Chemotherapy-induced gut microbiome disruption, inflammation, and cognitive decline in female patients with breast cancer.

Chemotherapy is notorious for causing behavioral side effects (e.g., cognitive decline). Notably, the gut microbiome has recently been reported to communicate with the brain to affect behavior, including cognition. Thus, the aim of this clinical longitudinal observational study was to determine whether chemotherapy-induced disruption of the gut microbial community structure relates to cognitive decline and circulating inflammatory signals. Fecal samples, blood, and cognitive measures were collected from 77 patients with breast cancer before, during, and after chemotherapy. Chemotherapy altered the gut microbiome community structure and increased circulating TNF-α. Both the chemotherapy-induced changes in microbial relative abundance and decreased microbial diversity were related to elevated circulating pro-inflammatory cytokines TNF-α and IL-6. Participants reported subjective cognitive decline during chemotherapy, which was not related to changes in the gut microbiome or inflammatory markers. In contrast, a decrease in overall objective cognition was related to a decrease in microbial diversity, independent of circulating cytokines. Stratification of subjects, via a reliable change index based on 4 objective cognitive tests, identified objective cognitive decline in 35% of the subjects. Based on a differential microbial abundance analysis, those characterized by cognitive decline had unique taxonomic shifts (Faecalibacterium, Bacteroides, Fusicatenibacter, Erysipelotrichaceae UCG-003, and Subdoligranulum) over chemotherapy treatment compared to those without cognitive decline. Taken together, gut microbiome change was associated with cognitive decline during chemotherapy, independent of chemotherapy-induced inflammation. These results suggest that microbiome-related strategies may be useful for predicting and preventing behavioral side effects of chemotherapy.

Key lessons from the establishment of a nurse-led infection prevention and control program for COVID-19 in an Australian hotel quarantine and isolation service.

BACKGROUND: A key aspect of Australia's response to the COVID-19 pandemic was to control transmission through legislated quarantine and isolation of overseas returning travellers and potentially infectious community members. In New South Wales, Special Health Accommodation (SHA) was rapidly established as a comprehensive health service for individuals that were at risk of having COVID-19, were confirmed to have COVID-19 or for those with complex health needs that were deemed inappropriate for management in Police managed Quarantine Hotels. SHA services were later expanded to care for community members who were COVID-19 positive and unable to effectively isolate, or contacts of individuals who were unable to quarantine effectively in their homes. SHA's unique nurse-led Infection Prevention and Control (IPC) program offers key lessons that may impact future programs. METHODS: A reflection on the experience of leading an Infection Prevention and Control program in SHA was undertaken. This was supported by a review of SHA admission, workforce and transmission data and data obtained from a cross-sectional questionnaire aimed to better understand the experiences of a novel population of health workers (HW) in a comprehensive health-led quarantine and isolation service. RESULTS: SHA program data demonstrates how its IPC program implementation prevented transmission of COVID-19 to SHA staff and patients. Responses from the questionnaire suggested staff felt safe and well-prepared through the IPC education they received. They also gained transferrable knowledge and skills, which they intend to use in future healthcare roles. CONCLUSION: The SHA nurse-led IPC program offered successful quarantine and isolation for COVID-19 in non-purpose-built facilities. A review of IPC strategies and key lessons from the establishment of the SHA IPC program are of critical importance to planning and management of current and future pandemics.

The effects of standing foot-transmitted vibration on self-reported discomfort ratings.

BACKGROUND: Occupational foot-transmitted vibration (FTV) exposure is common in industries like mining, construction, and agriculture, often leading to acute and chronic injuries. Vibration assessments require technical expertise and equipment which can be costly for employers to perform. Alternatively, researchers have observed that self-reported discomfort can be used as an effective indicator of injury risk. OBJECTIVE: This study aimed to investigate the effect of standing FTV exposure on self-reported ratings of discomfort, and whether these subjective ratings differed by body area and exposure frequency. METHODS: Participants (n = 30) were randomly exposed to standing FTV at six frequencies (25, 30, 35, 40, 45, and 50 Hz) for 20-45 seconds. Following each exposure, participants rated discomfort on a scale of 0-9 in four body areas: head and neck (HN), upper body (UB), lower body (LB), and total body. RESULTS: Results indicated that participants experienced the most discomfort in the LB at higher frequencies (p < 0.001), consistent with the resonance of foot structures. The HN discomfort tended to decrease as the exposure frequency increased, although not statistically significant (p > 0.0167). The UB discomfort remained relatively low across all frequencies. CONCLUSIONS: The study suggests a potential connection between resonant frequencies and discomfort, potentially indicating injury risk. Although self-reported discomfort is insufficient for directly assessing injury risk from FTV, it provides a simple method for monitoring potential musculoskeletal risks related to vibration exposure at resonant frequencies. While professional vibration assessment remains necessary, self-reported discomfort may act as an early indicated of vibration-induced injuries, aiding in implementing mitigation strategies.

