bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Outcomes and Qualitative Perceptions of In-person, Hybrid, and Virtual Cardiac Rehabilitation
Authors: Ganeshan Smitha , Jackson Hunter , Grandis Donald J. , Janke David , Murray Michelle L. , Valle Vanessa , Beatty Alexis L.
Published: April 2022

Purpose:

Cardiac rehabilitation (CR) is evolving to include both in-person and virtual delivery. Our objective was to compare, in CR patients, the association of in-person, hybrid, and virtual CR with change in performance on the 6-min walk test (6MWT) between enrollment and completion.

Methods:

Patients enrolled in CR between October 22, 2019, and May 10, 2021, were categorized into in-person, hybrid, or virtual groups by number of in-person and virtual visits. All patients received individualized exercise training and health behavior counseling. Cardiac rehabilitation was delivered to patients in the hybrid and virtual cohorts using synchronous video exercise and/or asynchronous telephone visits. Measurements at CR enrollment and completion included the 6MWT, blood pressure (BP), depression, anxiety, waist-to-hip ratio, and cardiac self-efficacy.

Results:

Of 187 CR patients, 37/97 (38.1%) were in-person patients and 58/90 (64.4%) were hybrid/virtual patients (P = .001). Compared to in-person (51.5 ± 59.4 m) improvement in the 6MWT was similar in hybrid (63.4 ± 55.6; P = .46) and virtual (63.2 ± 59.6; P = .55) compared with in-person (51.5 ± 59.4). Hybrid and virtual patients experienced similar improvements in BP control and anxiety. Virtual patients experienced less improvement in depression symptoms. There were no statistically significant changes in waist-to-hip ratio or cardiac self-efficacy. Qualitative themes included the adaptability of virtual CR, importance of relationships between patients and CR staff, and need for training and organizational adjustments to adopt virtual CR.

Conclusions:

Hybrid and virtual CR were associated with similar improvements in functional capacity to in-person. Virtual and hybrid CR have the potential to expand availability without compromising outcomes.
Non-tuberculous Mycobacterial Infection of the Retropharyngeal Space
Authors: Weng Alastair , Curtis Nigel , Kadambari Seilesh , Gardiner Kaya , Burgner David , Gwee Amanda
Published: April 2022

We report a case of Mycobacterium avium complex infection of the retropharyngeal space in a 20-month-old girl. We also summarize the published literature on the pathogenesis and management of nontuberculous mycobacterial infections of the retropharynx.
A Yersiniabactin-producing Klebsiella aerogenes Strain Causing an Outbreak in an Austrian Neonatal Intensive Care Unit
Authors: Baier-Grabner Sebastian , Equiluz-Bruck Susanne , Endress David , Blaschitz Marion , Schubert Sören , Indra Alexander , Fudel Marta , Frischer Thomas , Götzinger Florian
Published: April 2022

Background:

Yersiniabactin, a siderophore with a high affinity to iron, has been described as a potential virulence factor in Enterobacteriaceae. Klebsiella aerogenes is a Gram-negative rod known to cause invasive infection in very low birth weight infants but is an unusual pathogen to cause outbreaks in neonatal intensive care units (NICU).

Methods:

We performed a retrospective analysis of all patients colonized with K. aerogenes in our NICU from September to December 2018. Each infant with an occurrence of K. aerogenes in any microbiological culture was defined as a case. Clinical data were taken from medical charts. K. aerogenes isolates were genotyped using whole-genome sequencing combined with core genome multilocus sequencing type analysis. Yersiniabactin production was evaluated by luciferase assay.

Results:

In total 16 patients were colonized with K. aerogenes over the 3-month period and 13 patients remained asymptomatic or developed late-onset neonatal sepsis from another pathogen. Three patients developed necrotizing enterocolitis, 2 complicated by sepsis and 1 of them died. All symptomatic patients were premature infants with low birth weight. Genetic sequencing confirmed an outbreak with the same strain, all samples expressed the high-pathogenicity island, necessary for the production of yersiniabactin. Six exemplary cases were proven to produce yersiniabactin in vitro.

Conclusion:

This is the first report of an outbreak of a yersiniabactin-producing K. aerogenes strain causing invasive infection in preterm infants. We hypothesize that, due to improved iron uptake, this strain was associated with higher virulence than non-yersiniabactin-producing strains. Extended search for virulence factors and genetic sequencing could be pivotal in the management of NICU outbreaks in the future.
Screening for Immunodeficiencies in Children With Invasive Pneumococcal Disease: Six-year Experience From a UK Children’s Hospital
Authors: Bijker Else M. , Bateman Elizabeth A.L. , Trück Johannes , Patel Smita , Kelly Dominic F.
Published: April 2022

Background:

A previous study showed that investigation of children with invasive pneumococcal disease (IPD) revealed an immunodeficiency in up to 10% of cases. Following this report, we implemented a protocol to investigate children with IPD, to assess the proportion with an immunodeficiency in our setting.

Methods:

We retrospectively identified patients who presented with IPD from January 2015 to November 2020 and collected data from medical records. Immunological investigations included complement C3 and C4 levels, classical and alternative pathway complement function, IgG, IgA and IgM levels, specific IgG levels (H. influenza B, tetanus and pneumococcal serotypes), peripheral blood film, lymphocyte subsets, and CD62L-shedding upon activation with Toll-like receptor-agonists in selected cases.

