chain secretion, or both. The similarities found in the inherited factors together with the same environmental exposure in the siblings' first 20 years of life imply that the development of the same disease cannot be a coincidence

Addendum to: Capillary floating and the billiard ball problem

We compare the results of our earlier paper on the floating in neutral equilibrium at arbitrary orientation in the sense of Finn-Young with the literature on its counterpart in the sense of Archimedes. We add a few remarks of personal and social-historical character.Comment: This is an addendum to my article Capillary floating and the billiard ball problem, Journal of Mathematical Fluid Mechanics 14 (2012), 363 -- 38

On recurrence and ergodicity for geodesic flows on noncompact periodic polygonal surfaces

We study the recurrence and ergodicity for the billiard on noncompact polygonal surfaces with a free, cocompact action of $\Z$ or $\Z^2$. In the $\Z$-periodic case, we establish criteria for recurrence. In the more difficult $\Z^2$-periodic case, we establish some general results. For a particular family of $\Z^2$-periodic polygonal surfaces, known in the physics literature as the wind-tree model, assuming certain restrictions of geometric nature, we obtain the ergodic decomposition of directional billiard dynamics for a dense, countable set of directions. This is a consequence of our results on the ergodicity of \ZZ-valued cocycles over irrational rotations.Comment: 48 pages, 12 figure

A MADS-box gene-induced early flowering pear (Pyrus communis L.) for accelerated pear breeding

There have been a considerable number of studies that have successfully sped up the flowering cycle in woody perennial horticultural species. One particularly successful study in apple (Malus domestica) accelerated flowering using a silver birch (Betula pendula) APETALA1/FRUITFULL MADS-box gene BpMADS4, which yielded a good balance of vegetative growth to support subsequent flower and fruit development. In this study, BpMADS4 was constitutively expressed in European pear (Pyrus communis) to establish whether this could be used as a tool in a rapid pear breeding program. Transformed pear lines flowered within 6–18 months after grafting onto a quince (Cydonia oblonga) rootstock. Unlike the spindly habit of early flowering apples, the early flowering pear lines displayed a normal tree-like habit. Like apple, the flower appearance was normal, and the flowers were fertile, producing fruit and seed upon pollination. Seed from these transformed lines were germinated and 50% of the progeny flowered within 3 months of sowing, demonstrating a use for these in a fast breeding program

Frail2Fit study protocol: a feasibility and acceptability study of a virtual multimodal intervention delivered by volunteers to improve functional outcomes in older adults with frailty after discharge from hospital.

INTRODUCTION: Physical activity (PA) and replete nutritional status are key to maintaining independence and improving frailty status among frail older adults. In response to the COVID-19 pandemic, healthcare has increasingly turned to virtual modes of delivery and there is interest in the use of trained volunteers to deliver PA and nutrition interventions. We aim to evaluate the feasibility and acceptability of training hospital volunteers to deliver an online intervention, comprising exercise, behaviour change and nutrition support, to older people with frailty after discharge from hospital. METHODS: We will use a quasi-experimental mixed methods approach. Hospital volunteers (n=6) will be trained to deliver an online, 3-month, multimodal intervention to frail (Clinical Frailty Scale ≥5) adults ≥65 years (n=30) after discharge from hospital. Feasibility will be assessed by determining the number of volunteers recruited, trained and retained at the end of the study; the proportion of intervention sessions delivered; participant recruitment, retention and adherence to the intervention. To determine the acceptability of the intervention, interviews will be conducted among a purposive sample of older adults, and volunteers. Secondary outcomes will include physical function, appetite, well-being, quality of life, anxiety and depression, self-efficacy for managing chronic disease and PA. Outcomes will be measured at baseline, 3 months and 6 months. ANALYSIS: Descriptive statistics will be used to describe feasibility and adherence to the intervention. Secondary outcomes at baseline will be compared at 3 and 6 months. Interviews will be transcribed verbatim and analysed using thematic analysis. ETHICS AND DISSEMINATION: Health Research Authority ethical approval was obtained on 30 May 2022 (reference: 22/WA/0155). Results will be disseminated through peer-reviewed journal articles, volunteer organisations, National Health Service communication systems and social media platforms. A toolkit will be developed to facilitate roll out of volunteer training. TRIAL REGISTRATION NUMBER: NCT05384730

Engaging adolescents in changing behaviour (EACH-B): A study protocol for a cluster randomised controlled trial to improve dietary quality and physical activity

Background Poor diet and lack of physical activity are strongly linked to non-communicable disease risk, but modifying them is challenging. There is increasing recognition that adolescence is an important time to intervene; habits formed during this period tend to last, and physical and psychological changes during adolescence make it an important time to help individuals form healthier habits. Improving adolescents’ health behaviours is important not only for their own health now and in adulthood, but also for the health of any future children. Building on LifeLab—an existing, purpose-built educational facility at the University of Southampton—we have developed a multi-component intervention for secondary school students called Engaging Adolescents in Changing Behaviour (EACH-B) that aims to motivate and support adolescents to eat better and be more physically active. Methods A cluster randomised controlled trial is being conducted to evaluate the effectiveness of the EACH-B intervention. The primary outcomes of the intervention are self-reported dietary quality and objectively measured physical activity (PA) levels, both assessed at baseline and at 12-month follow-up. The EACH-B intervention consists of three linked elements: professional development for teachers including training in communication skills to support health behaviour change; the LifeLab educational module comprising in-school teaching of nine science lessons linked to the English National Curriculum and a practical day visit to the LifeLab facility; and a personalised digital intervention that involves social support and game features that promote eating better and being more active. Both the taught module and the LifeLab day are designed with a focus on the science behind the messages about positive health behaviours, such as diet and PA, for the adolescents now, in adulthood and their future offspring, with the aim of promoting personal plans for change. The EACH-B research trial aims to recruit approximately 2300 secondary school students aged 12–13 years from 50 schools (the clusters) from Hampshire and neighbouring counties. Participating schools will be randomised to either the control or intervention arm. The intervention will be run during two academic years, with continual recruitment of schools throughout the school year until the sample size is reached. The schools allocated to the control arm will receive normal schooling but will be offered the intervention after data collection for the trial is complete. An economic model will be developed to assess the cost-effectiveness of the EACH-B intervention compared with usual schooling. Discussion Adolescents’ health needs are often ignored and they can be difficult to engage in behaviour change. Building a cheap, sustainable way of engaging them in making healthier choices will benefit their long-term health and that of their future children. Trial registration ISRCTN 74109264. Registered on 30 August 2019. EACH-B is a cluster randomised controlled trial, funded by the National Institute for Health Research (RP-PG-0216-20004)

