bluuebunny/crossref_metadata_2025 huggingface dataset:
Testosterone is Sufficient to Impart Susceptibility to Isoflurane Neurotoxicity in Female Neonatal Rats
Authors: Chinn Gregory A. , Duong Katrina , Horovitz Tal R. , Sasaki Russell Jennifer M. , Sall Jeffrey W.
Published: June 2021

Background:

Volatile anesthetic exposure during development leads to long-term cognitive deficits in rats which are dependent on age and sex. Female rats are protected relative to male rats for the same exposure on postnatal day 7. Here we test our hypothesis that androgens can modulate chloride cotransporter expression to alter the susceptibility to neurotoxicity from GABAergic drugs using female rats with exogenous testosterone exposure.

Methods:

Female rats were injected with testosterone (100 μg/animal) or vehicle on postnatal days 1 to 6. On postnatal day 7, the animals were randomized to either isoflurane exposure or sham. Spatial memory was assessed with the Barnes maze starting on postnatal day 41. Western blots were run from testosterone treated postnatal day 7 animals to measure levels of chloride cotransporters sodium-potassium-chloride symporter (NKCC1) and chloride-potassium symporter 5 (KCC2).

Results:

Exogenous testosterone modulated isoflurane anesthetic neurotoxicity in female rats based on poor performance in the probe trial of the Barnes Maze. By contrast, females with vehicle and isoflurane exposure were able to differentiate the goal position. These behavioral differences corresponded to differences in the protein levels of NKCC1 and KCC2 after exogenous testosterone exposure, with NKCC1 increasing (P<0.001) and KCC2 decreasing (P=0.003) relative to female controls.

Conclusions:

The expression of chloride cotransporters, NKCC1 and KCC2, is altered by testosterone in female rats and corresponds to a cognitive deficit after isoflurane exposure. This confirms the role of androgens in perinatal anesthetic neurotoxicity and supports our hypothesis that the developing GABAergic system plays a critical role in the underlying mechanism.
The Impact of Magnetic Resonance Imaging on the Diagnosis of High-Energy Ipsilateral Femoral Neck and Shaft Fractures
Authors: Rennard Justin , Rogers Nathan , Achor Timothy , Kumaravel Manickam , Gary Joshua , Choo Andrew , Munz John , Routt Milton L. , Warner Stephen J.
Published: June 2021

Objective:

To evaluate the most common femoral shaft fracture morphology associated with an ipsilateral femoral neck fracture in high-energy blunt trauma using magnetic resonance imaging (MRI).

Design:

Retrospective review.

Setting:

Level 1 trauma center.

Patients/Participants:

219 consecutive patients sustaining 228 femoral shaft fractures from high-energy blunt trauma.

Main Outcome Measurements:

Fracture patterns were analyzed using the OTA/AO classification system. In addition, location of the fracture was measured as the distance from the distal aspect of the lesser trochanter to the center of the femoral shaft fracture.

Results:

An OTA/AO 31 type fracture was seen in 16.5% (20/121) of patients presenting with OTA/AO 32-A type fractures, 12% (6/50) of patients with OTA/AO 32-B type fractures, and 26.3% (15/57) of patients with OTA/AO 32-C type fractures. The fractures that occurred in the middle or distal third of the femur shaft constituted 95.1% (39/41).

Conclusions:

In this cohort, patients with middle and distal third OTA/AO 32-C type fractures had the highest association with an ipsilateral OTA/AO 31 type fracture. OTA/AO 32-A2 and 32-A3 type fractures had the highest association with femoral neck fractures seen only on MRI. The data presented suggest continued usage of the rapid sequence pelvic MRI for all patients with high-energy femoral shaft fractures in whom a femoral neck fracture was not seen on an x-ray or a computed tomography scan.

Level of Evidence:

Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Machine Learning–Based Discovery of a Gene Expression Signature in Pediatric Acute Respiratory Distress Syndrome
Authors: Grunwell Jocelyn R. , Rad Milad G. , Stephenson Susan T. , Mohammad Ahmad F. , Opolka Cydney , Fitzpatrick Anne M. , Kamaleswaran Rishikesan
Published: June 2021

Objectives:

To identify differentially expressed genes and networks from the airway cells within 72 hours of intubation of children with and without pediatric acute respiratory distress syndrome. To test the use of a neutrophil transcription reporter assay to identify immunogenic responses to airway fluid from children with and without pediatric acute respiratory distress syndrome.

Design:

Prospective cohort study.

SETTING:

Thirty-six bed academic PICU.

PATIENTS:

Fifty-four immunocompetent children, 28 with pediatric acute respiratory distress syndrome, who were between 2 days to 18 years old within 72 hours of intubation for acute hypoxemic respiratory failure.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We applied machine learning methods to a Nanostring transcriptomics on primary airway cells and a neutrophil reporter assay to discover gene networks differentiating pediatric acute respiratory distress syndrome from no pediatric acute respiratory distress syndrome. An analysis of moderate or severe pediatric acute respiratory distress syndrome versus no or mild pediatric acute respiratory distress syndrome was performed. Pathway network visualization was used to map pathways from 62 genes selected by ElasticNet associated with pediatric acute respiratory distress syndrome. The Janus kinase/signal transducer and activator of transcription pathway emerged. Support vector machine performed best for the primary airway cells and the neutrophil reporter assay using a leave-one-out cross-validation with an area under the operating curve and 95% CI of 0.75 (0.63–0.87) and 0.80 (0.70–1.0), respectively.

