bluuebunny/crossref_metadata_2025 huggingface dataset:
The delivery of obesity interventions to children and adolescents with physical disabilities: a systematic review
Authors: Matizanadzo Joshua T , Paudyal Priyamvada
Published: March 2021

Background

To examine the process and mechanisms of delivering obesity interventions to physically disabled children/adolescents.

Methods

PubMed, Medline, CINAHL Plus, Embase, Cochrane Library, Google Scholar, ClinicalTrials.gov, Science Direct were systematically and manually searched for studies conducted in physically disabled children/adolescents (0–18 years). Included interventions were physical activity, diet and obesity prevention education. Included outcomes were body mass index (BMI)/weight and obesity prevention knowledge. The Mixed Methods Appraisal Tool aided methodological quality assessments. Data were extracted and delivery models were synthesized and narratively summarized using the social ecological model.

Results

Seven studies of low (n = 4) and moderate (n = 3) scoring on methodological quality were eligible for inclusion. Study duration was 5 months or less (n = 5), 8 months (n = 1) and 2 years (n = 1). Interventions were delivered at home, school, hospital and rehabilitation centre through the internet, face-to-face and parents. No intervention was delivered at three or more levels of individual, interpersonal, institutional or community levels. No study reported significant outcomes on reduction in BMI/weight, or increase in obesity prevention knowledge.

Conclusions

Evidence reviewed in this study shows that obesity interventions for physically disabled children/adolescents lack both in delivery and design. Gaps revealed should be considered when developing interventions for this special population.
Effectiveness and safety of mizoribine for the treatment of IgG4-related disease: a retrospective cohort study
Authors: Fukui Sho , Kawaai Satoshi , Nakai Takehiro , Suda Masei , Ikeda Yukihiko , Nomura Atsushi , Tamaki Hiromichi , Kishimoto Mitsumasa , Ohde Sachiko , Okada Masato
Published: March 2021

Objective

Patients with IgG4-related disease (IgG4RD) usually require steroid-sparing agents due to relapse with tapering glucocorticoids (GC). We aimed to determine the efficacy and safety of mizoribine (MZR) among IgG4RD patients.

Methods

We retrospectively reviewed records of IgG4RD patients at Immuno-Rheumatology Center in St. Luke’s International Hospital, Tokyo, Japan. Patients treated with MZR were classified into the MZR group, and those treated with GC alone or with other immunosuppressants were included in the control group. Disease exacerbation, GC dose, IgG-IgG4 titre and adverse events were evaluated using univariate analyses, including the Kaplan–Meier method. The Cox proportional hazard model was used to evaluate risk factors for disease exacerbation.

Results

A total of 14 and 29 cases were included in the MZR and control group. Multiple organ involvement (three or more organs) was significantly more frequent in the MZR group [10 (71.4%) vs 9 (31.0%), P= 0.021]. Kaplan–Meier analysis revealed a significant reduction inexacerbation in patients with multiple organ involvement (P< 0.001) but not in total (P= 0.42). The adjusted hazard ratios of MZR use and multiple organ involvement for exacerbation were 0.34 (95%CI 0.12–1.01; P = 0.052) and 3.51 (95%CI 1.29–9.51; P= 0.014). The cumulative GC dose (mg per year, interquartile range) tended to be lower in the MZR group [1448 (1003–1642) vs 2179 (1264–3425); P= 0.09].

Conclusion

MZR decreased disease exacerbation among IgG4RD patients with multi-organ involvement and showed a steroid-sparing effect. MZR could be a treatment option for IgG4RD.
The Breast Imaging Medical Audit: What the Radiologist Needs to Know
Authors: Hussain Shehr , Omar Abdillahi , Shah Biren A.
Published: March 2021

The purpose of a medical audit is to ensure that there is consistency in the quality of patient care. The components of a medical audit include evaluation of treatment, comparison of care with established standards, and examining added changes to assess improvement.1 The medical audit not only helps improve patient outcomes, but also helps physicians assess their own performance and clinical practice, by comparing their patient outcomes to accepted standards. In turn, medical audits help close the gap between patient outcomes in practice and established standards.2
Changing Obstetrics and Gynecology Residency Education to Combat Reproductive Injustice
Authors: Finkbeiner Chelsea , Doria Celina , Ellis-Kahana Julia , Loder Charisse Marie
Published: March 2021

Although reproductive injustices and reproductive health disparities are well-documented in the United States, recent studies have begun to explore the health care professional's role in their perpetuation. We hypothesized that obstetrics and gynecology residents would observe reproductive injustices during their training. Thus, using a national survey, we asked obstetrics and gynecology residents to share clinical cases in which discrimination, bias, inequity, or injustice was involved in a patient's reproductive health care and queried their preparedness to respond. Through qualitative analysis, we found that respondents shared cases involving racism, discrimination, and structural barriers to care and that they felt poorly equipped to handle injustice. We call for clinician educators to combat reproductive injustice through three key changes to obstetrics and gynecology residency training: 1) incorporate reproductive justice training into formal residency education; 2) create safe spaces for residents to collectively debrief about their experiences with injustice and collaborate on care improvement; and 3) teach community engagement and advocacy skills that identify, center, and elevate local reproductive health priorities.
Implementation of a Universal Screening Process for Substance Use in Pregnancy
Authors: Ulrich Micah , Memmo Elise Petersen , Cruz Alissa , Heinz Alexandra , Iverson Ronald E.
Published: March 2021

OBJECTIVE:

To implement a standardized universal substance use screening process in an outpatient prenatal clinic at an urban tertiary care hospital.

