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The cuticle of the nematode Caenorhabditis elegans is a collagenous xtracellular matrix which forms the exoskeleton and defines the shape of the worm. We have characterized the C. elegans gene M142.2, and we show that this is a developmentally regulated gene important for cuticle structure. Transgenic worms expressing M142.2 promoter fused to green fluorescent protein showed that M142.2 is expressed in late embryos and L2d predauers, in the hypodermal cells which synthesize the cuticle. The same temporal pattern was seen by RT-PCR using RNA purified from specific developmental stages. A recombinant fragment of M142.2 was expressed in Escherichia coli and used to raise an antiserum. Immunohistochemistry using the antiserum localized M142.2 to the periphery of the alae of L1 and dauers, forming two longitudinal ribbons over the hypodermal cells. Loss-of-function of M142.2 by RNAi resulted in a novel phenotype: dumpy dauers which lacked alae. M142.2 therefore plays a major role in the assembly of the alae and the morphology of the dauer cuticle; because of its similarity to the other cut genes of the cuticle, we have named the gene cut-6. Keywords: Caenorhabditis elegans; Dauer; Cuticle; Extracellular matrix; ZP domain; VWFA domain

Objectives: To provide an overall perspective on musculoskeletal injury (MSI) epidemiology, risk factors, and preventive strategies in military personnel.Design: Narrative review.Methods: The thematic session on MSIs in military personnel at the 5th International Congress on Soldiers' Physical Performance (ICSPP) included eight presentations on the descriptive epidemiology, risk factor identification, and prevention of MSIs in military personnel. Additional topics presented were bone anabolism, machine learning analysis, and the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on MSIs. This narrative review focuses on the thematic session topics and includes identification of gaps in existing literature, as well as areas for future study.Results: MSIs cause significant morbidity among military personnel. Physical training and occupational tasks are leading causes of MSI limited duty days (LDDs) for the U.S. Army. Recent studies have shown that MSIs are associated with the use of NSAIDs. Bone MSIs are very common in training; new imaging technology such as high resolution peripheral quantitative computed tomography allows visualization of bone microarchitecture and has been used to assess new bone formation during military training. Physical activity monitoring and machine learning have important applications in monitoring and informing evidence-based solutions to prevent MSIs.Conclusions: Despite many years of research, MSIs continue to have a high incidence among military personnel. Areas for future research include quantifying exposure when determining MSI risk; understanding associations between health-related components of physical fitness and MSI occurrence; and application of innovative imaging, physical activity monitoring and data analysis techniques for MSI prevention and return to duty. [ABSTRACT FROM AUTHOR]

Despite being prioritized during initial COVID-19 vaccine rollout, vulnerable individuals at high risk of severe COVID-19 (hospitalization, intensive care unit admission, or death) remain underrepresented in vaccine effectiveness (VE) studies. The RAVEN cohort study (NCT05047822) assessed AZD1222 (ChAdOx1 nCov-19) two-dose primary series VE in vulnerable populations. Using the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub, linked to secondary care, death registration, and COVID-19 datasets in England, COVID-19 outcomes in 2021 were compared in vaccinated and unvaccinated individuals matched on age, sex, region, and multimorbidity. Over 4.5 million AZD1222 recipients were matched (mean follow-up ∼5 months); 68% were ≥50 years, 57% had high multimorbidity. Overall, high VE against severe COVID-19 was demonstrated, with lower VE observed in vulnerable populations. VE against hospitalization was higher in the lowest multimorbidity quartile (91.1%; 95% CI: 90.1, 92.0) than the highest quartile (80.4%; 79.7, 81.1), and among individuals ≥65 years, higher in the 'fit' (86.2%; 84.5, 87.6) than the frailest (71.8%; 69.3, 74.2). VE against hospitalization was lowest in immunosuppressed individuals (64.6%; 60.7, 68.1). Based on integrated and comprehensive UK health data, overall population-level VE with AZD1222 was high. VEs were notably lower in vulnerable groups, particularly the immunosuppressed. [Display omitted] • AZD1222 (ChAdOx1 nCoV-19) real-world vaccine effectiveness (VE) in 2021 was studied. • Over 4.5 million vaccinated individuals were assessed with ∼5 months mean follow-up. • VE was 84.1%/90.7%/85.9% for hospitalization/intensive care admission/death. • People with higher comorbidity burden or more severe frailty had lower VE. • Immunosuppressed individuals had the lowest VE from primary series vaccination. [ABSTRACT FROM AUTHOR]

