Discontinuation of Car Seat Tolerance Screening and Postdischarge Adverse Outcomes in Infants Born Preterm.

OBJECTIVE: To study the association between discontinuing predischarge car seat tolerance screening (CSTS) with 30-day postdischarge adverse outcomes in infants born preterm. STUDY DESIGN: Retrospective cohort study involving all infants born preterm from 2010 through 2021 who survived to discharge to home in a 14-hospital integrated health care system. The exposure was discontinuation of CSTS. The primary outcome was a composite rate of death, 911 call-triggered transports, or readmissions associated with diagnostic codes of respiratory disorders, apnea, apparent life-threatening event, or brief resolved unexplained events within 30 days of discharge. Outcomes of infants born in the periods of CSTS and after discontinuation were compared. RESULTS: Twelve of 14 hospitals initially utilized CSTS and contributed patients to the CSTS period; 71.4% of neonatal intensive care unit (NICU) patients and 26.9% of non-NICU infants were screened. All hospitals participated in the discontinuation period; 0.1% was screened. Rates of the unadjusted primary outcome were 1.02% in infants in the CSTS period (n = 21 122) and 1.06% after discontinuation (n = 20 142) (P = .76). The aOR (95% CI) was 0.95 (0.75, 1.19). Statistically insignificant differences between periods were observed in components of the primary outcome, gestational age strata, NICU admission status groups, and other secondary analyses. CONCLUSIONS: Discontinuation of CSTS in a large integrated health care network was not associated with a change in 30-day postdischarge adverse outcomes. CSTS's value as a standard predischarge assessment deserves further evaluation.

Regions of genetic divergence in depth-separated Sebastes rockfish species pairs: Depth as a potential driver of speciation.

Depth separation is a proposed driver of speciation in marine fishes, with marine rockfish (genus Sebastes) providing a potentially informative study system. Sebastes rockfishes are commercially and ecologically important. This genus encompasses more than one hundred species and the ecological and morphological variance between these species provides opportunity for identifying speciation-driving adaptations, particularly along a depth gradient. A reduced-representation sequencing method (ddRADseq) was used to compare 95 individuals encompassing six Sebastes species. In this study, we sought to identify regions of divergence between species that were indicative of divergent adaptation and reproductive barriers leading to speciation. A pairwise comparison of S. chrysomelas (black-and-yellow rockfish) and S. carnatus (gopher rockfish) FST values revealed three major regions of elevated genomic divergence, two of which were also present in the S. miniatus (vermilion rockfish) and S. crocotulus (sunset rockfish) comparison. These corresponded with regions of both elevated DXY values and reduced nucleotide diversity in two cases, suggesting a speciation-with-gene-flow evolutionary model followed by post-speciation selective sweeps within each species. Limited whole-genome resequencing was also performed to identify mutations with predicted effects between S. chrysomelas and S. carnatus. Within these islands, we identified important SNPs in genes involved in immune function and vision. This supports their potential role in speciation, as these are adaptive vectors noted in other organisms. Additionally, changes to genes involved in pigment expression and mate recognition shed light on how S. chrysomelas and S. carnatus may have become reproductively isolated.

Predictors for a dementia gene mutation based on gene-panel next-generation sequencing of a large dementia referral series.

Next-generation genetic sequencing (NGS) technologies facilitate the screening of multiple genes linked to neurodegenerative dementia, but there are few reports about their use in clinical practice. Which patients would most profit from testing, and information on the likelihood of discovery of a causal variant in a clinical syndrome, are conspicuously absent from the literature, mostly for a lack of large-scale studies. We applied a validated NGS dementia panel to 3241 patients with dementia and healthy aged controls; 13,152 variants were classified by likelihood of pathogenicity. We identified 354 deleterious variants (DV, 12.6% of patients); 39 were novel DVs. Age at clinical onset, clinical syndrome and family history each strongly predict the likelihood of finding a DV, but healthcare setting and gender did not. DVs were frequently found in genes not usually associated with the clinical syndrome. Patients recruited from primary referral centres were compared with those seen at higher-level research centres and a national clinical neurogenetic laboratory; rates of discovery were comparable, making selection bias unlikely and the results generalisable to clinical practice. We estimated penetrance of DVs using large-scale online genomic population databases and found 71 with evidence of reduced penetrance. Two DVs in the same patient were found more frequently than expected. These data should provide a basis for more informed counselling and clinical decision making.

