bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations Between Comorbidities and Severe Maternal Morbidity
Authors: Brown C.C. , Adams C.E. , George K.E. , Moore J.E.
Published: May 2021

(Obstet Gynecol. 2020;136:892–901)

Severe maternal morbidity (SMM) includes long- or short-term consequences to a woman’s health due to pregnancy and childbirth. Since 1993, the US has seen a two-fold increase in the rate of SMM. The rate of SMM is nearly double for non-Hispanic Black women compared to non-Hispanic white women. Compared to women without chronic conditions, women with multiple chronic conditions are 3.8 times more likely to experience severe maternal morbidity and mortality. This study investigated the differences in risk of SSM associated with having zero, one, two or three or more comorbidities. The hypothesis of the study was that a higher number of comorbidities would be associated with a greater risk of SMM, and that these associations would vary by race.
Novel Suction Tube Uterine Tamponade for Treating Intractable Postpartum Haemorrhage: Description of Technique and Report of Three Cases
Authors: Hofmeyr G.J. , Singata-Madlik M.I.
Published: May 2021

(BJOG. 2020;127:1280–1283)

Postpartum hemorrhage (PPH), when unresponsive to other treatments, can be treated with uterine balloon tamponade (UBT). There is a clear need for more research on all methods of UBT, and some studies have found worse outcomes with use of an improvised condom UBT in low-resource settings compared to no UBT. The uterine suction tamponade (UST) uses intrauterine negative pressure to induce contraction and retraction of the uterus. Studies on UST with purpose-designed UST cannulas found successful results, but these were limited in affordability and availability. This study described the use of a widely-available wide-bore flexible suction catheter as a suction tube uterine tamponade (STUT) and reported three cases of severe PPH in which STUT was used as a last resort treatment.
Delayed Versus Immediate Pushing in the Second Stage of Labor in Women With Neuraxial Analgesia: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Di Mascio D. , Saccone G. , Bellussi F. , Al-Kouatly H.B. , Brunelli R. , Panici P.B. , Liberati M. , D’Antonio F. , Berghella V.
Published: May 2021

(Am J Obstet Gynecol. 2020;223:189–203)

Maternal and perinatal outcomes are influenced by several variables in second-stage labor management, including neuraxial analgesia, oxytocin use, parity, fetal position, maternal characteristics, and neonatal birthweight. Thus, many strategies have been evaluated which assess proper management strategies for second-stage labor. Once a woman achieves complete cervical dilation, she can begin pushing immediately or she can delay pushing. The aim of this meta-analysis and systematic review was to evaluate the effects of immediate compared to delayed pushing during the second stage of labor on mode of delivery for women with neuraxial analgesia.
Killing the Pathogen and Sparing the Placenta
Authors: Mysorekar I.U.
Published: May 2021

(N Engl J Med. 2020;182:1125.e18–1139.e18)

During pregnancy, the maternal immune system must protect from bacteria, viruses and other pathogens, while not rejecting the fetus. Decidual natural killer (NK) cells, the most abundant immune cells at the maternal-fetal interface in the first trimester of pregnancy invade the maternal side of the placenta and release cytotoxic granules. Recently, Crespo and colleagues have reported on how NK cells are able to kill harmful pathogens without damaging the placenta.
Cystic fibrosis
Authors: Wendekier Camille , Wendekier-Raybuck Katheryn
Published: May 2021

Cystic fibrosis (CF) is an autosomal recessive genetic disorder that causes a lifetime of debilitating and life-threatening complications affecting the lungs and other organ systems. Over 1,700 gene mutations that cause this rare disorder have been identified. This article describes the current treatment landscape for adults with CF, including the 2019 FDA approval of a breakthrough triple-drug combination therapy that may significantly improve the quality of life for an estimated 90% of patients with CF.
Clinical Nurse Specialist: A Critical Member of the ICU Team
Authors: Gabbard Erika R. , Klein Deborah , Vollman Kathleen , Chamblee Tracy B. , Soltis Lisa M. , Zellinger Mary
Published: May 2021

OBJECTIVES:

To describe the role of the clinical nurse specialist, an advanced practice registered nurse in the intensive care setting. The value and impact of the clinical nurse specialist role as a member of the ICU is presented along with a review of clinical nurse specialist education, licensure, and certification requirements as well as a description of the clinical nurse specialist role, scope of practice, and competencies. In addition, a selected review of clinical nurse specialist–led quality improvement and research that resulted in improved patient outcomes is provided.

DATA SOURCES:

Review of published medical and nursing literature and expert opinion guidance from a collaborative effort between the Society of Critical Care Medicine, American Association of Critical Care Nurses, and National Association of Clinical Nurse Specialists.

STUDY SELECTION:

Not applicable.

DATA EXTRACTION:

Not applicable.

DATA SYNTHESIS:

Not applicable.

