bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary dementia care based on the individual needs of the patient: study protocol of the cluster randomized controlled trial, DemStepCare
Authors:   study group DemStepCare, Bablok Isabella , Binder Harald , Stelzer Dominikus , Kaier Klaus , Graf Erika , Wangler Julian , Jansky Michael , Löhr Michael , Schulz Michael , Kockläuner Marie , Geschke Katharina , Wuttke-Linnemann Alexandra , Fellgiebel Andreas , Farin Erik
Published: April 2021

Background

Most people with dementia (PwD) are cared for at home, with general practitioners (GPs) playing a key part in the treatment. However, primary dementia care suffers from a number of shortcomings: Often, diagnoses are made too late and therapies by GPs do not follow the guidelines. In cases of acute crises, PwD are too often admitted to hospital with adverse effects on the further course of the disease.

The aim of this study is to implement and evaluate a new GP-based, complex dementia care model, DemStepCare. DemStepCare aims to ensure demand-oriented, stepped care for PwD and their caregivers.

Methods/design

In a cluster randomized controlled trial, the care of PwD receiving a complex intervention, where the GP is supported by a multi-professional team, is compared to (slightly expanded) usual care.

GPs are clustered by GP practice, with 120 GP practices participating in total. GP practices are randomized to an intervention or a control group. 800 PwD are to be included per group. Recruitment takes place in Rhineland-Palatinate, Germany. In addition, a second control group with at least 800 PwD will be formed using aggregated routine data from German health insurance companies. The intervention comprises the training of GPs, case management including repeated risk assessment of the patients’ care situation, the demand-oriented service of an outpatient clinic, an electronic case record, external medication analyses and a link to regional support services. The primary aims of the intervention are to positively influence the quality of life for PwD, to reduce the caregivers’ burden, and to reduce the days spent in hospital. Secondary endpoints address medication adequacy and GPs’ attitudes and sensitivity towards dementia, among others.

Discussion

The GP-based dementia care model DemStepCare is intended to combine a number of promising interventions to provide a complex, stepped intervention that follows the individual needs of PwD and their caregivers. Its effectiveness and feasibility will be assessed in a formative and a summative evaluation.

Trial registration

German Register of Clinical Trials (Deutsches Register Klinischer Studien, DRKS),DRKS00023560. Registered 13 November 2020 - Retrospectively registered. HTML&TRIAL_ID=DRKS00023560.
Does the additional use of clomiphene citrate or letrozole for in vitro fertilization deserve more attention?
Authors: Liang Ying , Guo Qing , Wu Xiao-Hua , Zhang Li-Nan , Ge Jun , Xu Mei-Ling , Feng Zheng-Li , Wu Xiao-Qian
Published: April 2021

Background

Adding clomiphene citrate (CC) and/or letrozole (LE) to in vitro fertilization (IVF) cycles for mild ovarian stimulation is a general approach. Although lots of researches have demonstrated partial benefits of the strategy, all-around effects of oral medications remained deficient. This paper aims to assess whether an addition of oral medication will result in considerable outcomes on T-Gn (total dose of gonadotropin), Gn days, total retrieved ova, high quality embryos, blastocyst number, ovarian hyperstimulation syndrome (OHSS) rate, clinical pregnancy rate and cumulative pregnancy rate, even if it was not conventional mild/minimal stimulations.

Results

Participants were categorized to three diverse populations as high responders, normal responders and poor responders according to basal antral follicle count. T-Gn in patients treated with CC/LE distinctly decreased from 2496.96 IU/d to 1827.68 IU/d, from 2860.28 IU/d to 2119.99 IU/d, and from 3182.15 IU/d to 1802.84 IU/d, respectively. For high ovary responders and normal responders, the OHSS incidence rate also declined from 29.2 to 4.3% (P < 0.001) and from 1.1 to 0.0% (P = 0.090). Other, there was no statistical difference with respect to the T-retrieved ova (total retrieved ova), high quality embryos, cultured blastocyst and blastocyst number in high responders. For normal responders and poor ovary responders, T-Gn, Gn days, T-retrieved ova, high quality embryos, cultured blastocyst and blastocysts number in oral medications group all apparently decreased. Clinical pregnancy rate per fresh cycle of poor responders with prior oral medications was significantly decreased (25.7% vs. 50.8%, P = 0.005), and no significant differences in high responders and normal responders were expressed (52.5% vs. 44.2%, P = 0.310; 51.9% vs. 42.4%, P = 0.163) between two groups of participants. The numbers of cumulative pregnancy rates were lower in the conventional group compared to the add group for high (75.90% versus 81.03%, P = 0.279), normal (62.69% versus 71.36%, P = 0.016) and poor (39.74% versus 68.21%, P < 0.001) responders.