Retention in a 6-Month Smoking Cessation Study Among Alaska Native and American Indian People.

Participant retention in longitudinal health research is necessary for generalizable results. Understanding factors that correlate with increased retention could improve retention in future studies. Here, we describe how participant and study process measures are associated with retention in a longitudinal tobacco cessation research study performed in Anchorage, Alaska. Specifically, we conducted a secondary analysis exploring retention among 151 Alaska Native and American Indian (ANAI) people and described our study processes using study retention categories from a recent meta-analysis. We found that our study processes influence retention among ANAI urban residents more than measures collected about the participant. For study process measures, calls where a participant answered and calls participants placed to the study team were associated with higher retention. Calls where the participant did not answer were associated with lower retention. For participant measures, only lower annual income was associated with lower retention at 6 weeks. Promoting communication from participants to the study team could improve retention, and alternative communication methods could be used after unsuccessful calls. Finally, categorizing our study retention strategies demonstrated that additional barrier-reduction strategies might be warranted.

The impact of wait time on patient outcomes in knee and hip replacement surgery: a scoping review protocol.

BACKGROUND: Total hip and total knee replacement surgery are in high demand, leading to long wait times for many patients. While on the waiting list, patients may experience worsening pain, reduced mobility, and deteriorating health. Given that long wait times are common for lower joint replacement surgery, it is important to understand how patient health changes during the wait period and whether this impacts patient outcomes after surgery. The aim of this scoping review will be to identify and describe the evidence regarding the impact of wait time on patient outcomes for patients who undergo total knee and total hip replacement surgery. METHODS: This scoping review was designed with guidance from the Joanna Briggs Institute Manual for Evidence Synthesis, and results will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. EMBASE, Medline, PubMed, Scopus, CINAHL, and Cochrane electronic databases will be searched for English language articles published after 1999. Studies of adult patients with osteoarthritis undergoing primary knee or hip replacement surgery, which measure patient outcomes over the wait period for surgery, will be included. Two independent reviewers will screen titles and abstracts followed by full article review. Data will be extracted by two reviewers using a standardized form. Outcomes assessed during the wait period will be identified and described in tables. Factors associated with changes in health status during the wait period will be qualitatively described. DISCUSSION: This review will map the evidence regarding wait times for lower extremity joint replacement surgery. Better understanding of how the impact of wait times on patient health status is measured over the perioperative period will inform future research on wait times. SCOPING REVIEW REGISTRATION: Registered with Open Science Framework, Feb 14, 2021 DOI: https://doi.org/10.17605/OSF.IO/MV4FS.

COSMIC: High-Resolution Cancer Genetics Using the Catalogue of Somatic Mutations in Cancer.

COSMIC (http://cancer.sanger.ac.uk) is an expert-curated database of somatic mutations in human cancer. Broad and comprehensive in scope, recent releases in 2016 describe over 4 million coding mutations across all human cancer disease types. Mutations are annotated across the entire genome, but expert curation is focused on over 400 key cancer genes. Now encompassing the majority of molecular mutation mechanisms in oncogenetics, COSMIC additionally describes 10 million non-coding mutations, 1 million copy-number aberrations, 9 million gene-expression variants, and almost 8 million differentially methylated CpGs. This information combines a consistent interpretation of the data from the major cancer genome consortia and cancer genome literature with exhaustive hand curation of over 22,000 gene-specific literature publications. This unit describes the graphical Web site in detail; alternative protocols overview other ways the entire database can be accessed, analyzed, and downloaded. © 2016 by John Wiley & Sons, Inc.

Effects of exercise intensity on flow mediated dilation in healthy humans.

Previous studies have demonstrated conflicting results on the effects of acute exercise on FMD. The aim of the study was to examine brachial artery FMD before and after 3 bouts of acute exercise performed at different intensities. 10 healthy males (mean±SD age: 22±1 years) completed 30 min of cycling at 50, 70 and 85% maximal heart rate (HRmax). Brachial artery FMD and the shear rate area-under-the-curve (cuff deflation to peak dilation; SRAUC) were assessed pre- and immediately post-exercise using high-resolution echo-Doppler. A generalized estimating equation (GEE) analysis was used to estimate the effect magnitudes of exercise intensity and time (pre/post) on FMD, whilst controlling for the influence of baseline diameter and SRAUC. Both baseline diameter and SRAUC were elevated by exercise. With covariate-control of these variables, the decrease in brachial artery FMD was negligible after exercise at 50% HRmax (6.3±2.6 vs. 5.9±2.5%; 95%CI for difference: - 0.59-1.34%) with larger decreases in FMD after exercise at 70% (6.1±1.8 vs. 4.7±1.9%; 95%CI for difference: 0.08-2.58%) and at 85% HRmax (6.6±1.6 vs. 3.6±2.2%; 95%CI: 0.41-5.42%). In conclusion, even after accounting for exercise-mediated changes in shear and baseline diameter, our data indicate that a negative relationship exists between exercise intensity and FMD.