CONCLUSIONS:

The utilization of a clinical nurse specialist, an advanced practice role, in the ICU is a unique and valuable approach for organizations who strive to move evidence into sustainable practice and drive quality through an interprofessional approach. The valuable contributions made by the clinical nurse specialist efficiently and effectively meet the needs of patients, clinicians, and organizations while improving patient outcomes and optimizing cost avoidance strategies, which further lower economic demands on the healthcare system.
Nurse practitioner and physician assistant onboarding in a family medicine practice
Authors: Chaney Amanda , Martin Angela , Cardona Kathy , Presutti Richard J.
Published: May 2021

The nurse practitioner (NP) and physician assistant (PA) professions are rapidly growing. Historically, these professions have filled a health care delivery gap caused by lack of health care access and physician shortages. Many medical practices are more accustomed to adding new physicians as compared with adding new NPs or PAs. This article describes one institution's approach to develop and implement a successful NP/PA onboarding program. Several key components are discussed, including (1) established roles and responsibilities, (2) a clear timeline of the onboarding period including a foundational curriculum, (3) the mentor–mentee relationship, (4) the onboarding checklist, and (5) the onboarding itinerary. The objective was to have our NPs/PAs on a regular patient calendar within the 6-month period. The success rate with this has been 86%. In addition, there has been a 90% retention of NP/PA hires over the past 3 years. The authors believe this approach to NP/PA onboarding serves the patients well, providing excellent patient outcomes and patient experience.
Health IT advances for the 21st century
Authors: Jenkins Melinda L.
Published: May 2021

The United States is working toward a value-based health care system in which reimbursement will be based on quality outcomes rather than on Current Procedural Terminology payment codes. Health data will be more easily shared, and patients will have more control of their records. Health information technology advances in the federal 21st Century Cures Act follow earlier related legislation and regulation that moved clinical care and research forward. Policy analysis of the Cures Act is presented following the three phases of the Longest model (2010): formation, implementation, and modification. With the passage of the Cures Act and promulgation of its final rules, the formation phase is complete. The implementation phase has begun. Modification may occur, based on the evaluation of key deliverables over time. Advanced practice nurses are well-suited to the use of electronic tools to share data with patients and other providers. New competencies, tools, and infrastructure are needed for advanced practice nurses to fully participate in value-based health care. Full implementation of the 21st Century Cures Act with the use of coded concepts in standardized nursing terminologies will provide an ideal foundation for strong patient-centered care, population health, and reimbursement that takes advanced nursing practice into account.
Comparison of empagliflozin and sitagliptin therapy on myocardial perfusion reserve in diabetic patients with coronary artery disease
Authors: Oh Minyoung , Choi Joon Ho , Kim Seon-Ok , Lee Pil Hyung , Ahn Jung-Min , Lee Seung-Whan , Moon Dae Hyuk , Lee Cheol Whan
Published: May 2021

Background

Sodium-glucose co-transporter 2 inhibitors reduce the risk of cardiovascular events in type 2 diabetic patients with coronary artery disease (CAD); however, the underlying mechanisms remain unclear.

Objectives

We compared the effects of empagliflozin vs. sitagliptin therapy on myocardial perfusion reserve (MPR) using dynamic single-photon emission computed tomography (SPECT) imaging.

Methods

In total, 100 patients with type 2 diabetes, CAD and an MPR <2.5 were randomized to receive either empagliflozin (10 mg once daily) or sitagliptin (100 mg once daily). Dynamic SPECT examinations were performed at baseline and at 6 months. The primary endpoint was the percent change of global MPR. Evaluable SPECT data were available for 98 patients.

Results

Baseline clinical characteristics and SPECT data were well balanced between the two groups. At a 6-month follow-up, the fasting glucose and glycated hemoglobin levels significantly decreased in both groups. Hematocrit and hemoglobin levels significantly increased in the empagliflozin group but not in the sitagliptin group. The global MPR significantly improved after treatment in both groups (34.5 ± 70.6%; P = 0.005 for empagliflozin vs. 22.4 ± 45.7%; P = 0.024 for sitagliptin). However, there was no significant difference in the global MPR between the two groups (P = 0.934). Similar findings were detected with regard to the regional MPR.

Conclusion

Among patients with type 2 diabetes and CAD, both empagliflozin and sitagliptin significantly improved the global MPR with no significant difference between the groups.
Prospective evaluation of organ-specific dose and lesional doses following therapeutic [177Lu]Lu-EDTMP administration in patients with multiple skeletal metastases and its correlation with clinical hematological toxicity
Authors: Kamaldeep  , Thapa Pradeep , Wanage Gaurav , Tervankar Shriram , Kaisar Sushma , Ranade Rohit , Basu Sandip , Das Tapas , Banerjee Sharmila
Published: May 2021

Aim

In patients with multiple skeletal metastases, accurate estimation of absorbed doses to radiosensitive bone marrow in bone-directed systemic radionuclide therapies (RNT) is critically important from clinical dose determination standpoint. The primary aim of the present study was to estimate the radiation absorbed doses of therapeutic [177Lu]Lu-EDTMP to bone marrow by two methods viz. Medical Internal Radiation Dose (MIRD) schema and using OLINDA software and correlate with hematological toxicity.

Methods

A total of 15 patients diagnosed to have multiple painful skeletal metastases being treated with [177Lu]Lu-EDTMP for palliation of pain, were enrolled for this prospective study. For all patients, urine was collected immediately after infusion of [177Lu]Lu-EDTMP up to 24 h post-administration and cumulative activity excreted from body via urine was calculated. For dosimetry, patients underwent post-administration whole-body scintigraphy at five-time points: 0.5 (pre-void), 2, 24, 48 and 120 h (post-void). From the time-activity curves generated by drawing regions of interest (ROIs) on the images, number of disintegrations was determined. Absorbed doses for organs and bone lesions were calculated using OLINDA 2.2.0 software. For bone marrow dose estimates, in addition to OLINDA 2.2.0 software, MIRD schema was also adopted. Hematological profile was monitored in all patients during the treatment and post-treatment follow-up (estimating complete blood counts, every 15 d for 3 months after therapy).