Results:

We identified a total of 68 children with IPD, with a mortality of 6%. Immunological investigations were performed in 51 children. Four children (8%) had abnormal findings that were deemed of clinical significance. Two children had complement deficiencies (Factor I and C2 deficiency), one child had specific antibody deficiency, and another child had low IgM, low NK-cells and poor persistence of serotype-specific anti-pneumococcal IgG concentrations. Of the 17 children with IPD who were not tested for immunodeficiencies, 4 died and four had possible explanations for the infection.

Conclusions:

We identified clinically relevant abnormal immunological findings in 4/51 (8%) of children with IPD. Our results support the recommendation to perform immunological investigations in children with IPD, since this might reveal underlying immunodeficiencies, allowing for necessary preventive measures and close follow-up.
Use of Porcine Urinary Bladder Matrix in Socket Reconstruction After Pediatric Orbital Exenteration
Authors: Stevens Shanlee M. , Ohana Oded , Patel Umangi , Tse Brian C.
Published: April 2022

Reconstruction options after orbital exenteration can be challenging, time-consuming, and require intensive postoperative care. Engineered dermal acellular matrices offer a quick and easy option for wound healing that has proven to be successful in various settings. Specifically, the porcine urinary bladder matrix has demonstrated success in periocular and orbital wound healing. This report describes a pediatric patient who underwent repair with porcine urinary bladder matrix after orbital exenteration for recurrent alveolar rhabdomyosarcoma. The patient did not require any additional reconstructive procedures. To our knowledge, this is the youngest patient to receive a porcine urinary bladder matrix after exenteration.
Targeting intrinsically disordered regions facilitates discovery of calcium channels 3.2 inhibitory peptides for adeno-associated virus–mediated peripheral analgesia
Authors: Shin Seung Min , Lauzadis Justas , Itson-Zoske Brandon , Cai Yongsong , Fan Fan , Natarajan Gayathri K. , Kwok Wai-Meng , Puopolo Michelino , Hogan Quinn H. , Yu Hongwei
Published: April 2022

Ample data support a prominent role of peripheral T-type calcium channels 3.2 (CaV3.2) in generating pain states. Development of primary sensory neuron-specific inhibitors of CaV3.2 channels is an opportunity for achieving effective analgesic therapeutics, but success has been elusive. Small peptides, especially those derived from natural proteins as inhibitory peptide aptamers (iPAs), can produce highly effective and selective blockade of specific nociceptive molecular pathways to reduce pain with minimal off-target effects. In this study, we report the engineering of the potent and selective iPAs of CaV3.2 from the intrinsically disordered regions (IDRs) of CaV3.2 intracellular segments. Using established prediction algorithms, we localized the IDRs in CaV3.2 protein and identified several CaV3.2iPA candidates that significantly reduced CaV3.2 current in HEK293 cells stably expressing human wide-type CaV3.2. Two prototype CaV3.2iPAs (iPA1 and iPA2) derived from the IDRs of CaV3.2 intracellular loops 2 and 3, respectively, were expressed selectively in the primary sensory neurons of dorsal root ganglia in vivo using recombinant adeno-associated virus (AAV), which produced sustained inhibition of calcium current conducted by CaV3.2/T-type channels and significantly attenuated both evoked and spontaneous pain behavior in rats with neuropathic pain after tibial nerve injury. Recordings from dissociated sensory neurons showed that AAV-mediated CaV3.2iPA expression suppressed neuronal excitability, suggesting that CaV3.2iPA treatment attenuated pain by reversal of injury-induced neuronal hypersensitivity. Collectively, our results indicate that CaV3.2iPAs are promising analgesic leads that, combined with AAV-mediated delivery in anatomically targeted sensory ganglia, have the potential to be a selective peripheral CaV3.2-targeting strategy for clinical treatment of pain.
Physical Therapists
Authors: Lopker Morgan , DeLorm Paula , Gilroy Nikki L. , Norris Traci L. , Smith Ellen M. , Smith Jim , Tompkins James , Miller Kenneth L.
Published: April 2022

Background:

The physical therapist's (PT's) role on the interprofessional team is specialized to address a patient's functional needs.

Statement of the Problem:

Functional status is a key determinant for rehospitalization and is associated with the greatest risk of readmission, yet typical discharge planning teams do not include the PT as an integral member of the team. When PTs are involved, the likelihood of rehospitalization is much lower. The PT has an essential role in the discharge process to align the patient's capacity with the community resources that will best achieve a safe transition plan, facilitate restoration of functioning, and achieve an optimal outcome.

Impact Statement:

PTs are essential members of the care transitions team and improve patient outcomes across the health care system. This perspective highlights a critical nontraditional role for PTs to fill that will help improve health care decision-making and reduce the risk for rehospitalization and adverse health outcomes.
A Houttuynia cordata–based Chinese herbal formula improved symptoms of allergic rhinitis during the COVID-19 pandemic
Authors: Chang Kai-Wei , Lin Tung-Yi , Fu Shu-Ling , Ping Yueh-Hsin , Chen Fang-pey , Kung Yen-Ying
Published: April 2022

Background:

The symptoms of coronavirus disease 2019 (COVID-19) such as hyposmia, rhinorrhea, nasal obstruction, and cough are similar to those of chronic allergic rhinitis (AR). Such symptoms can easily lead AR patients to unnecessary anxiety, misdiagnosis, and invasive diagnostic tests in the COVID-19 pandemic. Interleukin-6 (IL-6) is an important mediator for chronic AR and plays a crucial role in the inflammation of COVID-19. Houttuynia cordata (HC) has been shown to reduce nasal congestion and swelling by suppressing the activation of IL-6 and is used to fight COVID-19. A novel HC-based Chinese herbal formula, Zheng-Yi-Fang (ZYF), was developed to test effects on nasal symptoms of patients with AR in the COVID-19 pandemic.