CYP4A11 variant is associated with high-density lipoprotein cholesterol in women.

The ω-hydroxylase CYP4A11 catalyzes the transformation of epoxyeicosatrienoic acids (EETs) to ω-hydroxylated EETs, endogenous peroxisome proliferator-activated receptor-α (PPARα) agonists. PPARα activation increases high-density lipoprotein cholesterol (HDL-C). A cytosine-for-thymidine (T8590C) variant of CYP4A11 encodes for an ω-hydroxylase with reduced activity. This study examined the relationship between CYP4A11 T8590C genotype and metabolic parameters in the Framingham Offspring Study and in a clinical practice-based biobank, BioVU. In women in the Framingham Offspring Study, the CYP4A11 8590C allele was associated with reduced HDL-C concentrations (52.1±0.5 mg dl(-1) in CYP4A11 CC- or CT-genotype women versus 54.8±0.5 mg dl(-1) in TT women at visit 2, P=0.02), and with an increased prevalence of low HDL-C, defined categorically as 50 mg dl(-1) (odds ratio 1.39 (95% CI 1.02-1.90), P=0.04). In the BioVU cohort, the CYP4A11 8590C allele was also associated with low HDL-C in women (odds ratio 1.69 (95% CI 1.03-2.77, P=0.04)). There was no relationship between genotype and HDL-C in men in either cohort.

Effects of continuous lactation and short dry periods on mammary function and animal health.

The dry period is required to facilitate cell turnover in the bovine mammary gland in order to optimize milk yield in the next lactation. Traditionally, an 8-week dry period has been a standard management practice for dairy cows based on retrospective analyses of milk yields following various dry period lengths. However, as milk production per cow has increased, transitioning cows from the nonlactating state to peak milk yield has grown more problematic. This has prompted new studies on dry period requirements for dairy cows. These studies indicate a clear parity effect on dry period requirement. First parity animals require a 60-day dry period, whereas lactations following later parities demonstrate no negative impact with 30-day dry period or even eliminating the dry period when somatotropin (ST) is also used to maintain milk yields. Shortened dry periods in first parity animals were associated with reduced mammary cell turnover during the dry period and early lactation and increased numbers of senescent cells and reduced functionality of lactating alveolar mammary cells postpartum. Use of ST and increased milking frequency postpartum reduced the impact of shortened dry periods. The majority of new intramammary infections occur during the dry period and persist into the following lactation. There is therefore the possibility of altering mastitis incidence by modifying or eliminating the dry period in older parity animals. As the composition of mammary secretions including immunoglobulins may be reduced when the dry period is reduced or eliminated, there is the possibility that the immune status of cows during the peripartum period is influenced by the length of the dry period.

Botulinum toxin injection into the superior rectus for treatment of strabismus.

Botulinum toxin injected into the superior rectus (SR) has rarely been described in the literature. We conducted a database search to identify all cases of SR toxin from 1982 to 2010 at our institution. Out of a total of 7575 patients in the database, only eight cases of SR toxin were identified, all of which had residual hypertropia following previous ocular surgery. This surgery comprised: retinal surgery (3 patients), strabismus surgery for thyroid eye disease (2), and transposition for VI nerve palsy (2 patients). In seven out of eight cases, a long-lasting mean reduction of 10(Δ) was achieved from between two and three injections. Ptosis occurred in all but one case, but resolved. We conclude that SR toxin injection has very limited indications, but may be considered in residual hypertropia presumed secondary to a tight or overacting SR where the patient can tolerate the temporary iatrogenic ptosis.

The management of patients with thyroid eye disease after bilateral orbital 3 wall decompression.