Ten Bird Species, Six Guilds, Three Habitats, and 59 Chlorinated and Brominated POPs: What do 64 Eggs from the Largest Economic Hub of Southern Africa tell us?

There is little information on how POPs in eggs of different terrestrial, wetland, and aquatic birds share a large urban and rural landscape relate. We collected and analysed 64 eggs belonging to ten species of six feeding guilds, and compared organic chlorinated pesticide (OCP), polychlorinated biphenyl (PCB), and brominated flame retardants (BFR) residue concentrations and compositions. The eggs were collected in the Gauteng and the northern part of the Free Sate provinces of South Africa, one of the largest economic hubs in Africa. White-breasted Cormorant and African Darter eggs (at the highest trophic level as large aquatic predators) had the highest ΣOCP and ΣPCB concentrations, and Cape Sparrow and Southern Masked Weaver (granivores) eggs had the lowest concentrations, corresponding to the lowest trophic level in our collection. The highest percentage p,p'-DDT were in eggs of the terrestrial insectivore Crowned Lapwing (24%) and the scavenging African Sacred Ibis (17%), and the lowest in African Darter (1.0%) and White-breasted Cormorant (0.9%) eggs, suggesting that recency of DDT releases in a region cannot be gauged by this metric. African Sacred Ibis and Southern Masked Weaver eggs had the highest ΣBFR concentrations, with Crowned Lapwing, Cattle Egret, and White-breasted Cormorant eggs the least. Based on feeding guilds, the mean ΣPOP concentrations increased from granivore, aquatic omnivore, scavenger, terrestrial insectivore, small aquatic predator, to large aquatic predator. Mean ΣPOP concentrations in eggs increased from terrestrial, to wetland, to aquatic habitat birds. Interesting patterns were observed with multivariate analyses. There were no significant regressions between egg size and any summed POP classes. ΣBFR concentrations were not correlated with ΣOCPs or ΣPCBs. Eggshell thinning of African Darter eggs was associated with p,p'-DDE and ΣPCB suggesting risk. Other metrics also suggest risk. Therefore, different species of terrestrial and aquatic birds from the same area acquire and deposit POPs in different proportions and quantities in their eggs. Trophic levels and habitat explain the overall patterns, but detailed differences were found, some of which we are unable to explain. Based on POPs residues in terrestrial, wetland, and aquatic bird eggs, different POPs classes behave differently in a shared large inland industrial area, complicating deductions about POPs and associated risks based on one or few species.

Differential plasticity of extensor and flexor motor cortex representations following visuomotor adaptation.

Representations within the primary motor cortex (M1) are capable of rapid functional changes following motor learning, known as use-dependent plasticity. GABAergic inhibition plays a role in use-dependent plasticity. Evidence suggests a different capacity for plasticity of distal and proximal upper limb muscle representations. However, it is unclear whether the motor cortical representations of forearm flexor and extensor muscles also have different capacities for plasticity. The current study used transcranial magnetic stimulation to investigate motor cortex excitability and inhibition of forearm flexor and extensor representations before and after performance of a visuomotor adaptation task that primarily targeted flexors and extensors separately. There was a decrease in extensor and flexor motor-evoked potential (MEP) amplitude after performing the extensor adaptation, but no change in flexor and extensor MEP amplitude after performing the flexor adaptation. There was also a decrease in motor cortical inhibition in the extensor following extensor adaptation, but no change in motor cortical inhibition in the flexor muscle following flexor adaptation or either of the non-prime mover muscles. Findings suggest that the forearm extensor motor cortical representation exhibits plastic change following adaptive motor learning, and broadly support the distinct neural control of forearm flexor and extensor muscles.

