bluuebunny/crossref_metadata_2025 huggingface dataset:
Acceptance of COVID-19 vaccination during pregnancy among Thai pregnant women and their spouses: a prospective survey
Authors: Pairat Kotchakorn , Phaloprakarn Chadakarn
Published: March 2022

Background

Vaccination is one of the most reliable interventions against coronavirus disease 2019 (COVID-19). Although pregnant women’s attitudes toward COVID-19 vaccination are well studied, husbands’ views toward COVID-19 vaccination for these women have not been surveyed. We aimed to determine the rates and associated factors of accepting attitudes toward COVID-19 vaccination during pregnancy among Thai pregnant women and their spouses and to evaluate the actual rate of vaccination during pregnancy among these women.

Methods

A prospective survey was conducted at a tertiary care center in Bangkok, Thailand. A total of 176 Thai pregnant woman/husband dyads who attended our antenatal care clinic between 1 July 2021 and 30 September 2021 were consecutively recruited for evaluations of their accepting attitudes toward COVID-19 vaccination during pregnancy. After delivery, data on COVID-19 vaccination during pregnancy among pregnant women were extracted from the hospital’s electronic database.

Results

After exclusion of five pregnant women with prepregnancy COVID-19 vaccination, 171 women and 176 male partners were included. The rates of accepting attitudes toward COVID-19 vaccination during pregnancy were 60.8% and 61.4%, respectively. Multivariate analysis showed that having a husband who favored COVID-19 vaccination for his wife was independently associated with COVID-19 vaccine acceptance among pregnant women (adjusted odds ratio 4.82; 95% confidence interval 2.34, 9.94). However, confidence in vaccine safety was an associated factor of the husband’s willingness to have his wife vaccinated for COVID-19 during pregnancy (adjusted odds ratio 12.56; 95% confidence interval 2.35, 67.18). The actual rate of vaccination during pregnancy was 88.3%.

Conclusions

Although the rates of accepting attitudes toward COVID-19 vaccination during pregnancy among Thai pregnant women and their spouses were modest, the actual rate of being vaccinated during pregnancy was high.
Molecular epidemiology of hepatitis B virus among HIV co-infected and mono-infected cohorts in Northwest Ethiopia
Authors: Belyhun Yeshambel , Liebert Uwe Gerd , Maier Melanie
Published: March 2022

Background

Hepatitis B virus (HBV) infection is a particular concern in human immunodeficiency virus (HIV) infected individuals. In Ethiopia, detailed clinical and virological descriptions of HBV prevailing during HIV co-infection and symptomatic liver disease patients are lacking. The aim of this study was to investigate HBV virological characteristics from Ethiopian HBV/HIV co-infected and HBV mono-infected individuals.

Methods

A total of 4105 sera from HIV positive individuals, liver disease patients, and blood donors were screened serologically for HBV. The overlapping polymerase/surface genome region of HBV from 180 infected individuals was extracted, amplified, and sequenced for genotypic analysis.

Results

The HBsAg seroprevalence was detected 43% in liver disease patients, 8.4% in blood donors, and 6.7% in HIV/HBV co-infected individuals. The occult HBV prevalence was 3.7% in HIV/HBV co-infected individuals and 2.8% in blood donors with an overall prevalence rate of 3.4%. A phylogenetic analysis showed three HBV genotypes; A (61.1%), D (38.3%) and E (0.6%). Genotype A belongs to subtypes A1 (99.1%) and A9 (0.9%), but genotype D showed heterogeneous subtypes; D2 (63.8%) followed by D4 (21.7%), D1 (8.7%), D3 (4.3%), and D10 (1.4%).

Conclusions

The HIV/HBV co-infected individuals and blood donors showed lower HBsAg seroprevalence compared to liver diseases patients. Occult HBV prevalence showed no difference between HIV/HBV co-infected and blood donor groups. This study demonstrated predominance distribution of HBV subtypes A1 and D2 in northwest Ethiopia. The observed virological characteristics could contribute for evidence-based management of viral hepatitis in Ethiopia where antiretroviral therapy guidelines do not cater for viral hepatitis screening during HIV co-infection.
Genetic characterization of atypical porcine pestivirus from neonatal piglets with congenital tremor in Hubei province, China
Authors: Ren Xujiao , Qian Ping , Hu Zihui , Chen Huanchun , Li Xiangmin
Published: March 2022

Background

Atypical porcine pestivirus (APPV) is a single-stranded RNA virus with high genetic variation that causes congenital tremor (CT) in newborn piglets, belonging to the genus Pestivirus of the family Flaviviridae. Increasing cases of APPV infection in China in the past few years would pose severe challenges to the development of pig production. In view of the high genetic variability of APPV, the genetic characteristics of APPV in Hubei province was determined.

Methods

52 tissue samples from 8 CT-affected newborn piglets were collected at two different periods in the same pig farm in Hubei province. Viral nucleic acid was extracted to detect pathogens that can cause CT in piglets or other common clinical pathogens by RT-PCR. Haematoxylin and eosin (HE) staining, immunohistochemical (IHC) analysis, and qRT-PCR were performed to observe histopathological changes and histological distribution, and detect the viral load of APPV in CT-affected piglets. The full-length genome of APPV was obtained and sequence analysis was conducted to determine the phylogenetic relationship.