Zinc is a ubiquitous biological metal in all living organisms. The spatiotemporal zinc dynamics in cells provide crucial cellular signaling opportunities, but also challenges for intracellular zinc homeostasis with broad disease implications. Zinc transporters play a central role in regulating cellular zinc balance and subcellular zinc distributions. The discoveries of two complementary families of mammalian zinc transporters (ZnTs and ZIPs) in the mid-1990s spurred much speculation on their metal selectivity and cellular functions. After two decades of research, we have arrived at a biochemical description of zinc transport. However, in vitro functions are fundamentally different from those in living cells, where mammalian zinc transporters are directed to specific subcellular locations, engaged in dedicated macromolecular machineries, and connected with diverse cellular processes. Hence, the molecular functions of individual zinc transporters are reshaped and deeply integrated in cells to promote the utilization of zinc chemistry to perform enzymatic reactions, tune cellular responsiveness to pathophysiologic signals, and safeguard cellular homeostasis. At present, the underlying mechanisms driving the functional integration of mammalian zinc transporters are largely unknown. This knowledge gap has motivated a shift of the research focus from in vitro studies of purified zinc transporters to in cell studies of mammalian zinc transporters in the context of their subcellular locations and protein interactions. In this review, we will outline how knowledge of zinc transporters has been accumulated from intest-tube to in-cell studies, highlighting new insights and paradigm shifts in our understanding of the molecular and cellular basis of mammalian zinc transporter functions. [ABSTRACT FROM AUTHOR]

To determine the prevalence of suicidal ideation and behaviour - and their correlates - in patients with persecutory delusions. 110 patients with persecutory delusions in the context of non-affective psychosis were assessed for suicidal thoughts and behaviours over the past month. Symptom and psychological assessments were also completed. The severity of suicidal ideation was: no suicidal ideation (n = 26, 23.6%); wish to be dead (n = 21, 19.1%); nonspecific active suicidal thoughts (n = 14, 12.7%); suicidal thoughts with methods but no intent (n = 29, 26.4%); suicidal thoughts with intent but no specific plan (n = 13, 11.8%); and suicidal intent with plan (n = 7, 6.4%). In the past month, five patients (4.5%) had made an actual, interrupted, or aborted suicide attempt. The severity of suicidal ideation was associated with higher levels of depression, paranoia, hallucinations, anger, insomnia, negative beliefs about the self and others, pessimism, worry, and delusion safety-seeking behaviours and lower levels of psychological well-being and reward responsiveness. Severity of ideation was not associated with cannabis or alcohol use, working memory, pain, or meaningful activity levels. Patients with persecutory delusions are typically in a severe state of psychological stress, and at risk of suicide, as indicated by very high levels of suicidal ideation. This exploratory study also identifies correlates of suicidal ideation that could be investigated in causal research designs. • Suicidal ideation is extremely common in patients with persecutory delusions. • Patients most typically had suicidal thoughts at least weekly, wanted to relieve pain, but reported deterrents to acting. • Severity of suicidal ideation was most associated with depression, negative self ideas, pessimism, worry, and low well-being. • The correlates found can inform future research that seeks to understand suicidal ideation in this patient group. [ABSTRACT FROM AUTHOR]

Lung cancer mortality can be reduced by 20% via low dose CT lung cancer screening (LCS) and treatment of early-stage disease. Providing tobacco use treatment to high risk cigarette smokers in the LCS setting may result in health benefits beyond the impact of LCS. As one of the nine trials in the National Cancer Institute's Smoking Cessation at Lung Examination (SCALE) collaboration, the goal of the Lung Screening, Tobacco, and Health (LSTH) trial is to develop a scalable and cost-effective cessation intervention for subsequent implementation by LCS programs. Guided by the RE-AIM Framework, the LSTH trial is a two-arm RCT (N = 1330) enrolling English- and Spanish-speaking smokers registered for LCS at one of seven collaborating sites. Participants are randomly assigned to Usual Care (UC; three proactive telephone counseling sessions/two weeks of nicotine patches) vs. Intensive Telephone Counseling (ITC; eight proactive sessions/eight weeks of nicotine patches, plus discussion of the LCS results to increase motivation to quit). Telephone counseling is provided by tobacco treatment specialists. To increase continuity of care, referring physicians are notified of participant enrollment and smoking status following the intervention. Outcomes include: 1) self-reported 7-day, 30-day, and sustained abstinence, and biochemically-verified at 3-, 6-, and 12-months post-randomization, 2) reach and engagement of the interventions, and 3) cost-effectiveness of the interventions. The Cancer Intervention and Surveillance Modeling Network (CISNET) will model long-term impacts of six SCALE trials on the cost per life year saved, quality-adjusted life years saved, lung cancer mortality reduction, and population mortality. The trial is registered at clinical trials.gov : NCT03200236. [ABSTRACT FROM AUTHOR]