METHODS:

Using a quality-improvement framework that involved process modeling, stakeholder analyses, and plan-do-study-act cycles, we implemented universal substance use screening for prenatal patients using a modified 5Ps screening tool (Parents, Peers, Partner, Past, Present). Implementation included an operational workflow based on the SBIRT (Screening, Brief Intervention, Referral to Treatment) model. The primary outcome measure was percentage of patients who were screened for substance use, with a goal of 90% screened. Secondary outcome measures were percentage who screened positive and percentage of the time a positive screen resulted in documentation of a brief intervention by a health care practitioner.

RESULTS:

Over a 19-month implementation period, 733 patient encounters were sampled. A substance use screen was completed in 618 (84%). We exceeded our goal of screening 90% of eligible patients for the final 6 months of data collection. Of the 618 completed screens, 124 (20%) screened positive. Health care practitioner documentation of brief interventions for patients with a positive screen reached 80% in the final phase of implementation, but then declined to 50% by the completion of the study period.

CONCLUSION:

A sustainable and generalizable process to carry out substance use screening within a large prenatal practice is feasible, and assisted with identification of patients not known to be at risk. Further efforts are needed to evaluate how to sustain health care practitioner documentation of intervention in response to positive screens.
Predictors of Initiation of Medication for Opioid Use Disorder and Retention in Treatment Among U.S. Pregnant Women, 2013–2017
Authors: Nguemeni Tiako Max Jordan , Friedman Ari , Culhane Jennifer , South Eugenia , Meisel Zachary F.
Published: March 2021

OBJECTIVE:

To describe trends and factors associated with medication administration for opioid use disorder (OUD) and retention in treatment among pregnant women with OUD.

METHODS:

This is a retrospective, nationwide, cross-sectional analysis of treatment episodes for primary OUD among pregnant women from 2013 to 2017. The primary outcome was initiation of methadone, buprenorphine, or naltrexone. Secondary outcomes were retention in treatment defined as length of treatment episode lasting six months or greater, and completion of treatment. Descriptive statistics and logistic regression were applied to describe trends in, and identify factors associated with the outcomes.

RESULTS:

There were 42,239 treatment episodes for primary OUD among pregnant women who reported using heroin (65.0%, 27,459), synthetic opioid (33.2%, 14,034), or nonprescribed methadone (1.8%, 746) between 2013 and 2017. Medications for OUD were administered in 47.4% (20,013) of episodes. Retention in treatment occurred in 16.6% of episodes without medications for OUD, and 37.8% of episodes with medications for OUD (P=.01). The rate of medication administration for OUD increased from 41.0% in 2013 to 52.0% in 2017; however, retention rates declined from 39.0% to 33.0% among treatment episodes with medication for OUD. History of at least one prior treatment episode was associated with both administration of medications for OUD and retention in treatment.

CONCLUSION:

In spite of current guidelines, most treatment episodes for OUD during pregnancy did not involve administration of medications for OUD. Although administration of medications for OUD has improved over time, retention in treatment is lagging. These findings highlight gaps in the U.S. addiction care system.
Length of the Second Stage of Labor in Women Delivering Twins
Authors: Levin Gabriel , Meyer Raanan , Many Ariel , Schwartz Anat , Tsur Abraham , Yinon Yoav , Yogev Yariv , Yagel Simcha , Rosenbloom Joshua I.
Published: March 2021

OBJECTIVE:

To evaluate the length of the second stage of labor in twin deliveries and to compare the length of the second stage in twin and singleton gestations.

METHODS:

This is a retrospective cohort study from three large hospitals in Israel. Clinical data were collected from the electronic medical record. The primary outcome was the length of the second stage (the time from documented 10-cm dilation until spontaneous vaginal delivery of the first twin). Multivariable linear regression was used to examine the association of clinical factors with the length of the second stage. The length of the second stage in twin and singleton pregnancies was compared.

RESULTS:

From 2011 to June, 2020, there were 2,009 twin deliveries and 135,217 singleton deliveries. Of the twin deliveries, 655 (32.6%) of the patients were nulliparous (95th percentile length of the second stage 3 hours and 51 minutes), 1,235 (61.5%) were parous (95th percentile 1 hour 56 minutes), and 119 (5.9%) were grand multiparous (five or more prior deliveries) (95th percentile 1 hour 24 minutes). In women delivering twins, epidural use was associated with a statistically significant increase in the length of the second stage of 40 minutes in nulliparous patients and 15 minutes in parous patients. In all groups, the length of the second stage was longer in patients delivering twins compared with singletons. Second-stage length longer than the 95th percentile in twins was associated with admission to the neonatal intensive care unit and need for phototherapy.

CONCLUSION:

Second-stage labor is longer in twins than singletons and is associated with obstetric history. Normal ranges for the second stage may be useful in guiding clinical practice.
Accuracy, Clinical Utility, and Usability of a Wireless Self-Guided Fetal Heart Rate Monitor
Authors: Porter Paul , Muirhead Fleur , Brisbane Joanna , Schneider Brooke , Choveaux Jennifer , Bear Natasha , Carson Jennie , Jones Kym , Silva Desiree , Neppe Cliff
Published: March 2021

OBJECTIVE:

To evaluate the accuracy, clinical utility, and usability of a wireless fetal and maternal heartbeat monitor to monitor fetal heart rate (FHR).

