Publications by authors named "Jennifer Hughes"

147 Publications

Large palindromes on the primate X Chromosome are preserved by natural selection.

Genome Res 2021 Aug 21;31(8):1337-1352. Epub 2021 Jul 21.

Whitehead Institute, Cambridge, Massachusetts 02142, USA.

Mammalian sex chromosomes carry large palindromes that harbor protein-coding gene families with testis-biased expression. However, there are few known examples of sex-chromosome palindromes conserved between species. We identified 26 palindromes on the human X Chromosome, constituting more than 2% of its sequence, and characterized orthologous palindromes in the chimpanzee and the rhesus macaque using a clone-based sequencing approach that incorporates full-length nanopore reads. Many of these palindromes are missing or misassembled in the current reference assemblies of these species' genomes. We find that 12 human X palindromes have been conserved for at least 25 million years, with orthologs in both chimpanzee and rhesus macaque. Insertions and deletions between species are significantly depleted within the X palindromes' protein-coding genes compared to their noncoding sequence, demonstrating that natural selection has preserved these gene families. The spacers that separate the left and right arms of palindromes are a site of localized structural instability, with seven of 12 conserved palindromes showing no spacer orthology between human and rhesus macaque. Analysis of the 1000 Genomes Project data set revealed that human X-palindrome spacers are enriched for deletions relative to arms and flanking sequence, including a common spacer deletion that affects 13% of human X Chromosomes. This work reveals an abundance of conserved palindromes on primate X Chromosomes and suggests that protein-coding gene families in palindromes (most of which remain poorly characterized) promote X-palindrome survival in the face of ongoing structural instability.
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http://dx.doi.org/10.1101/gr.275188.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327919PMC
August 2021

Impact of the COVID-19 pandemic on adults with current and prior depression: initial findings from the longitudinal Texas RAD study.

J Affect Disord 2021 Nov 2;294:103-108. Epub 2021 Jul 2.

Center for Depression Research and Clinical Care, Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, United States. Electronic address:

Background: Emerging work has suggested worsening mental health in the general population during the COVID-19 pandemic, but there is minimal data on individuals with a prior history of depression.

Methods: Data regarding depression, anxiety and quality of life in adult participants with a history of a depressive disorder (n = 308) were collected before and during the COVID-19 pandemic. Mixed effects regression models were fit for these outcomes over the period May - August 2020, controlling for pre-pandemic depressive groups (none, mild, moderate-to-severe), demographic characteristics, and early COVID-19 related experiences (such as disruptions in routines, mental health treatment, and social supports).

Results: In pre-to-early pandemic comparisons, the 3 pre-pandemic depressive categories varied significantly in anxiety (F = 7.93, p < 0.0005) and psychological QOL (F = 8.57, p = 0.0003). The mildly depressed group (F = 6.01, p = 0.02) and moderate-to-severely depressed group (F = 38.51, p < 0.0001) had a significant reduction in anxiety. There were no changes among the groups in any outcome from May to August 2020. However, early impact on mental health care access and disruption in routines predicted worse outcomes during this time.

Limitations: Follow-up data were self-reported. Furthermore, the duration was a relatively short span into the pandemic.

Conclusions: Symptoms of depression, anxiety, and quality of life were generally stable from 2019 throughout August 2020 in adults with a history of depression. Disruption in mental health care access and routines in May 2020 predicted worse symptom outcomes through August 2020.
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http://dx.doi.org/10.1016/j.jad.2021.06.071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433599PMC
November 2021

Psychometric Evaluation of the Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire in a General Youth Population.

Child Psychiatry Hum Dev 2021 Mar 13. Epub 2021 Mar 13.

Department of Psychiatry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX, 75390-9119, USA.

Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire is a brief 15-item self-report measure of quality of life and life satisfaction originally developed for clinical populations (6 to 17 years old). The current paper examines the initial factor structure proposed by the developers and underlying psychometric properties of the measure in a non-clinical population of teens. A cross-sectional adolescent sample (N = 3222) completed self-report measures as part of mental health promotion program. A confirmatory factor analysis was conducted with construct validity analyses. The original factor structure was replicated with strong internal consistency (Cronbach α = .912). Strong construct validity (e.g. resilience, well-being, depression, and anxiety) was found. Minimal differences were found based on gender, race, and ethnicity. PQ-LES-Q has strong, replicable psychometric properties, which makes it a generally reliable and valid assessment tool to evaluate the quality of life and life satisfaction in adolescents.
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http://dx.doi.org/10.1007/s10578-021-01148-zDOI Listing
March 2021

Decentralized Care for Rifampin-Resistant Tuberculosis, Western Cape, South Africa.