Results

The mean ± standard deviation activity of [177Lu]Lu-EDTMP administered per patient per cycle was 2.08 ± 0.45 GBq. The results demonstrated higher uptake of [177Lu]Lu-EDTMP in bone metastases compared to normal bones. Within 2 and 24 h of administration of [177Lu]Lu-EDTMP, [177Lu]Lu activity excreted from the body was 24 ± 9% and 39 ± 14%, respectively. The mean absorbed organ doses (mean ± SD) in Gy/GBq were as follows: osteogenic cells 3.15 ± 1.85, bone marrow 0.57 ± 0.31, kidneys 0.08 ± 0.05, urinary bladder 0.32 ± 0.04, and bone lesions 2.91 ± 1.88. Strong correlation was found between (a) MIRD schema and OLINDA 2.2.0 software method for estimation of bone marrow doses (r = 0.96; P = <0.0001) and (b) Bone marrow absorbed dose and hematological toxicity (r = 0.81, P = 0.0027).

Conclusion

Radiation absorbed doses to the bone marrow and skeletal metastatic lesions, following therapeutic [177Lu]Lu-EDTMP were estimated using a convenient and non-invasive quantitative imaging method. The estimated bone marrow absorbed dose, either by MIRD schema or the OLINDA 2.2.0 software method, demonstrated strong correlation. Strong correlation was also observed between bone marrow absorbed dose and hematological toxicity.
Reassessment of the lung dose limits for radioembolization
Authors: Kappadath S. Cheenu , Lopez Benjamin P. , Salem Riad , Lam Marnix G. E. H.
Published: May 2021

Radioembolization, also known as selective internal radiation therapy (SIRT), is an established treatment for the management of patients with unresectable liver tumors. Advances in liver dosimetry and new knowledge about tumor dose-response relationships have helped promote the well-tolerated use of higher prescribed doses, consequently transitioning radioembolization from palliative to curative therapy. Lung dosimetry, unfortunately, has not seen the same advances in dose calculation methodology and renewed consensus in dose limits as normal liver and tumor dosimetry. Therefore, the efficacy of curative radioembolization may be compromised in patients where the current lung dose calculations unnecessarily limit the administered activity. The field is thus at a stage where a systematic review and update of lung dose limits is necessary to advance the clinical practice of radioembolization. This work summarizes the historical context and literature for origins of the current lung dose limits following radioembolization, that is, the 25-year-old, single institution, small patient cohort series that helped establish the lung shunt fraction and dose limits. Newer clinical evidence based on larger patient cohorts that challenges the historical data on lung dose limits are then discussed. We conclude by revisiting the rationale for current lung dose limits and by proposing a staged approach to advance the field of lung dosimetry and thus the practice of radioembolization as a whole.
Quantitative evaluation of single-photon emission computed tomography findings in lower extremity possible without computed tomography-based attenuation correction
Authors: Tsuchitani Tatsuya , Kitajima Kazuhiro , Takahashi Yoshiyuki , Kotoura Noriko
Published: May 2021

Objective

For performing accurate quantitative analysis of single-photon emission computed tomography (SPECT)/computed tomography (CT) images, CT-based attenuation correction (CTAC) is considered to be necessary. However, the effect on quantitative values for an examined area close to the body surface, such as in the lower extremity, has yet to be elucidated. We performed the present investigation to determine the possibility of quantitative evaluation using a SPECT standalone device without CT.

Methods

Validation was performed using clinical data of patients who underwent a lower extremity SPECT/CT examination, with grouping based on presence or absence of CTAC, scatter correction and resolution recovery. Using a reference group in which all types of correction were applied, standardized uptake values (SUVs), including maximum (SUVmax) and peak (SUVpeak), were examined in each group and compared.

Results

As compared to the reference group, the difference in quantitative values became smaller in the order of the applied scatter correction and resolution recovery, applied resolution recovery, applied scatter correction, and neither scatter correction or resolution recovery applied groups, with no significant difference between the reference group and that with neither scatter correction or resolution recovery applied. A similar tendency was seen for both SUVmax and SUVpeak.

Conclusions

In bone SPECT quantitative examinations of the lower extremity, quantitative evaluation without CTAC is possible without the use of scatter correction or resolution recovery. Thus, quantitative evaluation can be performed with use of a standalone SPECT device without CT.
Identification of specific SUVmax ratios enhances diagnostic accuracy for staging of intrathoracic nodes in lung cancer
Authors: Pencharz Deborah , Matei Nadia , Jeon Justyn , Myerson James , Marchbank Nigel D
Published: May 2021

Introduction

Studies demonstrating limited accuracy of ‘positive’ and ‘negative’ lymph nodes on fluorodeoxyglucose (FDG) PET-CT in staging for lung cancer have led to guidelines stating mediastinal nodes enlarged on computed tomography, irrespective of FDG uptake, require endobronchial ultrasound (EBUS)-transbronchial needle aspiration (TBNA). However FDG uptake occurs on a continuous spectrum and the use of standardised uptake value (SUV)max ratios, rather than a binary classification, may have improved diagnostic accuracy.

Methods

This was a retrospective analysis of patients with lung cancer who had PET-CT and EBUS-TBNA in 2015–2018. Results from EBUS and the SUVmax ratio of sampled lymph nodes to mediastinal blood pool (SUVmax LN/MBP) were analysed.