Methods:

Participants aged between 20 and 60 years with at least a 2-year history of moderate to severe perennial AR were enrolled. Eligible participants were randomly allocated to either the intervention group (taking ZYF) or the control group (using regular western medicine) for 4 weeks. The Chinese version of the Rhinosinusitis Outcome Measures was used to evaluate impacts on quality of life and nasal symptoms of participants with AR. In addition, the effect of ZYF on lipopolysaccharide (LPS)-induced IL-6 was investigated.

Results:

Participants with AR taking ZYF improved their symptoms of nasal obstruction, nasal secretion, hyposmia, and postnasal drip in comparison with those of the control group. Meanwhile, ZYF exhibited inhibition of IL-6 secretion in the LPS-induced inflammatory model.

Conclusion:

ZYF has potential effects to relieve nasal symptoms for AR during the COVID-19 pandemic.
The Jarvik 2000 Left Ventricular Assist Device: Results of the United States Bridge to Transplant Trial
Authors: Selzman Craig H. , Feller Erika D. , Walker Jordan C. , Sheridan Brett C. , Silvestry Scott C. , Daly Richard C. , Anyanwu Ani C. , Madigan Dave , Liu Ping-Yu , Frazier O. Howard , Jorde Ulrich P. , Griffith Bartley P.
Published: April 2022

The Jarvik 2000 bridge to transplant investigational device exemption study was a multicentered, prospective study of 150 UNOS status I patients implanted with the Jarvik 2000 between 2005 and 2012. During the study period, there were numerous modifications of the system that included converting from pin to cone bearings. Results were analyzed for three cohorts: total (n = 150), pin (n = 128), and cone (n = 22). Baseline demographics included age (52 ± 13), gender (79% male), size (BSA 1.98), and etiology (37% idiopathic dilated cardiomyopathy; 43% Ischemic). Seventy percent of patients were either INTERMACS 1 or 2. The primary endpoint—defined as successful transplantation or listing at 180 days (prespecified at 65%; 95% lower CI: 57%)—was successfully achieved for the total cohort (67.3%; 95% CI: 59.5%–74.3%; p = 0.006). In subgroup analysis of the more contemporary, cone-bearing group, the primary endpoint was met in 91% (95% CI: 72%–97.5%; p = 0.001). Compared with pin patients, cone-bearing patients had less hemolysis as well as decreased end-organ dysfunction. Functional and quality of life scores improved after implantation independent type of bearing. In conclusion, despite a particularly sick patient population, the Jarvik 2000 was shown to be effective in supporting the advanced HF patient.
Comparison of therapeutic effects of different acupuncture and moxibustion therapies in the treatment of peripheral facial nerve paralysis
Authors: Li Ming , Ruan JianGuo , Zhang HuaJun , Wu JiuLong , Wang YuJuan , Zhu Shanshan
Published: April 2022

Background:

Previous evidences show that acupuncture and moxibustion therapy has positive effects on peripheral facial nerve paralysis (PFP), but there are many acupuncture treatments based on meridian theory, and there are differences in the efficacy of each program. This study will compare the clinical efficacy of different acupuncture treatments for PFP through mesh meta-analysis.

Methods:

Randomized controlled trials of acupuncture therapy in the treatment of PFP are going to be retrieved from 8 Science databases including CNKI, Wanfang, VIP and Chinese Biomedical Science, PubMed, Embase, Web of Science and the Cochrane Library from establishment to January 2022. We will use the Cochrane Risk Bias Assessment Tool to assess the quality of the studies and the grading of recommendation assessment, development and evaluation method to assess the strength of the evidence. All data analyses will be performed by Revman5.3, Gemtc 0.14.3, and Stata 14.0.

Results:

This study will evaluate the efficacy of different acupuncture treatments for PFP by evaluating clinical efficacy rate, facial nerve function score, facial disability score scale, facial electromyography, adverse reactions, etc, and further explore the mechanism of action of each therapy.

Conclusion:

This study will provide a reliable evidence-based basis for selecting the best acupuncture treatment for PFP.

Trial registration:

Open science framework registration number: DOI 10.17605/OSF.IO/XQRK9
Evaluation of efficacy and safety of esmolol in treating patients with septic shock
Authors: Hou Bin , Cai Ke , Li Yue , Hu Chunfang , Pu Xuehua
Published: April 2022

Background:

In septic shock cases, tachycardia and a hyperdynamic hemodynamic profile are characteristics of the condition. It has been reported that using beta antagonist esmolol constitutes a form of treatment to reduce heart rate to improve diastolic filling time and elevate cardiac output, which reduces vasopressor support. Still, there are controversial results. Therefore, in this study, the primary objective is to perform a meta-analysis by systematically evaluating the efficiency and security of using esmolol to treat septic shocks.

Methods:

A systematic literature search for relevant randomized controlled trials that report evaluations on the efficiency and safety of using esmolol to treat septic shock patients from their inception to February 2022 will be conducted in three databases containing publications in Chinese language (WanFang, Chinese BioMedical Literature Database, and China National Knowledge Infrastructure) and four databases containing English language publications (Cochrane Library, PubMed, Web of Science, and EMBASE). The screening of the relevant studies will be performed by a pair of authors independently, and the screening involves examining the title, abstract and full-text stages, data extraction, and bias risk assessment. The results are summarized through the fixed-effects and random-effects models, the respective models will be utilized for data pooling according to the heterogeneity of studies that will be included. Moreover, publication bias is assessed if more than ten studies are considered.