Emerg Infect Dis 2021 ;27(3):728-739

In 2011, South Africa implemented a policy to decentralize treatment for rifampin-resistant tuberculosis (TB) to reduce durations of hospitalization and enable local treatment. We assessed policy implementation in Western Cape Province, where services expanded from 6 specialized TB hospitals to 406 facilities, by analyzing National Health Laboratory Service data on TB during 2012-2015. We calculated the percentage of patients who visited a TB hospital <1 year after rifampin-resistant TB diagnosis, the median duration of their hospitalizations, and the total distance between facilities visited. We assessed temporal changes with linear regression and stratified results by location. Of 2,878 patients, 65% were from Cape Town. In Cape Town, 29% visited a TB hospital; elsewhere, 68% visited a TB hospital. We found that hospitalizations and travel distances were shorter in Cape Town than in the surrounding areas.
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http://dx.doi.org/10.3201/eid2703.203204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920662PMC
July 2021

Decentralized Care for Rifampin-Resistant Tuberculosis, Western Cape, South Africa.

Emerg Infect Dis 2021 ;27(3):728-739

In 2011, South Africa implemented a policy to decentralize treatment for rifampin-resistant tuberculosis (TB) to reduce durations of hospitalization and enable local treatment. We assessed policy implementation in Western Cape Province, where services expanded from 6 specialized TB hospitals to 406 facilities, by analyzing National Health Laboratory Service data on TB during 2012-2015. We calculated the percentage of patients who visited a TB hospital <1 year after rifampin-resistant TB diagnosis, the median duration of their hospitalizations, and the total distance between facilities visited. We assessed temporal changes with linear regression and stratified results by location. Of 2,878 patients, 65% were from Cape Town. In Cape Town, 29% visited a TB hospital; elsewhere, 68% visited a TB hospital. We found that hospitalizations and travel distances were shorter in Cape Town than in the surrounding areas.
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http://dx.doi.org/10.3201/eid2703.203204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920662PMC
July 2021

The Adolescent Resilience Questionnaire: Validation of a Shortened Version in U.S. Youths.

Front Psychol 2020 27;11:606373. Epub 2020 Nov 27.

Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, United States.

Introduction: Resilience is a factor in how youth respond to adversity. The 88-item Adolescent Resilience Questionnaire is a comprehensive, multi-dimensional self-report measure of resilience developed with Australian youth.

Methods: Using a cross-sectional adolescent population ( = 3,222), confirmatory factor analysis was conducted to replicate the original factor structure. Over half of the adolescents were non-white and 9th graders with a mean age of 15.5.

Results: Our exploratory factor analysis shortened the measure for which we conducted the psychometric analyses. The original factor structure was not replicated. The exploratory factor analysis provided a 49-item measure. Internal consistency reliability for all 12 factors ranged from acceptable (α> 0.70-0.80). The revised factor total scores were highly and significantly correlated with item-total correlation coefficients ( > 0.63, < 0.001).

Conclusion: This revised shorter 49-item version of the Adolescent Resilience Questionnaire could be deployed and has acceptable psychometric properties.
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http://dx.doi.org/10.3389/fpsyg.2020.606373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728789PMC
November 2020

Optimal lead follicle size for human chorionic gonadotropin trigger in clomiphene citrate and intrauterine insemination cycles: an analysis of 1,676 treatment cycles.

Fertil Steril 2021 04 4;115(4):984-990. Epub 2020 Dec 4.

Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, New York, New York.

Objective: To identify the optimal lead follicle size for hCG trigger in clomiphene citrate (CC)-intrauterine insemination (IUI) cycles.

Design: Retrospective cohort study.

Setting: University-affiliated center.

Patient(s): Patients <40 years of age with ovulatory dysfunction or unexplained infertility undergoing their first CC-IUI cycle.

Intervention(s): Ovulation induction, hCG trigger, and IUI.

Main Outcome Measure(s): Clinical pregnancy rate (CPR) was the primary outcome and was plotted against lead follicle size in increments of 1 mm. Odds ratios with 95% confidence intervals for associations between lead follicle size and CPR were calculated from a multivariable logistic regression model. A receiver operating characteristic (ROC) curve was generated for CPR as a function of lead follicle size.

Result(s): 1,676 cycles were included. The overall CPR was 13.8% (232/1,676). There was no difference in baseline demographics or ovulation induction parameters of patients who did or did not conceive. The odds of clinical pregnancy were 2.3 and 2.2 times higher with lead follicle sizes of 21.1-22.0 mm and >22.0 mm, respectively, compared with the referent category of 19.1-20.0 mm. Lead follicle size was an independent predictor of CPR, even after accounting for confounders. A lead follicle size of 22.1 mm corresponded to a sensitivity and specificity of 80.1% and 90.4% for clinical pregnancy, respectively, with an area under the ROC curve of 0.89.