INTRODUCTION: Thyroid eye disease is the most common cause of unilateral and bilateral proptosis in adults. Orbital decompression surgery may cause and/or worsen a pre-existing ocular motility disorder. METHODS: A retrospective review was carried out of all bilateral 3 wall orbital decompressions for severe thyroid eye disease performed between January 2002 and December 2004 by one surgeon. Subsequent surgeries were recorded. RESULTS: Seventy-four patients were identified, 59 (80%) females and 15 (20%) males. Mean age at the time of decompression was 46 years. Fifteen (20%) patients complained of diplopia due to strabismus prior to decompression surgery and 20 (27%) developed new diplopia postsurgery. Twenty patients (27%) required no further intervention following decompression surgery; the remainder underwent an average of 2.5 procedures. Strabismus surgery was performed in 32 (43%) patients. The mean time from the decompression to first strabismus surgery was 12 months. Forty-three (58%) patients underwent lid surgery. The mean time from decompression to first lid surgery was 16 months. CONCLUSION: This study demonstrates how this group of complex patients required multiple surgical procedures within an extended timescale, therefore requiring several in- and outpatient visits.

The impact of exercise training on the diameter dilator response to forearm ischaemia in healthy men.

AIM: Recent studies found differences between groups in the rate of diameter increase following the flow-mediated dilation (FMD). Whilst exercise training alters the magnitude of the FMD, little is known about the impact of exercise training on the rate of diameter increase. The aim of this study is to examine post-cuff deflation changes in brachial artery diameter following 5 min forearm ischaemia every 2 weeks across 8-weeks of a handgrip exercise training regimen. METHODS: Post-deflation changes in brachial artery diameter following 5-min of ischaemia were examined before, after and every 2-weeks across an 8-week handgrip training programme in healthy young men (n = 11) using echo-Doppler. RESULTS: The magnitude of dilation increased at week 2-4-6, but returned towards baseline values at week 8 (anova: P = 8.001). The time-to-peak diameter (42 ± 15s) demonstrated a significant prolongation at week 4 (77 ± 32s), but returned towards baseline values at weeks 6 and 8 (anova: P < 0.001). The rate of diameter increase did not differ across the intervention. CONCLUSION: Exercise training in healthy subjects is initially characterized by a larger dilation. Since the rate of dilation did not change, a longer time-to-peak dilation was necessary to achieve the increase in magnitude of dilation. As exercise training continues, the timing and magnitude of the peak diameter response returns to near baseline levels.

Optimization of the griddling process of kpejigaou (a traditional low fat nutritious cowpea food) using response surface methodology.

Kpejigaou is a griddled cowpea paste product eaten mainly in West Africa. As its processing does not involve the use of fat, it has the potential of meeting consumers' demand for healthy, low fat nutritious foods. Product texture is considered an important quality index by kpejigaou consumers. The objective of this study was to determine the optimum processing conditions of kpejigaou with respect to its textural properties. The study followed a 2 × 3 design with two processing variables each at three levels as follows: griddling temperature (130, 200, 270 °C) and time (5, 7.5 and 10 min). Texture Profile Analysis (TPA) was done on freshly processed samples. The data were fitted into multiple regression models from which the optimum griddling conditions for kpejigaou were determined. Kpejigaou processed at the optimum conditions was evaluated by untrained consumers for acceptability. Traditionally processed kpejigaou served as the control. The TPA results showed that hardness, chewiness and modulus of deformability were significantly affected by griddling conditions. Adjusted R(2) for the models for hardness, chewiness and modulus of deformability were 96%, 97% and 78%, respectively. Using response surface methodology, the optimum griddling conditions for kpejigaou (for acceptable textural properties) were determined to be 170 °C for 5-6 min. The texture of optimized kpejigaou was very much liked for its higher degree of sponginess as compared to the control. It also had acceptable sensory attributes of color, taste and flavor. These findings provide the basis for the development of a process for mass production and quality assurance of kpejigaou.

Presenting features and early management of childhood intermittent exotropia in the UK: inception cohort study.

AIM: To investigate factors associated with early management of intermittent exotropia (X(T)) in hospital eye departments in the UK in a prospective cohort study. METHODS: An inception cohort of 460 children aged <12 years with previously untreated X(T) (mean age 3.6 years, 55.9% girls) was recruited from 26 UK hospital children's eye clinics and orthoptic departments. Participants received a standard ophthalmic examination at recruitment and orthoptic assessment at three-monthly intervals thereafter. The influence of severity of exotropia (control measured by Newcastle Control Score (NCS), and angle of strabismus, visual acuity and stereoacuity) and age on the type of management was investigated. RESULTS: Within the first 12 months following recruitment, 297 (64.6%) children received no treatment, either for impaired visual acuity or for strabismus. Ninety-six (21%) children had treatment for impaired visual acuity. Eighty-nine (19.4%) received treatment for strabismus (22 of whom also received treatment for defective visual acuity); in 54 (11.7%) treatment was non-surgical and in 35 (7.6%) eye muscle surgery was performed. Children with poor (score 7-9) control of strabismus at recruitment were more likely to have surgery than children with good (score 1-3) control (p<0.001). Children who had no treatment were younger (mean age 3.38 years) than those who were treated (mean 4.07 years) (p<0.001). Stereoacuity and size of the angle of strabismus did not influence the type of management received. CONCLUSIONS: X(T) can be a presenting sign of reduced visual acuity. Most children with well controlled X(T) receive no treatment within 12 months following presentation.