• ZnR/GPR39 activates KCC3 in tamoxifen resistant breast cancer cells. • Zn2+ does not activate Ca2+ signaling or KCC3 in estrogen-dependent MCF-7 cells. • ZnR/GPR39-dependent KCC3 activation enhances cell proliferation and migration. Expression of the zinc receptor, ZnR/GPR39, is increased in higher grade breast cancer tumors and cells. Zinc, its ligand, is accumulated at larger concentrations in the tumor tissue and can therefore activate ZnR/GPR39-dependent Ca2+ signaling leading to tumor progression. The K+/Cl− co-transporters (KCC), activated by intracellular signaling, enhance breast cancer cell migration and invasion. We asked if ZnR/GPR39 enhances breast cancer cell malignancy by activating KCC. Activation of ZnR/GPR39 by Zn2+ upregulated K+/Cl− co-transport activity, measured using NH 4 + as a surrogate to K+ while monitoring intracellular pH. Upregulation of NH 4 + transport was monitored in tamoxifen resistant cells with functional ZnR/GPR39-dependent Ca2+ signaling but not in MCF-7 cells lacking this response. The NH 4 + transport was Na+-independent, and we therefore focused on KCC family members. Silencing of KCC3, but not KCC4, expression abolished Zn2+-dependent K+/Cl− co-transport, suggesting that KCC3 is mediating upregulated NH 4 + transport. The ZnR/GPR39-dependent KCC3 activation accelerated scratch closure rate, which was abolished by inhibiting KCC transport with [(DihydroIndenyl) Oxy] Alkanoic acid (DIOA). Importantly, silencing of either ZnR/GPR39 or KCC3 attenuated Zn2+-dependent scratch closure. Thus, a novel link between KCC3 and Zn2+, via ZnR/GPR39, promotes breast cancer cell migration and proliferation. [ABSTRACT FROM AUTHOR]

Objectives: Respiratory syncytial virus (RSV) causes respiratory infection across the world, with infants and the elderly at particular risk of developing severe disease and death. The replication-defective chimpanzee adenovirus (PanAd3-RSV) and modified vaccinia virus Ankara (MVA-RSV) vaccines were shown to be safe and immunogenic in young healthy adults. Here we report an extension to this first-in-man vaccine trial to include healthy older adults aged 60-75 years.Methods: We evaluated the safety and immunogenicity of a single dose of MVA-RSV given by intra-muscular (IM) injection (n = 6), two doses of IM PanAd3-RSV given 4-weeks apart (n = 6), IM PanAd3-RSV prime and IM MVA-RSV boost 8-weeks later (n = 6), intra-nasal (IN) spray of PanAd3-RSV prime and IM MVA-RSV boost 8-weeks later (n = 6), or no vaccine (n = 6). Safety measures included all adverse events within one week of vaccination and blood monitoring. Immunogenicity measures included serum antibody responses (RSV- and PanAd3-neutralising antibody titres measured by plaque-reduction neutralisation and SEAP assays, respectively), peripheral B-cell immune responses (frequencies of F-specific IgG and IgA antibody secreting cells and memory B-cells by ex vivo and cultured dual-colour ELISpot assays respectively), and peripheral RSV-specific T-cell immune responses (frequencies of IFNγ-producing T-cells by ex vivo ELISpot and CD4+/CD8+/Tfh-like cell frequencies by ICS/FACS assay).Results: The vaccines were safe and well tolerated. Compared with each individual baseline immunity the mean fold-changes in serum RSV-neutralising antibody, appearance and magnitude of F-specific IgG and IgA ASCs and expansion of CD4+/CD8+ IFNγ-producing T-cells in peripheral circulation were comparable to the results seen from younger healthy adults who received the same vaccine combination and dose. There were little/no IgA memory B-cell responses in younger and older adults. Expansion of IFNγ-producing T-cells was most marked in older adults following IM prime, with balanced CD4+ and CD8+ T cell responses. The RSV-specific immune responses to vaccination did not appear to be attenuated in the presence of PanAd3 (vector) neutralising antibody.Conclusions: PanAd3-RSV and MVA-RSV was safe and immunogenic in older adults and the parallel induction of RSV-specific humoral and cellular immunity merits further assessment in providing protection from severe disease. [ABSTRACT FROM AUTHOR]

Abstract Purpose We aimed to describe the incidence, timing, and predictors of recurrence following inguinal hernia repair (IHR) in children. Methods We used the TRICARE claims database, a national cohort of > 3 million child dependents of members of the U.S. Armed Forces. We abstracted data on children < 12y who underwent IHR (2005–2014). Our primary outcome was recurrence (ICD9-CM diagnosis codes). We calculated incidence rates for the population and stratified by age, time from repair to recurrence, and multivariable logistic regression to determine predictors. Results Nine thousand nine hundred ninety-three children met inclusion criteria. Age at time of IHR was ≤ 1y in 37%, 2-3y in 23%, 4–5y in 16%, and 5–12y in 24%. Median follow-up time was 3.5y (IQR:1.6–6.1). 137 patients recurred (1.4%), with an incidence of 3.46 per 1000 person-years. Over half occurred in children 0-1y at repair (60%). The majority occurred within a year following repair (median 209 days [IQR:79–486]). Children 0-1y had 2.53 times greater odds of recurrence (compared to > 5y). Children with multiple comorbidities had 5.45 times greater odds compared to those with no comorbidities. Conclusions The incidence of recurrence following IHR is 3.46 per 1000 person-years. The majority occurred within a year of repair. Children ≤ 1y and those with multiple comorbidities were at increased risk. Level of Evidence Prognosis Study, Level II. [ABSTRACT FROM AUTHOR]