Results

From 99 patients 102 malignant and 54 benign nodes were identified. The SUVmax range was 2.5–52 for malignant and 1.6–5.4 for benign nodes. The SUVmax LN/MBP was 1.3–23 for malignant and 0.7–2.3 for benign nodes. All nodes with SUVmax LN/MBP <1.3 were benign with 100% negative predictive value (NPV). All nodes with SUVmax LN/MBP >2.3 were malignant with 100% positive predictive value (PPV).

Conclusion

In this relatively small sample, SUVmax LN/MBP <1.3 had a NPV of 100% for excluding malignant nodes and SUVmax LN/MBP >2.3 had a PPV of 100% for diagnosing malignant nodes. Using SUVmax ratios could obviate the need for staging EBUS in selected patients with resultant time and cost savings. Selecting different SUVmax ratios, chosen to provide high accuracies for the parameter of interest to change management, is a potentially powerful diagnostic tool that is overlooked when FDG uptake is only classified as ‘positive’ or ‘negative’.
18F-FDG-PET/CT analysis in hospitalized patients affected by pulmonary disease: The experience of the Nuclear Medicine Unit of “Policlinico Tor Vegata”
Authors: Urbano Nicoletta , Scimeca Manuel , Tavolozza Mario , Bonanno Elena , Mauriello Alessandro , Schillaci Orazio
Published: May 2021

Objective

The main aim of this study was to retrospectively evaluate the clinical data and outcomes of a cohort of 492 hospitalized patients who underwent fluorine-18-fluorodeoxyglucose (F-FDG)-PET/CT analysis at the nuclear medicine unit of ‘Policlinico Tor Vergata’ in Rome during the years 2017 and 2018 with particular emphasis for patients affected by pulmonary diseases.

Methods

Anamnestic data (age and gender), main pathologic conditions, results of F-FDG-PET/CT examination, appropriateness of the request, and medical records of 492 consecutive hospitalized patients who underwent F-FDG-PET/CT analysis (55.38 ± 3.78 years; range 33–81 years) from January 2017 to December 2018 were obtained.

Results

Considering all examinations, positive results were observed in 66.9% of cases whereas it was not possible to perform a diagnosis in 12.7% of cases (doubt results). About 20-fold increase in the percentage of doubt results was observed in F-FDG-PET/CT analysis with no appropriateness as compared to those with double appropriateness (both the request and clinical). Noteworthy, our data showed a 95% higher concordance between the positive results of the F-FDG-PET/CT examination and the histologic diagnosis. Conversely, the concordance between the analysis of the bronchoalveolar lavages and the PET analysis was very low.

Conclusion

Data here reported showed the high accuracy of the F-FDG-PET/CT performed in our department, mainly for pulmonary diseases, also highlighting the importance of continuously updating the selection criteria for patients who need PET examinations.
A New Model for Specific Visualization of Skin Graft Neoangiogenesis Using Flt1-tdsRed BAC Transgenic Mice
Authors: Abdelhakim Mohamed , Dohi Teruyuki , Yamato Mizuho , Takada Hiroya , Sakai Atsushi , Suzuki Hidenori , Ema Masatsugu , Fukuhara Shigetomo , Ogawa Rei
Published: May 2021

Background:

Neovascularization plays a critical role in skin graft survival. Up to date, the lack of specificity to solely track the newly sprouting blood vessels has remained a limiting factor in skin graft transplantation models. Therefore, the authors developed a new model by using Flt1-tdsRed BAC transgenic mice. Flt1 is a vascular endothelial growth factor receptor expressed by sprouting endothelial cells mediating neoangiogenesis. The authors determined whether this model reliably visualizes neovascularization by quantifying tdsRed fluorescence in the graft over 14 days.

Methods:

Cross-transplantation of two full-thickness 1 × 1-cm dorsal skin grafts was performed between 6- to 8-week-old male Flt1 mice and KSN/Slc nude mice (n = 5). The percentage of graft area occupied by tdsRed fluorescence in the central and lateral areas of the graft on days 3, 5, 9, and 14 was determined using confocal-laser scanning microscopy.

Results:

Flt1+ endothelial cells migrating from the transgenic wound bed into the nude graft were first visible in the reticular dermis of the graft center on day 3 (0.5 ± 0.1; p < 0.05). Peak neovascularization was observed on day 9 in the lateral and central parts, increasing by 2- to 4-fold (4.6 ± 0.8 and 4.2 ± 0.9; p < 0.001). Notably, some limited neoangiogenesis was displayed within the Flt grafts on nude mice, particularly in the center. No neovascularization was observed from the wound margins.

Conclusion:

The ability of the Flt1-tdsRed transgenic mouse model to efficiently identify the origin of the skin-graft vasculature and visualize graft neovascularization over time suggests its potential utility for developing techniques that promote graft neovascularization.
Long Acellular Nerve Allografts Cap Transected Nerve to Arrest Axon Regeneration and Alter Upstream Gene Expression in a Rat Neuroma Model
Authors: Pan Deng , Bichanich Miles , Wood Ian S. , Hunter Daniel A. , Tintle Scott M. , Davis Thomas A. , Wood Matthew D. , Moore Amy M.
Published: May 2021

Background:

Treatments to manage painful neuroma are needed. An operative strategy that isolates and controls chaotic axonal growth could prevent neuroma. Using long acellular nerve allograft to “cap” damaged nerve could control axonal regeneration and, in turn, regulate upstream gene expression patterns.