Combined effect of aerobic interval training and selenium nanoparticles on expression of IL-15 and IL-10/TNF-α ratio in skeletal muscle of 4T1 breast cancer mice with cachexia.

Cancer cachexia is characterized by inflammation, loss of skeletal muscle and adipose tissue mass, and functional impairment. Oxidative stress and inflammation are believed to regulate pathways controlling skeletal muscle wasting. The aim of this study was to determine the effects of aerobic interval training and the purported antioxidant treatment, selenium nanoparticle supplementation, on expression of IL-15 and inflammatory cytokines in 4T1 breast cancer-bearing mice with cachexia. Selenium nanoparticle supplementation accelerated cachexia symptoms in tumor-bearing mice, while exercise training prevented muscle wasting in tumor-bearing mice. Also, aerobic interval training enhanced the anti-inflammatory indices IL-10/TNF-α ratio and IL-15 expression in skeletal muscle in tumor-bearing mice. However, combining exercise training and antioxidant supplementation prevented cachexia and muscle wasting and additionally decreased tumor volume in 4T1 breast cancer mice. These finding suggested that combining exercise training and antioxidant supplementation could be a strategy for managing tumor volume and preventing cachexia in breast cancer.

The societal cost of Huntington's disease: are we underestimating the burden?

BACKGROUND AND PURPOSE: Approximately 9000 people in the UK are affected by Huntington's disease (HD). People with HD require ongoing health and social care support. There is a knowledge gap about costs of health and social care use associated with HD in the UK. This paper estimates the economic cost in the UK. METHODS: Data on UK patients for the year 2013 were extracted from the European Huntington's Disease Network REGISTRY study, a full clinical dataset, including the full medical history and medication history for patients with HD. National unit costs for the price year 2013 were applied to health and social care services. RESULTS: Data were available for 131 people. The mean annual cost per person with HD was £21 605. The largest proportion of this cost (65%) was due to informal care (£14 085). CONCLUSIONS: Informal care was the largest driver of costs across all stages of HD; thus there is a need to also consider the needs of carers when planning services for people with HD.

Exercise testing and training in people with Huntington's disease.

OBJECTIVE: To explore exercise response in people with Huntington's disease (HD). DESIGN: Experimental observational study with a randomly allocated subgroup before/after interventional study. SETTING: Community. SUBJECTS: People with HD (n=30) and a healthy comparator group (n=20). Thirteen people from the HD group were randomly allocated to an exercise training program. MAIN MEASURES: Heart rate (HR) and perceived exertion on the Borg-CR10 scale (RPE) during a submaximal cycle ergometer exercise test (three minute unloaded and nine minute 65%-75%HRmaximum phase). Expired air and lactate measures were available for 8 people with HD during the exercise. INTERVENTION: A 12 week gym and home walking exercise programme (n=13). RESULTS: People with HD achieved a lower work rate at nine minutes (82±42(0-195) v 107±35(50 -185) Watts (p<0.05)), but higher RPE at both three (3±2(0-7) v 1±1(0-4)) and nine minutes (7±3(1-10) v 5± 2(2-9)) both p<0.01, compared to the healthy group and did not achieve a steady state HR during unloaded cycling. People with HD also demonstrated higher than expected lactate at three 2.5±2.5(1.1-8)mmo.L-1 and nine 3.8±1.9(1.2-6.6)mmo.L-1 minutes and respiratory exchange ratio at three 0.78±0.03 (0.74-0.81) and nine minutes 0.94±0.11(0.81-1.15). After exercise training there were no changes observed in HR or RPE responses during the exercise test. CONCLUSIONS: There was a large variability in the observed metabolic and physiological responses to exercise in people with HD. The observed exercise responses suggest that altered exercise prescription parameters may be required for people with HD and that exercise response and factors' affecting this requires further investigation.

Opiate Analgesics and the Perioperative Management of Patients with Obstructive Sleep Apnea.

As the rate of obesity and subsequently obstructive sleep apnea (OSA) continue to rise in North America and prescriptions for narcotic analgesics number in the tens of millions, it has become increasingly important to understand the interaction between OSA and opiate analgesics. Understanding the mechanism of action of opiate analgesics and the pathophysiology of OSA can help medical professionals understand the unique risks associated with pain management in this population of patients.

