Tag: nevin manimala

G3 (Bethesda). 2023 Sep 22:jkad219. doi: 10.1093/g3journal/jkad219. Online ahead of print.

ABSTRACT

Heterocyclic aromatic amines (HAAs) are potent carcinogenic agents found in charred meats and cigarette smoke. However, few eukaryotic resistance genes have been identified. We used Saccharomyces cerevisiae (budding yeast) to identify genes that confer resistance to 2-amino-3-methylimidazo[4,5-f] quinoline (IQ). CYP1A2 and NAT2 activate IQ to become a mutagenic nitrenium compound. Deletion libraries expressing human CYP1A2 and NAT2 or no human genes were exposed to either 400 or 800 µM IQ for five or ten generations. DNA barcodes were sequenced using the Illumina HiSeq 2500 platform and statistical significance was determined for exactly matched barcodes. We identified 424 ORFs, including 337 genes of known function, in duplicate screens of the “humanized” collection for IQ resistance; resistance was further validated for a select group of 51 genes by growth curves, competitive growth, or trypan blue assays. Screens of the library not expressing human genes identified 143 ORFs conferring resistance to IQ per se. Ribosomal protein and protein modification genes were identified as IQ resistance genes in both the original and “humanized” libraries, while nitrogen metabolism, DNA repair, and growth control genes were also prominent among the “humanized” library. Protein complexes identified included the casein kinase 2 (CK2) and histone chaperone (HIR) complex. Among DNA Repair and checkpoint genes, we identified those that function in post-replication repair (RAD18, UBC13, REV7), base excision repair (NTG1), and checkpoint signaling (CHK1, PSY2). These studies underscore the role of ribosomal protein genes in conferring IQ resistance, and illuminate DNA repair pathways for conferring resistance to activated IQ.

PMID:37738679 | DOI:10.1093/g3journal/jkad219

Neuro Oncol. 2023 Sep 22:noad182. doi: 10.1093/neuonc/noad182. Online ahead of print.

ABSTRACT

BACKGROUND: Comprehensive analysis of brain tumor incidence and survival in the Veteran population has been lacking.

METHODS: Veteran data was obtained from the Veterans Health Administration (VHA) Medical Centers via VHA Corporate Data Warehouse. Brain tumor statistics on the overall US population were generated from the Central Brain Tumor Registry of the US data. Cases were individuals (≥18 years) with a primary brain tumor, diagnosed between 2004-2018. The average annual age-adjusted incidence rates (AAIR) and 95% confidence intervals were estimated per 100,000 population and Kaplan-Meier survival curves evaluated overall survival outcomes among Veterans.

RESULTS: The Veteran population was primarily white (78%), male (93%), and between 60-64 years old (18%). Individuals with a primary brain tumor in the general US population were mainly female (59%) and between 18-49 years old (28%). The overall AAIR of primary brain tumors from 2004-2018 within the VA cancer registry was 11.6. Non-malignant tumors were more common than malignant tumors (AAIR:7.19 vs 4.42). The most diagnosed tumors in Veterans were non-malignant pituitary tumors (AAIR:2.96), non-malignant meningioma (AAIR:2.62), and glioblastoma (AAIR:1.96). In the Veteran population, survival outcomes became worse with age and were lowest among individuals diagnosed with glioblastoma.

CONCLUSIONS: Differences between Veteran and US populations can be broadly attributed to demographic composition differences of these groups. Prior to this, there have been no reports on national level incidence rates and survival outcomes for Veterans. These data provide vital information that can drive efforts to understand disease burden and improve outcomes for individuals with primary brain tumors.

PMID:37738677 | DOI:10.1093/neuonc/noad182

J Gerontol B Psychol Sci Soc Sci. 2023 Sep 22:gbad140. doi: 10.1093/geronb/gbad140. Online ahead of print.