Results:

The results are a high-quality synthesis of the most recent evidence for esmolol usage in septic shock treatment.

Conclusion:

Up-to-date evidence will be provided through the results of this systematic review related to assessing the efficacy and safeness of esmolol usage in treating septic shock.

Ethics and dissemination:

Ethical permissions are not required as prepublished data are used.

OSF registration number:

DOI 10.17605/OSF.IO/SKEZ7
miR-148a targets XBP1 to regulate trophoblast apoptosis induced by plasma reticulum stress in preeclampsia
Authors: Li Na , Li Jinqiong , Jia Jiantao , Yao Xia , Zhu Yan
Published: April 2022

To study the relationship between miR-148a and preeclampsia (PE), and clarify that miR-148a can regulate the endoplasmic reticulum stress (ERS) of placental trophoblasts by targeting the ERS protein X box binding protein 1 (XBP1).

Fifty patients with hypertension during pregnancy, patients with mild PE, patients with severe PE, and normal pregnant women were selected, and their placental tissues were collected. RT-polymerase chain reaction was used to detect the expression of miR-148a in placental tissues, and Western blot was used to detect XBP1 in placental tissues. Compare the expression differences of miR-148a and XBP1 in each group, and analyze the correlation between the expressions of the two.

Compared with the Neg-miR group, MTT experiment result in pre-miR-148a group was decreased. MTT experiment result in anti-miR-148a group was increased. Cell cycle test result in pre-miR-148a group [G1 (%)] was increased. Cell cycle test result in anti-miR-148a group [S (%)] was increased. Apoptosis test result in pre-miR-148a group [early apoptotic cells (%), late apoptotic cells (%)] was increased. Apoptosis test result in anti-miR-148a group [early apoptotic cells (%), late apoptotic cells (%)] was decreased. XBP1 expression result in pre-miR-148a group was increased. XBP1 expression result in anti-miR-148a group was decreased. Compared with the normal population, XBP1 is expressed in hypertension, mild eclampsia, severe eclampsia increased. GRP78, CHOP, and caspase-12 expression result in pre-miR-148a group was increased. GRP78, CHOP, and caspase-12 expression result in anti-miR-148a group was decreased.

miR-148a can regulate the ERS-mediated apoptosis by targeting XBP1, thereby intervening in the occurrence and development of PE.
Intervention for Nigerian preservice historians’ maladaptive academic perfectionism
Authors: Oloidi Frances Jumoke , Victor-Aigbodion Vera , Ossai Osita Victor , Ilechukwu Leonard C.
Published: April 2022

Background:

Individuals enrolled in a university program that will lead to a degree in history are considered preservice historians in the context of this study. Their goal is to become professional historians after graduating from the university. The purpose of this study was to determine whether cognitive behavioral coaching (CBC) had an effect on maladaptive academic perfectionism in Nigerian preservice historians.

Method:

The study included a randomized sample of 98 preservice historians from Nigerian public universities in the country's Southeast zone [49 preservice historians were assigned to the cognitive behavioral coaching group—CBC Group, while 49 preservice historians were assigned to the waitlist control group—Waitlist control Group].

Results:

The finding indicate that preservice historians’ maladaptive academic perfectionism decreased significantly following cognitive behavioral coaching. There was also a significant interaction effect of time and group on the reduction of preservice historians’ maladaptive academic perfectionism.

Conclusion:

This study suggests that cognitive behavioral coaching is an effective intervention for preservice historians who struggle with maladaptive academic perfectionism. The study's implications for history lecturers were discussed. Future study could investigate how maladaptive academic perfectionism affects postgraduate history students and how CBC can help them.
Survey Research
Authors: Speroni Karen Gabel , Budhathoki Chakra , Walters Cynthia , Dutton Suzanne , Mackay Periwinkle , Oguariri Raphael M.
Published: April 2022

OBJECTIVE

Researchers examined professional nursing governance perception differences by RN type (clinical, manager, and other RNs), and nurse-related outcome associations.

BACKGROUND

Shared governance is associated with improved nurse-related outcomes. Understanding differences in RN types regarding shared governance perceptions is important and not well studied.

METHODS

Mean Index of Professional Nursing Governance (IPNG) scores from 3 hospitals' 502 RNs were used to evaluate associations by RN type and unit-based nurse-related outcomes. Descriptive and inferential statistical methods were used.

RESULTS

Shared governance was the predominant finding (overall score and 4 of 6 subscale scores) with no significant differences by RN type. Traditional governance was scored for 1 subscale (control over personnel), which was not significant. There were no significant differences in the IPNG score associations with outcomes data by RN type.