Results

Histopathological observation and histological distribution analysis showed that the histological lesions and distribution of APPV were mainly in central nervous system (CNS) tissues and immune tissues. Viral load analysis revealed that the viral copy number was higher in the cerebellum, submaxillary lymph nodes, tonsil, and serum than in other tissues. Phylogenetic analysis showed that CH-HB2020 and CH-HB2021 belonged to Clade I.3, and is most closely related to APPV_CH-GX2016. Sequence alignment based on APPV encoding sequences (CDS) showed that the nucleotide identities of CH-HB2020 or CH-HB2021 with Clade I, Clade II, and Clade III strains were 83.5–98.6%, 83.1–83.5%, and 81.1–81.4%, respectively, while the amino acid identities were 91.9–99.2%, 91.2–95.3%, and 90.77–91.4%, respectively. No recombination event was observed in CH-HB2020 or CH-HB2021 strains.

Conclusions

These findings enhance our understanding of the pathogenesis of APPV and may provide potential molecular evidence for its prevalence and transmission.
Nitrogen-doped graphene quantum dots induce ferroptosis through disrupting calcium homeostasis in microglia
Authors: Wu Tianshu , Wang Xinyu , Cheng Jin , Liang Xue , Li Yimeng , Chen Min , Kong Lu , Tang Meng
Published: March 2022

Background

Along with the wild applications of nitrogen-doped graphene quantum dots (N-GQDs) in the fields of biomedicine and neuroscience, their increasing exposure to the public and potential biosafety problem has gained more and more attention. Unfortunately, the understanding of adverse effects of N-GQDs in the central nervous system (CNS), considered as an important target of nanomaterials, is still limited.

Results

After we found that N-GQDs caused cell death, neuroinflammation and microglial activation in the hippocampus of mice through the ferroptosis pathway, microglia was used to assess the molecular mechanisms of N-GQDs inducing ferroptosis because it could be the primary target damaged by N-GQDs in the CNS. The microarray data suggested the participation of calcium signaling pathway in the ferroptosis induced by N-GQDs. In microglial BV2 cells, when the calcium content above the homeostatic level caused by N-GQDs was reversed, the number of cell death, ferroptosis alternations and excessive inflammatory cytokines release were all alleviated. Two calcium channels of L-type voltage-gated calcium channels (L-VGCCs) in plasma membrane and ryanodine receptor (RyR) in endoplasmic reticulum (ER) took part in N-GQDs inducing cytosolic calcium overload. L-VGCCs and RyR calcium channels were also involved in promoting the excess iron influx and triggering ER stress response, respectively, which both exert excessive ROS generation and result in the ferroptosis and inflammation in BV2 cells.

Conclusion

N-GQDs exposure caused ferroptosis and inflammatory responses in hippocampus of mice and cultured microglia through activating two calcium channels to disrupt intracellular calcium homeostasis. The findings not only posted an alert for biomedical applications of N-GQDs, but also highlighted an insight into mechanism researches of GQDs inducing multiple types of cell death in brain tumor therapy in the future.

Graphical abstract
Meta-synthesis and science mapping analysis of HIV/HPV co-infection: a global perspective with emphasis on Africa
Authors: Onohuean Hope , Aigbogun Eric O. , Igere Bright E.
Published: March 2022

Background

Viral infections are emerging with diverse clinical relevance both in endemic environments and non-endemic regions of the world. Some of the viruses cause co-infections that are of public health importance. The progress of studies on human immunodeficiency virus / Human papillomavirus (HIV/HPV) co-infection is not well documented especially in Africa where cases are endemic.

Method

Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a global three-decade meta-synthesis and science mapping analysis on HIV/HPV co-infections. Assessment of progress, Author/Country productivity/trends, topic conceptual framework, and international collaborative networks were analyzed.

Results

We recovered 196 documents of 115 sources from the web of science database. The meta-synthesis revealed 1203 prolific authors containing nine solo authors, an annual growth rate of 8.09%, a significant average citation per article of 20.7%, and an average citation per year per document of 2.1. A significant high correlation between the mean/TC per article and the mean total citation (TC) per year showed 80.98% of the articles produced between 2005 and 2007 on HPV/HIV co-infection. The co-author per document index were 7.0 and the collaboration index was 6.4. The meta-analysis also revealed inadequate funding from individual or governmental organizations; among the 196 documents dataset, 114 (58.2%) were funded, and only 31 (15.8%) were funded in Africa where HIV/HPV co-infection cases are endemic.

Conclusions

Authors’ collaboration network, countries’ collaboration, authors’ citations and implementation of research-based finding in previous studies are yet to receive the relevant outcome, especially as various countries in the African continent have received poor funding with a repeated reporting of co-infection associated with HIV/HPV. African needs to re-awaken and stir up research-based interest in HPV/HIV co-infection studies to resolve indigenous public health concerns associated with the viral endemicity.
Irrigation and debridement for knee osteoarthritis patients with suspected infection by intra-articular injection before total knee arthroplasty: a retrospective study
Authors: Jiang Haochen , Yuan Hengfeng , Hu Hai
Published: March 2022

Background

Patients suffer from knee osteoarthritis (KOA) pain may seek for intra-articular injections before total knee arthroplasty (TKA), which have a possibility of causing the joint sepsis. However, the management and clinical outcomes of these patients following TKA remain uncertain.