Conclusion(s): hCG administration at a lead follicle size of 21.1-22.0 mm is associated with higher odds of clinical pregnancy in patients undergoing their first CC-IUI cycles for ovulatory dysfunction or unexplained infertility.
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http://dx.doi.org/10.1016/j.fertnstert.2020.10.026DOI Listing
April 2021

Sequence analysis in reveals pervasiveness of X-Y arms races in mammalian lineages.

Genome Res 2020 12 18;30(12):1716-1726. Epub 2020 Nov 18.

Whitehead Institute, Cambridge, Massachusetts 02142, USA.

Studies of Y Chromosome evolution have focused primarily on gene decay, a consequence of suppression of crossing-over with the X Chromosome. Here, we provide evidence that suppression of X-Y crossing-over unleashed a second dynamic: selfish X-Y arms races that reshaped the sex chromosomes in mammals as different as cattle, mice, and men. Using super-resolution sequencing, we explore the Y Chromosome of (bull) and find it to be dominated by massive, lineage-specific amplification of testis-expressed gene families, making it the most gene-dense Y Chromosome sequenced to date. As in mice, an X-linked homolog of a bull Y-amplified gene has become testis-specific and amplified. This evolutionary convergence implies that lineage-specific X-Y coevolution through gene amplification, and the selfish forces underlying this phenomenon, were dominatingly powerful among diverse mammalian lineages. Together with Y gene decay, X-Y arms races molded mammalian sex chromosomes and influenced the course of mammalian evolution.
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http://dx.doi.org/10.1101/gr.269902.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706723PMC
December 2020

A threat to decentralised care for drug-resistant tuberculosis.

Lancet Respir Med 2020 10;8(10):950-952

Institute for Global Health, University College London, London, UK; Medical Research Council Clinical Trials Unit, University College London, London, UK; Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa. Electronic address:

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http://dx.doi.org/10.1016/S2213-2600(20)30392-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524514PMC
October 2020

Multidrug-resistant tuberculosis in children and adolescents: current strategies for prevention and treatment.

Expert Rev Respir Med 2021 Feb 10;15(2):221-237. Epub 2020 Oct 10.

Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University , Stellenbosch, South Africa.

Introduction: An estimated 30,000 children develop multidrug-resistant (MDR) tuberculosis (TB) each year, with only a small proportion diagnosed and treated. This field has historically been neglected due to the perception that children with MDR-TB are challenging to diagnose and treat. Diagnostic and therapeutic developments in adults have improved pediatric management, yet further pediatric-specific research and wider implementation of evidence-based practices are required.

Areas Covered: This review combines the most recent data with expert opinion to highlight best practice in the evaluation, diagnosis, treatment, and support of children and adolescents with MDR-TB disease. A literature search of PubMed was carried out on topics related to MDR-TB in children. This review provides practical advice on MDR-TB prevention and gives updates on new regimens and novel treatments. The review also addresses host-directed therapy, comorbid conditions, special populations, psychosocial support, and post-TB morbidity, as well as identifying outstanding research questions.

Expert Opinion: Increased availability of molecular diagnostics has the potential to aid with the diagnosis of MDR-TB in children. Shorter MDR-TB disease treatment regimens have made therapy safer and shorter and further developments with novel agents and repurposed drugs should lead to additional improvements. The evidence base for MDR-TB preventive therapy is increasing.
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http://dx.doi.org/10.1080/17476348.2021.1828069DOI Listing
February 2021

Responding to SARS-CoV-2 in South Africa: what can we learn from drug-resistant tuberculosis?

Eur Respir J 2020 07 23;56(1). Epub 2020 Jul 23.

Dept of Medicine and Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch, South Africa.

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http://dx.doi.org/10.1183/13993003.01369-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7257618PMC
July 2020

Parental feeding concerns of infants and young children with oesophageal atresia.

J Paediatr Child Health 2020 Nov 28;56(11):1791-1794. Epub 2020 May 28.

Department of Nutrition and Dietetics, Sydney Children's Hospital, Sydney, New South Wales, Australia.

Aim: Feeding problems have been described in young children with oesophageal atresia (OA). The primary aim of this study was to determine the specific concerns of parents and carers of infants and young children with OA regarding introducing solids and moving up to family foods.

Methods: A questionnaire was developed for parents and carers of infants and children with OA, aged 12 months to 6 years. Questionnaires were completed by 20 parents attending a multidisciplinary OA clinic between June 2016 and June 2017. Demographics and parental concern regarding feeding milestones were collected. The Montreal Children's Hospital Feeding Scale was completed.

