Association between Periodontitis and mortality in stages 3-5 Chronic Kidney Disease: NHANES III and linked mortality study

INTRODUCTION: Periodontitis may add to the systemic inflammatory burden in individuals with chronic kidney disease (CKD), thereby contributing to an increased mortality rate. This study aimed to determine the association between periodontitis and mortality rate (all‐cause and cardiovascular disease‐related) in individuals with stage 3–5 CKD, hitherto referred to as “CKD”. METHODS: Survival analysis was carried out using the Third National Health and Nutrition Examination Survey (NHANES III) and linked mortality data. Cox proportional hazards regression was employed to assess the association between periodontitis and mortality, in individuals with CKD. This association was compared with the association between mortality and traditional risk factors in CKD mortality (diabetes, hypertension and smoking). RESULTS: Of the 13,784 participants eligible for analysis in NHANES III, 861 (6%) had CKD. The median follow‐up for this cohort was 14.3 years. Adjusting for confounders, the 10‐year all‐cause mortality rate for individuals with CKD increased from 32% (95% CI: 29–35%) to 41% (36–47%) with the addition of periodontitis. For diabetes, the 10‐year all‐cause mortality rate increased to 43% (38–49%). CONCLUSION: There is a strong, association between periodontitis and increased mortality in individuals with CKD. Sources of chronic systemic inflammation (including periodontitis) may be important contributors to mortality in patients with CKD

CRISPR-Cas9 correction of OPA1 c.1334G>A: p.R445H restores mitochondrial homeostasis in dominant optic atrophy patient-derived iPSCs.

Autosomal dominant optic atrophy (DOA) is the most common inherited optic neuropathy in the United Kingdom. DOA has an insidious onset in early childhood, typically presenting with bilateral, central visual loss caused by the preferential loss of retinal ganglion cells. 60%-70% of genetically confirmed DOA cases are associated with variants in OPA1, a ubiquitously expressed GTPase that regulates mitochondrial homeostasis through coordination of inner membrane fusion, maintenance of cristae structure, and regulation of bioenergetic output. Whether genetic correction of OPA1 pathogenic variants can alleviate disease-associated phenotypes remains unknown. Here, we demonstrate generation of patient-derived OPA1 c.1334G>A: p.R445H mutant induced pluripotent stem cells (iPSCs), followed by correction of OPA1 through CRISPR-Cas9-guided homology-directed repair (HDR) and evaluate the effect of OPA1 correction on mitochondrial homeostasis. CRISPR-Cas9 gene editing demonstrated an efficient method of OPA1 correction, with successful gene correction in 57% of isolated iPSCs. Correction of OPA1 restored mitochondrial homeostasis, re-establishing the mitochondrial network and basal respiration and ATP production levels. In addition, correction of OPA1 re-established the levels of wild-type (WT) mitochondrial DNA (mtDNA) and reduced susceptibility to apoptotic stimuli. These data demonstrate that nuclear gene correction can restore mitochondrial homeostasis and improve mtDNA integrity in DOA patient-derived cells carrying an OPA1 variant

Prostate Surgery for Men with Lower Urinary Tract Symptoms: Do We Need Urodynamics to Find the Right Candidates?:Exploratory Findings from the UPSTREAM Trial

BackgroundIdentifying men whose lower urinary tract symptoms (LUTS) may benefit from surgery is challenging.ObjectiveTo identify routine diagnostic and urodynamic measures associated with treatment decision-making, and outcome, in exploratory analyses of the UPSTREAM trial.Design, setting, and participantsA randomised controlled trial was conducted including 820 men, considering surgery for LUTS, across 26 hospitals in England (ISCTRN56164274).InterventionMen were randomised to a routine care (RC) diagnostic pathway (n = 393) or a pathway that included urodynamics (UDS) in addition to RC (n = 427).Outcome measurements and statistical analysisMen underwent uroflowmetry and completed symptom questionnaires, at baseline and 18 mo after randomisation. Regression models identified baseline clinical and symptom measures that predicted recommendation for surgery and/or surgical outcome (measured by the International Prostate Symptom Score [IPSS]). We explored the association between UDS and surgical outcome in subgroups defined by routine measures.Results and limitationsThe recommendation for surgery could be predicted successfully in the RC and UDS groups (area under the receiver operating characteristic curve 0.78), with maximum flow rate (Qmax) and age predictors in both groups. Surgery was more beneficial in those with higher symptom scores (eg, IPSS >16), age 47.6, and bladder contractility index >123.0. In the UDS group, urodynamic measures were more strongly predictive of surgical outcome for those with Qmax >15, although patient-reported outcomes were also more predictive in this subgroup.ConclusionsTreatment decisions were informed with UDS, when available, but without evidence of change in the decisions reached. Despite the small group sizes, exploratory analyses suggest that selective use of UDS could detect obstructive pathology, missed by routine measures, in certain subgroups.Patient summaryBaseline clinical and symptom measurements were able to predict treatment decisions. The addition of urodynamic test results, while useful, did not generally lead to better surgical decisions and outcomes over routine tests alone