Methods:

Rat sciatic nerve was transected, and the distal nerve end was reversed and ligated to generate a model end-neuroma. Three groups were used to assess their effects immediately following this nerve injury: no treatment (control), traction neurectomy, or 5-cm acellular nerve allograft cap attached to the proximal nerve. Regeneration of axons from the injured nerve was assessed over 5 months and paired with concurrent measurements of gene expression from upstream affected dorsal root ganglia.

Results:

Both control and traction neurectomy groups demonstrated uncontrolled axon regeneration revealed using Thy1-GFP rat axon imaging and histomorphometric measures of regenerated axons within the most terminal region of regenerated tissue. The acellular nerve allograft group arrested axons within the acellular nerve allograft, where no axons reached the most terminal region even after 5 months. At 5 months, gene expression associated with regeneration and pain sensitization, including Bdnf, cfos, and Gal, was decreased within dorsal root ganglia obtained from the acellular nerve allograft group compared to control or traction neurectomy group dorsal root ganglia.

Conclusions:

Long acellular nerve allografts to cap a severed nerve arrested axon regeneration within the acellular nerve allograft. This growth arrest corresponded with changes in regenerative and pain-related genes upstream. Acellular nerve allografts may be useful for surgical intervention of neuroma.
The other side of screening: predictors of treatment and follow-up for anal precancers in a large health system
Authors: Silvera Richard , Martinson Tyler , Gaisa Michael M. , Liu Yuxin , Deshmukh Ashish A. , Sigel Keith
Published: May 2021

Background:

Anal cancer disproportionately affects people with HIV (PWH). High-grade squamous intraepithelial lesions (HSIL) are cancer precursors and treating them might prevent anal cancer. Data on adherence to HSIL treatment and surveillance is limited but needed to identify deficiencies of screening strategies.

Methods:

We collected data on high-resolution anoscopy (HRA) attendance and outcomes from 2009 to 2019 in a large urban anal cancer-screening program. Patients with an initial HSIL diagnosis were followed for return for HSIL electrocautery ablation within 6 months of index HSIL diagnosis, and follow-up HRA within 18 months of index HSIL diagnosis. We also evaluated predictors of these outcomes in univariable and multivariable analyses.

Results:

One thousand one hundred and seventy-nine unique patients with an anal HSIL diagnosis were identified and 684 (58%) returned for electrocautery ablation. Of those treated, only 174 (25%) and only 9% of untreated HSIL patients (47 of 495) underwent surveillance HRA within 18 months of index HSIL diagnosis. In multivariable analyses, black patients and PWH regardless of virologic control were less likely to undergo HSIL ablation within 6 months of HSIL diagnosis whereas patients with commercial insurance were more likely to be treated within 6 months of diagnosis. Among treated HSIL patients, PWH with viremia had a lower likelihood of engaging in post-treatment surveillance within 18 months of HSIL diagnosis.

Discussion:

Even in large specialized anal cancer screening programs adherence to HSIL treatment and surveillance is low. Psychosocial and economic determinants of health may impact retention in care. Addressing both personal and structural barriers to patient engagement may improve the effectiveness of anal cancer screening.
Detection of parC gene mutations associated with quinolone resistance in Mycoplasma genitalium: evaluation of a multiplex real-time PCR assay
Authors: Bodiyabadu Kaveesha , Danielewski Jennifer , Garland Suzanne M. , Machalek Dorothy A. , Bradshaw Catriona S. , Birnie Joshua , Ebeyan Samantha , Lundgren Marie , Murray Gerald
Published: May 2021

Introduction. Increasing levels of antibiotic resistance are complicating treatment for the sexually transmitted pathogen

Mycoplasma genitalium

. Resistance to fluoroquinolones is associated with mutations in the parC gene. Although the precise mutations conferring resistance are not fully understood, the single nucleotide polymorphism (SNP) G248T/S83I is most implicated.

Aim. To evaluate the performance of the MG+parC(beta2) assay (SpeeDx, Australia), which detects single nucleotide polymorphisms (SNPs) in the parC gene at amino acid position S83 (A247C/S83R, G248T/S83I, G248A/S83N) and D87 (G259A/D87N, G259T/D87Y, G259C/D87H).

Methods. Clinical samples were analysed by MG+parC(beta2) assay and results compared to Sanger sequencing. Sensitivity, specificity, and predictive value for treatment failure were calculated.

Results. From analysis of 205 samples, the MG+parC(beta2) assay performed with a high sensitivity 98.2% (95% CI:90.3–100) and specificity 99.3% (95% CI:96.3–100) for parC SNP detection with a kappa of 0.97 (95% CI:0.94–1.00). The predictive value of G248T/S83I detection (the most common SNP, prevalence of 13% in the study population) was analysed with respect to treatment failure (patients received sequential doxycycline-moxifloxacin). The positive-predictive-value for moxifloxacin failure after detection of S83I was only 44% (95% CI:24.4–65.1), while negative-predictive-value was high at 96.9% (95% CI:92.7–99.0), suggesting that other SNPs are contributing to resistance.