Background The importance of smoking cessation interventions in lung cancer screening participants has been highlighted. This study aimed to describe the smoking habits of individuals who were ineligible for lung cancer screening and to investigate whether this encounter may represent an opportunity to reduce tobacco use. Methods Ever smokers between the ages of 55 and 80 and ≥1.5% lung cancer risk over 6 years or having smoked ≥30 pack-years and with no more than 15 years of smoking abstinence were eligible to participate in the Alberta Lung Cancer Screening Program (ALCSP). A baseline questionnaire exploring tobacco use was administered to all interested individuals as part of the eligibility determination for the program. Results Among 504 individuals, 254 (50.4%) met the criteria for the ALCSP and 250 (49.6%) were non-eligible for screening. Non-eligible individuals were slightly younger (mean = 60.2 vs. 63.1 years, p-value <0.001), and less likely to be current smokers (26.0% vs. 48.8%, p-value <0.001). Non-eligible smokers had a lower degree of addiction compared to eligible group, as measured by the Fagerström Test of Nicotine Dependence (Median = 4.0 vs 6.0, p-value = 0.001), but still in the “moderately dependent” range for this test. There were no significant differences in motivation to quit (98.5% vs. 97.6%, p-value = 0.689), or motivation to receive help with their quit attempt (89.2% vs. 90.3%, p-value = 0.813) between these two groups. Only 7.7% of non-eligible and 2.4% of eligible current smokers were currently in a smoking cessation program. Conclusion A significant proportion of individuals applying to, but not qualifying for a lung cancer screening program are active smokers with significant nicotine dependence. Very few are currently participating in active smoking cessation programs but almost all are interested in quitting and in receiving help with quit attempts. Future studies need to investigate the most effective approaches for smoking cessation in this substantial group of older, long-term smokers, capitalizing on their motivation to receive cessation assistance. [ABSTRACT FROM AUTHOR]

Incorporating effective smoking cessation interventions into lung cancer screening (LCS) programs will be essential to realizing the full benefit of screening. We conducted a pilot randomized trial to determine the feasibility and efficacy of a telephone-counseling (TC) smoking cessation intervention vs. usual care (UC) in the LCS setting. In collaboration with 3 geographically diverse LCS programs, we enrolled current smokers (61.5% participation rate) who were: registered to undergo LCS, 50–77 years old, and had a 20+ pack-year smoking history. Eligibility was not based on readiness to quit. Participants completed pre-LCS (T0) and post-LCS (T1) telephone assessments, were randomized to TC ( N = 46) vs. UC ( N = 46), and completed a final 3-month telephone assessment (T2). Both study arms received a list of evidence-based cessation resources. TC participants also received up to 6 brief counseling calls with a trained cessation counselor. Counseling calls incorporated motivational interviewing and utilized the screening result as a motivator for quitting. The outcome was biochemically verified 7-day point prevalence cessation at 3-months post-randomization. Participants (56.5% female) were 60.2 (SD = 5.4) years old and reported 47.1 (SD = 22.2) pack years; 30% were ready to stop smoking in the next 30 days. TC participants completed an average of 4.4 (SD = 2.3) sessions. Using intent-to-treat analyses, biochemically verified quit rates were 17.4% (TC) vs. 4.3% (UC), p < .05. This study provides preliminary evidence that telephone-based cessation counseling is feasible and efficacious in the LCS setting. As millions of current smokers are now eligible for lung cancer screening, this setting represents an important opportunity to exert a large public health impact on cessation among smokers who are at very high risk for multiple tobacco-related diseases. If this evidence-based, brief, and scalable intervention is replicated, TC could help to improve the overall cost-effectiveness of LCS. Trial registration NCT02267096 , https://clinicaltrials.gov [ABSTRACT FROM AUTHOR]