Detection and Verification of Mammalian Mirtrons by Northern Blotting

microRNAs (miRNAs) have vital roles in regulating gene expression—contributing to major diseases like cancer and heart disease. Over the last decade, thousands of miRNAs have been discovered through high throughput sequencing-based annotation. Different classes have been described, as well as a great dynamic range of expression levels. While sequencing approaches provide insight into biogenesis and allow confident identification, there is a need for additional methods for validation and characterization. Northern blotting was one of the first techniques used for studying miRNAs, and remains one of the most valuable as it avoids enzymatic manipulation of miRNA transcripts. Blotting can also provide insight into biogenesis by revealing RNA processing intermediates. Compared to sequencing, however, northern blotting is a relatively insensitive technology. This creates a challenge for detecting low expressed miRNAs, particularly those produced by inefficient, non-canonical pathways. In this chapter, we describe a strategy to study such miRNAs by northern blotting that involves ectopic expression of both miRNAs and miRNA-binding Argonaute (Ago) proteins. Through use of epitope tags, this strategy also provides a convenient method for verification of small RNA competency to be loaded into regulatory complexes

Plant growth retardation and conserved miRNAs are correlated to hibiscus chlorotic ringspot virus infection

10.1371/journal.pone.0085476PLoS ONE812-POLN

Identification and Characterization of Novel MicroRNAs from Schistosoma japonicum

Background: Schistosomiasis japonica remains a major public health problem in China. Its pathogen, Schistosoma japonicum has a complex life cycle and a unique repertoire of genes expressed at different life cycle stages. Exploring schistosome gene regulation will yield the best prospects for new drug targets and vaccine candidates. MicroRNAs (miRNAs) are a highly conserved class of noncoding RNA that control many biological processes by sequence-specific inhibition of gene expression. Although a large number of miRNAs have been identified from plants to mammals, it remains no experimental proof whether schistosome exist miRNAs. Methodology and Results: We have identified novel miRNAs from Schistosoma japonicum by cloning and sequencing a small (18–26 nt) RNA cDNA library from the adult worms. Five novel miRNAs were identified from 227 cloned RNA sequences and verified by Northern blot. Alignments of the miRNAs with corresponding family members indicated that four of them belong to a metazoan miRNA family: let-7, miR-71, bantam and miR-125. The fifth potentially new (non conserved) miRNA appears to belong to a previously undescribed family in the genus Schistosome. The novel miRNAs were designated as sja-let-7, sja-miR-71, sja-bantam, sja-miR-125 and sja-miR-new1, respectively. Expression of sja-let-7, sja-miR-71 and sjabantam were analyzed in six stages of the life cycle, i.e. egg, miracidium, sporocyst, cercaria, schistosomulum, and adult worm, by a modified stem-loop reverse transcribed polymerase chain reaction (RT-PCR) method developed in ou

Risk factors for treatment failure and mortality among hospitalized patients with complicated urinary tract infection: A multicenter retrospective cohort study (RESCUING study group)

Background. Complicated urinary tract infections (cUTIs) are responsible for a major share of all antibiotic consumption in hospitals. We aim to describe risk factors for treatment failure and mortality among patients with cUTIs. Methods. A multinational, multicentre retrospective cohort study, conducted in 20 countries in Europe and the Middle East. Data were collected from patients' files on hospitalised patients with a diagnosis of cUTI during 2013-2014. Primary outcome was treatment failure, secondary outcomes included 30 days all-cause mortality,among other outcomes. Multivariable analysis using a logistic model and the hospital as a random variable was performed to identify independent predictors for these outcomes. Results. A total of 981 patients with cUTI were included. Treatment failure was observed in 26.6% (261/981), all cause 30-day mortality rate was 8.7% (85/976), most of these in patients with catheter related UTI (CaUTI). Risk factors for treatment failure in multivariable analysis were ICU admission (OR 5.07, 95% CI 3.18-8.07), septic shock (OR 1.92, 95% CI 0.93-3.98), corticosteroid treatment (OR 1.92, 95% CI 1.12-3.54), bedridden (OR 2.11, 95%CI 1.4-3.18), older age (OR 1.02, 95% CI 1.0071.03-), metastatic cancer (OR 2.89, 95% CI 1.46-5.73) and CaUTI (OR 1.48, 95% CI 1.04-2.11). Management variables, such as inappropriate empirical antibiotic treatment or days to starting antibiotics were not associated with treatment failure or 30-day mortality. More patients with pyelonephritis were given appropriate empirical antibiotic therapy than other CaUTI [110/171; 64.3% vs. 116/270; 43%, p <0.005], nevertheless, this afforded no advantage in treatment failure rates nor mortality in these patients. Conclusions. In patients with cUTI we found no benefit of early appropriate empirical treatment on survival rates or other outcomes. Physicians might consider supportive treatment and watchful waiting in stable patients until the causative pathogen is defined