METHODS:

We conducted a prospective, single-center study of a convenience sample of women aged 18 years or older with a singleton pregnancy of at least 12 weeks of gestation. Fetal heart rate recordings were performed using both the heartbeat monitor and cardiotocography to evaluate accuracy. Clinicians used the heartbeat monitor in the clinic. Women used the device, unassisted, during a clinic visit or at home. Obstetricians assessed the clinical utility of FHR traces. Women rated the heartbeat monitor using the System Usability Scale.

RESULTS:

A total of 81 participants provided 126 recordings. The accuracy of the heartbeat monitor was excellent compared with cardiotocography, with limits of agreement (95%) for mean FHR between −1.6 (CI −2.0 to 1.3) and +1.0 (CI 0.7–1.4) beats per minute (bpm), mean difference −0.3 bpm, intraclass coefficient 0.99. The FHR was detected on all occasions. Clinicians took a median (interquartile range) of 0.5 (0.2–1.2) minutes to detect the FHR, obtaining a continuous trace of longer than 1 minute in 95% (39/41) of occasions. Home users took a median of 0.5 (0.2–2.0) minutes to detect the FHR, obtaining a continuous trace of longer than 1 minute in 92% (24/26) of occasions, with a median total trace time of 4.6 (4.4–4.8) minutes. The traces were deemed clinically useful in 100% (55/55) of clinician and 97% (31/32) of home recordings. The heartbeat monitor ranked in the 96–100th percentile for usability and learnability.

CONCLUSION:

The heartbeat monitor was accurate and easy for clinicians and participants to use. Data recorded at home were equivalent to those obtained using current assessment protocols for low-risk pregnancies, potentially allowing the device to be used in telehealth consultations.

CLINICAL TRIAL REGISTRATION:

Australian New Zealand Clinical Trial Registry, ACTRN12620000739910.

FUNDING SOURCES:

The HeraBEAT devices used in this study were loaned by HeraMED Pty Ltd (HeraMED, Netanya, ISRAEL). The study was supported by PHI Research Group (not-for-profit), which was responsible for Statistician fees and Research Assistants' salaries. Joondalup Health Campus provided infrastructure support, and IT services in-kind to the PHI research group.
Behavioral Smoking Cessation Counseling During Pregnancy
Authors: Bacheller Hannah L. , Hersh Alyssa R. , Caughey Aaron B.
Published: March 2021

OBJECTIVE:

To examine the cost effectiveness of using behavioral smoking cessation counseling during pregnancy.

METHODS:

We designed a decision-analytic model using TreeAge Pro 2020 software to compare the cost effectiveness and outcomes among women who received behavioral smoking cessation counseling compared with women who received usual care during pregnancy. We used a theoretical cohort of 285,000 women, the approximate number of pregnant women who smoke each year in the United States. Outcomes included maternal abstinence from smoking, fetal growth restriction, stillbirth, preterm delivery, neonatal death, and cerebral palsy, in addition to cost and quality-adjusted life-years (QALYs) for both the woman and the neonate. All model inputs were derived from the literature, and a willingness-to-pay threshold was set at $100,000 per QALY. Sensitivity analyses were performed to determine the robustness of baseline assumptions.

RESULTS:

In our theoretical cohort, behavioral smoking cessation counseling compared with usual care was associated with 9,019 additional women stopping smoking during pregnancy (34,604 vs 25,585). Smoking cessation counseling also resulted in 911 fewer cases of fetal growth restriction, 20 fewer stillbirths, 250 fewer preterm deliveries, 11 fewer neonatal deaths, and one less case of cerebral palsy. Using behavioral smoking cessation counseling interventions during pregnancy led to better outcomes despite higher costs, with an incremental cost-effectiveness ratio of $71,658 per QALY, which was below our willingness-to-pay threshold of $100,000 per QALY, making the intervention cost effective. Sensitivity analyses demonstrated that the counseling intervention was cost effective at probabilities of smoking cessation greater than 11.6% (baseline input: 12.1%) or the cost of the behavioral intervention was less than $475.21 (baseline input: $368.78).

CONCLUSION:

Behavioral smoking cessation counseling during pregnancy was associated with fewer adverse neonatal outcomes and was cost effective. Increasing utilization of such interventions and increasing insurance coverage of this care are important initiatives to improve outcomes in this at-risk population.
Perioperative Outcomes Following Combined Versus Isolated Colorectal and Liver Resections
Authors: Ward William H. , Hui Jane , Davis Catherine H. , Li Tianyu , Goel Neha , Handorf Elizabeth , Ross Eric A. , Curley Steven A. , Karachristos Andreas , Esnaola Nestor F.
Published: March 2021

Objectives:

Our objective was to compare outcomes following combined versus isolated resections for metastatic colorectal cancer and/or liver metastases using a large, contemporary national database.

Background:

Controversy persists regarding optimal timing of resections in patients with synchronous colorectal liver metastases.

Methods:

We analyzed 11,814 patients with disseminated colorectal cancer and/or liver metastases who underwent isolated colon, rectal, or liver resections (CRs, RRs, or LRs) or combined colon/liver or rectal/liver resections (CCLRs or CRLRs) in the National Surgical Quality Improvement Program Participant Use File (2011–2015). We examined associations between resection type and outcomes using univariate/multivariate analyses and used propensity adjustment to account for nonrandom receipt of isolated versus combined resections.