ABSTRACT

OBJECTIVE: This feasibility study explored the impact of fostering a shelter cat on loneliness and well-being in older adults living alone without a pet. The study also examined the effect of cat fostering on older adults’ interest in cat adoption when perceived barriers to adoption were removed.

METHOD: Twenty-nine adults (age >60) were paired with a cat and asked to foster for a minimum of 4 months (with an option to adopt). Participants completed surveys before placement with cats, with a follow-up at 1 and 4 months post-placement and 12 months if they adopted their cat. The survey included scales of loneliness, physical and mental health, self-efficacy, positive and negative affect, and comfort from a companion animal. Scores were compared across time using a multivariate Linear Mixed Model.

RESULTS: Twenty-three of 29 (79.3%) participants remained in the study for at least 4 months, and a majority (95.7%) adopted their cat. Estimated mean differences in marginal means (adjusted for physical health) showed a significant improvement in loneliness from baseline to 4 months (p =0.029). A similar 4-month improvement that approached statistical significance (adjusted p = 0.079) was observed for mental health. No other scales showed statistically significant changes across time.

CONCLUSION: Fostering a shelter cat with the option for adoption may be an effective solution for alleviating loneliness and improving mental health in older adults. Interest in adopting foster cats was high when perceived barriers to adoption were removed.

PMID:37738674 | DOI:10.1093/geronb/gbad140

Int J Epidemiol. 2023 Sep 21:dyad127. doi: 10.1093/ije/dyad127. Online ahead of print.

ABSTRACT

Competing risks issues are common in clinical trials and epidemiological studies for patients in follow-up who may experience a variety of possible outcomes. Under such competing risks, two hazard-based statistical methods, cause-specific hazard (CSH) and subdistribution hazard (SDH), are frequently used to assess treatment effects among groups. However, the outcomes of the CSH-based and SDH-based methods have a close connection with the proportional hazards (CSH or SDH) assumption and may have an non-intuitive interpretation. Recently, restricted mean time lost (RMTL) has been used as an alternative summary measure for analysing competing risks, due to its clinical interpretability and robustness to the proportional hazards assumption. Considering the above approaches, we summarize the differences between hazard-based and RMTL-based methods from the aspects of practical interpretation, proportional hazards model assumption and the selection of restricted time points, and propose corresponding suggestions for the analysis of between-group differences under competing risks. Moreover, an R package ‘cRMTL’ and corresponding step-by-step guidance are available to help users for applying these approaches.

PMID:37738672 | DOI:10.1093/ije/dyad127

J Infect Dis. 2023 Sep 21:jiad412. doi: 10.1093/infdis/jiad412. Online ahead of print.

ABSTRACT

BACKGROUND: The value of the widely applied maternal cytomegalovirus (CMV) serological testing approach in predicting intrauterine transmission in highly seroprevalent regions remains unknown.

METHODS: A nested case‒control study was conducted based on a maternal-child cohort study. Newborns with congenital CMV (cCMV) infection were included, and each of them was matched to 3 newborns without cCMV infection. Retrospective samples were tested for immunoglobulin G (IgG) avidity and immunoglobulin M (IgM) antibodies in maternal serum and CMV DNA in maternal blood and urine to analyse their associations with cCMV infection.

RESULTS: Forty-eight newborns with cCMV infection and 144 matched newborns without infection were included in the study. Maternal IgM antibodies and IgG avidity during pregnancy were not statistically associated with intrauterine transmission. The presence of CMV DNAemia indicated a higher risk of cCMV infection, with the OR values as 5.7, 6.5 and 13.0 in early, middle and late pregnancy, respectively. However, the difference in CMV shedding rates in transmitters and nontransmitters was not significant in urine.

CONCLUSION: The value of current maternal CMV serological testing in regions with high seropositivity rates is very limited and should be reconsidered. The detection of DNAemia would be helpful in assessing the risk of intrauterine transmission.