Introduction: The literature on the effect of head injuries on the risk of PD is inconclusive. Some researchers have hypothesized that studies that have seen an effect are simply capturing injury related to pre-clinical PD. However in animal models brain inflammation, which can be initiated by head trauma, has been shown to produce PD-like effects. Furthermore, animal studies have found that early life inflammation in particular is of relevance for PD pathology.Methods: We conducted an unmatched case-control study of 379 neurologist confirmed PD patients and 230 controls from the greater Boston, Massachusetts area with questionnaire data on history of head injury and other covariates. We used multivariable logistic regression to estimate adjusted odds ratios (OR) and their corresponding 95% confidence intervals (CI) for PD.Results: When we excluded injuries that occurred less than 10 years prior to the diagnosis of PD (in order to avoid reverse causation), we found an increased risk of PD associated with a head injury that resulted in a loss of consciousness, but it did not reach statistical significance (OR = 1.57; 95% CI = 0.89-2.80). We found a significant (p = 0.04) effect of age at first head injury. For every 5 year earlier age at first head injury with loss of consciousness the OR for PD was 1.37 (95% CI: 1.01-1.86).Conclusion: Our results suggest that head injury in early life increases the risk of PD. [ABSTRACT FROM AUTHOR]

Objectives: referrals between health care facilities are important in low-resource settings, particularly in maternal and child health, to transfer pregnant patients to the appropriate level of obstetric care. Our aim was to characterise the obstetrical referrals from a rural clinic to a community referral hospital in Honduras, to identify barriers in effective transport/referral, and to describe subsequent patient outcomes. Methods: we performed a descriptive retrospective study of patients referred during a 9-month period. We reviewed patient charts to review diagnosis, referral, and treatment times at both sites to understand the continuity of care. Results: ninety-two pregnant patients were referred from the rural clinic to the community hospital. Twenty six pregnant patients (28%) did not have complete and accurate medical records and were excluded from the study. The remaining 66 patients were our study population. Of the 66 patients, 54 (82%) received antenatal care with an average of 5.5 ± 2.4 visits. The most common diagnoses requiring referral were non-reassuring fetal status, hypertensive disorders of pregnancy, and preterm labour. The time spent in the rural clinic until transfer was 7.35 ± 8.60 hours, and transport times were 4.42 ± 1.07 hours. Of the 66 women transferred, 24 (36%) had different primary diagnoses and 16 (24%) had additional diagnoses after evaluation in the community hospital, whereas the remaining 26 (40%) had diagnoses that remained the same. No system was in place to give feedback to the referring clinic doctors regarding their primary diagnoses. Conclusions: our results demonstrate challenges seen in obstetric transport from a rural clinic to a community hospital in Honduras. Further research is needed for reform of emergency obstetric care management, targeting both healthcare personnel and medical referral infrastructure. The example of Honduras can be taken to motivate change in other resource-limited areas. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To determine factors influencing Family Physician (FP) uptake of non government-funded vaccines, and to explore FP attitudes towards the introduction and use of a new vaccine to protect against serogroup B meningococcal disease to inform its future introduction into the Australian Immunisation Schedule. DESIGN SETTING AND PARTICIPANTS: Quantitative, self-administered state-wide questionnaire mailed to all FPs in South Australia (n=1786). Results from 523 FP respondents in South Australia, collected between June and October 2013. MAIN OUTCOME MEASURES: Self-reported immunisation counselling practices; and knowledge, attitudes and barriers to prescribing of Meningococcal B (Men B) vaccine and other recommended, non-funded immunisations. RESULTS: The response rate was 30% (n=523). While most (59%) respondents had worked in general practice for over 20 years, only 39% of all respondents had ever had personal or professional experience with a case of invasive meningococcal disease (IMD). Most FPs (63%) were aware that a meningococcal B vaccine was being developed, and 93% of respondents agreed that this vaccine should be government-funded. FPs ranked Men B vaccine as the highest priority to receive funding of eight currently non-funded immunisation strategies. High vaccine cost and low patient socioeconomic status were identified as definite barriers to prescribing non-funded vaccines by 59% of respondents. Past IMD experience significantly affected attitudes and prescribing practices. CONCLUSIONS: IMD, while encountered rarely in clinical practice, is considered an important disease to vaccinate against by FPs. Cost and perceived low socioeconomic status of patients are substantial barriers to FPs prescribing Men B and other non-funded vaccines, and inclusion of such vaccines on the National Immunisation Program is likely to improve equity of access. [ABSTRACT FROM AUTHOR]

Abstract: Triple assessment in men varies, possibly in response to currently published non-specific guidance. The study aims to assess the efficacy of triple assessment as part of an age related protocol currently used in the clinical setting. 1141 referrals between 01.01.01 and 31.12.09 were evaluated. Patient age ranged from 29 to 89 years. Mammography (M) was performed in men ≥35years. Sensitivity for clinical examination (CE) was 64.0%, M 77.8%, US 92.0%. 25 cancers were diagnosed, 24 aged >40years, 1 aged 29. 2 presented with nipple discharge. The cancer <40years was diagnosed with CE and US, all others had suspicious CE and/or M necessitating US and biopsy. We suggest a protocol incorporating mammography in men ≥40years would capture all cancers. Combined specificities approaching 100% suggest men >40 years scored benign after CE and M warrant no further assessment. Bloody nipple discharge is a suspicious sign and the reassurance of non-bloody discharge should be treated with caution. [Copyright &y& Elsevier]