Results:

Two thousand four hundred thirty-seven (20.6%); 2108 (17.8%); and 6243 (52.8%) patients underwent isolated CR, RR, or LR; 557 (4.7%) and 469 (4.0%) underwent CCLR or CRLR. Three thousand three hundred ninety-five patients (28.7%) had serious complications (SCs). One hundred forty patients (1.2%) died, of which 113 (80.7%) were failure to rescue (FTR). One thousand three hundred eighty-six (11.7%) patients experienced unplanned readmission. After propensity adjustment and controlling for procedural complexity, wound class, and operation year, CCLR/CRLR was independently associated with increased risk of SC, as well as readmission (compared with LR). CCLR was also independently associated with increased risk of FTR and death (compared with LR).

Conclusions:

Combined resection uniformly confers increased risk of SC and increased risk of mortality after CCLR; addition of colorectal to LR increases risk of readmission. Combined resections are less safe, and potentially more costly, than isolated resections. Effective strategies to prevent SC after combined resections are warranted.
Utilization of a Novel Negative Pressure Platform Wound Dressing on Surgical Incisions: A Case Series
Authors: Cooper Laura E. , O’Toole Megan C. , Fields Kristopher L. , Eriksson Elof K. , Chan Rodney K.
Published: March 2021

Background:

Closed incision negative pressure therapy (ciNPT) has been shown to improve wound healing for patients at high risk for wound complications. Current devices consist of opaque interface dressings that do not allow ongoing visual evaluation of the surgical incision and utilize a negative pressure of −80 mm Hg to −125 mm Hg. The Negative Pressure Platform Wound Dressing (NP-PWD) was developed to address these aspects. This case series is the first evaluation of the NP-PWD in a clinical setting.

Methods:

Patients aged 18–85 undergoing an operation with an anticipated incision and primary closure were screened. Demographics, comorbidities, and operation performed were recorded. Following closure, the incision was measured and photographed before NP-PWD placement. The NP-PWD was removed at the first postoperative check (POC) between postoperative days (PODs) 3–5. Subjects were followed until PODs 9–14. POCs consisted of incision assessment, measurement, photography, and adverse event monitoring.

Results:

A total of 8 patients with 10 incisions were included in the study. Five patients were men. Median age was 56 years (IQR 53–74 years). All incisions were intact and without inflammation or infection at all POCs. Three adverse events, including small blisters and interruption of therapy, were noted.

Conclusions:

This case series reports that patients tolerated the NP-PWD on closed surgical incisions well and that all incisions were intact without evidence of inflammation or infection after 2 weeks of follow-up. Future controlled, clinical studies should further examine the safety and efficacy of the use of the NP-PWD.
The partial saphenous nerve injury model of pain impairs reward-related learning but not reward sensitivity or motivation
Authors: Phelps Caroline E. , Lumb Bridget M. , Donaldson Lucy F. , Robinson Emma S.
Published: March 2021

Chronic pain is highly comorbid with affective disorders, including major depressive disorder. A core feature of major depressive disorder is a loss of interest in previously rewarding activities. Major depressive disorder is also associated with negative affective biases where cognitive processes are modulated by the affective state. Previous work from our laboratory has shown that reward-related learning and memory is impaired in rodent models of depression generated through a variety of different manipulations. This study investigated different aspects of reward-related behaviour in a rodent model of chronic pain, the partial saphenous nerve injury (PSNI). Using our reward-learning assay, an impairment in reward learning was observed with no difference in sucrose preference, consistent with a lack of effect on reward sensitivity and similar to the effects seen in depression models. In a successive negative contrast task, chronic pain was not associated with changes in motivation for reward either under normal conditions or when reward was devalued although both sham and PSNI groups exhibited the expected negative contrast effect. In the affective bias test, PSNI rats developed a positive affective bias when treated with gabapentin, an effect not seen in the controls suggesting an association with the antinociceptive effects of the drug inducing a relatively more positive affective state. Together, these data suggest that there are changes in reward-related cognition in this chronic pain model consistent with previous findings in rodent models of depression. The effects seen with gabapentin suggest that pain-associated negative affective state may be remediated by this atypical analgesic.
Percutaneous Cryoablation for Treatment of Biopsy-proven Fibroadipose Vascular Anomaly
Authors: Eskew Jacob E. , Gill Anne E. , Swerdlin Rachel , Shah Jay H. , Variyam Darshan E. , Yin Hong , Hawkins C. Matthew
Published: March 2021

Objective:

To evaluate the clinical outcomes of patients with fibroadipose vascular anomaly (FAVA) treated via percutaneous cryoablation.

Design:

A 14-month retrospective study identified patients (<21 years old) with biopsy-proven diagnoses of FAVA. Appropriate evaluation in the vascular anomalies clinic preceded imaging, biopsy, and ablation therapy. Studied parameters included postablation MRI findings, pain, motor function, and complications of ablation therapy.

Setting:

A single, tertiary care pediatric hospital.

Patients:

Nine patients (median 12 years, range 8–16 years; 8 females, 1 male) met inclusion criteria.

Interventions:

Percutaneous cryoablation.

Primary Outcome Measurement:

Clinical success of cryoablation, defined as improvement of patient symptoms, including pain, functional restriction, and swelling.

Results:

Percutaneous biopsy demonstrated histological consistency with FAVA for all lesions. All patients underwent technically successful cryoablation therapy. One patient required repeat ablation. Symptoms resolved in 5 patients and improved in 4 patients. There were 5 minor complications and no major complications.