Methods

Patients with a history of intra-articular injection, in which a joint sepsis was suspected, were included. The patients received joint irrigation and debridement (I&D) and antibiotic treatment until serum inflammatory indicators returned to normal level before TKA. The information of joint fluid routine and culture, synovium section and culture, and serum inflammatory indicator values were collected. Range of motion, Knee Society Scores (KSS) and Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) were used for functional evaluations.

Results

A total of 17 patients with 17 knee joints were included, all with elevated C-reactive protein (CRP) levels (23.5 ± 8.7 mg/L) as well as increased number of white blood cells (WBC) in the aspiration (50.8 ± 15.3) × 109/L, but no positive cultures were found. The culture of synovium detected three positive results: two Staphylococcus epidermidis and one S. aureus. I&D treatment had no obvious effect on the functional outcomes of KOA, but alleviated the joint pain (p < 0.01). Furthermore, we found that I&D pretreatment could increase the operation time with about 10 min longer than the primary TKA (p < 0.01). With respect to TKA outcomes, I&D had a slight influence on the knee flexion (p < 0.01), but no significant difference was identified between the two groups for KSS and WOMAC (all p values > 0.05). In addition, there was no significant difference in complication rates between the two groups in the last follow-up.

Conclusion

I&D treatment is a valuable procedure for suspected knee infection, which has a higher incidence of detecting microorganisms while does not influence the functional outcomes and complication rates of TKA. However, further larger studies are required to confirm these findings.
A novel approach to distal femur: a minimally invasive technique for supracondylar and intercondylar fracture
Authors: Wu Tsung-Mu , Chien Chi-Sheng , Lin Sheng-Hui
Published: March 2022

Background

For treating distal femur fractures, minimally invasive plating techniques with indirect reduction of the metadiaphysis while minimizing the damage to the peripheral soft tissue has gradually become the standard. However, all the current approaches use a straight or lazy curved incision adjacent to the patella or along the lateral side of the femur, which allows for easier proximal extension but increases the incision length.

Methods

In order to achieve a more physiological and esthetic outcome while leaving the metadiaphysis untouched, we developed an approach using a lambda-shaped incision, which sacrifices the potential for proximal extension but preserves much more peripheral soft tissue. Here, we describe our technique and our experience with it in 19 patients (12 men and 7 women).

Results

Fractures healing by first intention was observed in all patients. The postoperative knee range of motion can reach up to 90° in most of the patient. Clinically, 9 patients had excellent results, 6 had good results, 3 had fair results, and 2 had loss of follow-up.

Conclusions

Our minimally invasive lambda-incision approach allows sufficient visual access to almost the entire joint surface, including the entire lateral femoral condyle, trochlear surface, and distal medial condyle, where reduction is required. The lambda incision provides a much larger window than that offered by a same-length straight incision. The vertical turn at the mid-patellar level parallels the skin crease and geniculate artery, reducing soft tissue damage and resulting in a smooth healing wound. Moreover, plate and distal screw insertion is easier than that through a straight incision. Because the metadiaphysis region is mostly left untouched, ideal fracture-healing environment is preserved.
The road to successful people-centric research in rare diseases: the web-based case study of the Immunology and Congenital Disorders of Glycosylation questionnaire (ImmunoCDGQ)
Authors: Francisco Rita , Brasil Sandra , Pascoal Carlota , Jaeken Jaak , Liddle Merell , Videira Paula A. , dos Reis Ferreira Vanessa
Published: March 2022

Background

Congenital Disorders of Glycosylation (CDG) are a complex family of rare metabolic diseases. Robust clinical data collection faces many hurdles, preventing full CDG biological and clinical comprehension. Web-based platforms offer privileged opportunities for biomedical data gathering, and participant recruitment, particularly in rare diseases. The immunology and CDG electronic (e-) questionnaire (ImmunoCDGQ) explores this paradigm, proposing a people-centric framework to advance health research and participant empowerment.

Objective

The objectives of this study were to: (1) Describe and characterize the ImmunoCDGQ development, engagement, recruitment, participation, and result dissemination strategies; (2) To critically compare this framework with published literature and making recommendations.

Methods

An international, multistakeholder people-centric approach was initiated to develop and distribute the ImmunoCDGQ, a multi-lingual e-questionnaire able to collect immune-related data directly from patients and family caregivers. An adapted version was produced and distributed among the general “healthy” population (ImmunoHealthyQ), serving as the control group. Literature screening was performed to identify and analyze comparable studies.

Results

The ImmunoCDGQ attained high participation and inclusion rates (94.6%, 209 out of 221). Comparatively to the control, CDG participants also showed higher and more variable questionnaire completion times as well as increased English version representativeness. Additionally, 20% of the CDG group (42 out of 209) chose not to complete the entire questionnaire in one go. Conditional logic structuring guided participant data provision and accurate data analysis assignment. Multi-channel recruitment created sustained engagement with Facebook emerging as the most followed social media outlet. Still, most included ImmunoCDGQ questionnaires (50.7%, 106 out of 209) were submitted within the first month of the project’s launch. Literature search and analysis showed that most e-questionnaire-based studies in rare diseases are author-built (56.8%, 25 out of 44), simultaneously addressing medical and health-related quality of life (HRQoL) and/or information needs (79.5%, 35 out of 44). Also, over 68% of the studies adopt multi-platform recruitment (30 out of 44) actively supported by patient organizations (52.3%, 23 out of 44).