PMID:37738651 | DOI:10.1093/infdis/jiad412

J Appl Clin Med Phys. 2023 Sep 22:e14143. doi: 10.1002/acm2.14143. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of this study is to assess the quality of automatic planned O-Ring Halcyon linac SBRT plans for pelvic lymph node metastases and to establish an absolute PTV volume threshold as a plan quality prediction criterion. Compliance of the plans to institutional SBRT plan evaluation criteria and differences in plan quality and treatment delivery times between Halcyon Linac and CyberKnife robotic SBRT were evaluated.

METHODS: Twenty-one CyberKnife treatment plans were replanned for Halcyon. Prescription doses range was 26-40 Gy in mean three fractions. The mean/median planning target volume was 4.0/3.6 cm³ . Institutional criteria for the plan evaluation were: New Conformity Index (NCI), Conformity Index (CI), Modified Gradient Index (MGI), selectivity index reciprocal (PIV/TV_PIV ), and the target coverage by prescription isodose (%PIV). Statistical analysis based on the receiver operating characteristic (ROC) curve was used to determine a plan quality predictor threshold of the PTV volume. Comparative analysis of normal tissue complication probabilities (NTCP) was used to assess the risk of toxicity in healthy tissues.

RESULTS: Seventy-one percent (n = 15)/95% (n = 20) of Halcyon and 81% (n = 17)/100% (n = 21) of CK plans fulfilled all ideal/tolerance criteria. For PTVs above a found optimal threshold of 2.6 cm³ (71%, n = 15), no statistically significant difference was observed between the CI, NCI, PIV/TV_PIV , and MGI indexes of both groups, while the coverage (%PIV) was statistically but not clinically significantly different between cohorts. Significantly shorter delivery times are expected with Halcyon. No significant differences in NTCP were observed.

CONCLUSION: All but one automatically optimized Halcyon treatment plans demonstrated ideal or acceptable performance. PTV threshold of 2.6 cm³ can be used as decision criteria in clinical settings. The results of our study demonstrated the promising performance of the Halcyon for pelvic SBRT, although plan-specific QA is required to verify machine performance during plan delivery.

PMID:37738649 | DOI:10.1002/acm2.14143

Ann Behav Med. 2023 Sep 21:kaad052. doi: 10.1093/abm/kaad052. Online ahead of print.

ABSTRACT

BACKGROUND: Cigarette pack inserts with messages on cessation benefits and advice are a promising labeling policy that may help promote smoking cessation.

PURPOSE: To assess insert effects, with and without accompanying pictorial health warning labels(HWLs), on hypothesized psychosocial and behavioral outcomes.

METHODS: We conducted a 2 × 2 between-subject randomized trial (inserts with efficacy messages vs. no inserts; large pictorial HWLs vs. small text HWLs), with 367 adults who smoked at least 10 cigarettes a day. Participants received a 14-day supply of their preferred cigarettes with packs modified to reflect their experimental condition. Over 2 weeks, we surveyed participants approximately 4-5 times a day during their smoking sessions, querying feelings about smoking, level of worry about harms from smoking, self-efficacy to cut down on cigarettes, self-efficacy to quit, hopefulness about quitting, and motivation to quit. Each evening, participants reported their perceived susceptibility to smoking harms and, for the last 24 hr, their frequency of thinking about smoking harms and cessation benefits, conversations about smoking cessation or harms, and foregoing or stubbing out cigarettes before they finished smoking. Mixed-effects ordinal and logistic models were estimated to evaluate differences between groups.

RESULTS: Participants whose packs included inserts were more likely than those whose packs did not include inserts to report foregoing or stubbing out of cigarettes (OR = 2.39, 95% CI = 1.36, 4.20). Otherwise, no statistically significant associations were found between labeling conditions and outcomes.

CONCLUSIONS: This study provides some evidence, albeit limited, that pack inserts with efficacy messages can promote behaviors that predict smoking cessation attempts.