Conclusions:

These findings further validate previously published cohorts and demonstrate that percutaneous cryoablation is a potentially efficacious treatment option for FAVA with a favorable safety profile.
Autoimmune regulation of chronic pain
Authors: Lacagnina Michael J. , Heijnen Cobi J. , Watkins Linda R. , Grace Peter M.
Published: March 2021

Chronic pain is an unpleasant and debilitating condition that is often poorly managed by existing therapeutics. Reciprocal interactions between the nervous system and the immune system have been recognized as playing an essential role in the initiation and maintenance of pain. In this review, we discuss how neuroimmune signaling can contribute to peripheral and central sensitization and promote chronic pain through various autoimmune mechanisms. These pathogenic autoimmune mechanisms involve the production and release of autoreactive antibodies from B cells. Autoantibodies—ie, antibodies that recognize self-antigens—have been identified as potential molecules that can modulate the function of nociceptive neurons and thereby induce persistent pain. Autoantibodies can influence neuronal excitability by activating the complement pathway; by directly signaling at sensory neurons expressing Fc gamma receptors, the receptors for the Fc fragment of immunoglobulin G immune complexes; or by binding and disrupting ion channels expressed by nociceptors. Using examples primarily from rheumatoid arthritis, complex regional pain syndrome, and channelopathies from potassium channel complex autoimmunity, we suggest that autoantibody signaling at the central nervous system has therapeutic implications for designing novel disease-modifying treatments for chronic pain.
Profiles of mutations in hepatitis B virus surface and polymerase genes isolated from treatment-naïve Nigerians infected with genotype E
Authors: Olusola Babatunde A. , Faneye Adedayo O. , Oluwasemowo Olukunle O. , Motayo Babatunde O. , Adebayo Sopeju , Oludiran-Ayoade Ayomide E. , Aleru Bisola , George Uwem E. , Oragwa Arthur O.
Published: March 2021

Introduction. Hepatitis B virus (HBV) infection is the leading cause of hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). HBV genotype E (HBV/E) is the predominant genotype in West Africa and has been linked epidemiologically with chronic and occult HBV infections as well as development of HCC. Mutations in the surface and polymerase genes of HBV have been associated with occult infection, drug resistance, vaccine escape, as well as HCC.

Hypothesis/Gap Statement. There is limited data on the occurrence and patterns of mutations associated with occult infection, drug resistance, vaccine escape and HCC for HBV/E.

Aim. This study characterized amino acid (aa) substitutions in the major hydrophilic (MHR) and reverse transcriptase (RT) regions of the surface and polymerase genes respectively of HBV sequences from a group of Nigerians with genotype E infection. The CpG islands of the PreC/C and PreS/S regions of these sequences were also described.

Methodology. HBV surface and polymerase genes were detected using PCR techniques. Occurrence of new and previously described mutations in these genes were analysed using phylogenetic techniques.

Results. Overall 13 HBV isolates were each sequenced for polymerase and surface genes mutations. Thirteen and nine PreS/S and PreC/C HBV genes respectively were analysed for CpG islands. Mutations in the MHR and a-determinants region of the S protein were discovered in eleven and nine of the 13 tested isolates respectively. These mutations were concomitant with aa changes in the RT functional domains of the isolates. Mutations associated with vaccine escape, occult infection and poor HCC prognosis were identified in HBV/E isolated in this study. Furthermore, all the isolates had at least one putative nucleotide analogue resistance mutations. Drug resistance mutations had the highest association with CpG islands.

Conclusion. The results of this study contribute to further understanding of HBV variability in Nigeria and the West African region. This will aid the planning of adequate HBV immunization and treatment programmes for the countries in the region.
Analysis of Polycerate Mutants Reveals the Evolutionary Co-option of
HOXD1 to Determine the Number and Topology of Horns in
Bovidae
Authors: Allais-Bonnet Aurélie , Hintermann Aurélie , Deloche Marie-Christine , Cornette Raphaël , Bardou Philippe , Naval-Sanchez Marina , Pinton Alain , Haruda Ashleigh , Grohs Cécile , Zakany Jozsef , Bigi Daniele , Medugorac Ivica , Putelat Olivier , Greyvenstein Ockert , Hadfield Tracy , Ben Jemaa Slim , Bunevski Gjoko , Menzi Fiona , Hirter Nathalie , Paris Julia M. , Hedges John , Palhiere Isabelle , Rupp Rachel , Lenstra Johannes A. , Gidney Louisa , Lesur Joséphine , Schafberg Renate , Stache Michael , Wandhammer Marie-Dominique , Arbogast Rose-Marie , Guintard Claude , Blin Amandine , Boukadiri Abdelhak , Riviere Julie , Esquerré Diane , Donnadieu Cécile , Danchin-Burge Coralie , Reich Coralie M , Riley David , van Marle-Koster Este , Cockett Noelle , Hayes Benjamin J. , Drögemüller Cord , Kijas James , Pailhoux Eric , Tosser-Klopp Gwenola , Duboule Denis , Capitan Aurélien
Published: March 2021

In the course of evolution, pecorans (i.e. higher ruminants) developed a
remarkable diversity of osseous cranial appendages, collectively referred to as
‘headgear’, which likely share the same origin and genetic basis. However, the
nature and function of the genetic determinants underlying their number and
position remain elusive. Jacob and other rare populations of sheep and goats,
are characterized by polyceraty, the presence of more than two horns. Here, we
characterize distinct POLYCERATE alleles in each
species, both associated with defective HOXD1
function. We show that haploinsufficiency at this locus results in the splitting
of horn bud primordia, likely following the abnormal extension of an initial
morphogenetic field. These results highlight the key role played by this gene in
headgear patterning and illustrate the evolutionary co-option of a gene involved
in the early development of bilateria to properly fix the position and number of
these distinctive organs of Bovidae.
Age-related changes in physiology in individuals with bipolar disorder
Authors: Mutz Julian , Lewis Cathryn M.
Published: March 2021

Objectives

Individuals with bipolar disorder have reduced life expectancy and may experience accelerated biological ageing. In individuals with bipolar disorder and healthy controls, we examined differences in age-related changes in physiology.