Effect of thermal stress on Frank-Starling relations in humans.

The Frank-Starling 'law of the heart' is implicated in certain types of orthostatic intolerance in humans. Environmental conditions have the capacity to modulate orthostatic tolerance, where heat stress decreases and cooling increases orthostatic tolerance. The objective of this project was to test the hypothesis that heat stress augments and cooling attenuates orthostatic-induced decreases in stroke volume (SV) via altering the operating position on a Frank-Starling curve. Pulmonary artery catheters were placed in 11 subjects for measures of pulmonary capillary wedge pressure (PCWP) and SV (thermodilution derived cardiac output/heart rate). Subjects experienced lower-body negative-pressure (LBNP) of 0, 15 and 30 mmHg during normothermia, skin-surface cooling (decrease in mean skin temperature of 4.3 +/- 0.4 degrees C (mean +/- s.e.m.) via perfusing 16 degrees C water through a tubed-lined suit), and whole-body heating (increase in blood temperature of 1.0 +/- 0.1 degrees C via perfusing 46 degrees C water through the suit). SV was 123 +/- 8, 121 +/- 10, 131 +/- 7 ml prior to LBNP, during normothermia, skin-surface cooling, and whole-body heating, respectfully (P = 0.20). LBNP of 30 mmHg induced greater decreases in SV during heating (-48.7 +/- 6.7 ml) compared to normothermia (-33.2 +/- 7.4 ml) and to cooling (-10.3 +/- 2.9 ml; all P < 0.05). Relating PCWP to SV indicated that cooling values were located on the flatter portion of a Frank-Starling curve because of attenuated decreases in SV per decrease in PCWP. In contrast, heating values were located on the steeper portion of a Frank-Starling curve because of augmented decreases in SV per decrease in PCWP. These data suggest that a Frank-Starling mechanism may contribute to improvements in orthostatic tolerance during cold stress and orthostatic intolerance during heat stress.

Alterations in oestrogen metabolism: implications for higher penetrance of familial pulmonary arterial hypertension in females.

Mutations in bone morphogenetic protein receptor type 2 (BMPR2) cause familial pulmonary arterial hypertension (FPAH), but the penetrance is reduced and females are significantly overrepresented. In addition, gene expression data implicating the oestrogen-metabolising enzyme CYP1B1 suggests a detrimental role of oestrogens or oestrogen metabolites. We examined genetic and metabolic markers of altered oestrogen metabolism in subjects with a BMPR2 mutation. Genotypes for CYP1B1 Asn453Ser (N453S) were determined for 140 BMPR2 mutation carriers (86 females and 54 males). Nested from those subjects, a case-control study of urinary oestrogen metabolite levels (2-hydroxyoestrogen (2-OHE) and 16alpha-hydroxyoestrone (16alpha-OHE(1))) was conducted in females (five affected mutation carriers versus six unaffected mutation carriers). Among females, there was four-fold higher penetrance among subjects homozygous for the wild-type genotype (N/N) than those with N/S or S/S genotypes (p = 0.005). Consistent with this finding, the 2-OHE/16alpha-OHE(1) ratio was 2.3-fold lower in affected mutation carriers compared to unaffected mutation carriers (p = 0.006). Our findings suggest that variations in oestrogens and oestrogen metabolism modify FPAH risk. Further investigation of the role of oestrogens in this disease with profound sex bias may yield new insights and, perhaps, therapeutic interventions.

The Catalogue of Somatic Mutations in Cancer (COSMIC).

COSMIC is currently the most comprehensive global resource for information on somatic mutations in human cancer, combining curation of the scientific literature with tumor resequencing data from the Cancer Genome Project at the Sanger Institute, U.K. Almost 4800 genes and 250000 tumors have been examined, resulting in over 50000 mutations available for investigation. This information can be accessed in a number of ways, the most convenient being the Web-based system which allows detailed data mining, presenting the results in easily interpretable formats. This unit describes the graphical system in detail, elaborating an example walkthrough and the many ways that the resulting information can be thoroughly investigated by combining data, respecializing the query, or viewing the results in different ways. Alternate protocols overview the available precompiled data files available for download.