Conclusions

The addition of CC/LE to the ovulation induction during IVF has certain efficacy in terms of low cost, low OHSS incidence. CC/LE deserves more recommendations as a responsible strategy in high responders due to advantageous pregnancy outcomes. For normal responders, the strategy needs to be considered with more comprehensive factors.
Anti-IL17 antibody Secukinumab therapy is associated with ossification in giant cell tumor of bone: a case report of pathologic similarities and therapeutic potential similar to Denosumab
Authors: Chandler Andrew , Bartelstein Meredith K. , Fujiwara Tomohiro , Antonescu Cristina R. , Healey John H. , Vaynrub Max
Published: April 2021

Background

Giant cell tumor of bone is a benign, locally aggressive neoplasm. Surgical resection is the preferred treatment method. However, for cases in which resection poses an increased risk to the patient, denosumab (anti-RANKL monoclonal antibody) is considered. Secukinumab is an anti-IL-17 antibody that is used in psoriatic arthritis to reduce bone resorption and articular damage.

Case presentation

One case of giant cell tumor of bone (GCTB) in a patient treated with secukinumab for psoriatic arthritis demonstrated findings significant for intra-lesional calcifications. Histologic examination showed ossification, new bone formation, and remodeling. A paucity of osteoclast type giant cells was noted. Real-time quantitative polymerase-chain-reaction (qRT-PCR) analysis revealed decreased osteoclast function compared to treatment-naive GCTB.

Conclusions

Secukinumab may play a role in bone remodeling for GCTB. Radiologists, surgeons, and pathologists should be aware of this interaction, which can cause lesional ossification. Further research is required to define the therapeutic potential of this drug for GCTB and osteolytic disease.
Inflammatory indexes in preoperative blood routine to predict early recurrence of hepatocellular carcinoma after curative hepatectomy
Authors: Wu YiFeng , Tu ChaoYong , Shao ChuXiao
Published: April 2021

Background

The inflammation indexes in blood routine play an essential role in evaluating the prognosis of patients with hepatocellular carcinoma, but the effect on early recurrence has not been clarified. The study aimed to investigate the risk factors of early recurrence (within 2 years) and recurrence-free survival after curative hepatectomy and explore the role of inflammatory indexes in predicting early recurrence.

Methods

The baseline data of 161 patients with hepatocellular carcinoma were analyzed retrospectively. The optimal cut-off value of the inflammatory index was determined according to the Youden index. Its predictive performance was compared by the area under the receiver operating characteristic curve. Logistic and Cox regression analyses were used to determine the risk factors of early recurrence and recurrence-free survival.

Results

The area under the curve of monocyte to lymphocyte ratio (MLR) for predicting early recurrence was 0.700, which was better than systemic inflammatory response index (SIRI), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and systemic immune-inflammatory index (SII). MLR, tumour size, tumour differentiation and BCLC stage are all risk factors for early recurrence and recurrence-free survival of HCC. Combining the above four risk factors to construct a joint index, the area under the curve for predicting early recurrence was 0.829, which was better than single MLR, tumour size, tumour differentiation and BCLC stage. Furthermore, with the increase of risk factors, the recurrence-free survival of patients is worse.