CONCLUSIONS:

We identified gene networks important to the pediatric acute respiratory distress syndrome airway immune response using semitargeted transcriptomics from primary airway cells and a neutrophil reporter assay. These pathways will drive mechanistic investigations into pediatric acute respiratory distress syndrome. Further studies are needed to validate our findings and to test our models.
Assessment of a Cellular Host Response Test as a Sepsis Diagnostic for Those With Suspected Infection in the Emergency Department
Authors: O’Neal Hollis R. , Sheybani Roya , Caffery Terrell S. , Musso Mandi W. , Hamer Diana , Alwood Shannon M. , Berlinger Matthew S. , Jagneaux Tonya , LaVie Katherine W. , O’Neal Catherine S. , Sanchez Michael A. , Walker Morgan K. , Shah Ajay M. , Tse Henry T. K. , Thomas Christopher B.
Published: June 2021

Objectives:

Sepsis is a common cause of morbidity and mortality. A reliable, rapid, and early indicator can help improve efficiency of care and outcomes. To assess the IntelliSep test, a novel in vitro diagnostic that quantifies the state of immune activation by measuring the biophysical properties of leukocytes, as a rapid diagnostic for sepsis and a measure of severity of illness, as defined by Sequential Organ Failure Assessment and Acute Physiology and Chronic Health Evaluation-II scores and the need for hospitalization.

Design, Setting, SUBJECTS:

Adult patients presenting to two emergency departments in Baton Rouge, LA, with signs of infection (two of four systemic inflammatory response syndrome criteria, with at least one being aberration of temperature or WBC count) or suspicion of infection (a clinician order for culture of a body fluid), were prospectively enrolled. Sepsis status, per Sepsis-3 criteria, was determined through a 3-tiered retrospective and blinded adjudication process consisting of objective review, site-level clinician review, and final determination by independent physician adjudicators.

MEASUREMENTS AND MAIN RESULTS:

Of 266 patients in the final analysis, those with sepsis had higher IntelliSep Index (median = 6.9; interquartile range, 6.1–7.6) than those adjudicated as not septic (median = 4.7; interquartile range, 3.7–5.9; p < 0.001), with an area under the receiver operating characteristic curve of 0.89 and 0.83 when compared with unanimous and forced adjudication standards, respectively. Patients with higher IntelliSep Index had higher Sequential Organ Failure Assessment (3 [interquartile range, 1–5] vs 1 [interquartile range, 0–2]; p < 0.001) and Acute Physiology and Chronic Health Evaluation-II (7 [interquartile range, 3.5–11.5] vs 5 [interquartile range, 2–9]; p < 0.05) and were more likely to be admitted to the hospital (83.6% vs 48.3%; p < 0.001) compared with those with lower IntelliSep Index.

CONCLUSIONS:

In patients presenting to the emergency department with signs or suspicion of infection, the IntelliSep Index is a promising tool for the rapid diagnosis and risk stratification for sepsis.
Physical Functioning After Admission to the PICU: A Scoping Review
Authors: Bossen Daniël , de Boer Rosa M. , Knoester Hendrika , Maaskant Jolanda M. , van der Schaaf Marike , Alsem Mattijs W. , Gemke Reinoud J. B. J. , van Woensel Job B. M. , Oosterlaan Jaap , Engelbert Raoul H. H.
Published: June 2021

Objectives:

To conduct a scoping review to 1) describe findings and determinants of physical functioning in children during and/or after PICU stay, 2) identify which domains of physical functioning are measured, 3) and synthesize the clinical and research knowledge gaps.

Data Sources:

A systematic search was conducted in PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library databases following the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews guidelines.

Study Selection:

Two investigators independently screened and included studies against predetermined criteria.

Data Extraction:

One investigator extracted data with review by a second investigator. A narrative analyses approach was used.

Data Synthesis:

A total of 2,610 articles were identified, leaving 68 studies for inclusion. Post-PICU/hospital discharge scores show that PICU survivors report difficulties in physical functioning during and years after PICU stay. Although sustained improvements in the long-term have been reported, most of the reported levels were lower compared with the reference and baseline values. Decreased physical functioning was associated with longer hospital stay and presence of comorbidities. A diversity of instruments was used in which mobility and self-care were mostly addressed.

CONCLUSIONS:

The results show that children perceive moderate to severe difficulties in physical functioning during and years after PICU stay. Longitudinal assessments during and after PICU stay should be incorporated, especially for children with a higher risk for poor functional outcomes. There is need for consensus on the most suitable methods to assess physical functioning in children admitted to the PICU.
Humanizing the ICU Patient: A Qualitative Exploration of Behaviors Experienced by Patients, Caregivers, and ICU Staff
Authors: Basile Melissa J. , Rubin Eileen , Wilson Michael E. , Polo Jennifer , Jacome Sonia N. , Brown Samuel M. , Heras La Calle Gabriel , Montori Victor M. , Hajizadeh Negin
Published: June 2021

Objectives:

To understand how patients and family members experience dehumanizing or humanizing treatment when in the ICU.

Design:

Qualitative study included web-based focus groups and open-ended surveys posted to ICU patient/family social media boards. Focus groups were audio recorded and transcribed. Social media responses were collected and organized by stakeholder group. Data underwent qualitative analysis.

Setting:

Remote focus groups and online surveys.

Patients:

ICU patient survivors, family members, and ICU teams.