CONCLUSIONS

Clinical nurses, managers, and other RN types perceived their governance as shared, without significant difference in the nurses' perceptions based on role.
Nursing Challenges and Strategies During the COVID-19 Pandemic
Authors: Lorentz Paul A. , Wannarka Emily J. , O’Meara Richard J. , Wolf Sherry L. , Nelson Dawn E. , Banitt Samantha C. , Johnson LeAnn M.
Published: April 2022

The COVID-19 pandemic has required healthcare organizations to creatively address patient care needs. The pandemic-induced disruption resulted in multiple examples of disruptive innovation. Several innovative strategies and learnings identified during the COVID-19 pandemic have resulted in approaches to nursing education and staffing, which will serve to optimize the future healthcare environment. The solutions identified by the nursing workforce during the COVID-19 pandemic can readily be replicated in similar or dissimilar healthcare environments.
Compliance study of hip protector users for prevention of fragility fracture: A pilot randomized trial
Authors: Wong Man Sang , Wu Hui Dong , Beygi Babak Hassan , Zhang Qian , Lin Yangmin , Chan Wing Sheung , Lou Edmond
Published: April 2022

Background:

Hip protectors have been widely used for hip fracture prevention in the elderly, but its efficacy remains controversial. Users' compliance to hip protector is an important factor for its efficacy. However, the assessment of users' compliance tended to be subjective and unreliable in the past.

Objectives:

To quantify the elderly's compliance to hip protectors and investigate the effect of different underpant designs on the elderly's compliance.

Study Design:

A pilot randomized trial.

Methods:

Thirty-one participants were recruited and provided with hip protectors in which compliance monitors were installed and delivered with three pairs of either the conventional underpants or the purpose-design underpants randomly. Participants were encouraged to use the hip protectors with the assigned underpants for whole day. After 4 weeks, compliance data were downloaded from the compliance monitors. Participants were also asked to fill a survey form for acceptance analysis. The Spearman correlation coefficient and the Wilcoxon signed-rank test/2 independent samples t test/Mann-Whitney U test were used for the corresponding statistical analyses.

Results:

Thirty-one participants were recruited initially. Eighteen participants were excluded from instrumented compliance analysis because of limited or no data collection. The data of the resting 13 participants (six in the conventional underpants group and seven in purpose-design underpants group) were analyzed and showed an average instrumented compliance of 77.5% which was lower than the average self-reporting compliance (83.3%) of all the available 23 participants (eight of 31 became wheelchair-bounded). Participants' compliance was positively correlated with their acceptance to the hip protectors and significantly higher in the purpose-design underpants group than in the conventional underpants group (P < 0.05).

Conclusions:

This pilot study demonstrated a feasible protocol for compliance quantification of the elderly to the hip protectors, the importance to have an objective compliance measure to assess users' actual compliance, and purpose-design underpants could improve the users' compliance. Future studies with long-term observation and large sample size deserve further proof of the current findings.
Effect of COVID-19 on Female Pelvic Medicine and Reconstructive Surgery Fellowship Education and Training
Authors: Butler Brandy M. , Biller Daniel H.
Published: April 2022

Importance

The COVID-19 pandemic has caused a noticeable disruption in national medical and surgical care, including medical training.

Objectives

We designed a survey to examine the educational effect of the pandemic on female pelvic medicine and reconstructive surgery (FPMRS) training and secondarily to identify areas for innovation and opportunity in FPMRS fellowship training.

Study Design

We used an online survey, approved by the American Urogynecologic Society Scientific Committee and distributed it to FPMRS fellows with responses obtained and stored in REDCap. Demographic data, educational and surgical experiences, the implications of the changes, and data regarding working from home were collected.

Results

The survey was completed by 88 fellows, with 92% of respondents being obstetrics and gynecology- based. All 10 geographic regions had at least one response. Six regions had a 50% or greater redeployment rate. Only 16% of respondents were not redeployed or on-call to be redeployed. Eighty-five percent of the ob/gyn fellow redeployments were within their home department. There was no relationship between training region and redeployment. Only 31.7% of the respondents continued to perform any FPMRS surgery. Approximately 35% of the fellows desired the opportunity for surgical simulation training because surgical cases were reduced.

No relationship was seen between either redeployment status and needs (P = 0.087–0.893) or difficulties (P = 0.092–0.864) nor training location and needs (P = 0.376–0.935) or difficulties (P = 0.110–0.921).

Conclusions

There was a high rate of redeployment among fellows; however, this was not associated with their reported needs and difficulties. The FPMRS-related surgical experience was affected during this time, and the fellows desired increased surgical simulation training.
The Role of Pessaries in the Treatment of Women With Stress Urinary Incontinence: A Systematic Review and Meta-Analysis
Authors: Klein Julia , Stoddard Michelina , Rardin Charles , Menefee Shawn , Sedrakyan Art , Sansone Stephanie , Chughtai Bilal
Published: April 2022

Importance

Pessaries are an important conservative therapy for stress urinary incontinence (SUI), but few studies have comprehensively evaluated their utility.

Objective

The objective of this study is to evaluate the existing evidence on the efficacy and safety of pessaries for the treatment of SUI.

Study Design

We searched for the terms “stress urinary incontinence” and “pessar/y/ies/ium” in PubMed, Embase, and Cinhal on June 10, 2020. Studies that characterized subjective and/or objective data were included. Studies performed in pediatric populations, pregnancy, and use of pessaries not for SUI were excluded. Two reviewers independently screened and assessed data quality and risk of bias according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Results

Ten studies, including 376 patients, were included. In terms of subjective outcomes, 76% of 72 patients reported feeling continent after pessary treatment compared with 0% of 86 patients surveyed before pessary use (P < 0.0001). Both Urinary Distress Inventory and Incontinence Impact Questionnaire scores decreased significantly by 46.7% (n = 155 baseline, n = 139 follow-up; P < 0.0001) and 67.8% (n = 139 baseline, n = 107 follow-up; P < 0.0001), respectively. Significant objective measures associated with pessary use included increased urethral closure pressure (n = 122; g = 0.56; 95% confidence interval [CI], −0.66 to 1.77; P < 0.049) and decreased pad weight (n = 129 baseline; n = 118 follow-up; g = −0.89; 95% CI, −1.986 to 0.19; P = 0.009). Adverse events significantly decreased at greater than 6 months follow-up compared with less than 6 months follow-up, including pain (31.5%, n = 29/92 vs 14.3%, n = 5/35; P = 0.0513) and discomfort (50%, n = 46/92 vs 29.3%, n = 12/41; P = 0.0268).