Conclusion

The combination of MLR and clinical risk factors is helpful for clinicians to identify high-risk patients with early recurrence and carry out active postoperative adjuvant therapy to improve the prognosis of patients.
Dietary phytochemical index in relation to risk of glioma: a case-control study in Iranian adults
Authors: Rigi Somaye , Shayanfar Mehdi , Mousavi Seyed Mohammad , Mohammad-Shirazi Minoo , Sharifi Giuve , Esmaillzadeh Ahmad
Published: April 2021

Background & aim

No study is available that explores the association of dietary phytochemical index (DPI) with glioma. The objective of the current study was to assess this association in Iranian adults.

Methods

This hospital-based case-control study included 128 newly-diagnosed cases of glioma and 256 age- and sex-matched controls. Data collection on dietary intakes was done using a 123-item validated food frequency questionnaire. Calculation of DPI was done as (dietary energy derived from phytochemical-rich foods (kcal)/total daily energy intake (kcal)) × 100. Logistic regression models were used to examine the association between DPI and glioma.

Results

Individuals in the top tertile of DPI were more likely to be older and female. Before taking potential confounders into account, subjects in the top tertile of DPI tended to have a 40% reduced chance of glioma than those in the bottom tertile (OR: 0.60; 95% CI: 0.35–1.02, P = 0.06). After controlling for age, sex, energy intake, several demographic variables and dietary intakes, the association between DPI and glioma became strengthened (OR: 0.43; 95% CI: 0.19–0.97, P = 0.04).

Conclusion

High intakes of phytochemical-rich foods were associated with a lower risk of glioma in adults. High consumption of phytochemical-rich foods might be recommended to prevent glioma. However, further studies with a prospective design are needed to confirm our findings.
Low serum vitamin D concentrations are associated with obese but not lean NAFLD: a cross-sectional study
Authors: Wang Qinqiu , Shi Xiaoying , Wang Jinghua , Zhang Juanwen , Xu Chengfu
Published: April 2021

Background

A low serum vitamin D concentration has been reported to be associated with an increased risk of non-alcoholic fatty liver disease (NAFLD); however, whether lean or obese individuals show a similar association between vitamin D and NAFLD remains speculative. This study aimed to explore the relationship between serum vitamin D concentration and NAFLD in lean and obese Chinese adults.

Methods

This cross-sectional study included 2538 participants (1360 men and 1178 women) who underwent health checkups at the First Affiliated Hospital, Zhejiang University School of Medicine in 2019. NAFLD was diagnosed by liver ultrasound excluding other causes. The association of serum vitamin D concentration with NAFLD was analyzed in lean and obese participants.

Results

The overall prevalence of NAFLD was 33.61% (13.10% in lean and 53.32% in obese) in this study population. The serum vitamin D levels of obese NAFLD patients were lower than those of obese NAFLD-free controls. However, the serum vitamin D levels of lean NAFLD patients were comparable to those of lean NAFLD-free controls. Serum vitamin D level was negatively correlated with the prevalence of NAFLD in obese but not lean participants. Serum vitamin D level was independently associated with the risk of NAFLD in obese participants, with an adjusted odds ratio (95% CI) of 0.987 (0.981–0.993). However, serum vitamin D level was not related to the risk of NAFLD in lean participants.

Conclusions

A low serum vitamin D level is associated with NAFLD in obese but not lean participants.
Correction to: System dynamics modelling of health workforce planning to address future challenges of Thailand’s Universal Health Coverage
Authors: Leerapan Borwornsom , Teekasap Pard , Urwannachotima Nipaporn , Jaichuen Wararat , Chiangchaisakulthai Kwanpracha , Udomaksorn Khunjira , Meeyai Aronrag , Noree Thinakorn , Sawaengdee Krisada
Published: April 2021

An amendment to this paper has been published and can be accessed via the original article.
Gene signature and immune cell profiling by high-dimensional, single-cell analysis in COVID-19 patients, presenting Low T3 syndrome and coexistent hematological malignancies
Authors: Sciacchitano Salvatore , De Vitis Claudia , D’Ascanio Michela , Giovagnoli Simonetta , De Dominicis Chiara , Laghi Andrea , Anibaldi Paolo , Petrucca Andrea , Salerno Gerardo , Santino Iolanda , Amodeo Rachele , Simmaco Maurizio , Napoli Christian , Tafuri Agostino , Di Napoli Arianna , Sacconi Andrea , Salvati Valentina , Ciliberto Gennaro , Fanciulli Maurizio , Piaggio Giulia , de Latouliere Luisa , Ricci Alberto , Mancini Rita
Published: April 2021