Connectivity between white shark populations off Central California, USA and Guadalupe Island, Mexico

Marine animals often move beyond national borders and exclusive economic zones resulting in a need for trans-boundary management spanning multiple national jurisdictions. Highly migratory fish vulnerable to over-exploitation require protections at international level, as exploitation practices can be disparate between adjacent countries and marine jurisdictions. In this study we collaboratively conducted an analysis of white shark connectivity between two main aggregation regions with independent population assessment and legal protection programs; one off central California, USA and one off Guadalupe Island, Mexico. We acoustically tagged 326 sub-adult and adult white sharks in central California (n=210) and in Guadalupe Island (n=116) with acoustic transmitters between 2008-2019. Of the 326 tagged white sharks, 30 (9.20%) individuals were detected at both regions during the study period. We used a Bayesian implementation of logistic regression with a binomial distribution to estimate the effect of sex, maturity, and tag location to the response variable of probability of moving from one region to the other. While nearly one in ten individuals in our sample were detected in both regions over the study period, the annual rate of trans-regional movement was low (probability of movement = 0.015 yr-1, 95% credible interval = 0.002, 0.061). Sub-adults were more likely than adults to move between regions and sharks were more likely to move from Guadalupe Island to central California, however, sex, and year were not important factors influencing movement. This first estimation of demographic-specific trans-regional movement connecting US and Mexico aggregations with high seasonal site fidelity represents an important step to future international management and assessment of the northeastern Pacific white shark population as a whole

Recognition of cancer warning signs and anticipated time to help-seeking in a population sample of adults in the UK

Background: Not recognising a symptom as suspicious is a common reason given by cancer patients for delayed help-seeking; but inevitably this is retrospective. We therefore investigated associations between recognition of warning signs for breast, colorectal and lung cancer and anticipated time to help-seeking for symptoms of each cancer. Methods: Computer-assisted telephone interviews were conducted with a population-representative sample (N=6965) of UK adults age greater than or equal to50 years, using the Awareness and Beliefs about Cancer scale. Anticipated time to help-seeking for persistent cough, rectal bleeding and breast changes was categorised as >2 vs less than or equal to2 weeks. Recognition of persistent cough, unexplained bleeding and unexplained lump as cancer warning signs was assessed (yes/no). Associations between recognition and help-seeking were examined for each symptom controlling for demographics and perceived ease of health-care access. Results: For each symptom, the odds of waiting for >2 weeks were significantly increased in those who did not recognise the related warning sign: breast changes: OR=2.45, 95% CI 1.47–4.08; rectal bleeding: OR=1.77, 1.36–2.30; persistent cough: OR=1.30, 1.17–1.46, independent of demographics and health-care access. Conclusion: Recognition of warning signs was associated with anticipating faster help-seeking for potential symptoms of cancer. Strategies to improve recognition are likely to facilitate earlier diagnosis

Lizards Cooperatively Tunnel to Construct a Long-Term Home for Family Members

Constructing a home to protect offspring while they mature is common in many vertebrate groups, but has not previously been reported in lizards. Here we provide the first example of a lizard that constructs a long-term home for family members, and a rare case of lizards behaving cooperatively. The great desert skink, Liopholis kintorei from Central Australia, constructs an elaborate multi-tunnelled burrow that can be continuously occupied for up to 7 years. Multiple generations participate in construction and maintenance of burrows. Parental assignments based on DNA analysis show that immature individuals within the same burrow were mostly full siblings, even when several age cohorts were present. Parents were always captured at burrows containing their offspring, and females were only detected breeding with the same male both within- and across seasons. Consequently, the individual investments made to construct or maintain a burrow system benefit their own offspring, or siblings, over several breeding seasons