Interventions:

Not available.

Measurements and Main Results:

Semi-structured questions and open-ended survey responses. We enrolled 40 patients/family members and 31 ICU team members. Focus groups and surveys revealed three primary themes orienting humanizing/dehumanizing ICU experiences: 1) communication, 2) outcomes, and 3) causes of dehumanization. Dehumanization occurred during “communication” exchanges when ICU team members talked “over” patients, made distressing remarks when patients were present, or failed to inform patients about ICU-related care. “Outcomes” of dehumanization were associated with patient loss of trust in the medical team, loss of motivation to participate in ICU recovery, feeling of distress, guilt, depression, and anxiety. Humanizing behaviors were associated with improved recovery, well-being, and trust. “Perceived causes” of dehumanizing behaviors were linked to patient, ICU team, and healthcare system factors.

CONCLUSIONS:

Behaviors of ICU clinicians may cause patients and families to feel dehumanized when in the ICU. Negative behaviors are noticed by patients and families, possibly contributing to poor outcomes including mental health, recovery, and lack of trust in ICU teams. Supporting ICU clinicians may enable a more empathic environment and in turn more humanizing clinician-patient encounters.
PARACENTRAL ACUTE MIDDLE MACULOPATHY ASSOCIATED WITH COCAINE USE
Authors: Arepalli Sruthi , Ehlers Justis P.
Published: June 2021

Background/Purpose:

To report a case of paracentral acute middle maculopathy in association with cocaine use.

Methods:

This is a case report of a 26-year-old man presented with acute vision loss in the left eye following cocaine use.

Results:

Fundus examination demonstrated faint retinal, whereas optical coherence tomography displayed hyperreflectivity predominantly in the middle retinal layers. Because of associated loss-of-consciousness and vision loss, a stroke work-up was initiated and ruled-out embolic and neurologic causes. The vision loss was attributed to paracentral acute middle maculopathy secondary to cocaine. The vision and retinal alterations on optical coherence tomography improved with observation.

Conclusion:

This case demonstrates a potential unique etiology of paracentral acute middle maculopathy following exposure to cocaine. Paracentral acute middle maculopathy may occur in the setting of cocaine use. Optical coherence tomography evaluation with close surveillance can be helpful to identify the often subtle findings of paracentral acute middle maculopathy in cases of vision loss associated with illicit drug use.
IRIS METASTASIS FROM BREAST CANCER SUCCESSFULLY TREATED WITH ABEMACICLIB AND LETROZOLE
Authors: Goduni Lediana , Ashkenazy Noy , Hansen Eric , Soyano-Muller Aixa , Correa Zelia M. , Harbour J. William
Published: June 2021

Purpose:

To describe a patient with an unusual presentation of iris metastasis from breast cancer and her response to systemic therapy.

Methods:

Retrospective chart review of one patient.

Results:

A 57-year-old woman presented with a superonasal translucent vascularized iris stromal mass with fish egg–like structures budding from the surface. High-frequency anterior segment ultrasonography demonstrated a solid iris stromal mass measuring 6.0 mm × 3.3 mm × 1.9 mm. On optical coherence tomography, the egglike structures appeared as hyperreflective spheres, some of which were detached from the main iris stromal tumor. Oncologic evaluation revealed metastatic breast cancer involving the brain and lung. She was treated with oral abemaciclib and letrozole, as well as external beam radiotherapy to the brain. The iris mass had completely regressed within 4 months and remained undetectable through the 8-month follow-up. The other metastatic lesions responded well to therapy.

Conclusion:

A case of iris metastasis was reported as the presenting sign of cancer dissemination that was successfully treated with targeted systemic therapy without ocular radiotherapy.
Comparison of Corneal Wave Speed and Ocular Rigidity in Normal and Glaucomatous Eyes
Authors: Kazemi Arash , Zhou Boran , Zhang Xiaoming , Sit Arthur J.
Published: June 2021

Precis:

Ocular biomechanics were compared between treated glaucoma patients and healthy subjects matched for age, intraocular pressure (IOP), and axial length. There was no difference in corneal wave propagation speed, but ocular rigidity was lower in glaucomatous eyes.

Purpose:

Ocular biomechanical properties are important in understanding glaucoma pathogenesis but the affected tissues are unclear. In this study, we compared corneal wave speed (a measure of corneal elasticity) and ocular rigidity coefficient between glaucomatous and normal eyes.

Materials and Methods:

Twenty glaucomatous eyes from 10 patients and 20 normal eyes from 13 controls, matched for age, IOP, and axial length were included. Ocular rigidity was calculated based on the difference in supine IOP by pneumatonometry with and without a 10-g weight. Corneal wave speed was determined by ultrasound surface wave elastography. A small, 0.1-second harmonic vibration at 100 Hz was generated through the closed eyelids. Wave propagation was captured by an ultrasound transducer, and wave speed was determined from the phase change with distance. Comparisons were performed using generalized estimating equation models.

Results:

There were no significant differences in corneal wave speed between glaucomatous and normal eyes (2.16±0.25 vs. 2.07±0.16 m/s, P=0.17). However, ocular rigidity was significantly lower in glaucomatous eyes (0.0218±0.0033 vs. 0.0252±0.0050/μL, P=0.01). Corneal wave speed was not correlated with age and IOP in either group (P≥0.23) but was correlated with ocular rigidity (R=0.48, P=0.02) and inversely correlated with axial length (R=−0.53, P=0.01) in glaucomatous eyes.