Conclusions

Based on both subjective and objective measures, pessaries are an effective conservative treatment option for SUI. This supports pessary use, though larger studies with longer-term follow-up are warranted.
Assessing the Content and Readability of Robotic and Laparoscopic Sacrocolpopexy Information Online
Authors: Lim Remington , Wang Joanna C. , Wang Liz B. , Ng Linda , Wason Shaun E. , Wang David S.
Published: April 2022

Importance

Apical pelvic organ prolapse is a common condition that affects women. Currently, sacrocolpopexy is considered the criterion standard surgical treatment, with an increasing preference for minimally invasive techniques.

Objective

In this study, the content and readability of select internet pages describing robotic and laparoscopic sacrocolpopexy were evaluated.

Study Design

Using an online key word planner, the phrases “robotic sacrocolpopexy” and “laparoscopic sacrocolpopexy” were determined to be the most popular search terms. These terms were systematically browsed in incognito mode in 3 of the most popular web search engines: Google, Yahoo, and Bing. Links that were nontext primary, duplicate, irrelevant, and non-English were excluded. The Flesch-Kincaid Grade Level and Flesch-Kincaid Reading Ease indices were used to assess readability.

Results

The average readability of all sites was 12.9, requiring at least a 12th-grade reading level, which is significantly higher than the recommended American Medical Association/National Institutes of Health (AMA/NIH) level of sixth-grade or below. One hundred percent of all analyzed sites were above this recommended sixth-grade reading level. There was no significant difference between mean grade level or reading ease score from the type of web source (P = 0.32 and 0.34, respectively), approach of surgery (P = 0.91, 0.70), or specialty (P = 0.48, 0.36).

Conclusions

Almost all websites require at least a high school education to properly comprehend, regardless of source or specialty. It is important that health care providers be aware of available information, so they may direct patients to specific resources that are personally validated or provide in-office materials at an appropriate reading level.
Trends Among Female Pelvic Medicine and Reconstructive Surgery Fellowships and Graduates
Authors: Gerjevic Kristen A. , Brandes Eileen , Gormley E. Ann , Auty Samantha G. , Strohbehn Kris
Published: April 2022

Importance

Understanding differences in female pelvic medicine and reconstructive surgery (FPMRS) urology and gynecology-based fellowships is important because both are accredited by the American Board of Medical Subspecialties.

Objective

The aim of the study was to characterize urology-based and gynecology-based FPMRS fellowships.

Material and Methods

An institutional review board–approved 21-item survey was emailed to Accreditation Council for Graduate Medical Education-accredited FPMRS fellowship program directors from January 8 through March 9, 2021. The survey aimed to characterize fellowships through a series of common and specialty-specific questions. Responses were collected with Qualtrics and analyzed using STATA/MP Version 16.1.

Results

The response rate was 75% (52/69). Many programs accept both gynecology- and urology-trained applicants (urology-based fellowships, 45.4%; gynecology-based fellowships, 68.3%) since the Accreditation Council for Graduate Medical Education accreditation in 2012. Within the gynecology-based cohort, there have been 10 urology-trained graduates among 7 programs (n = 1–2). Barriers to accepting urology applicants were limited gynecologic knowledge/experience (n = 14) and length of training (n = 11). Thirty-seven (94.8%) reported their graduates log more than 30 hysterectomies and 8.3% (n = 3) log 3 or more urinary diversions.

Within the urology-based cohort, there have been 16 gynecology-trained graduates among 4 programs (n = 2–7). Lack of urologic clinical knowledge (n = 4) and training length (n = 2) were cited as barriers to accepting gynecology-trained applicants. Three (27%) reported that their graduates log more than 30 hysterectomies, while 8 (72.7%) reported that graduates log 3 or more urinary diversions.

Conclusions

Despite many FPMRS programs stating that they accept gynecology or urology-trained applicants, few fellows graduate from outside specialty FPMRS training programs. Several barriers were identified that may prevent trainees acceptance outside of their residency specialty. Procedural training experience differs between urology- and gynecology-based fellowships.
Expert Consensus on the Use of Teprotumumab for the Management of Thyroid Eye Disease Using a Modified-Delphi Approach
Authors: Douglas Raymond S. , Kossler Andrea L. , Abrams Jody , Briceño Cesar A. , Gay David , Harrison Andrew , Lee Michael , Nguyen John , Joseph Shannon S. , Schlachter Dianne , Tan Jeremy , Lynch Judah , Oliver Louisa , Perry Richard , Ugradar Shoaib
Published: April 2022

Background:

Teprotumumab is the first treatment for thyroid eye disease (TED), a debilitating autoinflammatory condition, approved by the Food and Drug Administration in the United States, which reduces proptosis and improves quality of life. In the absence of guidelines, clinical recommendations were developed for using teprotumumab in patients with TED in the United States.