Pain management in the geriatric population.

Pain is a highly prevalent and clinically important problem in the elderly. Unfortunately, due to difficulties in assessing pain in geriatric patients, the complexities of multiple comorbidities, and the high prevalence of polypharmacy, many practitioners are reluctant to treat pain aggressively in this unique patient population. Safe and effective treatment therefore, requires a working knowledge of the physiologic changes associated with aging, the challenges of accurately assessing pain, the unique effects of common therapeutic agents upon the elderly as well as the importance of adjunctive therapies. The following review is intended to provide the practitioner with practical knowledge for safer and more effective treatment of pain.

Inactivation of Listeria monocytogenes by Hydrogen Peroxide Addition in Commercial Cheese Brines.

Commercial cheese brines are used repeatedly over extended periods, potentially for years, and can be a reservoir for salt-tolerant pathogens, such as Listeria monocytogenes. The objective of this study was to determine the inactivation of L. monocytogenes in cheese brines treated with hydrogen peroxide (H2O2) (0, 50, and 100 ppm) at holding temperatures representing manufacturing conditions. In experiment one, four fresh cheese brines were prepared with 10 or 20% salt and pH 4.6 or 5.4 (2x2 design; duplicate trials). Brines were inoculated with L. monocytogenes, treated with H2O2, and stored at 10 and 15.6°C. For experiment two, seven used commercial brines (representing five cheese types, 15-30% NaCl, pH 4.5-5.5; three seasonal trials) were inoculated with L. monocytogenes or S. aureus, treated with H2O2, and stored at 12.8°C (both L. monocytogenes and S. aureus), 7.2 and 0°C (L. monocytogenes only). Each treatment was assayed on Days 0, 1, and 7 for microbial populations and residual H2O2. Data revealed that pathogen populations decreased ≤1 log in cheese brines with no hydrogen peroxide stored for 7 days, regardless of the storage temperature. In fresh brine treated with 50 or 100 ppm of H2O2, populations of L. monocytogenes were reduced to less than the detectable limit by 7 days at 10 and 15.6°C (>4 log reduction). For unfiltered used brines, H2O2 had no effect on L. monocytogenes populations in Brick J (pH 5.4, 15% NaCl) due to rapid inactivation of H2O2, likely by indigenous yeasts (∼3-log CFU/ml). For the remaining brines, the addition of 100 ppm H2O2 killed >4 log L. monocytogenes when stored at 7.2 or 12.8°C for 1 week, but only 3-4 log reduction when stored at 0°C. The addition of 50 ppm H2O2 had similar lethal effects at 12.8°C but was less effective at 7.2 or 0°C. Inactivation rates of S. aureus were similar to that of L. monocytogenes. This study confirmed that high salt, warmer temperature, and 100-ppm H2O2 accelerated the inactivation of L. monocytogenes in cheese brines. Data also suggest that the presence of catalase-positive indigenous microorganisms may neutralize the effect of H2O2.

Carcinoid syndrome with right-sided valve involvement - a case report and review of the literature.

BACKGROUND: The survival of patients with neuroendocrine tumors has substantially improved with modern treatment options. Although the associated carcinoid syndrome can be diagnosed early and controlled effectively, cardiologists still encounter patients with cardiac manifestations, particularly among individuals with persistently high levels of vasoactive mediators. Treatment options have been limited to surgical valve replacement in fully manifested disease. Since surgery is not always feasible, transcatheter valve implantation is becoming an interesting alternative. CASE: A case of a 50-year-old woman with carcinoid syndrome and right-sided valvular heart disease is presented. Moderate pulmonary valve stenosis and severe tricuspid valve regurgitation were diagnosed during the evaluation and treatment of neuroendocrine tumor. The possibility of rare valve involvement and the need for interdisciplinary cooperation in the diagnosis, monitoring and treatment of patients with neuroendocrine tumors producing vasoactive substances must be emphasized. CONCLUSION: The patient had a typically presenting carcinoid syndrome with a rare cardiac manifestation. Although monitoring and treatment were carried out in accordance with recommendations and appropriate to the clinical condition, rapid progression of the metastatic disease ultimately precluded invasive cardiac intervention.