Conclusion:

Glaucomatous eyes tend to have lower ocular rigidity than healthy eyes with similar age, IOP, and axial length. However, the lack of a difference in corneal wave speed suggests that corneal tissue may not be significantly affected, and scleral changes likely play a more important role in glaucoma.
The other connective tissue disease-associated interstitial lung diseases: Sjogren's syndrome, mixed connective tissue disease, and systemic lupus erythematosus
Authors: Lee Cathryn T. , Strek Mary E.
Published: June 2021

Purpose of review

We review the clinical manifestations of three less common connective tissue disease (CTD)-associated interstitial lung diseases (ILDs): Sjogren's syndrome (SjS), mixed CTD (MCTD), and systemic lupus erythematosus (SLE).

Recent findings

SjS is classically associated with lymphocytic interstitial pneumonia and cystic lung disease, but the most common type of ILD in Sjogren's patients is nonspecific interstitial pneumonia. ILD is prevalent in MCTD and associated with worse survival. SLE-associated ILD, while rare, is more common in those with CTD overlap syndromes. Regardless of underlying cause, a subset of patients with fibrotic CTD-associated ILD develop a progressive course for which antifibrotic agents and lung transplantation should be considered.

An understanding of the characteristics of ILD in SjS, MCTD, and SLE is important for the pulmonary specialist. Future research should identify risk factors for progression and develop additional treatment modalities for both CTD-related autoimmune features and progressive ILD.
At a crossroads: coronavirus disease 2019 recovery and the risk of pulmonary vascular disease
Authors: Cascino Thomas M. , Desai Ankit A. , Kanthi Yogendra
Published: June 2021

Purpose of review

The coronavirus disease 2019 (COVID-19) pandemic has led to almost 3,000,000 deaths across 139 million people infected worldwide. Involvement of the pulmonary vasculature is considered a major driving force for morbidity and mortality. We set out to summarize current knowledge on the acute manifestations of pulmonary vascular disease (PVD) resulting from COVID-19 and prioritize long-term complications that may result in pulmonary hypertension (PH).

Recent findings

Acute COVID-19 infection can result in widespread involvement of the pulmonary vasculature, myocardial injury, evidence of persistent lung disease, and venous thromboembolism. Post COVID-19 survivors frequently report ongoing symptoms and may be at risk for the spectrum of PH, including group 1 pulmonary arterial hypertension, group 2 PH due to left heart disease, group 3 PH due to lung disease and/or hypoxia, and group 4 chronic thromboembolic PH.

The impact of COVID-19 on the pulmonary vasculature is central to determining disease severity. Although the long-term PVD manifestations of COVID-19 are currently uncertain, optimizing the care of risk factors for PH and monitoring for the development of PVD will be critical to reducing long-term morbidity and improving the health of survivors.
Sudden unexpected death in children: myth or reality?
Authors: Enner Stephanie , Pavkovic Ivan , Kothare Sanjeev V.
Published: June 2021

Purpose of review

Despite many years of study, sudden unexplained death remains a tenuous diagnosis of exclusion. Here, we discuss the current science behind the uncertainties of sudden death, as well as the questions that still remain.

Recent findings

Failure in any part of the complex interplay between peripheral sensors and central cardiorespiratory regulation can result in sudden death. Diagnostic testing with electrocardiograms, electroencephalogram, sleep studies, or even genetic studies have increased our ability to identify patients at the highest risk.

Advances in the understanding of sudden unexplained death in children may show common pathways leading to sudden death from multiple different diseases. Although rare, the devastating implication prioritizes the importance in educating patients about how to live with the risk of sudden death.
Covid-19 skin manifestations: an update
Authors: Sanchez-Flores Xavier , Huynh Thy , Huang Jennifer T.
Published: June 2021

Purpose of review

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or COVID-19 is a multisystemic disease manifesting mainly with dry cough, fever, and pneumonia and can present with a myriad of cutaneous manifestations. This chapter will review SARS-CoV-2 associated cutaneous findings, including incidence and relevance to the pediatric population.

Recent findings

The most commonly reported cutaneous findings described for COVID-19 in adults and children were chilblains-like lesions, followed by maculopapular eruption, urticarial lesions, vesicular lesions, and livedoid lesions. Children can also present with erythema multiforme (EM)-like lesions and skin findings associated with multisystem inflammatory syndrome in children (MIS-C).

There are numerous cutaneous manifestations of COVID-19, some of which are unique to children such as EM-like lesions and skin findings for MIS-C. Livedoid lesions do not commonly occur in the pediatric population. In mild cases, supportive care is indicated, whereas severe cases warrant intensive care and hospitalization.
Shared decision making in pediatric dermatology: context, opportunities, and practical examples
Authors: Kozina Yuliya , Politi Mary C. , Coughlin Carrie C.
Published: June 2021

Purpose of review

Shared decision making (SDM) is an important part of patient-centered care. However, it is neither widely practiced nor researched in pediatric dermatology. In this article, we provide practical examples of how to engage in SDM in pediatric dermatology, and identify future areas of research.

Recent findings

Children and parents/guardians desire SDM in clinical encounters. The process is applicable to discussions of medical as well as surgical care. Additionally, SDM can help prepare children for the transition from pediatric to adult/general providers. Clinicians often want more guidance on its implementation, and there is a dearth of research on SDM or decision tools specific to pediatric dermatology.