Methods:

A 3-round modified-Delphi panel was conducted between October 2020 and February 2021 with experts in the management of patients with TED. Key areas regarding the use of teprotumumab were investigated, including eligible patient populations, concomitant treatments, and assessment of response and adverse events. This used 2 survey rounds via an online questionnaire, where statements were scored using 9-point Likert scales. Statements with conflict were included in the third round, involving a consensus meeting via videoconference.

Results:

Consensus was obtained for all statements (n = 75); of which, 56% were revised to enable agreement of the group. The consensus meeting provided agreement regarding which populations should receive teprotumumab therapy, including all adult patients with TED with a clinical activity score of ≥4. Treatment with teprotumumab can also be considered for TED patients displaying the following characteristics: a CAS of <3, lid retraction of ≥2, and mild or early optic neuropathy with close clinical observation. Further recommendations included suitability of treatment for those beyond 16 months following the initial diagnosis of TED, low CAS concomitant treatment with steroids in some cases, retreatment for those who have relapses, and finally a recommendation to continue therapy for all 8 infusions despite the lack of response by the fourth infusion.

Conclusions:

This work constitutes the first consensus on guidelines for the use of teprotumumab. The modified Delphi approach involved physicians with significant experience with the clinical use of teprotumumab, and recommendations were based on current evidence.
Development of highly specific singleplex and multiplex real-time reverse transcription PCR assays for the identification of SARS-CoV-2 Omicron BA.1, BA.2 and Delta variants
Authors: Garson Jeremy A. , Badru Samuel , Badhan Anjna , Dustan Simon , Tedder Richard S.
Published: April 2022

The Omicron variant of SARS-CoV-2 (B.1.1.529), first identified during November 2021, is rapidly spreading throughout the world, replacing the previously dominant Delta variant. Omicron has a high number of mutations in the spike gene, some of which are associated with greatly increased transmissibility and immune evasion. The BA.1 sublineage has been most prevalent but there is recent evidence that the BA.2 sublineage is increasing in proportion in many countries. Genome sequencing is the gold standard for Omicron identification but is relatively slow, resource intensive, of limited capacity and often unavailable. We therefore developed a simple, rapid reverse transcription PCR (RT-PCR) method for sensitive and specific detection of the Omicron variant, including both the BA.1 and BA.2 sublineages. The assay targets a total of 5 nucleotide mutations in the receptor binding domain of the spike gene that give rise to 4 amino acid substitutions at G339D, S371L, S373P and S375F. The forward primer was designed as a double-mismatch allele specific primer (DMAS) with an additional artificial mismatch located four nucleotides from the 3’ end to enhance binding specificity. Assay specificity was confirmed by testing a wide range of previously-sequenced culture-derived viral isolates and clinical samples including the Alpha, Beta and Delta variants and ‘wild type’ SARS-CoV-2. Respiratory syncytial virus and influenza A were also tested. The assay can be run in singleplex format, or alternatively as a multiplex RT-PCR to enable Omicron and Delta variants to be detected and distinguished within the same reaction by means of probes labelled with different fluorescent dyes. Sublineages BA.1 and BA.2 can be differentiated if required. The methods presented here can readily be established in any PCR laboratory and should provide valuable support for epidemiologic surveillance of Omicron infections, particularly in those regions that lack extensive sequencing facilities.
Broadly neutralizing and protective nanobodies against diverse sarbecoviruses
Authors: Li Mingxi , Ren Yifei , Aw Zhen Qin , Chen Bo , Yang Ziqing , Lei Yuqing , Cheng Lin , Liang Qingtai , Hong Junxian , Yang Yiling , Chen Jing , Wong Yi Hao , Shan Sisi , Zhang Senyan , Ge Jiwan , Wang Ruoke , Shi Xuanling , Zhang Qi , Zhang Zheng , Chu Justin Jang Hann , Wang Xinquan , Zhang Linqi
Published: April 2022

As SARS-CoV-2 Omicron and other variants of concern continue spreading around the world, development of antibodies and vaccines to confer broad and protective activity is a global priority. Here, we report on the identification of a special group of nanobodies from immunized alpaca with exceptional breadth and potency against diverse sarbecoviruses including SARS-CoV-1, Omicron BA.1, and BA.2. Crystal structure analysis of one representative nanobody, 3-2A2-4, revealed a highly conserved epitope between the cryptic and the outer face of the receptor binding domain (RBD). The epitope is readily accessible regardless of RBD in “up” or “down” conformation and distinctive from the receptor ACE2 binding site. Passive delivery of 3-2A2-4 protected K18-hACE2 mice from infection of authentic SARS-CoV-2 Delta and Omicron. This group of nanobodies and the epitope identified should provide invaluable reference for the development of next generation antibody therapies and vaccines against wide varieties of SARS-CoV-2 infection and beyond.
Heavy metal pollution impacts soil bacterial community structure and antimicrobial resistance at the Birmingham 35th Avenue Superfund Site
Authors: Goswami Anuradha , Adkins-Jablonsky Sarah J. , Barreto Filho Marcelo Malisano , Schilling Michelle D. , Dawson Alex , Heiser Sabrina , O’Connor Aisha , Walker Melissa , Roberts Qutia , Morris J. Jeffrey
Published: April 2022