Conclusion. MG+parC(beta2) performed with high concordance compared to Sanger sequencing. Such qPCR assays can assist in understanding causes of treatment failure, inform the development of diagnostic assays, and can be applied to surveillance of mutations in populations. Due to an incomplete understanding of the basis for fluoroquinolone resistance, such tests do not appear to be ready for clinical application.
The long-term effects of free care on birth outcomes: Evidence from a national policy reform in Zambia
Authors: Lagarde Mylene , Lepine Aurelia , Chansa Collins
Published: May 2021

As women in many countries still fail to give birth in facilities due to financial barriers, many see the abolition of user fees as a key step on the path towards universal coverage. We exploited the staggered removal of user charges in Zambia from 2006 to estimate the effect of user fee removal over up to five years after the policy change. We used data from the birth histories of two nationally representative Demographic and Health Surveys to implement a difference-in-differences analysis and identify the causal impact of removing user charges on institutional and assisted deliveries, caesarean sections and neonatal deaths. We also used the rich survey data to explore heterogeneous effects of the policy. Removing fees had little effect in the short term but large positive effects appeared about two years after the policy change. Institutional deliveries in treated areas increased by 25 to 35%, driven entirely by a reduction in home births. However, there was no evidence that the reform changed the behaviours of women with lower education, the proportion of caesarean sections or reduced neonatal mortality. Institutional deliveries increased where care quality was high, but not where it was low. While abolishing user charges may reduce financial hardship from healthcare payments, it does not necessarily improve equitable access to care or health outcomes. Shifting away from user fees is a necessary but insufficient step towards universal health coverage, and concurrent reforms are needed to target vulnerable populations and improve quality of care.
Loss of intestinal ChREBP impairs absorption of dietary sugars and prevents glycemic excursion curves
Authors: Charifi W , Fauveau V , Francese L , Grosfeld A , Le Gall M , Ourabah S , Ellero-Simatos S , Viel T , Cauzac M , Gueddouri D , Benhamed F , Tavitian B , Dentin R , Burnol AF , Postic C , Guilmeau S
Published: May 2021

Increased sugar consumption is a risk factor for features of the metabolic syndrome including obesity, hypertriglyceridemia, insulin resistance, diabetes, and nonalcoholic fatty liver disease. The gut epithelium, which plays a central role in dietary sugar digestion, absorption and metabolism has emerged a key actor of metabolic disorders. While the transcription factor ChREBP (Carbohydrate response element binding protein) has been established as a key player of the adaptive reprograming of cellular metabolism in various tissues upon glucose or fructose challenge, its specific contribution to the regulation of blood glucose upon dietary sugar intake was not previously addressed.

We demonstrate here that ChREBP is abundantly expressed in the proximal gut epithelium, where carbohydrate digestion and absorption primarily occur and in particular L cells, which produce the glucoincretin GLP-1. The inducible deletion of ChREBP specifically in the mouse gut epithelium (ChΔGUT mice) resulted in the reduction of early glycemic excursion upon oral glucose load. Surprisingly, despite being associated with reduced GLP-1 production, loss of gut ChREBP activity significantly dampened glucose transepithelial flux, and thereby delayed glucose distribution to peripheral tissues. Among the underlying mechanisms, we unveil that ChΔGUT mice show an impaired expression of key intestinal hexose (glucose, galactose, fructose) transporters and metabolic enzymes as well as brush border dissacharidases. In agreement, intestinal ChREBP deficiency was accompanied by a precocious intolerance to both high-lactose and high-sucrose diets concomitant with mild galactose and severe fructose malabsorption syndromes.

Altogether, our study demonstrates that, by transcriptionally orchestrating local digestion and absorption of dietary sugars, ChREBP activity in the mouse gut epithelium controls glucose appearance rate into systemic circulation and prevents against intolerance to mono- and disaccharides.
How to Assemble a Scale-Invariant Gradient
Authors: Datta Arnab , Ghosh Sagnik , Kondev Jane
Published: May 2021

Intracellular protein gradients serve a variety of functions, such as the establishment of cell polarity and to provide positional information for gene expression in developing embryos. Given that cell size in a population can vary considerably, for the protein gradients to work properly they often have to be scaled to the size of the cell. Here we examine a model of protein gradient formation within a cell that relies on cytoplasmic diffusion and cortical transport of proteins toward a cell pole. We show that the shape of the protein gradient is determined solely by the cell geometry. Furthermore, we show that the length scale over which the protein concentration in the gradient varies is determined by the linear dimensions of the cell, independent of the diffusion constant or the transport speed. This gradient provides scale-invariant positional information within a cell, which can be used for assembly of intracellular structures whose size is scaled to the linear dimensions of the cell, as was recently reported for the cytokinetic ring and actin cables in budding yeast cells.
Strategies that make vaccination easy and promote autonomy could increase COVID-19 vaccination in those who remain hesitant
Authors: Eshun-Wilson Ingrid , Mody Aaloke , Tram Khai Hoan , Bradley Cory , Sheve Alexander , Fox Branson , Thompson Vetta , Geng Elvin H
Published: May 2021

The COVID-19 vaccination campaign in the US has been immensely successful in vaccinating those who are receptive, further increases in vaccination rates however will require more innovative approaches to reach those who remain hesitant, deliberative or indifferent. Phenomena such empty mass vaccination sites and wasted vaccine doses in some regions suggest that in addition to dispelling misinformation and building trust, developing more person-centered vaccination strategies, that are modelled on what people want could further increase uptake. To inform vaccine distribution strategies that are aligned with public preferences for COVID-19 vaccination campaign features we conducted a survey and discrete choice experiment among a representative sample of 2,895 people in the US, between March 15 and March 22, 2021. We found that on average the public prioritized ease, preferring single to two dose vaccinations, vaccinating once rather than annually and reduced waiting times at vaccination sites - for some these were the primary preference drivers. Vaccine enforcement reduced overall vaccine acceptance, with a trend of increasing ‘control aversion’ with increasing vaccine hesitancy, particularly among those who were young, Black/African American or Republican. These data suggest that making vaccination easy and promoting autonomy by offering the public choices of vaccination brands and locations may increase uptake, and that vaccine mandates could compromise autonomy and increase control aversion in those who are hesitant - reducing vaccination in such groups and potentially undermining the goals of COVID-19 vaccination campaigns.