Arterial blood gas analysers: accuracy in determining haemoglobin, glucose and electrolyte concentrations in critically ill adult patients.

Arterial blood gas (ABG) machines are vital tools in the assessment of critically ill patients. Current ABG point-of-care (POC) analysers provide information on concentrations of haemoglobin, glucose and electrolytes in addition to acid-base balance. Awaiting results from venous analysers may present a significant delay in diagnosis and management, thus reliance on arterial blood gas determination of these parameters is increasing. However, published data on the concordance between the two modalities are limited. This study aims to assess the concordance of ABG machines in analysing haemoglobin, glucose and electrolyte concentrations compared to standard venous analysers as the gold standard. Results from 100 patients undergoing ABG analysis and simultaneous venous sampling without therapeutic intervention between sampling were compared. Differences in haemoglobin, glucose, sodium and potassium concentrations were determined and analysed using statistical software (Statview). There was a significant difference (P < 0.02, paired signed test) in the mean haemoglobin concentration between the two modalities of 0.91 g/dL (range: 0-4.3 g/dL). Mean discrepancy in glucose concentrations was 1.16 mmol/L (range: 0-10.5 mmol/L; P < 0.012, paired-signed test). Sodium and potassium showed no significant difference within the physiological range. At higher concentrations of potassium (> 5 mmol/L), ABG readings varied significantly (P < 0.0013, paired sign test) from standard venous estimates (mean difference: 0.44 mmol/L). Arterial blood gas analysers are invaluable for rapid assessment of critically ill patients; however, estimations of haemoglobin, glucose and potassium concentrations (> 5 mmol/L) obtained from such machines should be interpreted with caution and confirmed using standard venous samples.

Pain management mini-series part III. Procedural sedation for the non-anesthesia provider.

Diagnostic and therapeutic procedures performed outside of the operating room can necessitate the administration of sedation by non-anesthesia trained personnel. Risks associated with procedural sedation can be decreased through proper patient evaluation and selection. Understanding sedative pharmacology, dosing and delivery, monitoring and airway rescue techniques are essential to safely provide sedation. Supervision of sedation policies should occur via a carefully constructed sedation policy and ongoing sedation committee evaluation and review to ensure adequate patient care.

Pain management mini-series. Part II. Chronic opioid drug therapy: implications for perioperative anesthesia and pain management.

In the U.S., there is a growing percentage of chronic pain patients requiring surgery. Chronic pain patients require careful evaluation and planning to achieve appropriate acute pain management. Peri-surgical pain management often requires continuation of previously prescribed chronic pain modalities and careful selection of multimodal acute pain interventions. This article will provide a broad overview of chronic pain, definitions, and current recommendations for the treatment of perioperative pain in patients maintained on opioid therapy.

Small-molecule kinase inhibitors provide insight into Mps1 cell cycle function.

Mps1, a dual-specificity kinase, is required for the proper functioning of the spindle assembly checkpoint and for the maintenance of chromosomal stability. As Mps1 function has been implicated in numerous phases of the cell cycle, the development of a potent, selective small-molecule inhibitor of Mps1 should facilitate dissection of Mps1-related biology. We describe the cellular effects and Mps1 cocrystal structures of new, selective small-molecule inhibitors of Mps1. Consistent with RNAi studies, chemical inhibition of Mps1 leads to defects in Mad1 and Mad2 establishment at unattached kinetochores, decreased Aurora B kinase activity, premature mitotic exit and gross aneuploidy, without any evidence of centrosome duplication defects. However, in U2OS cells having extra centrosomes (an abnormality found in some cancers), Mps1 inhibition increases the frequency of multipolar mitoses. Lastly, Mps1 inhibitor treatment resulted in a decrease in cancer cell viability.

Synthetic lethal targeting of MYC by activation of the DR5 death receptor pathway.