Results: The majority of children (95%) had type C OA. Eleven (55%) parents agreed/strongly agreed that they were concerned about their child's feeding prior to the introduction of solids and about moving to more textured solids. The most common concern was choking and food impaction for both time points. Twelve (60%) parents agreed/strongly agreed that the majority of mealtimes in their child's first 1-2 years of life were stressful. Thirteen (65%) parents reported avoiding particular foods due to their child's OA. The majority of children (n = 17) had no feeding difficulty according to an objective scale, and the rest had minor difficulty.

Conclusions: Parental concern around feeding still exists in infants and children without a severe feeding difficulty. Multidisciplinary involvement, including a dietitian and speech pathologist, from an early age is important for infants and children with OA.
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http://dx.doi.org/10.1111/jpc.14840DOI Listing
November 2020

Parental feeding concerns of infants and young children with oesophageal atresia.

J Paediatr Child Health 2020 Nov 28;56(11):1791-1794. Epub 2020 May 28.

Department of Nutrition and Dietetics, Sydney Children's Hospital, Sydney, New South Wales, Australia.

Aim: Feeding problems have been described in young children with oesophageal atresia (OA). The primary aim of this study was to determine the specific concerns of parents and carers of infants and young children with OA regarding introducing solids and moving up to family foods.

Methods: A questionnaire was developed for parents and carers of infants and children with OA, aged 12 months to 6 years. Questionnaires were completed by 20 parents attending a multidisciplinary OA clinic between June 2016 and June 2017. Demographics and parental concern regarding feeding milestones were collected. The Montreal Children's Hospital Feeding Scale was completed.

Results: The majority of children (95%) had type C OA. Eleven (55%) parents agreed/strongly agreed that they were concerned about their child's feeding prior to the introduction of solids and about moving to more textured solids. The most common concern was choking and food impaction for both time points. Twelve (60%) parents agreed/strongly agreed that the majority of mealtimes in their child's first 1-2 years of life were stressful. Thirteen (65%) parents reported avoiding particular foods due to their child's OA. The majority of children (n = 17) had no feeding difficulty according to an objective scale, and the rest had minor difficulty.

Conclusions: Parental concern around feeding still exists in infants and children without a severe feeding difficulty. Multidisciplinary involvement, including a dietitian and speech pathologist, from an early age is important for infants and children with OA.
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http://dx.doi.org/10.1111/jpc.14840DOI Listing
November 2020

Oesophageal atresia: The growth gap.

World J Gastroenterol 2020 Mar;26(12):1262-1272

School of Women's and Children's Health, University of New South Wales, Sydney, NSW 2052, Australia.

Poor growth is an under-recognised yet significant long-term sequelae of oesophageal atresia (OA) repair. Few studies have specifically explored the reasons for growth impairment in this complex cohort. The association between poor growth with younger age and fundoplication appears to have the strongest supportive evidence, highlighting the need for early involvement of a dietitian and speech pathologist, and consideration of optimal medical reflux management prior to referring for anti-reflux surgery. However, it remains difficult to reach conclusions regarding other factors which may negatively influence growth, due to conflicting findings, inconsistent definitions and lack of validated tool utilisation. While swallowing and feeding difficulties are particularly frequent in younger children, their relationship with growth remains unclear. It is possible that these morbidities impact on the diet of children with OA, but detailed analysis of dietary composition and quality, and its relationship with these complications and growth, has not yet been conducted. Another potential area of research in OA is the role of the microbiota in growth and nutrition. While the microbiota has been linked to growth impairment in other paediatric conditions, it is yet to be investigated in OA. Further research is needed to identify the most important contributory factors to poor growth, the role of the intestinal microbiota, and effective interventions to maximise growth and nutritional outcomes in this cohort.
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http://dx.doi.org/10.3748/wjg.v26.i12.1262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109272PMC
March 2020

Injectable-free regimens containing bedaquiline, delamanid, or both for adolescents with rifampicin-resistant tuberculosis in Khayelitsha, South Africa.

EClinicalMedicine 2020 Mar 3;20:100290. Epub 2020 Mar 3.

Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Desmond Tutu TB Centre, Stellenbosch University, P.O. Box 241, Cape Town 8000, South Africa.

Background: Limited data exist on the use of bedaquiline and delamanid in adolescents with rifampicin-resistant tuberculosis (RR-TB). We describe RR-TB treatment of adolescents (10-19 years) with injectable-free regimens containing these drugs in Khayelitsha, South Africa.