Conclusions

The ImmunoCDGQ, its methodology and the CDG Community served as models for health research, hence paving a successful and reproducible road to people-centricity in biomedical research.
Systemic therapy of necrobiotic xanthogranuloma: a systematic review
Authors: Steinhelfer Lisa , Kühnel Thomas , Jägle Herbert , Mayer Stephanie , Karrer Sigrid , Haubner Frank , Schreml Stephan
Published: March 2022

Background

Even though a plethora of systemic therapies have been proposed for necrobiotic xanthogranuloma (NXG), there is no systematic review on this topic in literature.

Objective

To review all existing literature on the systemic therapy of NXG in order to identify the most effective therapies.

Methods

All reported papers in the literature were screened for systemic treatments of NXG. Papers without proper description of the therapies, papers describing topical therapy, and articles without assessment of effectiveness were excluded. Subsequently, we analyzed 79 papers and a total of 175 cases.

Results

The most effective treatments for NXG are intravenous immunoglobulins (IVIG), corticosteroids, and combination therapies including corticosteroids.

Conclusions

Corticosteroids and IVIG should therefore be considered first-line treatments in patients with NXG.
Ethylene glycol toxicosis in milk-fed dairy calves
Authors: Agerholm Jørgen Steen , Hansen Kirsten Søndergaard , Voogd Hanne Lerche , Krogh Anne Kirstine Havnsøe
Published: March 2022

Background

Ethylene glycol (EG) (antifreeze) toxicosis has mostly been reported in dogs and cats, while reports on EG toxicosis in cattle are sparse. We report EG toxicosis in 25 milk-fed calves associated with a leak in the cooling pipes in a milk taxi. The milk taxi was connected to a geothermal heating system in which EG was used as antifreeze.

Case presentation

Although the assistant responsible for feeding milk to the calves observed a few blue-colored droplets of liquid on the surface of the milk in the milk taxi and suspected EG contamination, the milk was fed to the calves. Within hours, the calves became depressed and some died within the next 2 days. Necropsy and histopathology revealed widespread severe acute renal tubular necrosis with numerous birefringent crystals in the tubular lumen. Biochemical analysis of serum showed severe damage to the kidneys (marked azotemia) and hypochloremia, hyponatremia and hyperkalemia; findings consisting with metabolic acidosis. After feeding the calves, the assistant inspected the milk taxi and found a leaking cooling pipe.

Conclusions

The suspected EG toxicosis was confirmed by the observation of renal tubular necrosis, numerous intratubular crystals, and metabolic acidosis. EG toxicosis due to leaking pipes connected to a geothermal heating system has not been reported previously. Alternative antifreeze products that are less toxic than EG are recommended for use if there is a risk of contamination of human and animal foodstuffs in case of a leak in the system.
Current clinical management of constitutional delay of growth and puberty
Authors: Gaudino Rossella , De Filippo Gianpaolo , Bozzola Elena , Gasparri Manuela , Bozzola Mauro , Villani Alberto , Radetti Giorgio
Published: March 2022

Background

Constitutional delay of growth and puberty (CDGP) is classified as the most frequent cause of delayed puberty (DP). Finding out the etiology of DP during first evaluation may be a challenge. In details, pediatricians often cannot differentiate CDGP from permanent hypogonadotropic hypogonadism (PHH), with definitive diagnosis of PHH awaiting lack of puberty by age 18 yr. Neverthless, the ability in providing a precise and tempestive diagnosis has important clinical consequences.

Main text

A growth failure in adolescents with CDGP may occur until the onset of puberty; after that the growth rate increases with rapidity. Bone age is typically delayed. CDGP is generally a diagnosis of exclusion. Nevertheless, other causes of DP must be evaluated. A family history including timing of puberty in the mother and in the father as well as physical examination may givee information on the cause of DP. Patients with transient delay in hypothalamic-pituitary-gonadal axis maturation due to associated conditions, such as celiac disease, inflammatory bowel diseases, kidney insufficiency and anorexia nervosa, may experience a functional hypogonadotropic hypogonadism. PHH revealing testosterone or estradiol low serum values and reduced FSH and LH levels may be connected to abnormalities in the central nervous system. So, magnetic resonance imaging is required in order to exclude either morphological alterations or neoplasia. If the adolescent with CDGP meets psychological difficulties, treatment is recommended.

Conclusion

Even if CDGP is considered a variant of normal growth rather than a disease, short stature and retarded sexual development may led to psychological problems, sometimes associated to a poor academic performance. A prompt and precise diagnosis has an important clinical outcome. Aim of this mini-review is throwing light on management of patients with CDGP, emphasizing the adolescent diagnosis and trying to answer all questions from paediatricians.
Mutational analysis of compound heterozygous mutation p.Q6X/p.H232R in SRD5A2 causing 46,XY disorder of sex development
Authors: Li Liwei , Zhang Junhong , Li Qing , Qiao Li , Li Pengcheng , Cui Yi , Li Shujun , Hao Shirui , Wu Tongqian , Liu Lili , Yin Jianmin , Hu Pingsheng , Dou Xiaowei , Li Shuping , Yang Hui
Published: March 2022

Background

Over 100 mutations in the SRD5A2 gene have been identified in subjects with 46,XY disorder of sex development (DSD). Exploration of SRD5A2 mutations and elucidation of the molecular mechanisms behind their effects should reveal the functions of the domains of the 5α-reductase 2 enzyme and identify the cause of 46,XY DSD. Previously, we reported a novel compound heterozygous p.Q6X/p.H232R mutation of the SRD5A2 gene in a case with 46,XY DSD. Whether the compound heterozygous p.Q6X/p.H232R mutation in this gene causes 46,XY DSD requires further exploration.