SDM is underused and understudied in pediatric dermatology. This article highlights how to engage in SDM and presents opportunities for research and implementation in pediatric dermatology.
Antibiotic resistance: still a cause of concern?
Authors: DeBaun Malcolm R. , Lai Cara , Sanchez Mark , Chen Michael J. , Goodnough L. Henry , Chang Amy , Bishop Julius A. , Gardner Michael J.
Published: June 2021

Antibiotic resistance remains a global public health concern with significant patient morbidity and tremendous associated health care costs. Drivers of antibiotic resistance are multifaceted and differ between developing and developed countries. Under evolutionary pressure, microbes acquire antibiotic tolerance through a variety of mechanisms at the cellular level. Patients after orthopaedic trauma are vulnerable to drug-resistant pathogens, particularly after open fractures. Traumatologists practicing appropriate antibiotic prophylaxis and treatment regimens mitigate infection and propagation of antibiotic resistance.
Frequency of post treatment control varies by antiretroviral therapy restart and viral load criteria
Authors: Fajnzylber Jesse , Sharaf Radwa , Hutchinson John N. , Aga Evgenia , Bosch Ronald J. , Hartogensis Wendy , Jacobson Jeffrey M. , Connick Elizabeth , Volberding Paul , Skiest Daniel J. , Margolis David , Sneller Michael C. , Little Susan J. , Gulick Roy M. , Mellors John W. , Gandhi Rajesh T. , Schooley Robert T. , Henry Keith , Tebas Pablo , Deeks Steve , Chun Tae-Wook , Collier Ann C. , Hecht Frederick M. , Li Jonathan Z.
Published: June 2021

Clinical trials including an analytical treatment interruption (ATI) are vital for evaluating the efficacy of novel strategies for HIV remissions. We briefly describe an interactive tool for predicting viral rebound timing in ATI trials and the impact of posttreatment controller (PTC) definitions on PTC frequency estimates. A 4-week viral load threshold of 1000 cps/ml provides both high specificity and sensitivity for PTC detection. PTC frequency varies greatly based on the definition of a PTC.
Persistently lower bone mass and bone turnover among South African children living with well controlled HIV
Authors: Shen Yanhan , Shiau Stephanie , Strehlau Renate , Burke Megan , Patel Faeezah , Johnson Cara T. , Rizkalla Bridgette , Dympna Gallagher , Kuhn Louise , Coovadia Ashraf , Yin Michael T. , Arpadi Stephen M.
Published: June 2021

Objective:

We evaluated longitudinal trends and associations between bone mass, bone turnover and inflammatory markers among South African children living with HIV (CLHIV) and controls.

Design:

We previously reported decreased bone mass among CLHIV independent of marked inflammation and increased bone turnover. The goal of this study was to evaluate longitudinal changes in bone mass, bone turnover and inflammation over 2 years.

Methods:

Longitudinal analyses were conducted among 220 CLHIV and 220 controls. Anthropometric measurements, physical activity, antiretroviral regimen, virologic and immunologic status, whole body (WB) and lumbar spine (LS) bone mineral content (BMC) and bone mineral density (BMD) were collected (enrollment, 12 and 24 months). Bone turnover markers including C-telopeptide of type I collagen (CTx) and procollagen type I N-terminal propeptide (P1NP) and inflammatory markers including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble CD14 and high-sensitivity C-reactive protein (hsCRP) were collected at enrollment and 24 months.

Results:

Compared with controls, CLHIV had significantly lower mean WB-BMC, WB-BMD, WB-BMC z scores, LS-BMC and LS-BMD as well as lower bone formation (P1NP) and resorption (CTx), and higher hsCRP and soluble CD14 over 24 months. CLHIV on efavirenz (EFV) had consistently lower TNF-alpha and IL-6 compared with those on ritonavir-boosted lopinavir (LPV/r) at all time points.

Conclusion:

Over 2 years of follow-up, South African CLHIV had persistently lower bone mass, bone turnover, and macrophage activation. Lower bone mass and higher pro-inflammatory cytokine profiles were consistently observed among those on LPV/r-based compared with EFV-based regimens.
The symptomatology of cerebrospinal fluid HIV RNA escape: a large case-series
Authors: Chan Terrence Y.-H. , De Zan Valentina , Gregg Alistair , Alagaratnam Jasmini , Gerevini Simonetta , Antinori Andrea , D’Arminio Monforte Antonella , Saracino Annalisa , Trunfio Mattia , Everitt Alex , Rackstraw Simon , Marta Monica , Calcagno Andrea , Cinque Paola , Winston Alan
Published: June 2021

Objective:

To characterize the clinical, laboratory and radiological characteristics of persons with HIV (PWH) presenting with cerebrospinal fluid (CSF) HIV RNA escape.

Design:

Retrospective case review of PWH presenting with symptomatic CSF HIV RNA escape at seven tertiary HIV clinical sites in the United Kingdom and Italy.

Method:

PWH with symptomatic CSF HIV RNA escape episodes were identified and data obtained from medical records. CSF HIV RNA escape was defined as quantifiable CSF HIV RNA in unquantifiable plasma HIV RNA or CSF HIV RNA greater than plasma HIV RNA in cases where plasma HIV RNA was quantifiable. The onset of clinical symptoms was classified as acute (<2 weeks–6 months), or chronic (>6 months) and differences in presentation in those with CSF HIV RNA below and above 1000 copies/ml determined.