Renin-angiotensin-aldosterone system inhibitors prevent the progression of kidney disease in patients with diabetic nephropathy, and we studied how that benefit varies by the type of diabetes and baseline urinary albumin. We pooled data from 49 randomized controlled trials in a meta-analysis using the ratio of endpoint urinary albumin levels in those treated compared to those untreated with renin-angiotensin-aldosterone system inhibitors in both fixed- and random-effects models. The urinary albumin excretion for treated microalbuminuric patients with Type 1 diabetes was on average 60% lower at the end of the trial compared with patients not treated with renin-angiotensin-aldosterone system inhibitors using the fixed-effects model and 67% lower using the random-effects model. There was no significant effect of treatment in patients with normal albumin excretion. For normoalbuminuric patients with Type 2 diabetes, urinary albumin excretion was on average 12% lower after treatment using the fixed-effects model compared to 21% lower using the random-effects model. For microalbuminuric patients, urinary albumin excretion was on average 23% lower using the fixed-effects model and 27% lower using the random-effects model. Thus, renin-angiotensin-aldosterone system inhibition reduced urinary albumin excretion for Type 1 diabetic patients with micro-, but not those with normoalbuminuria. Treatment reduced urinary albumin excretion for Type 2 diabetic patients with and without microalbuminuria. [ABSTRACT FROM AUTHOR]

Summary: Background: Lung cancer screening may serve as a ‘teachable moment’ for smoking cessation, a brief period in which motivation to stop smoking is enhanced. Within the context of two NCI-funded randomized lung screening trials, we conducted an ancillary study to explore the impact of screening on smoking cessation and readiness to stop smoking. Methods: We accrued a sample of current and former smokers participating at the Georgetown University site of the Lung Screening Study (LSS; N =144) and of the National Lung Screening Trial (NLST; N =169). In each sample, we assessed reasons for trial participation, interest in smoking cessation interventions, motivations for stopping smoking, and the impact of undergoing screening on tobacco use and readiness to stop smoking. Telephone interviews were conducted prior to screening, and 1-month following receipt of the screening result. The samples were analyzed separately due to differences in age and level of nicotine dependence. Results: The majority of the findings were consistent across the two samples. Frequently endorsed reasons for trial participation among both current and former smokers included psychological reasons (e.g., wanting peace of mind about lung cancer) and altruism (e.g., wanting to make a contribution to science). Nicotine replacement therapy and free counseling were the cessation methods that were of most interest, and fear of lung health problems was the most frequently endorsed motivation for quitting smoking. Regarding readiness to stop smoking, approximately 20% were ready to stop in the next 30 days, 45% were ready to stop in the next 6 months, while 35% were not thinking of stopping. At the follow-up, 7% of current smokers at baseline reported abstinence, and 4% of former smokers at baseline reported having relapsed. The findings differed across the two samples when considering the readiness to quit outcome. At the 1-month follow-up of the NLST sample, participants became more ready to stop smoking (p <.05). Screening result did not moderate this finding. In the LSS sample, among younger participants (≤64), an abnormal screening result was significantly associated with becoming more ready to stop smoking, whereas a normal result was associated with becoming less ready to stop smoking (p =.02). Conclusions: The current findings demonstrated the feasibility of enrolling lung screening participants into a smoking-related research study, as well as the high level of interest in stopping smoking and in smoking cessation interventions. These data indicate that lung cancer screening may serve as a teachable moment for smoking cessation, and suggest that a smoking cessation trial within the context of lung cancer screening is feasible. [Copyright &y& Elsevier]

Significant demands are being placed on the informal caregivers of chronically ill patients, including those suffering from cancer. Health care professionals need to be aware of these demands, and they need effective tools to assess the impact these demands place on the caregivers. Over the past 25 years, researchers have developed self-report instruments to assess informal caregivers. These instruments assess various aspects of the caregiving experience, including caregiver burden, needs, and quality of life. The purpose of this review was to identify and critically evaluate these instruments. MEDLINE and PUBMED were searched from 1966 to 2002. After an extensive literature search and review, and utilizing specific inclusion criteria, 28 instruments were identified and evaluated in terms of their development, content, and psychometric properties. In addition, a history of the construct and measurement development in the areas of caregiver burden, needs, and quality of life are discussed. Although some further development and refinement of instruments could benefit the field, depending on the questions researchers or clinicians seek to pursue, there are many proven tools available for their use. Future research needs to use these instruments to assess the effectiveness of interventions aimed at improving the care of the caregivers. [Copyright &y& Elsevier]