Methods

The two 46,XY DSD cases were identified and sequenced. In order to identify the source of the compound heterozygous p.Q6X/p.H232R mutation, the parents, maternal grandparents, and maternal uncle were sequenced. Since p.Q6X mutation is a nonsense mutation, p.H232R mutation was transfected into HEK293 cells and dihydrotestosterone (DHT) production were analyzed by liquid chromatography–mass spectrometry (LC–MS) for 5α-reductase 2 enzyme activities test. Apparent michaelis constant (Km) were measured of p.H232R mutation to analyze the binding ability change of 5α-reductase 2 enzyme with testosterone (T) or NADPH.

Results

The sequence results showed that the two 46,XY DSD cases were the compound heterozygous p.Q6X/p.H232R mutation, of which the heterozygous p.Q6X mutation originating from maternal family and heterozygous p.H232R mutation originating from the paternal family. The function analysis confirmed that p.H232R variant decreased the DHT production by LC–MS test. The Km analysis demonstrated that p.H232R mutation affected the binding of SRD5A2 with T or NADPH.

Conclusions

Our findings confirmed that the compound heterozygous p.Q6X/p.H232R mutation in the SRD5A2 gene is the cause of 46,XY DSD. p.H232R mutation reduced DHT production while attenuating the catalytic efficiency of the 5α-reductase 2 enzyme.
Epidemiology of traumatic cervical spinal fractures in a general Norwegian population
Authors: Utheim Nils Christian , Helseth Eirik , Stroem Mona , Rydning Paal , Mejlænder-Evjensvold Magnus , Glott Thomas , Hoestmaelingen Christina Teisner , Aarhus Mads , Roenning Paal Andre , Linnerud Hege
Published: March 2022

Background

In Western countries, the typical cervical spine fracture (CS-Fx) patient has historically been a young male injured in a road traffic accident. Recent reports and daily clinical practice clearly indicate a change in the typical patient from a young male to an elderly male or female with comorbidities. This study aimed to establish contemporary population-based epidemiological data of traumatic CS-Fx for use in health-care planning and injury prevention.

Methods

This is a population-based retrospective database study (with prospectively collected data) from the Southeast Norway health region with 3.0 million inhabitants. We included all consecutive cases diagnosed with a CS-Fx between 2015 and 2019. Information regarding demographics, preinjury comorbidities, trauma mechanisms, injury description, treatment, and level of hospital admittance is presented.

Results

We registered 2153 consecutive cases with CS-Fx during a 5-year period, with an overall crude incidence of CS-Fx of 14.9/100,000 person-years. Age-adjusted incidences using the standard population for Europe and the World was 15.6/100,000 person-years and 10.4/100,000 person-years, respectively. The median patient age was 62 years, 68% were males, 37% had a preinjury severe systemic disease, 16% were under the influence of ethanol, 53% had multiple trauma, and 12% had concomitant cervical spinal cord injury (incomplete in 85% and complete in 15%). The most common trauma mechanisms were falls (57%), followed by bicycle injuries (12%), and four-wheel motorized vehicle accidents (10%). The most common upper CS-Fx was C2 odontoid Fx, while the most common subaxial Fx was facet joint Fx involving cervical level C6/C7. Treatment was external immobilization with a stiff neck collar alone in 65%, open surgical fixation in 26% (giving a 3.7/100,000 person-years surgery rate), and no stabilization in 9%. The overall 90-day mortality was 153/2153 (7.1%).

Conclusions

This study provides an overview of the extent of the issue and patient complexity necessary for planning the health-care management and injury prevention of CS-Fx. The typical CS-Fx patient was an elderly male or female with significant comorbidities injured in a low-energy trauma. The overall crude incidences of CS-Fx and surgical fixation of CS-Fx in Southeast Norway were 14.9/100,000 person-years and 3.7/100,000 person-years, respectively.
Formulation of oxybutynin chloride microparticle-loaded suppositories: in vitro characterization and in vivo pharmacokinetic study
Authors: Bedse Anjali , Mahajan Hitendra , Dhamane Suchita
Published: March 2022

Background

Oxybutynin chloride (OXC) is used to treat overactive urinary bladder. OXC is metabolized in the liver to N-desethyloxybutynin, which is mainly responsible for the anticholinergic side effects of OXC. Conventional oxybutynin suppositories formulated earlier have shown most common side effects, such as dry mouth, constipation and serious anticholinergic reaction. Hence the present research work deals with the formulation and characterization of OXC microparticle-loaded mucoadhesive suppositories which may remain adhered in the lower rectum and avoid first pass metabolism. The emulsification–ionic gelation method is employed to prepare OXC microparticles. Two formulation factors at three levels, i.e. polymer concentration and stirring speed, were selected. Sodium alginate (concentration 1–2%) and 1% w/v Carbopol 971P were used to prepare OXC microparticles. OXC microparticles were evaluated for various parameters such as production yield, entrapment efficiency, mucoadhesive strength, shape, size, zeta potential, Fourier Transform Infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, in vitro dissolution studies and stability studies. Suppositories loaded with OXC microparticles were prepared by the fusion method using Poloxamer 188 and propylene glycol and evaluated for various parameters like weight variation, disintegration time, in vitro dissolution study, stability study and pharmacokinetic study.