Results:

We identified 106 PWH with CSF HIV RNA escape (65 male); 68 (64%) PWH had acute presentations and 38 (36%) had chronic presentations. Cognitive decline (n = 54; 50.9%), confusion (n = 20; 18.9%) and headache (n = 28; 26.4%) were the most common presentations, with cognitive decline being more common in PWH who presented chronically compared with PWH who presented acutely (73.7% vs. 35.3%, P = 0.0002). Sixty PWH had CSF HIV RNA at least 1000 copies/ml and presented more frequently with confusion (n = 15/60; 25.0%) compared with PWH with CSF HIV RNA less than 1000 copies/ml at presentation (n = 5/46; 10.9%; P = 0.03).

Conclusion:

Cognitive decline, confusion and headache are the most frequent presenting symptoms of CSF HIV RNA escape and their relative frequency varied according to symptom onset and CSF HIV RNA concentration.
Infection prevention measures in acute care settings based on severe acute respiratory syndrome coronavirus 2 transmission patterns and risk: a review
Authors: Yen Christina F. , van den Berg Polly , Pepe Dana E.
Published: June 2021

Purpose of review

During the coronavirus disease 2019 pandemic, when facing extraordinary infection prevention challenges, acute care settings have balanced routine patient safety needs while minimizing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission risk to patients and healthcare personnel (HCP). Mitigation strategies in acute care settings are based on a combination of basic science, environmental, and epidemiologic evidence. Here, we review the literature on SARS-CoV-2 transmission, how it has shaped infection prevention interventions in acute care settings, and the results of such measures to reduce transmission.

Recent findings

HCP adherence to transmission-based precautions in acute care settings, such as the use of personal protective equipment (PPE), is essential to mitigating SARS-CoV-2 spread. Although the SARS-CoV-2 virus has been isolated in nonrespiratory body sites, such exposure has not been shown to definitively cause transmission in humans. Epidemiologic evidence has demonstrated that implementation and adherence to infection prevention strategies reduces acute setting transmission.

Given SARS-CoV-2 infection occurs primarily through respiratory transmission, preventing HCP acquisition requires fidelity to consistent PPE usage. Infection prevention strategies and implementation of transmission-based precautions have reduced spread and outbreaks. Epidemiologic studies of acute care outbreaks often include reports of PPE nonadherence and community exposure contributing to SARS-CoV-2 transmission within this setting.
The oldest peracarid crustacean reveals a Late Devonian freshwater colonization by isopod relatives
Authors: Robin N. , Gueriau P. , Luque J. , Jarvis D. , Daley A. C. , Vonk R.
Published: June 2021

Peracarida (e.g. woodlice and side-swimmers) are, together with their sister-group Eucarida (e.g. krill and decapods), the most speciose group of modern crustaceans, suggested to have appeared as early as the Ordovician. While eucarids' incursion onto land consists of mainly freshwater and littoral grounds, some peracarids have evolved fully terrestrial ground-crawling ecologies, inhabiting even our gardens in temperate regions (e.g. pillbugs and sowbugs). Their fossil record extends back to the Carboniferous and consists mainly of marine occurrences. Here, we provide a complete re-analysis of a fossil arthropod—Oxyuropoda—reported in 1908 from the Late Devonian floodplains of Ireland, and left with unresolved systematic affinities despite a century of attempts at identification. Known from a single specimen preserved in two dimensions, we analysed its anatomy using digital microscopy and multispectral macroimaging to enhance the contrast of morphological structures. The new anatomical characters and completeness ofOxyuropoda, together with a phylogenetic analysis with representatives of all major Eumalacostraca groups, indicate thatOxyuropodais a crown peracarid, part of a clade including amphipods and isopods. As such,Oxyuropodais the oldest known species Peracarida, and provides evidence that derived peracarids had an incursion into freshwater and terrestrial environments as early as the Famennian, more than 360 Ma.
Is the diatom sex clock a clock?
Authors: Fuhrmann-Lieker Thomas , Kubetschek Nico , Ziebarth Jonas , Klassen Roland , Seiler Werner
Published: June 2021

The unique life cycle of diatoms with continuous decreasing and restoration of the cell size leads to periodic fluctuations in cell size distribution and has been regarded as a multi-annual clock. To understand the long-term behaviour of a population analytically, generic mathematical models are investigated algebraically and numerically for their capability to describe periodic oscillations. Whereas the generally accepted simple concepts for the proliferation dynamics do not sustain oscillating behaviour owing to broadening of the size distribution, simulations show that a proposed limited lifetime of a newly synthesized cell wall slows down the relaxation towards a time-invariant equilibrium state to the order of a hundred thousand generations. In combination with seasonal perturbation events, the proliferation scheme with limited lifetime is able to explain long-lasting rhythms that are characteristic for diatom population dynamics. The life cycle thus resembles a pendulum clock that has to be wound up from time to time by seasonal perturbations rather than an oscillator represented by a limit cycle.
Nucleosome-induced homology recognition in chromatin
Authors: Hedley Jonathan G. , Teif Vladimir B. , Kornyshev Alexei A.
Published: June 2021