Background

Low T3 syndrome is frequent in patients admitted to intensive care units for critical illness and pneumonia. It has been reported also in patients with COVID-19, Hodgkin disease and chronic lymphocytic leukemia. We analyzed the clinical relevance of Low T3 syndrome in COVID-19 patients and, in particular, in those with associated hematological malignancies.

Methods

Sixty-two consecutive patients, hospitalized during the first wave of SARS-CoV-2 outbreak in Sant’Andrea University Hospital in Rome, were subdivided in 38 patients (Group A), showing low levels of FT3, and in 24 patients (Group B), with normal FT3 serum values. During the acute phase of the disease, we measured serum, radiologic and clinical disease severity markers and scores, in search of possible correlations with FT3 serum values. In addition, in 6 COVID-19 patients, 4 with Low T3 syndrome, including 2 with a hematological malignancy, and 2 with normal FT3 values, we performed, high-dimensional single-cell analysis by mass cytometry, multiplex cytokine assay and gene expression profiling in peripheral blood mononuclear cells (PBMC).

Results

Low FT3 serum values were correlated with increased Absolute Neutrophil Count, NLR and dNLR ratios and with reduced total count of CD3+, CD4+ and CD8+ T cells. Low FT3 values correlated also with increased levels of inflammation, tissue damage and coagulation serum markers as well as with SOFA, LIPI and TSS scores. The CyTOF analysis demonstrated reduction of the effector memory and terminal effector subtypes of the CD4+ T lymphocytes. Multiplex cytokine assay indicates that mainly IL-6, IP-10 and MCAF changes are associated with FT3 serum levels, particularly in patients with coexistent hematological malignancies. Gene expression analysis using Nanostring identified four genes differently expressed involved in host immune response, namely CD38, CD79B, IFIT3 and NLRP3.

Conclusions

Our study demonstrates that low FT3 serum levels are associated with severe COVID-19. Our multi-omics approach suggests that T3 is involved in the immune response in COVID-19 and coexistent hematological malignancy and new possible T3 target genes in these patients have been identified.
Correction to: 2-Pentadecyl-2-oxazoline ameliorates memory impairment and depression-like behaviour in neuropathic mice: possible role of adrenergic alpha2- and H3 histamine autoreceptors
Authors: Boccella Serena , Guida Francesca , Iannotta Monica , Iannotti Fabio Arturo , Infantino Rosmara , Ricciardi Flavia , Cristiano Claudia , Vitale Rosa Maria , Amodeo Pietro , Marabese Ida , Belardo Carmela , de Novellis Vito , Paino Salvatore , Palazzo Enza , Calignano Antonio , Di Marzo Vincenzo , Maione Sabatino , Luongo Livio
Published: April 2021

An amendment to this paper has been published and can be accessed via the original article.
HNRNPA2B1 promotes multiple myeloma progression by increasing AKT3 expression via m6A-dependent stabilization of ILF3 mRNA
Authors: Jiang Fengjie , Tang Xiaozhu , Tang Chao , Hua Zhen , Ke Mengying , Wang Chen , Zhao Jiamin , Gao Shengyao , Jurczyszyn Artur , Janz Siegfried , Beksac Meral , Zhan Fenghuang , Gu Chunyan , Yang Ye
Published: April 2021