Methods

UK Biobank recruited >500,000 participants, aged 37-73, between 2006–2010. Generalised additive models were used to examine associations between age and grip strength, cardiovascular function, body composition, lung function and bone mineral density. Analyses were conducted separately in males and females with bipolar disorder compared to healthy controls.

Results

Analytical samples included up to 272,462 adults (mean age = 56.04 years, SD = 8.15; 49.51% females). We found statistically significant differences between bipolar disorder cases and controls for grip strength, blood pressure, pulse rate and body composition, with standardised mean differences of up to −0.238 (95% CI −0.282 to −0.193). There was limited evidence of differences in lung function, heel bone mineral density or arterial stiffness. Case-control differences were most evident for age-related changes in cardiovascular function (in both sexes) and body composition (in females). These differences did not uniformly narrow or widen with age and differed by sex. For example, the difference in systolic blood pressure between male cases and controls was −1.3 mmHg at age 50 and widened to −4.7 mmHg at age 65. Diastolic blood pressure in female cases was 1.2 mmHg higher at age 40 and −1.2 mmHg lower at age 65.

Conclusions

Differences in ageing trajectories between bipolar disorder cases and healthy controls were most evident for cardiovascular and body composition measures and differed by sex.
Sleep, pain, and neurodegeneration: A Mendelian randomization study
Authors: Grover Sandeep ,   International Age-related Macular Degeneration Consortium (IAMDGC), Sharma Manu
Published: March 2021

Objective

To examine whether sleep and pain-related traits have a causal effect on the risk of neurodegeneration.

Design

Two-sample Mendelian randomization using an inverse-variance weighted (IVW) estimate of the summary effect estimates.

Setting

Genetic data on sleep and pain-related traits and neurodegenerative disorders (NDD) from various cohorts comprising individuals predominantly of European ancestry.

Participants

Participants from the International Sleep Genetic Epidemiology Consortium (ISGEC), UK Biobank sleep and chronotype research group, International Genomics of Alzheimer’s patients (IGAP), project MinE, International Age-related Macular Degeneration Consortium (IAMDGC), International Multiple Sclerosis Genetics Consortium (IMSGC), International Parkinson’s Disease Genomics Consortium (IPDGC)

Exposures

Self-reported chronotype (CHR), morning preference (MP), insomnia symptoms (INS), sleep duration (SP), short sleep (SS), long sleep (LS), and multisite chronic pain (MCP)

Main outcome measures

Age-related macular degeneration (AMD), Alzheimer’s disease (AD), Amyotrophic lateral sclerosis (ALS), Multiple sclerosis (MS), and Parkinson’s disease (PD)

Results

We considered a threshold of P=0.00142 as significant accounting for multiple testing, and P<0.05 was considered to be suggestive evidence for a potential association. Using direct MR, MP was observed as the strongest risk factor for AMD (ORIVW = 1.19, 95% CI 1.08, 1.32, P = 0.00073). We observed suggestive evidence of influence of different sleep traits on neurodegeneration: CHR on AMD (ORIVW = 1.27, 95% CI 1.08, 1.49, P = 0.0034), SS on AD (ORIVW 1.26, 95% CI 1.08, 1.46, P = 0.0044), and INS on ALS (ORIVW 1.55, 95% CI 1.12, 2.14, P = 0.0123). The association of SS with AD was, however, lost after the exclusion of overlapping UKB samples. Using pain as exposure, our study failed to observe any role of pain in neurodegeneration. Results were largely robust to reverse causal analyses and sensitivity analyses accounting for horizontal pleiotropy.

Conclusions

Our study highlighted the role of morning preference as a risk factor for AMD and provided suggestive evidence of different sleep traits on a wide spectrum of neurodegenerative diseases.
Functional Antibodies in COVID-19 Convalescent Plasma
Authors: Herman Jonathan D. , Wang Chuangqi , Loos Carolin , Yoon Hyunah , Rivera Johanna , Dieterle M. Eugenia , Haslwanter Denise , Jangra Rohit K. , Bortz Robert H. , Bar Katharine J. , Julg Boris , Chandran Kartik , Lauffenburger Douglas , Pirofski Liise-anne , Alter Galit
Published: March 2021