One of the least understood properties of chromatin is the ability of its similar regions to recognize each other through weak interactions. Theories based on electrostatic interactions between helical macromolecules suggest that the ability to recognize sequence homology is an innate property of the non-ideal helical structure of DNA. However, this theory does not account for the nucleosomal packing of DNA. Can homologous DNA sequences recognize each other while wrapped up in the nucleosomes? Can structural homology arise at the level of nucleosome arrays? Here, we present a theoretical model for the recognition potential well between chromatin fibres sliding against each other. This well is different from the one predicted for bare DNA; the minima in energy do not correspond to literal juxtaposition, but are shifted by approximately half the nucleosome repeat length. The presence of this potential well suggests that nucleosome positioning may induce mutual sequence recognition between chromatin fibres and facilitate the formation of chromatin nanodomains. This has implications for nucleosome arrays enclosed between CTCF–cohesin boundaries, which may form stiffer stem-like structures instead of flexible entropically favourable loops. We also consider switches between chromatin states, e.g. through acetylation/deacetylation of histones, and discuss nucleosome-induced recognition as a precursory stage of genetic recombination.
Efficient and effective single-step screening of individual samples for SARS-CoV-2 RNA using multi-dimensional pooling and Bayesian inference
Authors: Sobczyk Juliana , Pyne Michael T. , Barker Adam , Mayer Jeanmarie , Hanson Kimberly E. , Samore Matthew H. , Noriega Rodrigo
Published: June 2021

Rapid and widespread implementation of infectious disease surveillance is a critical component in the response to novel health threats. Molecular assays are the preferred method to detect a broad range of viral pathogens with high sensitivity and specificity. The implementation of molecular assay testing in a rapidly evolving public health emergency, such as the ongoing COVID-19 pandemic, can be hindered by resource availability or technical constraints. We present a screening strategy that is easily scaled up to support a sustained large volume of testing over long periods of time. This non-adaptive pooled-sample screening protocol employs Bayesian inference to yield a reportable outcome for each individual sample in a single testing step (no confirmation of positive results required). The proposed method is validated using clinical specimens tested using a real-time reverse transcription polymerase chain reaction test for SARS-CoV-2. This screening protocol has substantial advantages for its implementation, including higher sample throughput, faster time to results, no need to retrieve previously screened samples from storage to undergo retesting, and excellent performance of the algorithm's sensitivity and specificity compared with the individual test's metrics.
Evolution of an asymptomatic first stage of infection in a heterogeneous population
Authors: Saad-Roy Chadi M. , Grenfell Bryan T. , Levin Simon A. , van den Driessche P. , Wingreen Ned S.
Published: June 2021

Pathogens evolve different life-history strategies, which depend in part on differences in their host populations. A central feature of hosts is their population structure (e.g. spatial). Additionally, hosts themselves can exhibit different degrees of symptoms when newly infected; this latency is a key life-history property of pathogens. With an evolutionary-epidemiological model, we examine the role of population structure on the evolutionary dynamics of latency. We focus on specific power-law-like formulations for transmission and progression from the first infectious stage as a function of latency, assuming that the across-group to within-group transmission ratio increases if hosts are less symptomatic. We find that simple population heterogeneity can lead to local evolutionarily stable strategies (ESSs) at zero and infinite latency in situations where a unique ESS exists in the corresponding homogeneous case. Furthermore, there can exist more than one interior evolutionarily singular strategy. We find that this diversity of outcomes is due to the (possibly slight) advantage of across-group transmission for pathogens that produce fewer symptoms in a first infectious stage. Thus, our work reveals that allowing individuals without symptoms to travel can have important unintended evolutionary effects and is thus fundamentally problematic in view of the evolutionary dynamics of latency.
An integrated platform to facilitate the calculation, validation and visualization of optical flow velocities in biological images
Authors: Yong Xianbin , Huang Cheng-Kuang , Lim Chwee Teck
Published: June 2021

Optical flow algorithms have seen poor adoption in the biological community compared with particle image velocimetry for quantifying cellular dynamics because of the lack of proper validation and an intuitive user interface. To address these challenges, we present OpFlowLab, an integrated platform that integrates our motion estimation workflow. Using routines in our workflow, we demonstrate that optical flow algorithms are more accurate than PIV in simulated images of the movement of nuclei. Qualitative assessment with actual nucleus images further supported this finding. Additionally, we show that refinement of the optical flow velocities is possible with a simple object-matching procedure, opening up the possibility of obtaining reasonable velocity estimates under less ideal imaging conditions. To visualize velocity fields, we employ artificial tracers to allow for the drawing of pathlines. Through the adoption of OpFlowLab, we are confident that optical flow algorithms will allow for the exploration of dynamic biological systems in greater accuracy and detail.
IMPACT OF COVID-19 PANDEMIC ON SICKNESS ABSENCE FOR MENTAL ILL HEALTH IN NATIONAL HEALTH SERVICE STAFF
Authors: van der Plaat Diana A , Edge Rhiannon , Coggon David , van Tongeren Martie , Muiry Rupert , Parsons Vaughan , Cullinan Paul , Madan Ira
Published: June 2021

Objective

To explore the patterns of sickness absence in National Health Service (NHS) staff attributable to mental ill health during the first wave of the Covid-19 epidemic in March – July 2020

Design

Case-referent analysis of a secondary data set

Setting

NHS Trusts in England

Participants

Pseudonymised data on 959,356 employees who were continuously employed by NHS trusts during 1 January 2019 to 31 July 2020

Main Outcome Measures

Trends in the burden of sickness absence due to mental ill health from 2019 to 2020 according to demographic, regional and occupational characteristics.