Methods: This retrospective study included adolescents initiating injectable-free RR-TB treatment regimens containing bedaquiline and/or delamanid from February 2015 to June 2018. We report adverse events (AEs) of interest, sputum culture conversion (SCC), and final end-of-treatment outcomes.

Findings: Twenty-two patients were included; median age at treatment initiation was 17 years (interquartile range [IQR] 15-18), and six (27%) were HIV-positive (median CD4 count 191 cells/mm3 [IQR 157-204]). Eight (36%) patients had RR-TB with fluoroquinolone resistance; ten (45%), eight (36%), and four (18%) patients received regimens containing bedaquiline, delamanid, or the combination of bedaquiline and delamanid, respectively. The median durations of exposure to bedaquiline and delamanid were 5·6 (IQR 5·5-8·4) and 9·4 (IQR 5·9-14·4) months, respectively. There were 49 AEs of interest which occurred in 17 (77%) patients. Fourteen (64%) patients had pulmonary TB with positive sputum cultures at bedaquiline and/or delamanid initiation; among these SCC at month 6 was 79%. Final end-of-treatment outcomes for the 22 adolescent were: 17 (77%) successfully treated, two (9%) lost-to-follow-up, two (9%) treatment failed, and one (5%) died.

Interpretation: This study found that injectable-free regimens containing bedaquiline and/or delamanid in a programmatic setting were effective and well tolerated in adolescents and should be routinely provided for RR-TB treatment in this age group as recommended by the World Health Organisation.
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http://dx.doi.org/10.1016/j.eclinm.2020.100290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057194PMC
March 2020

Maternal and Infant Outcomes Among Pregnant Women Treated for Multidrug/Rifampicin-Resistant Tuberculosis in South Africa.

Clin Infect Dis 2021 04;72(7):1158-1168

Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, South Africa.

Background: Data on safety and efficacy of second-line tuberculosis drugs in pregnant women and their infants are severely limited due to exclusion from clinical trials and expanded access programs.

Methods: Pregnant women starting treatment for multidrug/rifampicin-resistant (MDR/RR)-tuberculosis at King Dinuzulu Hospital in KwaZulu-Natal, South Africa, from 1 January 2013 to 31 December 2017, were included. We conducted a record review to describe maternal treatment and pregnancy outcomes, and a clinical assessment to describe infant outcomes.

Results: Of 108 pregnant women treated for MDR/RR-tuberculosis, 88 (81%) were living with human immunodeficiency virus.. Favorable MDR/RR-tuberculosis treatment outcomes were reported in 72 (67%) women. Ninety-nine (91%) of the 109 babies were born alive, but overall, 52 (48%) women had unfavorable pregnancy outcomes. Fifty-eight (54%) women received bedaquiline, and 49 (45%) babies were exposed to bedaquiline in utero. Low birth weight was reported in more babies exposed to bedaquiline compared to babies not exposed (45% vs 26%; P = .034). In multivariate analyses, bedaquiline and levofloxacin, drugs often used in combination, were both independently associated with increased risk of low birth weight. Of the 86 children evaluated at 12 months, 72 (84%) had favorable outcomes; 88% of babies exposed to bedaquiline were thriving and developing normally compared to 82% of the babies not exposed.

Conclusions: MDR/RR-tuberculosis treatment outcomes among pregnant women were comparable to nonpregnant women. Although more babies exposed to bedaquiline were of low birth weight, over 80% had gained weight and were developing normally at 1 year.
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http://dx.doi.org/10.1093/cid/ciaa189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028100PMC
April 2021

Maternal and Infant Outcomes Among Pregnant Women Treated for Multidrug/Rifampicin-Resistant Tuberculosis in South Africa.

Clin Infect Dis 2021 04;72(7):1158-1168

Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, South Africa.

Background: Data on safety and efficacy of second-line tuberculosis drugs in pregnant women and their infants are severely limited due to exclusion from clinical trials and expanded access programs.

Methods: Pregnant women starting treatment for multidrug/rifampicin-resistant (MDR/RR)-tuberculosis at King Dinuzulu Hospital in KwaZulu-Natal, South Africa, from 1 January 2013 to 31 December 2017, were included. We conducted a record review to describe maternal treatment and pregnancy outcomes, and a clinical assessment to describe infant outcomes.

Results: Of 108 pregnant women treated for MDR/RR-tuberculosis, 88 (81%) were living with human immunodeficiency virus.. Favorable MDR/RR-tuberculosis treatment outcomes were reported in 72 (67%) women. Ninety-nine (91%) of the 109 babies were born alive, but overall, 52 (48%) women had unfavorable pregnancy outcomes. Fifty-eight (54%) women received bedaquiline, and 49 (45%) babies were exposed to bedaquiline in utero. Low birth weight was reported in more babies exposed to bedaquiline compared to babies not exposed (45% vs 26%; P = .034). In multivariate analyses, bedaquiline and levofloxacin, drugs often used in combination, were both independently associated with increased risk of low birth weight. Of the 86 children evaluated at 12 months, 72 (84%) had favorable outcomes; 88% of babies exposed to bedaquiline were thriving and developing normally compared to 82% of the babies not exposed.