The genetic concept of synthetic lethality provides a framework for identifying genotype-selective anticancer agents. In this approach, changes in cellular physiology that arise as a consequence of oncogene activation or tumor suppressor gene loss, rather than oncoproteins themselves, are targeted to achieve tumor selectivity. Here we show that agonists of the TRAIL death receptor DR5 potently induce apoptosis in human cells overexpressing the MYC oncogene, both in vitro and as tumor xenografts in vivo. MYC sensitizes cells to DR5 in a p53-independent manner by upregulating DR5 cell surface levels and stimulating autocatalytic processing of procaspase-8. These results identify a novel mechanism by which MYC sensitizes cells to apoptosis and validate DR5 agonists as potential MYC-selective cancer therapeutics.

Evaluation of the impact of human immunodeficiency virus pre-exposure prophylaxis on new human immunodeficiency virus diagnoses during the COVID-19 pandemic.

AIMS: The national PrEP programme launched in Ireland in November 2019 with tenofovir/emtricitabine free to those meeting eligibility criteria. We assessed the impact of the first year of the PrEP programme on new HIV diagnoses in the largest sexual health and HIV service in Ireland. METHODS: A free PrEP service was established in November 2019. We reviewed the number of new diagnoses of HIV between November 2018-2019, before the introduction of the national PrEP programme and compared this with the number of new HIV diagnosis between November 2019-2020. RESULTS: There were 95 new HIV diagnoses (63.3% MSM) between November 2018 and 2019 and 73 new HIV diagnoses (65.7% MSM) between November 2019 and 2020. There was a statistically significant decline in new HIV diagnoses between the 2 years (P = 0.0003). 546 patients were prescribed PrEP as of December 2020.106 patients (19.4%) changed their PrEP dosing regimen due to lockdown. 178 individuals (32.6%) had a rectal infection diagnosed. CONCLUSION: There has been a reduction in new HIV diagnoses in our cohort (although this has occurred during a global pandemic). It is too early to say if PrEP reduces late presentations of HIV based on our findings. A significant number of rectal infections were identified in the PrEP clinic suggesting ongoing risk despite pandemic restrictions. Further research into sexual practices during COVID-19 is needed to assess if this had an impact on the lower rates of HIV acquisition.

Identifying predictors of ventral hernia recurrence: systematic review and meta-analysis.

BACKGROUND: Ventra hernias are increasing in prevalence and many recur despite attempted repair. To date, much of the literature is underpowered and divergent. As a result there is limited high quality evidence to inform surgeons succinctly which perioperative variables influence postoperative recurrence. This systematic review aimed to identify predictors of ventral hernia recurrence. METHODS: PubMed was searched for studies reporting prognostic data of ventral hernia recurrence between 1 January 1995 and 1 January 2018. Extracted data described hernia type (primary/incisional), definitions of recurrence, methods used to detect recurrence, duration of follow-up, and co-morbidity. Data were extracted for all potential predictors, estimates and thresholds described. Random-effects meta-analysis was used. Bias was assessed with a modified PROBAST (Prediction model Risk Of Bias ASsessment Tool). RESULTS: Screening of 18 214 abstracts yielded 274 individual studies for inclusion. Hernia recurrence was defined in 66 studies (24.1 per cent), using 41 different unstandardized definitions. Three patient variables (female sex, age 65 years or less, and BMI greater than 25, 30, 35 or 40 kg/m2), five patient co-morbidities (smoking, diabetes, chronic obstructive pulmonary disease, ASA grade III-IV, steroid use), two hernia-related variables (incisional/primary, recurrent/primary), six intraoperative variables (biological mesh, bridged repair, open versus laparoscopic surgery, suture versus mesh repair, onlay/retrorectus, intraperitoneal/retrorectus), and six postoperative variables (any complication, surgical-site occurrence, wound infection, seroma, haematoma, wound dehiscence) were identified as significant prognostic factors for hernia recurrence. CONCLUSION: This study summarized the current evidence base for predicting ventral hernia recurrence. Results should inform best practice and future research.