Zinc is an essential ion for cells with a vital role to play in controlling the cellular processes of the cell, such as growth, development and differentiation. Specialist proteins called zinc transporters control the level of intracellular zinc in cells. In mammals, the ZIP family of zinc transporters has a pivotal role in maintaining the correct level of intracellular zinc by their ability to transport zinc into cells from outside, although they may also transport metal ions other than zinc. There are now recognised to be four subfamilies of the ZIP transporters, including the recently discovered LIV-1 subfamily which has similarity to the oestrogen-regulated gene LIV-1, previously implicated in metastatic breast cancer. We call this new subfamily LZT, for LIV-1 subfamily of ZIP zinc Transporters. Here we document current knowledge of this previously uncharacterised group of proteins, which includes the KE4 proteins. LZT proteins are similar to ZIP transporters in secondary structure and ability to transport metal ions across the plasma membrane or intracellular membranes. However, LZT proteins have a unique motif (HEXPHEXGD) with conserved proline and glutamic acid residues, unprecedented in other zinc transporters. The localisation of LZT proteins to lamellipodiae mirrors cellular location of the membrane-type matrix metalloproteases. These differences to other zinc transporters may be consistent with an alternative role for LZT proteins in cells, particularly in diseases such as cancer. [Copyright &y& Elsevier]

Genes involved in normal developmental processes often have a role in tumour progression. Epithelial-mesenchymal transition (EMT) is a general phenomenon that is an essential event in embryonic development, tissue remodelling and wound repair. Genes that regulate EMT are attracting significant attention as mediators of tumour progression. Indeed, EMT is considered an important event during the evolution of malignant tumours and their progression to metastasis, with several reports of molecules involved in this process facilitating migration and invasion of epithelial tumour cells. Recent work linking the zinc transporter LIV-1 with the transcription factors STAT3 and Snail in zebrafish embryogenesis, throws new light on this transition and has important implications for the development of cancer. [Copyright &y& Elsevier]

Zinc ions serve as second messengers in major cellular pathways, including the regulation pathways of proliferation and their proper regulation is necessary for homeostasis and a healthy organism. Accordingly, expression of zinc transporters can be altered in various cancer cell lines and is often involved in producing elevated intracellular zinc levels. In this study, human B cells were infected with Epstein-Barr virus (EBV) to generate immortalized cells, which revealed traits of tumor cells, such as high proliferation rates and an extended lifespan. These cells showed differentially altered zinc transporter expression with ZIP7 RNA and protein expression being especially increased as well as a corresponding increased phosphorylation of ZIP7 in EBV-transformed B cells. Accordingly, free zinc levels were elevated within these cells. To prove whether the observed changes resulted from immortalization or rather high proliferation, free zinc levels in in vitro activated B cells and in freshly isolated B cells expressing the activation marker CD69 were determined. Here, comparatively increased zinc levels were found, suggesting that activation and proliferation, but not immortalization, act as crucial factors for the elevation of intracellular free zinc. [ABSTRACT FROM AUTHOR]

Abstract: We report a rare case of a female patient that developed a recurrence of a clival chordoma in the pathway of surgical access following prior resection. We review the world literature regarding surgical pathway recurrences. An 18-year-old female patient presented with a 4cm×3cm mass in the midline of the hard palate. She had a history of a large clival chordoma resected via a transoral transpalatal approach 2 years previously. She was diagnosed as having a recurrence of the chordoma following implantation in the surgical pathway. She was treated with a transoral radical resection of the hard palate followed by a radial free forearm flap reconstruction. Chordomas are locally aggressive, slow growing tumors with a high local recurrence rate. A rare mechanism of treatment failure is recurrence along the pathway of surgical access. Only isolated cases of this phenomenon have been reported in the world literature. We review the world literature regarding surgical pathway recurrences. [Copyright &y& Elsevier]

The progress in wireless communications and information access has demanded the use of electronic ceramics exhibiting desired properties. To further our understanding of these properties, compounds in the Ln2Ti2–2xM2xO7 (Ln=Gd, Er; M=Zr, Sn, Si) systems were synthesized by ceramic methods and characterized by powder X-ray diffraction. The ZrO2–doped Gd2Ti2−2xZr2xO7 compounds adopt the pyrochlore structure type and form a complete solid solution. Er2Ti2−2xZr2xO7 forms a pyrochlore solid solution for x<0.1. However, stoichiometric Er2Zr2O7 does not form; instead Er4Zr3O12 forms a with defect fluorite structure. The Sn–doped Ln2Ti2−2xSn2xO7 (Ln=Gd, Er) compounds form complete solid solutions, and the Si compounds adopt the pyrochlore structure up to x=0.05. At ambient temperature, dielectric constants range from 10 to 61 for Er2Ti2−2xZr2xO7 and 16–31 for Gd2Ti2−2xZr2xO7 with low dielectric loss (1×10−3) at 1 GHz. [ABSTRACT FROM AUTHOR]