Results

Results of in vitro characterization revealed that optimized batch of OXC loaded microparticles exhibited production yield 94.024% entrapment efficiency 95.378% and mucoadhesion strength 95.544%, particle size range 764.04–894.13 µm, zeta potential − 14.5 mV, with 0.946 desirability. Consequences of DSC and XRPD evaluation shown that drug was effectively entrapped inside the microparticles. In vitro release studies revealed improvement in drug dissolution as a consequence of its entrapment into microparticles. SEM results showed that micelles were sphere-shaped. On rectal administration of OXC microparticles loaded suppository in male Sprague–Dawley Rats, the relative bioavailability was found 173.72%.

Conclusion

In vivo study elicits rapid increase in absorption of drug from microparticles loaded suppository when compared with the oral formulation and drug loaded suppository in rats. OXC microparticles loaded suppository is novel and promising drug delivery system for rectal administration and may avoid anticholinergic side effects of hepatic metabolite, N-desethyloxybutynin. These rectal drug delivery systems will be advantageous for efficient absorption of drugs and to avoid first pass metabolism.
Cultivating PhD Aspirations during College
Authors: Jones Daniela S. , Gillette Devyn D. , Cooper Paige E. , Salinas Raquel Y. , Hill Jennifer L. , Black Sherilynn J. , Lew Daniel J. , Canelas Dorian A.
Published: March 2022

This article compares the experiences and outcomes of 2069 unique students who belong to groups either historically well represented (WR) or underrepresented (UR) in science and describes the Biosciences Collaborative for Research Engagement (BioCoRE) undergraduate program using longitudinal data. BioCoRE aims to increase the number of people from historically UR groups in science PhD pipelines.
Lidocaine Infusion for the Treatment of Headache Associated With Subarachnoid Hemorrhage: A Case Report
Authors: Salgado Fernando , Douangpraseuth Sounida , Dickerson John R. , Crowley John W. , Newton Felecia A.
Published: March 2022

Headache after subarachnoid hemorrhage and corresponding craniotomy with aneurysm clipping can be severe and difficult to treat. Currently accepted analgesic therapies are often ineffective at treating the pain without incurring unacceptable side effects. We present an innovative approach wherein intravenous lidocaine infusions were used to successfully treat 2 patients with hyperalgesia refractory to traditional analgesic therapies. Opioid consumption fell to zero for both patients during lidocaine infusions without lidocaine toxicity. Moreover, after discontinuation of lidocaine infusions, both patients reported good pain control using only standard oral medications.
They like to move it (move it): walking kinematics of balitorid loaches of Thailand
Authors: Crawford Callie H. , Webber-Schultz Amani , Hart Pamela B. , Randall Zachary S. , Cerrato-Morales Cristian , Kellogg Audrey B. , Amplo Haley E. , Suvarnaraksha Apinun , Page Lawrence M. , Chakrabarty Prosanta , Flammang Brooke E.
Published: March 2022

Balitorid loaches are a family of fishes that exhibit morphological adaptations to living in fast flowing water, including an enlarged sacral rib that creates a ‘hip’-like skeletal connection between the pelvis and the axial skeleton. The presence of this sacral rib, the robustness of which varies across the family, is hypothesized to facilitate terrestrial locomotion seen in the family. Terrestrial locomotion in balitorids is unlike that of any known fish: the locomotion resembles that of terrestrial tetrapods. Emergence and convergence of terrestrial locomotion from water to land has been studied in fossils; however, studying balitorid walking provides a present-day natural laboratory to examine the convergent evolution of walking movements. We tested the hypothesis that balitorid species with more robust connections between the pelvic and axial skeleton (M3 morphotype) are more effective at walking than species with reduced connectivity (M1 morphotype). We predicted that robust connections would facilitate travel per step and increase mass support during movement. We collected high-speed video of walking in seven balitorid species to analyze kinematic variables. The connection between internal anatomy and locomotion on land are revealed herein with digitized video analysis, μCT scans, and in the context of the phylogenetic history of this family of fishes. Our species sampling covered the extremes of previously identified sacral rib morphotypes, M1 and M3. Although we hypothesized the robustness of the sacral rib to have a strong influence on walking performance, there was not a large reduction in walking ability in the species with the least modified rib (M1). Instead, walking kinematics varied between the two balitorid subfamilies with a generally more ‘walk-like’ behavior in the Balitorinae and more ‘swim-like’ behavior in the Homalopteroidinae. The type of terrestrial locomotion displayed in balitorids is unique among living fishes and aids in our understanding of the extent to which a sacral connection facilitates terrestrial walking.
Modular lung ventilation in Boa constrictor
Authors: Capano John G. , Boback Scott M. , Weller Hannah I. , Cieri Robert L. , Zwemer Charles F. , Brainerd Elizabeth L.
Published: March 2022