Significance

DCE’s are a novel tool in public health that allow examination of preferences for a product, service or policy, identifying how the public prioritizes personal risks and cost in relation to health behaviors. Using this method to establish preferences for COVID-19 vaccination campaign strategies, our results suggest that: firstly, vaccination should be made as easy as possible for the public, second, that individuals should be offered choices of vaccine brand and vaccination location, and third, that vaccine enforcement could activate ‘control aversion’ in the public and particularly in those who are most hesitant – potentially causing these groups to double down on vaccine resistance, a scenario which would impede the success of vaccination programs in the US.
Higher body mass index raises immature platelet count: evidence from Mendelian randomization analyses
Authors: Goudswaard Lucy J. , Corbin Laura J. , Burley Kate L. , Mumford Andrew , Akbari Parsa , Soranzo Nicole , Butterworth Adam S. , Watkins Nicholas A. , Pournaras Dimitri J. , Harris Jessica , Timpson Nicholas J. , Hers Ingeborg
Published: May 2021

A higher body mass index (BMI) is a recognised risk factor for thrombosis. Platelets are essential for haemostasis but also contribute to thrombosis when activated pathologically. We hypothesised that an increase in BMI may lead to changes in platelet characteristics, thereby contributing to increased thrombotic risk.

The effect of BMI on platelet traits measured by Sysmex XN-1000 was explored in 33388 UK blood donors from the INTERVAL study. Linear regression was used for observational analyses between BMI and platelet characteristics. Mendelian randomization (MR) was used to estimate a causal effect with BMI proxied by a genetic risk score. Follow-up analysis explored the relevance of platelet characteristics on whole blood platelet aggregation in a pre-operative cardiac cohort (COPTIC) using linear regression.

Observationally, higher BMI was positively associated with greater plateletcrit (PCT), platelet count (PLT), immature platelet count (IPC) and side fluorescence (SFL, a measure of mRNA content used to derive IPC). MR provided causal estimates for a positive effect of BMI on both SFL and IPC (IPC 0.06 SDs higher per SD higher BMI, 95% CI 0.006 to 0.12, P=0.03), but there was no strong evidence for a causal effect of BMI on PCT or PLT. The COPTIC study provided observational evidence for a positive association between IPC and whole blood platelet aggregation induced by adrenaline, TRAP-6 and ADP. Our results indicate that higher BMI raises the number of immature platelets, which is associated with greater whole blood platelet aggregation. Higher IPC could therefore contribute to obesity-related thrombosis.

Essentials

A higher body mass index (BMI) is associated with thrombotic disorders.

We explored whether BMI is associated with platelets traits, key cells involved in thrombosis.

We found causal evidence for higher BMI raising immature platelet count (IPC).

Higher IPC is associated with enhanced platelet aggregation in a cardiac surgery cohort.
SARS-CoV-2 screening prevalence in educational staff in Berlin, Germany, June-December 2020
Authors: Kindzierski Sophia , van Loon Welmoed , Theuring Stefanie , Hommes Franziska , Thombansen Eberhard , Böttcher Malik , Matthes Harald , Rössig Heike , Weiger David , Wiesmann Christof , Kurth Tobias , Kirchberger Valerie , Seybold Joachim , Mockenhaupt Frank P , Gertler Maximilian
Published: May 2021

SARS-CoV-2 infections in childcare and school settings potentially bear occupational risks to educational staff. We analyzed data derived from voluntary, PCR-based screening of childcare educators and teachers attending five testing sites in Berlin, Germany, between June and December 2020.

Within seven months, 17,491 tests were performed (4,458 educators, 13,033 teachers). Participants were largely female (72.9%), and median age was 41 years. Overall, SARS-CoV-2 infection prevalence was 1.2% (95%CI, 1.1-1.4%). Prevalence in educational staff largely resembled community incidence until the start of the second pandemic wave in mid-September 2020, when an unsteady prevalence plateau was reached. Then, infection prevalence in teachers (1.2% [95%CI, 0.8-1.8%]) did not significantly differ from the population prevalence (0.9% [0.6-1.4%]) but it was increased in educators (2.6% [1.6-4.0%]; aOR, 1.6 [1.3-2.0]). Irrespective of occupation, those that reported contact to a confirmed SARS-CoV-2 case outside of work had increased risk of infection (aOR, 3.0 [95%CI, 1.5-5.5]). In a step-wise backwards selection, the best set of associated factors with SARS-CoV-2 infection involved age, occupation, and calendar week.