Heavy metals (HMs) are known to modify bacterial communities both in the laboratory and in situ. As a consequence, soils in HM contaminated sites like the U.S. Environmental Protection Agency (EPA) Superfund sites are predicted to have altered ecosystem functioning, with potential ramifications for the health of organisms, including humans, that live nearby. Further, several studies have shown that metal tolerant bacteria are often also resistant to antimicrobial agents (AMR), and therefore HM contaminated soils could potentially act as reservoirs that could disseminate AMR genes into human-associated pathogenic bacteria. To explore this possibility soil samples were collected from six public locations in the zip code 35207 (the home of the North Birmingham 35th Avenue Superfund site) and in six public areas in a neighboring reference zip code (35214). Sequencing of the V4 region of the bacterial 16S rRNA gene revealed that elevated concentrations of HMs As, Mn, Pb, and Zn reduced microbial diversity and altered community structure within each zip code. While there was no difference between zip codes in the proportion of total culturable microbes that survived antimicrobial or metal exposure, bacterial isolates with HMR almost always also exhibited AMR. Metagenomes inferred using PICRUST2 also predicted significantly higher mean relative frequencies in 35207 for several AMR genes related to both specific and broad-spectrum AMR phenotypes. Together, these results support the hypothesis that chronic HM pollution alters soil bacterial community structure in ecologically meaningful ways and may also select for bacteria with increased potential to contribute to AMR in human bacterial disease.
Relative infectivity of the SARS-CoV-2 Omicron variant in human alveolar cells
Authors: Kim Taewoo , Min Kyoung Il , Yang Jeong-Sun , Kim Jun Won , Cho Junhyung , Kim Yun Ho , Lee Jeong Seok , Kim Young Tae , Kim Kyung-Chang , Kim Jeong Yeon , Na Kwon Joong , Lee Joo-Yeon , Ju Young Seok
Published: April 2022

With the emergence of multiple highly transmissible SARS-CoV-2 variants during the recent pandemic, the comparison of their infectivity has become a substantially critical issue for public health. However, a direct assessment of these viral characteristics has been challenging due to the lack of appropriate experimental models and efficient methods. Here, we integrated human alveolar organoids and single-cell transcriptome sequencing techniques to facilitate the evaluation. In a proof-of-concept study using the assay with four highly transmissible SARS-CoV-2 variants, including GR (B.1.1.119), Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron (BA.1), a rapid evaluation of the relative infectivity was possible. Our results demonstrate that the Omicron (BA.1) variant is 3-5-fold more infectious to human alveolar cells than the other SARS-CoV-2 variants at the early phase of infection. To our knowledge, this study provides the first direct measurement of the infectivity of the Omicron variant and new experimental procedures that can be applied for monitoring newly emerging viral variants.
SARS-CoV-2 Omicron BA.1 variant infection of human colon epithelial cells
Authors: Antia Avan , Alvarado David M. , Zeng Qiru , Davis Deanna L. , Ciorba Matthew A. , Ding Siyuan
Published: April 2022

Omicron B.1.1.529 became the predominant SARS-CoV-2 variant in early 2022, causing a new wave of public anxiety. Compared to the ancestral strain, Omicron has 50 mutations, with over 30 mutations in the spike protein. These differences likely underlie the changes in Omicron biology noted in other studies, including an attenuation in the lung parenchyma, compared to the ancestral SARS-CoV-2 strain and other variants, as well as a preference for endosomal entry, in place of the TMPRSS2-mediated membrane fusion pathway. This raises questions on Omicron tropism and infectivity in various target organ systems, including the gastrointestinal (GI) tract. Up to 70% of COVID-19 patients report GI symptoms, including nausea, vomiting, and diarrhea. Here, we show that in the context of donor intrinsic genetic heterogeneity, the SARS-CoV-2 Omicron variant infects human colonoids similarly, if not less effectively, than the ancestral WT (WA1) strain or the Delta variant. Additionally, we note a higher ratio of viral RNA to infectious virus titer, which may suggest that Omicron is potentially less infectious in the intestine. This study lays the foundation for further work defining mechanisms mediating intestinal infection and pathogenesis by Omicron.
Single-chain and condensed-state behavior of hnRNPA1 from molecular simulations
Authors: Bauer D. Janka , Stelzl Lukas S. , Nikoubashman Arash
Published: April 2022

Intrinsically disordered proteins (IDPs) are essential components for the formation of membraneless organelles, which play key functional and regulatory roles within biological systems. These complex assemblies form and dissolve spontaneously over timevialiquid-liquid phase separation of IDPs. Mutations in their amino acid sequence can alter their phase behavior, which has been linked to the emergence of severe diseases such as cancer and neurodegenerative diseases including amyotrophic lateral sclerosis. In this work, we study the conformation and phase behavior of a low-complexity domain of heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), using coarse-grained implicit solvent molecular dynamics simulations. We systematically analyze how these properties are affected by the number of aromatic residues within the examined sequences. We find a significant compaction of the chains and an increase in the critical temperature with increasing number of aromatic residues within the IDPs. Comparing single-chain and condensed state simulations, we find much more collapsed polymer conformations in the dilute systems, even at temperatures well above the estimatedθ-temperature of the solution. These observations strongly support the hypothesis that aromatic residues play a dominant role for condensation, which is further corroborated by a detailed analysis of the intermolecular contacts, and conversely that important properties of condensates are captured in coarse-grained simulations. Interestingly, we observe density inhomogeneities within the condensates near criticality, which are driven by electrostatic interactions. Finally, we find that the relatively small fraction of hydrophobic residues in the IDPs results in interfacial tensions which are significantly lower compared to typical combinations of immiscible simple liquids.