In the absence of an effective vaccine or monoclonal therapeutic, transfer of convalescent plasma (CCP) was proposed early in the SARS-CoV-2 pandemic as an easily accessible therapy. However, despite the global excitement around this historically valuable therapeutic approach, results from CCP trials have been mixed and highly debated. Unlike other therapeutic interventions, CCP represents a heterogeneous drug. Each CCP unit is unique and collected from an individual recovered COVID-19 patient, making the interpretation of therapeutic benefit more complicated. While the prevailing view in the field would suggest that it is administration of neutralizing antibodies via CCP that centrally provides therapeutic benefit to newly infected COVID-19 patients, many hospitalized COVID-19 patients already possess neutralizing antibodies. Importantly, the therapeutic benefit of antibodies can extend far beyond their simple ability to bind and block infection, especially related to their ability to interact with the innate immune system. In our work we deeply profiled the SARS-CoV-2-specific Fc-response in CCP donors, along with the recipients prior to and after CCP transfer, revealing striking SARS-CoV-2 specific Fc-heterogeneity across CCP units and their recipients. However, CCP units possessed more functional antibodies than acute COVID-19 patients, that shaped the evolution of COVID-19 patient humoral profiles via distinct immunomodulatory effects that varied by pre-existing SARS-CoV-2 Spike (S)-specific IgG titers in the patients. Our analysis identified surprising influence of both S and Nucleocapsid (N) specific antibody functions not only in direct antiviral activity but also in anti-inflammatory effects. These findings offer insights for more comprehensive interpretation of correlates of immunity in ongoing large scale CCP trials and for the design of next generation therapeutic design.
Proteome-wide Mendelian randomization identifies causal links between blood proteins and severe COVID-19
Authors: Palmos Alish B. , Millischer Vincent , Menon David K. , Nicholson Timothy R. , Taams Leonie , Michael Benedict ,   COVID Clinical Neuroscience Study Consortium, Hübel Christopher , Breen Gerome
Published: March 2021

The COVID-19 pandemic death toll now surpasses two million individuals and there is a need for early identification of individuals at increased risk of mortality. Host genetic variation partially drives the immune and biochemical responses to COVID-19 that lead to risk of mortality. We identify and prioritise blood proteins and biomarkers that may indicate increased risk for severe COVID-19, via a proteome Mendelian randomization approach by collecting genome-wide association study (GWAS) summary statistics for >4,000 blood proteins. After multiple testing correction, troponin I3, cardiac type (TNNI3) had the strongest effect (odds ratio (O.R.) of 6.86 per standard deviation increase in protein level), with proteinase 3 (PRTN3) (O.R.=2.48), major histocompatibility complex, class II, DQ alpha 2 (HLA-DQA2) (O.R.=2.29), the C4A-C4B heterodimer (O.R.=1.76) and low-density lipoprotein receptor-related protein associated protein 1 (LRPAP1) (O.R.=1.73) also being associated with higher odds of severe COVID-19. Conversely, major histocompatibility complex class I polypeptide-related sequence A (MHC1A) (O.R.=0.6) and natural cytotoxicity triggering receptor 3 (NCR3) (O.R.=0.46) were associated with lower odds. These proteins are involved in heart muscle contraction, natural killer and antigen presenting cells, and the major histocompatibility complex. Based on these findings, it may be possible to better predict which patients may develop severe COVID-19 and to design better treatments targeting the implicated mechanisms.
Point-of-care ultrasonography for risk stratification of non-critical suspected COVID-19 patients on admission (POCUSCO): a prospective binational study
Authors: Morin François , Douillet Delphine , François Hamel Jean , Savary Dominique , Aubé Christophe , Tazarourte Karim , Marouf Kamélia , Dupriez Florence , Le Conte Philipe , Flament Thomas , Delomas Thomas , Taalba Mehdi , Marjanovic Nicolas , Couturaud Francis , Peschanski Nicolas , Boishardy Thomas , Riou Jérémie , Dubée Vincent , Roy Pierre-Marie
Published: March 2021

Background

Lung point-of-care ultrasonography (L-POCUS) is highly effective in detecting pulmonary peripheral patterns and may allow early identification of patients who are likely to develop an acute respiratory distress syndrome (ARDS). We hypothesized that L-POCUS performed during the initial examination would identify non-severe COVID-19 patients with a high risk of getting worse.

Methods

POCUSCO was a prospective, multicenter study. Non-critical adult patients who were admitted to the emergency department (ED) for suspected or confirmed COVID-19 were included and had L-POCUS performed within 48 hours following admission. The severity of lung damage was assessed using the L-POCUS score based on 36 points for ARDS. The primary outcome was the rate of patients requiring intubation or who died within 14 days following inclusion.

Results

Among 296 participating patients, 8 (2.7%) had primary outcome. The area under the curve (AUC) of the receiver operating characteristic of L-POCUS was 0.80 [95%CI:0.60-0.94]. The score values which achieved a sensibility > 95% in defining low-risk patients and a specificity > 95% in defining high-risk patients were <1 and ≥16, respectively. The rate of patients with an unfavorable outcome was 0/95 (0%[95%CI:0-3.9]) for low-risk patients (score=0) versus 4/184 (2.17%[95%CI:0.8-5.5]) for intermediate-risk patients (score 1-15) and 4/17 (23.5%[95%CI:11.4-42.4]) for high-risk patients (score ≥16). In patients with confirmed COVID-19 (n=58), the AUC of L-POCUS was 0.97 [95%CI:0.92-1.00].

Conclusions

L-POCUS allows risk-stratification of patients with suspected or confirmed COVID-19. These results should be confirmed in a population with a higher risk of an unfavorable outcome.