The evolution of constriction and of large prey ingestion within snakes are key innovations that may explain the remarkable diversity, distribution and ecological scope of this clade, relative to other elongate vertebrates. However, these behaviors may have simultaneously hindered lung ventilation such that early snakes may have had to circumvent these mechanical constraints before those behaviors could evolve. Here, we demonstrate that Boa constrictor can modulate which specific segments of ribs are used to ventilate the lung in response to physically hindered body wall motions. We show that the modular actuation of specific segments of ribs likely results from active recruitment or quiescence of derived accessory musculature. We hypothesize that constriction and large prey ingestion were unlikely to have evolved without modular lung ventilation because of their interference with lung ventilation, high metabolic demands and reliance on sustained lung convection. This study provides a new perspective on snake evolution and suggests that modular lung ventilation evolved during or prior to constriction and large prey ingestion, facilitating snakes’ remarkable radiation relative to other elongate vertebrates.
Liver T1 relaxation time of the ‘normal liver’ in healthy Asians: measurement with MOLLI and B1-corrected VFA methods at 3T
Authors: Ghavamian Armin , Liu Cuihong , Kang Bing , Yuan Xianshun , Wang Ximing , Gao Ling , Zhao Xinya
Published: March 2022

Objectives:

Liver T1 is a potential magnetic resonance imaging biomarker for liver diseases. This study aimed to determine the T1 relaxation time of the normal liver (PDFF<5%) in healthy Asian volunteers using modified look-locker inversion recovery (MOLLI) and B1 inhomogeneity-corrected variable flip angle (B1-corrected VFA).

Methods:

60 healthy Asian volunteers without focal or diffuse liver disease underwent a liver scan at 3T magnetic resonance. Proton density fat fraction (PDFF) and liver stiffness measurements were applied for the quantification of liver fat and fibrosis. T1 mapping was performed with MOLLI and B1-corrected VFA sequences. Bland-Altman, linear regression, Student t-test, and one-way analysis of variance were used for statistical analysis.

Results:

The mean T1 relaxation times of the whole liver were 901 ± 34 ms by MOLLI, and 948 ± 29 ms by B1-corrected VFA in healthy volunteers. There was a strong correlation (r = 0.86, p < 0.0001) for liver T1 between two T1 mapping methods. There were significant differences between the right and left lobes in liver T1 relaxation times using both methods (p < 0.05). Gender and Asian ethnic disparities had no impact on liver T1 relaxation times.

Conclusion:

T1 relaxation times of the normal liver (PDFF<5%) in healthy volunteers were established by MOLLI and B1-corrected VFA T1 mapping methods at 3T. It may provide suitable and robust baseline values for the assessment of liver diseases.

Advances in knowledge:

Gender and Asian ethnic disparities do not impact liver T1 relaxation time measurements.
Shaming for Tax Enforcement
Authors: Dwenger Nadja , Treber Lukas
Published: March 2022

We investigate company reactions to the threat of reputational losses. To do so, we leverage the introduction of a naming-and-shaming policy for tax debt enforcement in Slovenia in 2012. The policy was announced four months before its implementation, which allows us to separate responses to the threat of shaming from the responses to actual shaming. Our extensive administrative tax data cover taxes owed and paid for the universe of taxpayers in Slovenia. Based on a quasi-experimental research design, we document that corporations significantly reduce their tax debt in response to the threat of shaming, particularly in industries in which reputational concerns are likely to be important. Self-employed individuals also reduce their tax debt but to a lesser extent. The publication of the first naming-and-shaming list further reduced tax debt among shamed taxpayers. However, the effect of actual shaming is marginal compared with that of the threat of shaming and reduces quickly. Previously compliant taxpayers remained compliant throughout.

This paper was accepted by Yan Chen, decision analysis.

Funding: This work was supported by Deutscher Akademischer Austauschdienst [Grant 91537728/211483], Deutsche Forschungsgemeinschaft [Grant DW 75/1-1], and Norges Forskningsråd [Grant 314479].

Supplemental Material: The online appendix and data are available at https://doi.org/10.1287/mnsc.2021.4295 .
Mis-Nudging Morality
Authors: Morvinski Coby , Saccardo Silvia , Amir On
Published: March 2022

Morals constrain self-serving behavior. Yet, self-regulation failures in the face of monetary temptation are common at the workplace. To limit such failures, organizations can design environments that limit the temptation to behave self-servingly, nudging workers to uphold their morals. In a series of experiments where participants may be tempted to take excessive pay after exerting effort, we study whether a simple intervention—asking individuals to state the wage they believe should be paid ex ante, before facing the temptation to take excessive compensation—prevents self-serving behavior. In contrast to lay beliefs and the predictions from prior work, we find that such an intervention is not effective, leading to self-serving behavior. However, a more realistic elicitation procedure of the appropriate wage mitigates this effect. These findings contribute to work on the malleability of moral behavior showing that simple interventions thought to effectively mitigate self-serving behavior can prompt individuals to stretch their moral boundaries. They also stress the importance of properly testing interventions that might seem intuitive.

This paper was accepted by Yan Chen, behavioral economics and decision analysis.

Funding: Financial support from the Israel Science Foundation [Grant 766/19] is gratefully acknowledged.