Numerous zinc ectoenzymes are metalated by zinc and activated in the compartments of the early secretory pathway before reaching their destination. Zn transporter (ZNT) proteins located in these compartments are essential for ectoenzyme activation. We have previously reported thatZNTproteins, specifically ZNT5-ZNT6 heterodimers and ZNT7 homodimers, play critical roles in the activation of zinc ectoenzymes, such as alkaline phosphatases (ALPs), by mobilizing cytosolic zinc into these compartments. However, this process remains incompletely understood. Here, using genetically-engineered chicken DT40 cells, we first determined that Zrt/Irt-like protein (ZIP) transporters that are localized to the compartments of the early secretory pathway play only a minor role in the ALP activation process. These transporters included ZIP7, ZIP9, and ZIP13, performing pivotal functions in maintaining cellular homeostasis by effluxing zinc out of the compartments. Next, using purified ALP proteins, we showed that zinc metalation on ALP produced in DT40 cells lacking ZNT5-ZNT6 heterodimers and ZNT7 homodimers is impaired. Finally, by genetically disrupting both ZNT5 and ZNT7 in human HAP1 cells, we directly demonstrated that the tissue-nonspecific ALP-activating functions of both ZNT complexes are conserved in human cells. Furthermore, using mutant HAP1 cells, we uncovered a previouslyunrecognized and unique spatial regulation of ZNT5-ZNT6 heterodimer formation, wherein ZNT5 recruits ZNT6 to the Golgi apparatus to form the heterodimeric complex. These findings fill in major gaps in our understanding of the molecular mechanisms underlying zinc ectoenzyme activation in the compartments of the early secretory pathway. [ABSTRACT FROM AUTHOR]

• Many efficacious interventions exist that could be implemented by screening sites. • Cessation estimates are lower than the general population. • Multi-modality interventions appear to be most efficacious. • Cessation persists at 12-months in two intervention categories. Current guidelines recommend delivery of smoking cessation interventions with lung cancer screening (LCS). Unfortunately, there are limited data to guide clinicians and policy-makers in choosing cessation interventions in this setting. Several trials are underway to fill this evidence gap, but results are not expected for several years. We conducted a systematic review and meta-analysis of current literature on the efficacy of smoking cessation interventions among populations eligible for LCS. We searched PubMed, Medline, and PsycINFO for randomized controlled trials of smoking cessation interventions published from 2010–2017. Trials were eligible for inclusion if they sampled individuals likely to be eligible for LCS based on age and smoking history, had sample sizes >100, follow-up of 6- or 12-months, and were based in North America, Western Europe, Australia, or New Zealand. Three investigators independently screened 3,813 abstracts and identified 332 for full-text review. Of these, 85 trials were included and grouped into categories based on the primary intervention: electronic/web-based, in-person counseling, pharmacotherapy, and telephone counseling. At 6-month follow-up, electronic/web-based (odds ratio [OR] 1.14, 95% CI 1.03–1.25), in-person counseling (OR 1.46, 95% CI 1.25–1.70), and pharmacotherapy (OR 1.53, 95% CI 1.33–1.77) interventions significantly increased the odds of abstinence. Telephone counseling increased the odds but did not reach statistical significance (OR 1.21, 95% CI 0.98–1.50). At 12-months, in-person counseling (OR 1.28 95% CI 1.10–1.50) and pharmacotherapy (OR 1.46, 95% CI 1.17–1.84) remained efficacious, although the decrement in efficacy was of similar magnitude across all intervention categories. Several categories of cessation interventions are promising for implementation in the LCS setting. [ABSTRACT FROM AUTHOR]

Highlights • Body fat is associated with permethrin exposure from wearing newly treated uniforms. • Physical activity increased permethrin exposure when wearing newly treated uniforms. • Uniform laundering and wear-time duration significantly impact permethrin exposure. Abstract Wearing of permethrin treated clothing is becoming more prevalent in military and outdoor occupational and recreational settings, as a personal protection measure against vector borne diseases transmitted through arthropods (e.g., malaria, Lyme disease). The goal of the study was to prospectively examine permethrin exposure among new U.S. Army recruits who had just been issued permethrin-treated uniforms over a 10-week military training period and whether individual body composition (percent body fat, %BF) and physical workload (total energy expenditure, TEE) influenced the exposure. Exposure was assessed by quantification in urine of three permethrin metabolites, 3-phenoxybenzoic acid (3-PBA), and cis- and trans- 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid. Although there was individual variability, urinary concentrations and estimated dose levels decreased over the 10-week period. Mixed models demonstrated that 10% higher %BF was significantly associated with 4.42% higher 3-PBA concentrations and a 10% higher daily TEE was significantly associated with a 10.57% higher 3-PBA concentrations. Additional factors influencing exposure included sex, number of uniform launderings, and wear- time (hours per previous day). [ABSTRACT FROM AUTHOR]