Conclusions: MDR/RR-tuberculosis treatment outcomes among pregnant women were comparable to nonpregnant women. Although more babies exposed to bedaquiline were of low birth weight, over 80% had gained weight and were developing normally at 1 year.
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http://dx.doi.org/10.1093/cid/ciaa189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028100PMC
April 2021

Comprehensive phenotyping of depression disease trajectory and risk: Rationale and design of Texas Resilience Against Depression study (T-RAD).

J Psychiatr Res 2020 03 10;122:22-32. Epub 2019 Dec 10.

Center for Depression Research and Clinical Care, Department of Psychiatry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390-9119, USA.

Depression has a chronic and recurrent course often with early onset and is the leading cause of disability worldwide. In contrast to diagnoses for other conditions which rely on precise medical tests, the diagnosis of depression still focuses exclusively on symptom reports. As a result, heterogeneous patient groups are included under broad categories. Furthermore, in the absence of companion diagnostic tests, choosing specific treatments for patients remains imprecise with only one-third of patients entering remission with initial treatment, with others requiring multiple intervention steps to achieve remission. In addition to improving treatment outcomes, disease prevention is essential to reduce overall disease burden. Adolescence is a critical window where complex emotional, social, familial, and biological shifts may predispose to lifelong depression. Thus, personalized medicine, integrating individual variability in genes, brain function, and clinical phenotypes, can offer a comprehensive approach to provide precise diagnosis, novel drug development, optimal treatment assignment, and prevention of illness and its associated burden. Texas Resilience Against Depression study (T-RAD) encompasses two natural history, longitudinal (10 + years), prospective studies (D2K and RAD), each enrolling 2500 participants. The D2K study follows participants (ages 10 years and older) who have a current or past diagnosis of depression or bipolar disorder. The RAD study follows participants aged 10-24 years who are at risk for depression but not yet suffering from the disease. The T-RAD study will help to uncover the socio-demographic, lifestyle, clinical, psychological, and neurobiological factors that contribute to mood disorder onset, recurrence, progression, and differential treatment response.
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http://dx.doi.org/10.1016/j.jpsychires.2019.12.004DOI Listing
March 2020

(±)-Equol does not interact with genistein on estrogen-dependent breast tumor growth.

Food Chem Toxicol 2020 Feb 28;136:110979. Epub 2019 Nov 28.

Department of Food Science and Human Nutrition, University of Illinois Urbana-Champaign, 61801, USA. Electronic address:

Equol (EQ) is a prominent microbial metabolite of the soy isoflavone, daidzein, with estrogen-like properties. The major soy isoflavone, genistein (GEN), stimulated growth of estrogen-dependent breast cancer (EDBC) cells in vitro and tumor growth in vivo but EQ did not. To understand possible interactions of EQ and GEN on EDBC, EQ was used with GEN in combination in vitro and in vivo. Effects of EQ, GEN and EQ + GEN were evaluated using MCF-7 and T47D EDBC. Ovariectomized athymic mice were used as a model for in vivo tumor growth. Dietary EQ had no effect on MCF-7 tumor growth and the absence of effect was confirmed using a T47D EDBC in vivo model. EQ alone or in combination with GEN increased EDBC cell proliferation in vitro. EQ alone neither stimulated EDBC tumor growth in vivo at various doses nor suppressed tumor growth induced by dietary GEN. In summary, EQ has similar estrogenic effect as GEN in vitro but does not interact with GEN on EDBC tumor growth. Based on the evidence presented here, dietary EQ is unlikely to have estrogenic effects in vivo.
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http://dx.doi.org/10.1016/j.fct.2019.110979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7254865PMC
February 2020

(±)-Equol does not interact with genistein on estrogen-dependent breast tumor growth.

Food Chem Toxicol 2020 Feb 28;136:110979. Epub 2019 Nov 28.