Trial registration number

NCT04338100
Exploring the short-term role of particulate matter in the COVID-19 outbreak in USA cities
Authors: Kamigauti Leonardo Yoshiaki , Palma Perez Gabriel Martins , Souto-Oliveira Carlos Eduardo , Cowdery Elizabeth , Hilário Nascimento Saldiva Paulo , de Fatima Andrade Maria
Published: March 2021

The role of particulate matter (PM) in the COVID-19 pandemic is currently being discussed by the scientific community. Long-term (years) exposure to PM is known to affect human health by increasing susceptibility to viral infections as well as to the development of respiratory and cardiovascular symptoms. In the short-term (days to months), PM has been suggested to assist airborne viral transmission. However, confounding factors such as urban mobility prevent causal conclusions. In this study, we explore short-term relationships between PM concentrations and the evolution of COVID-19 cases in a number of cities in the United States of America. We focus on the role of PM in facilitating viral transmission in early stages of the pandemic. We analyzed PM concentrations in two particle size ranges, < 2.5 µm, and between 10 and 2.5 µm (PM2.5 and PM10 respectively) as well as carbon monoxide (CO) and nitrogen dioxide (NO2). Granger causality analysis was employed to identify instantaneous and lagged effects of pollution in peaks of COVID-19 new daily cases in each location. The effect of pollution in shaping the disease spread was evaluated by correlating the logistic growth rate of accumulated cases with pollutants concentrations for a range of time lags and accumulation windows. PM2.5 shows the most significant results in Granger causality tests in comparison with the other pollutants. We found a strong and significant association between PM2.5 concentrations and the growth rate of accumulated cases between the 1st and 18th days after the report of the infection, peaking at the 8th day. By comparing results of PM2.5 with PM10, CO and NO2 we rule out confounding effects associated with mobility. We conclude that PM2.5 is not a first order effect in the cities considered; however, it plays a significant role in facilitating the COVID-19 transmission. We estimate that the growth rate of COVID-19 cases would be risen by 12.5% if PM2.5 is increased from 25 to 35 µg m−3.
Polypide anatomy of hornerid bryozoans (Stenolaemata: Cyclostomatida)
Authors: Tamberg Yuta , Batson Peter B. , Napper Ruth
Published: March 2021

Bryozoans are small colonial coelomates whose colonies are made of individual modules (zooids). Like most coelomate animals, bryozoans have a characteristic body wall composition, including epidermis, extracellular matrix (ECM) and coelothelium, all pressed together. The order Cyclostomatida, however, presents the most striking deviation, in which the ECM and the corresponding coelothelium underlying major parts of the skeletal wall epidermis are “;peeled off” to form an independent membranous sac. The polypide anatomy and ultrastructure of this group is best known from one family, the Crisiidae (Articulata). Here we examined four species from the phylogenetically and ecologically contrasting family Horneridae (Cancellata) from New Zealand. Here we provide the first detailed ultrastructural examination of the hornerid polypide, including tentacles, mouth region, digestive system and the funiculus. We were able to trace continuity and transitions of cell and ECM layers throughout the whole polypide. In addition we identified that the funiculus is a lumen-free ECM cord with two associated muscles, disconnected from interzooidal pores. While agreeing with the general cyclostomate body plan, hornerids have some unique traits that make them worthy of additional study.

Highlights

Hornerids share a general cyclostomate body plan. The frontal tentacle ECM transitions into oral sphincter ECM, the abfrontal lophophore ECM becomes a septum between coelomic compartments, and the funuculus is a solid ECM cord supplied with muscles.
Mechanism of praziquantel action at a parasitic flatworm ion channel
Authors: Park Sang-Kyu , Friedrich Lukas , Yahya Nawal A. , Rohr Claudia , Chulkov Evgeny G. , Maillard David , Rippmann Friedrich , Spangenberg Thomas , Marchant Jonathan S.
Published: March 2021

Praziquantel (PZQ) is an essential medicine for treating parasitic flatworm infections such as schistosomiasis, which afflicts over 250 million people. However, PZQ is not universally effective, lacking activity against the liver flukeFasciola. The reason for this insensitivity is unclear, as the mechanism of PZQ action is unknown. Here, we show PZQ activates a transient receptor potential melastatin ion channel (TRPMPZQ) in schistosomes by engaging a hydrophobic ligand binding pocket within the voltage-sensor like domain to cause Ca2+entry and worm paralysis. PZQ activates TRPMPZQhomologues in other PZQ-sensitive flukes, but notFasciola. However, a single amino acid change in theFasciolaTRPMPZQbinding pocket, to mimic schistosome TRPMPZQ, confers PZQ sensitivity. After decades of clinical use, the basis of PZQ action at a druggable TRP channel is resolved.
MEYE: Web-app for translational and real-time pupillometry
Authors: Mazziotti Raffaele , Carrara Fabio , Viglione Aurelia , Lupori Leonardo , Verde Luca Lo , Benedetto Alessandro , Ricci Giulia , Sagona Giulia , Amato Giuseppe , Pizzorusso Tommaso
Published: March 2021

Pupil dynamics alterations have been found in patients affected by a variety of neuropsychiatric conditions, including autism. Studies in mouse models have used pupillometry for phenotypic assessment and as a proxy for arousal. Both in mice and humans, pupillometry is non-invasive and allows for longitudinal experiments supporting temporal specificity, however its measure requires dedicated setups. Here, we introduce a Convolutional Neural Network that performs on-line pupillometry in both mice and humans in a web app format. This solution dramatically simplifies the usage of the tool for non-specialist and non-technical operators. Because a modern web browser is the only software requirement, this choice is of great interest given its easy deployment and set-up time reduction. The tested model performances indicate that the tool is sensitive enough to detect both spontaneous and evoked pupillary changes, and its output is comparable with state-of-the-art commercial devices.