These results are in line with findings that teachers do not bear an increased risk of SARS-CoV-2 infection, while childcare educators do. Infection control and prevention measures need to be strengthened in child care settings to further reduce respective occupational hazards. At the same time, the private environment appears to be the main source of SARS-CoV-2 infection for educational staff.
Semaphorin3f as an intrinsic regulator of chamber-specific heart development
Authors: Halabi R , Cechmanek P.B. , Hehr C.L. , McFarlane S.
Published: May 2021

During development a pool of precursors form a heart with atrial and ventricular chambers that exhibit distinct transcriptional and electrophysiological properties. Normal development of these chambers is essential for full term survival of the fetus, and deviations result in congenital heart defects. The large number of genes that may cause congenital heart defects when mutated, and the genetic variability and penetrance of the ensuing phenotypes, reveals a need to understand the molecular mechanisms that allow for the formation of chamber-specific cardiomyocyte differentiation. We find that in the developing zebrafish heart, mRNA for a secreted Semaphorin (Sema), Sema3fb, is expressed by all cardiomyocytes, whereas mRNA for its receptor Plexina3 (Plxna3) is expressed by ventricular cardiomyocytes. In sema3fb CRISPR zebrafish mutants, ventricular chamber development is impaired; the ventricles of mutants are smaller in size than their wild type siblings, apparently because of differences in cell size and not cell numbers, with ventricular cardiomyocytes failing to undergo normal developmental hypertrophy. Analysis of chamber differentiation indicates defects in chamber specific gene expression at the border between the ventricular and atrial chambers, with spillage of ventricular chamber genes into the atrium, and vice versa, and a failure to restrict bmp4a mRNA to the atrioventricular canal. The disrupted atrioventricular border region in mutants is accompanied by hypoplastic heart chambers and impaired cardiac function. These data suggest a model whereby cardiomyocytes secrete a Sema cue that, through spatially restricted expression of the receptor, signals in a ventricular chamber-specific manner to establish a distinct border between atrial and ventricular chambers that is important for functional development of the heart.
Neuronal mitochondria transport Pink1 mRNA via Synaptojanin 2 to support local mitophagy
Authors: Harbauer Angelika B. , Wanderoy Simone , Hees J. Tabitha , Gibbs Whitney , Ordonez Martha , Cai Zerong , Cartoni Romain , Ashrafi Ghazaleh , Wang Chen , He Zhigang , Schwarz Thomas L.
Published: May 2021

PTEN-induced kinase 1 (PINK1) is a very short-lived protein that is required for the removal of damaged mitochondria through Parkin translocation and mitophagy. Because the short half-life of PINK1 limits its ability to be trafficked into neurites, local translation is required for this mitophagy pathway to be active far from the soma. The Pink1 transcript is associated with and cotransported with neuronal mitochondria. In concert with translation, the mitochondrial outer membrane protein Synaptojanin 2 binding protein (SYNJ2BP) and Synaptojanin 2 (SYNJ2) are required for tethering Pink1 mRNA to mitochondria via an RNA-binding domain in SYNJ2. This neuron-specific adaptation for local translation of PINK1 provides distal mitochondria with a continuous supply of PINK1 for activation of mitophagy.
Bio-hybrid micro-swimmers propelled by flagella isolated from C. reinhardtii†
Authors: Ahmad Raheel , Bae Albert J , Su Yu-Jung , Pozveh Samira Goli , Bodenschatz Eberhard , Pumir Alain , Gholami Azam
Published: May 2021

Bio-hybrid micro-swimmers, composed of biological entities integrated with synthetic constructs, actively transport cargo by converting chemical energy into mechanical work in a fluid at low Reynolds number, where viscous drag dominates over inertia. Here, using isolated and demembranated flagella from green algae Chlamydomonas reinhardtii (C. reinhardtii), we build efficient axonemally-driven micro-swimmers that consume ATP to propel micron-sized beads. Depending on the calcium concentration, we observed two main classes of motion: Whereas beads move along curved trajectories at calcium concentrations below 0.03 mM, they are propelled along straight paths when the calcium concentration increases. In this regime, they reached velocities of approximately 20 μm/sec, comparable to human sperm velocity in vivo. We relate this transition to the properties of beating axonemes, in particular the reduced static curvature with increasing calcium concentration. To quantify the motion, we used mode decomposition of the flagellar waveform, and we studied both analytically and numerically the propulsion of the bead as a function of the axonemal waveform and bead-axoneme attachment geometry. While our analysis semi-quantitatively describes the experimental results, it also reveals the existence of a counter-intuitive propulsion regime where the speed of the axonemally-driven bead increases with the size of the bead. Moreover, we demonstrated that asymmetric, sideways attachment of the axoneme to the bead can also contribute to the rotational velocity of the micro-swimmer. The uncovered mechanism has potential applications in the fabrication of synthetic micro-swimmers, and in particular, bio-actuated medical micro-robots for targeted drug delivery.
Spatial redistribution of neurosecretory vesicles upon stimulation accelerates their directed transport to the plasma membrane
Authors: Schenk Elaine B. , Meunier Frederic A. , Oelz Dietmar B.
Published: May 2021

Through the integration of results from an imaging analysis of intracellular trafficking of labelled neurosecretory vesicles in chromaffin cells, we develop a Markov state model to describe their transport and binding kinetics. Our simulation results indicate that a spatial redistribution of neurosecretory vesicles occurs upon secretagogue stimulation leading vesicles to the plasma membrane where they undergo fusion thereby releasing adrenaline and noradrenaline. Furthermore, we find that this redistribution alone can explain the observed up-regulation of vesicle transport upon stimulation and its directional bias towards the plasma membrane. Parameter fitting indicates that in the deeper compartment within the cell, vesicle transport is asymmetric and characterised by a bias towards the plasma membrane. We also find that crowding of neurosecretory vesicles undergoing directed transport explains the observed accelerated recruitment of freely diffusing vesicles into directed transport upon stimulation.