Department of Food Science and Human Nutrition, University of Illinois Urbana-Champaign, 61801, USA. Electronic address:

Equol (EQ) is a prominent microbial metabolite of the soy isoflavone, daidzein, with estrogen-like properties. The major soy isoflavone, genistein (GEN), stimulated growth of estrogen-dependent breast cancer (EDBC) cells in vitro and tumor growth in vivo but EQ did not. To understand possible interactions of EQ and GEN on EDBC, EQ was used with GEN in combination in vitro and in vivo. Effects of EQ, GEN and EQ + GEN were evaluated using MCF-7 and T47D EDBC. Ovariectomized athymic mice were used as a model for in vivo tumor growth. Dietary EQ had no effect on MCF-7 tumor growth and the absence of effect was confirmed using a T47D EDBC in vivo model. EQ alone or in combination with GEN increased EDBC cell proliferation in vitro. EQ alone neither stimulated EDBC tumor growth in vivo at various doses nor suppressed tumor growth induced by dietary GEN. In summary, EQ has similar estrogenic effect as GEN in vitro but does not interact with GEN on EDBC tumor growth. Based on the evidence presented here, dietary EQ is unlikely to have estrogenic effects in vivo.
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http://dx.doi.org/10.1016/j.fct.2019.110979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7254865PMC
February 2020

Adolescent tuberculosis.

Lancet Child Adolesc Health 2020 01 18;4(1):68-79. Epub 2019 Nov 18.

Clinical Research Department, Medical Research Centre Unit, The Gambia; Biomedical Research and Training Institute, Harare, Zimbabwe. Electronic address:

Adolescence is characterised by a substantial increase in the incidence of tuberculosis, a known fact since the early 20th century. Most of the world's adolescents live in low-income and middle-income countries where tuberculosis remains common, and where they comprise a quarter of the population. Despite this, adolescents have not yet been addressed as a distinct population in tuberculosis policy or within tuberculosis treatment services, and emerging evidence suggests that current models of care do not meet their needs. This Review discusses up-to-date information about tuberculosis in adolescence, with a focus on the management of infection and disease, including HIV co-infection and rifampicin-resistant tuberculosis. We outline the progress in vaccine development and highlight important directions for future research.
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http://dx.doi.org/10.1016/S2352-4642(19)30337-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291359PMC
January 2020

Challenges and controversies in childhood tuberculosis.

Lancet 2019 Sep;394(10202):967-978

Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA. Electronic address:

Children bear a substantial burden of suffering when it comes to tuberculosis. Ironically, they are often left out of the scientific and public health advances that have led to important improvements in tuberculosis diagnosis, treatment, and prevention over the past decade. This Series paper describes some of the challenges and controversies in paediatric tuberculosis, including the epidemiology and treatment of tuberculosis in children. Two areas in which substantial challenges and controversies exist (ie, diagnosis and prevention) are explored in more detail. This Series paper also offers possible solutions for including children in all efforts to end tuberculosis, with a focus on ensuring that the proper financial and human resources are in place to best serve children exposed to, infected with, and sick from all forms of tuberculosis.
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http://dx.doi.org/10.1016/S0140-6736(19)32045-8DOI Listing
September 2019

Maternal transmission of an Igf2r domain 11: IGF2 binding mutant allele (Igf2r) results in partial lethality, overgrowth and intestinal adenoma progression.

Sci Rep 2019 08 6;9(1):11388. Epub 2019 Aug 6.

Tumour Growth Group, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, South Parks Road, OX1 3RE, Oxford, United Kingdom.

The cation-independent mannose 6-phosphate/insulin-like growth factor-2 receptor (M6P/IGF2R or IGF2R) traffics IGF2 and M6P ligands between pre-lysosomal and extra-cellular compartments. Specific IGF2 and M6P high-affinity binding occurs via domain-11 and domains-3-5-9, respectively. Mammalian maternal Igf2r allele expression exceeds the paternal allele due to imprinting (silencing). Igf2r null-allele maternal transmission results in placenta and heart over-growth and perinatal lethality (>90%) due to raised extra-cellular IGF2 secondary to impaired ligand clearance. It remains unknown if the phenotype is due to either ligand alone, or to both ligands. Here, we evaluate Igf2r specific loss-of-function of the domain-11 IGF2 binding site by replacing isoleucine with alanine in the CD loop (exon 34, I1565A), a mutation also detected in cancers. Igf2r maternal transmission (heterozygote), resulted in placental and embryonic over-growth with reduced neonatal lethality (<60%), and long-term survival. The perinatal mortality (>80%) observed in homozygotes (Igf2r) suggested that wild-type paternal allele expression attenuates the heterozygote phenotype. To evaluate Igf2r tumour suppressor function, we utilised intestinal adenoma models known to be Igf2 dependent. Bi-allelic Igf2r expression suppressed intestinal adenoma (Apc). Igf2r in a conditional model (Lgr5-Cre, Apc) resulted in worse survival and increased adenoma proliferation. Growth, survival and intestinal adenoma appear dependent on IGF2R-domain-11 IGF2 binding.
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http://dx.doi.org/10.1038/s41598-019-47827-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684648PMC
August 2019

Conservation, acquisition, and functional impact of sex-biased gene expression in mammals.