Results

Over the study period, 164,202 new sickness absence episodes for mental ill health were recorded in 12.5% (119,525) of the study sample. There was a spike of sickness absence for mental ill health in March-April 2020 (899,730 days lost) compared with 519,807 days in March-April 2019; the surge was driven by an increase in new episodes of long-term absence and had diminished by May/June 2020. The increase was greatest in those aged >60 years (227%) and among employees of Asian and Black ethnic origin (109%-136%). Among doctors and dentists the number of days absent declined by 12.7%. The biggest increase was in London (122%) and the smallest in the East Midlands (43.7%); the variation between regions reflected the rates of Covid-19 sickness absence during the same period.

Conclusion

Although the Covid-19 epidemic led to an increase in sickness absence attributed to mental ill health in NHS staff, this had substantially declined by May/June 2020, corresponding with the decrease in pressures at work as the first wave of the epidemic subsided.

Article Summary

Strengths and limitations of this study

Large study population

Study population were not self-selected

Job exposure matrix allowed adjustment for occupational exposure

Data did not extend to the start of the second wave in September 2020
Reopening International Borders without Quarantine: Contact Tracing Integrated Policy against COVID-19
Authors: Yu Zidong , Zhu Xiaolin , Liu Xintao , Chen Xiang , Wei Tao , Yuan Hsiang-Yu , Xu Yang , Zhu Rui , He Huan , Wang Hui , Wong Man-sing , Jia Peng , Shi Wen-zhong , Chen Wu
Published: June 2021

With the COVID-19 vaccination widely implemented in most countries, propelled by the need to revive the tourism economy, there is a growing prospect for relieving the social distancing regulation and reopening borders in tourism-oriented countries and regions. The need incentivizes stakeholders to develop border control strategies that fully evaluate health risks if mandatory quarantines are lifted. In this study, we have employed a computational approach to investigate the contact tracing integrated policy in different border reopening scenarios in Hong Kong, China. Built on a modified SEIR epidemic model with a 30% vaccination coverage, the results suggest that scenarios with digital contact tracing and quick isolation intervention can reduce the infectious population by 92.11% compared to those without contact tracing. By further restricting the inbound population with a 10,000 daily quota and applying moderate-to-strong community non-pharmacological interventions (NPIs), the average daily confirmed cases in the forecast period of 60 days can be well controlled at around 9 per day (95% CI: 7–12). Two main policy recommendations are drawn from the study. First, digital contact tracing would be an effective countermeasure for reducing local virus spread, especially when it is applied along with a moderate level of vaccination coverage. Second, implementing a daily quota on inbound travelers and restrictive community NPIs would further keep the local infection under control. This study offers scientific evidence and prospective guidance for developing and instituting plans to lift mandatory border control policies in preparing for the global economic recovery.
The prevalence, incidence, prognosis and risk factors for depression and anxiety in a UK cohort during the COVID-19 pandemic
Authors: Jia Ru , Ayling Kieran , Chalder Trudie , Massey Adam , Gasteiger Norina , Broadbent Elizabeth , Coupland Carol , Vedhara Kavita
Published: June 2021

Background

The COVID-19 pandemic had profound immediate impacts on population mental health. However, in whom the effects may be prolonged is less clear.

Aims

To investigate the prevalence, incidence, prognosis, and risk factors for depression and anxiety reported in a UK cohort over three distinct periods in the pandemic in 2020.

Method

An online survey was distributed to a UK community cohort (n=3097) at three points: April (baseline), July-September (T2) and November-December (T3). Participants completed validated measures of depression and anxiety on each occasion and we prospectively explored the role of socio-demographic factors and psychological factors (loneliness, positive mood, perceived risk of and worry about COVID-19) as risk factors.

Results

Depression (PHQ-9 means - baseline: 7.69, T2: 5.53, T3: 6.06) and anxiety scores (GAD-7 means -baseline: 6.59, T2: 4.60, T3: 4.98) were considerably greater than pre-pandemic population norms. Women reported greater depression and anxiety than men. Being younger, having prior mental health disorders, more negative life events due to COVID-19, as well as greater loneliness and lower positive mood at baseline were significant predictors of poorer mental health outcomes.

Conclusion

The negative impact of the COVID-19 pandemic on mental health has persisted to some degree. Younger people and individuals with prior mental health disorders were at greatest risk. Easing of restrictions might bring the opportunity for a return to social interaction, which could mitigate the risk factors of loneliness and positive mood.
A pan-European study of SARS-CoV-2 variants in wastewater under the EU Sewage Sentinel System
Authors: Agrawal Shelesh , Orschler Laura , Schubert Selina , Zachmann Kira , Heijnen Leo , Tavazzi Simona , Gawlik Bernd Manfred , de Graaf Miranda , Medema Gertjan , Lackner Susanne
Published: June 2021

Wastewater based surveillance employing qPCR has already shown its utility for monitoring SARS-CoV-2 at community level, and consequently the European Commission has recommended the implementation of an EU Sewage Sentinel System. However, using sequencing for the determination of genomic variants in wastewater is not fully established yet. Therefore, we focused on the sequencing analysis of SARS-CoV-2 RNA in wastewater samples collected across 20 European countries including 54 municipalities. Our results provide unprecedented insight into the abundance and the profile of the mutations associated with the variants of concerns: B.1.1.7, P.1, B.1.351 and B.1.617.2, which were present in various wastewater samples. This study shows that integrating genomic and wastewater-based epidemiology (WBE) can support the identification of variants circulating in a city at community level.