Supplemental Material: The online appendix and data are available at https://doi.org/10.1287/mnsc.2022.4344 .
A First-Order Approach to Accelerated Value Iteration
Authors: Goyal Vineet , Grand-Clément Julien
Published: March 2022

Markov decision processes (MDPs) are used to model stochastic systems in many applications, but computing good policies becomes hard when the effective horizon become very large. In “A First-Order Approach to Accelerated Value Iteration,” Goyal and Grand-Clément present a connection between value iteration (VI) algorithms and gradient descent methods from convex optimization and use acceleration and momentum to design faster algorithms, with convergence guarantees for the computation of the value function of a fixed policy for reversible MDP instances. The authors provide a lower bound on the convergence properties of any first-order algorithm for solving MDPs, where no algorithm can converge faster than VI. Finally, the authors introduce safe accelerated value iteration (S-AVI), which alternates between accelerated updates and value iteration updates. The algorithm S-AVI is worst-case optimal and retains the theoretical convergence properties of VI while exhibiting strong empirical performances and providing significant speedups when compared with classical approaches for a large test bed of MDP instances.
Implantable cardioverter defibrillator deactivation: opportunities and good practice
Authors: Paul Geeta , Eftekhari Helen
Published: March 2022

This literature review examines recommendations regarding good decision making for the deactivation of implantable cardioverter defibrillators in individuals who are nearing the end of life. Implantable cardioverter defibrillators are considered the first line of treatment in individuals presenting with life-threatening arrhythmias. However, there comes a time when individuals may experience unwanted shocks from the implantable cardioverter defibrillator in the last phases of life. This article reviews the complexities surrounding discussions about deactivation, including missed opportunities for these discussions during an individual's healthcare journey. Guidelines suggest that healthcare providers should have timely discussions regarding the deactivation of an implantable cardioverter defibrillator with patients and their families, empowering individuals to make an informed decision. This involves exploring the patient's values, cultural beliefs and preferences for care based on a full understanding of all options. It is recognised that good collaboration between multidisciplinary teams within secondary and primary healthcare teams plays a fundamental role in care planning. Health professionals should identify and address high levels of anxiety in patients and promote effective communication throughout the decision-making process. The nursing role should be central to this process in order to facilitate advanced care planning and enable the best healthcare outcomes for the patient. Specialist nurses play an integral part in the care of patients nearing the end of life and represent a positive force within the healthcare system in providing holistic, evidence-based care.
Surviving acute aortic dissection: one nurse's mission to guide and support patients on their daunting journey
Authors: Hope Emma
Published: March 2022

As the specialist nursing roles within the cardiac sphere become increasingly diverse, Emma Hope provides some insight into the role of an aortic specialist nurse and the patient journey with acute aortic dissection.
Housing temporalities: state narratives and precarity in the Global South
Authors: Lall Ruchika
Published: March 2022

In the Global South, urban space is appropriated through diverse informal housing arrangements, with characteristic inherent and relational temporalities. While these forms of housing often consolidate through incremental growth, change in materials and perceived security, they also exist precariously through changing circumstances. While some urban scholars have discussed the characteristic in-betweenness of informality, others have noted the conceptual tension that policy holds in addressing this temporality. This article builds on these discussions to argue that the temporality within and across diverse informal housing arrangements matters not due to the ways in which it manifests, but due to what happens within it as a space of transformation, that is, of socio-economic and political mobility. It draws from literature across disciplines on mobilities, poverty and capabilities to posit that a conceptual frame of choice and agency is key to policy engagement with housing temporalities. The article locates this discussion in the city of Delhi, where cycles of evictions have broken large ‘slum’ clusters, or bastis, into further spatial and temporal configurations. The article uses two distinct housing models to illustrate narratives of the state across two sites: Savda Ghevra, a case of peripheral resettlement; and Kathputli Colony, a case of in-situ redevelopment. It reveals how the state not only does not recognise the temporality of self-made housing practices, but also sets into motion temporalities that, through the absence of choice and agency, create conditions for precarity, highlighting the need to keep choice and agency central to discourses on housing and well-being.
Structural dynamics of receptor recognition and pH-induced dissociation of full-length Clostridioides difficile Toxin B
Authors: Jiang Mengqiu , Shin Joonyoung , Simeon Rudo , Chang Jeng-Yih , Meng Ran , Wang Yuhang , Shinde Omkar , Li Pingwei , Chen Zhilei , Zhang Junjie
Published: March 2022

Clostridioides difficile secretes Toxin B (TcdB) as one of its major virulence factors, which binds to intestinal epithelial and subepithelial receptors, including frizzled proteins and chondroitin sulfate proteoglycan 4 (CSPG4). Here, we present cryo-EM structures of full-length TcdB in complex with the CSPG4 domain 1 fragment (D1401-560) at cytosolic pH and the cysteine-rich domain of frizzled-2 (CRD2) at both cytosolic and acidic pHs. CSPG4 specifically binds to the autoprocessing and delivery domains of TcdB via networks of salt bridges, hydrophobic and aromatic/proline interactions, which are disrupted upon acidification eventually leading to CSPG4 drastically dissociating from TcdB. In contrast, FZD2 moderately dissociates from TcdB under acidic pH, most likely due to its partial unfolding. These results reveal structural dynamics of TcdB during its preentry step upon endosomal acidification, which provide a basis for developing therapeutics against C. difficile infections.