Science 2019 07;365(6450)

Whitehead Institute, Cambridge, MA 02142, USA.

Sex differences abound in human health and disease, as they do in other mammals used as models. The extent to which sex differences are conserved at the molecular level across species and tissues is unknown. We surveyed sex differences in gene expression in human, macaque, mouse, rat, and dog, across 12 tissues. In each tissue, we identified hundreds of genes with conserved sex-biased expression-findings that, combined with genomic analyses of human height, explain ~12% of the difference in height between females and males. We surmise that conserved sex biases in expression of genes otherwise operating equivalently in females and males contribute to sex differences in traits. However, most sex-biased expression arose during the mammalian radiation, which suggests that careful attention to interspecies divergence is needed when modeling human sex differences.
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http://dx.doi.org/10.1126/science.aaw7317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896219PMC
July 2019

Sleep quality prediction in caregivers using physiological signals.

Comput Biol Med 2019 07 20;110:276-288. Epub 2019 May 20.

Department of Geriatrics, Boonshoft School of Medicine, Wright State University, Dayton, OH, USA. Electronic address:

Most caregivers of people with dementia (CPWD) experience a high degree of stress due to the demands of providing care, especially when addressing unpredictable behavioral and psychological symptoms of dementia. Such challenging responsibilities make caregivers susceptible to poor sleep quality with detrimental effects on their overall health. Hence, monitoring caregivers' sleep quality can provide important CPWD stress assessment. Most current sleep studies are based on polysomnography, which is expensive and potentially disrupts the caregiving routine. To address these issues, we propose a clinical decision support system to predict sleep quality based on trends of physiological signals in the deep sleep stage. This system utilizes four raw physiological signals using a wearable device (E4 wristband): heart rate variability, electrodermal activity, body movement, and skin temperature. To evaluate the performance of the proposed method, analyses were conducted on a two-week period of sleep monitored on eight CPWD. The best performance is achieved using the random forest classifier with an accuracy of 75% for sleep quality, and 73% for restfulness, respectively. We found that the most important features to detect these measures are sleep efficiency (ratio of amount of time asleep to the amount of time in bed) and skin temperature. The results from our sleep analysis system demonstrate the capability of using wearable sensors to measure sleep quality and restfulness in CPWD.
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http://dx.doi.org/10.1016/j.compbiomed.2019.05.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6655554PMC
July 2019

Sleep quality prediction in caregivers using physiological signals.

Comput Biol Med 2019 07 20;110:276-288. Epub 2019 May 20.

Department of Geriatrics, Boonshoft School of Medicine, Wright State University, Dayton, OH, USA. Electronic address:

Most caregivers of people with dementia (CPWD) experience a high degree of stress due to the demands of providing care, especially when addressing unpredictable behavioral and psychological symptoms of dementia. Such challenging responsibilities make caregivers susceptible to poor sleep quality with detrimental effects on their overall health. Hence, monitoring caregivers' sleep quality can provide important CPWD stress assessment. Most current sleep studies are based on polysomnography, which is expensive and potentially disrupts the caregiving routine. To address these issues, we propose a clinical decision support system to predict sleep quality based on trends of physiological signals in the deep sleep stage. This system utilizes four raw physiological signals using a wearable device (E4 wristband): heart rate variability, electrodermal activity, body movement, and skin temperature. To evaluate the performance of the proposed method, analyses were conducted on a two-week period of sleep monitored on eight CPWD. The best performance is achieved using the random forest classifier with an accuracy of 75% for sleep quality, and 73% for restfulness, respectively. We found that the most important features to detect these measures are sleep efficiency (ratio of amount of time asleep to the amount of time in bed) and skin temperature. The results from our sleep analysis system demonstrate the capability of using wearable sensors to measure sleep quality and restfulness in CPWD.
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http://dx.doi.org/10.1016/j.compbiomed.2019.05.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6655554PMC
July 2019

Palliative care in emergency medicine: A perennial skill with a new emphasis.

Authors:
Jennifer Hughes

CJEM 2019 03;21(2):163-164

*Cumming School of Medicine,University of Calgary,Calgary,AB.

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http://dx.doi.org/10.1017/cem.2019.7DOI Listing
March 2019

Palliative care in emergency medicine: A perennial skill with a new emphasis.

Authors:
Jennifer Hughes

CJEM 2019 03;21(2):163-164

*Cumming School of Medicine,University of Calgary,Calgary,AB.

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http://dx.doi.org/10.1017/cem.2019.7DOI Listing
March 2019
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