PMID:37738629 | DOI:10.1093/abm/kaad052

Inflamm Bowel Dis. 2023 Sep 21:izad215. doi: 10.1093/ibd/izad215. Online ahead of print.

NO ABSTRACT

PMID:37738577 | DOI:10.1093/ibd/izad215

Pain Med. 2023 Sep 21:pnad128. doi: 10.1093/pm/pnad128. Online ahead of print.

ABSTRACT

OBJECTIVE: This case series retrospectively reviewed the outcomes in patients implanted with combined, synchronous dorsal root ganglion stimulation (DRGS) and spinal cord stimulation (SCS) connected to a single implantable pulse generator (IPG) in a tertiary referral neuromodulation centre in the United Kingdom.

MATERIALS AND METHODS: Twenty-six patients underwent a trial of DRGS+SCS for treating focal neuropathic pain between January 2016 and December 2019, with a follow-up in February 2022. A Transgrade approach was employed for DRGS. Patients were provided with three possible stimulation programmes: DRGS-only, SCS-only, or DRGS+SCS. Patients were assessed for pain intensity, patients’ global impression of change (PGIC), preferred lead(s) and complications.

RESULTS: Twenty patients were successful and went on for full implantation. The most common diagnosis was Complex Regional Pain Syndrome. After an average of 3.1 years follow-up, one patient was lost to follow-up, and two were non-responders. Of the remaining 17 patients, 16 (94%) continued to report a PGIC of 7. The average pain intensity at Baseline was 8.5 on an NRS scale of 0-10. At the last follow-up, the average NRS reduction overall was 78.9% with no statistical difference between those preferring DRGS+SCS (n = 9), SCS-only (n = 3) and DRGS-only (n = 5). The combination of DRGS+SCS was preferred by 53% at the last follow-up. There were no serious neurological complications.

CONCLUSION: This retrospective case series demonstrates the potential effectiveness of combined DRGS+SCS with sustained analgesia observed at an average follow-up of over three years. Implanting combined DRGS+SCS may provide programming flexibility and therapeutic alternatives.

PMID:37738574 | DOI:10.1093/pm/pnad128

Clin Infect Dis. 2023 Sep 21:ciad552. doi: 10.1093/cid/ciad552. Online ahead of print.

ABSTRACT

BACKGROUND: Widespread outbreaks of person-to-person transmission of hepatitis A virus (HAV), particularly among people who inject drugs (PWID), continue across the United States and globally. However, the herd immunity threshold and vaccination coverage required to prevent outbreaks is unknown. We aimed to use surveillance data and dynamic modeling to estimate herd immunity thresholds among PWID in 16 U.S. states.

METHODS: We used a previously published dynamic transmission model of HAV transmission, calibrated to surveillance data from outbreaks involving PWID in 16 states. Using state-level calibrated models, we estimated the basic reproduction number (R0) and herd immunity threshold for PWID in each state. We performed a meta-analysis of herd immunity thresholds to determine the critical vaccination coverage required to prevent most HAV outbreaks among PWID.

RESULTS: Estimates of R0 for HAV infection ranged from 2.2 (95% CI 1.9-2.5) for North Carolina to 5.0 (95% CI 4.5-5.6) for West Virginia. Corresponding herd immunity thresholds ranged from 55% (95% CI 47-61%) for North Carolina to 80% (95% CI 78-82%) for West Virginia. Based on the meta-analysis, we estimated a pooled herd immunity threshold of 64% (95% CI 61-68%, 90% prediction interval 52-76%) among PWID. Using the prediction interval upper bound (76%) and assuming 95% vaccine efficacy, we estimate a vaccination coverage of 80% could prevent most HAV outbreaks.

CONCLUSIONS: Hepatitis A vaccination programs in the United States may need to achieve vaccination coverage of at least 80% among PWID in order to prevent most HAV outbreaks among this population.

PMID:37738564 | DOI:10.1093/cid/ciad552