N6-methyladenosine (m6A) modification is the most prevalent modification in eukaryotic RNAs while accumulating studies suggest that m6A aberrant expression plays an important role in cancer. HNRNPA2B1 is a m6A reader which binds to nascent RNA and thus affects a perplexing array of RNA metabolism exquisitely. Despite unveiled facets that HNRNPA2B1 is deregulated in several tumors and facilitates tumor growth, a clear role of HNRNPA2B1 in multiple myeloma (MM) remains elusive. Herein, we analyzed the function and the regulatory mechanism of HNRNPA2B1 in MM. We found that HNRNPA2B1 was elevated in MM patients and negatively correlated with favorable prognosis. The depletion of HNRNPA2B1 in MM cells inhibited cell proliferation and induced apoptosis. On the contrary, the overexpression of HNRNPA2B1 promoted cell proliferation in vitro and in vivo. Mechanistic studies revealed that HNRNPA2B1 recognized the m6A sites of ILF3 and enhanced the stability of ILF3 mRNA transcripts, while AKT3 downregulation by siRNA abrogated the cellular proliferation induced by HNRNPA2B1 overexpression. Additionally, the expression of HNRNPA2B1, ILF3 and AKT3 was positively associated with each other in MM tissues tested by immunohistochemistry. In summary, our study highlights that HNRNPA2B1 potentially acts as a therapeutic target of MM through regulating AKT3 expression mediated by ILF3-dependent pattern.
libxtc: an efficient library for reading XTC-compressed MD trajectory data
Authors: Krylov Nikolay A. , Efremov Roman G.
Published: April 2021

Objective

The purpose of this work is to optimize the processing of molecular dynamics (MD) trajectory data obtained for large biomolecular systems. Two popular software tools were chosen as the reference: the tng and the xdrfile libraries. Current implementation of tng algorithms and library is either fast or storage efficient and xdrfile is storage efficient but slow. Our aim was to combine speed and storage efficiency through the xdrfile’s code modification.

Results

Here we present libxtc, a ready-to-use library for reading MD trajectory files in xtc format. The effectiveness of libxtc is demonstrated for several biomolecular systems of various sizes (~ 2 × 104 to ~ 2 × 105 atoms). In sequential mode, the performance of libxtc is up to 1.8 times higher and 1.4 times lower than xdrfile and tng, respectively. In parallel mode, libxtc is about 3 and 1.3 times faster than xdrfile and tng. At the same time, MD data stored in the xtc format require about 1.3 times less disk space than those treated with the tng algorithm in the fastest reading mode, which is a noticeable saving especially when the MD trajectory is long and the number of atoms is large—this applies to most biologically relevant systems.
A novel age-informed approach for genetic association analysis in Alzheimer’s disease
Authors:   for the Alzheimer’s Disease Neuroimaging Initiative, Le Guen Yann , Belloy Michael E. , Napolioni Valerio , Eger Sarah J. , Kennedy Gabriel , Tao Ran , He Zihuai , Greicius Michael D.
Published: April 2021

Background

Many Alzheimer’s disease (AD) genetic association studies disregard age or incorrectly account for it, hampering variant discovery.

Methods

Using simulated data, we compared the statistical power of several models: logistic regression on AD diagnosis adjusted and not adjusted for age; linear regression on a score integrating case-control status and age; and multivariate Cox regression on age-at-onset. We applied these models to real exome-wide data of 11,127 sequenced individuals (54% cases) and replicated suggestive associations in 21,631 genotype-imputed individuals (51% cases).

Results

Modeling variable AD risk across age results in 5–10% statistical power gain compared to logistic regression without age adjustment, while incorrect age adjustment leads to critical power loss. Applying our novel AD-age score and/or Cox regression, we discovered and replicated novel variants associated with AD onKIF21B, USH2A, RAB10, RIN3, andTAOK2genes.

Conclusion

Our AD-age score provides a simple means for statistical power gain and is recommended for future AD studies.
An integrative multi-omics approach reveals new central nervous system pathway alterations in Alzheimer’s disease
Authors: Clark Christopher , Dayon Loïc , Masoodi Mojgan , Bowman Gene L. , Popp Julius
Published: April 2021

Background

Multiple pathophysiological processes have been described in Alzheimer’s disease (AD). Their inter-individual variations, complex interrelations, and relevance for clinical manifestation and disease progression remain poorly understood. We hypothesize that specific molecular patterns indicating both known and yet unidentified pathway alterations are associated with distinct aspects of AD pathology.

Methods

We performed multi-level cerebrospinal fluid (CSF) omics in a well-characterized cohort of older adults with normal cognition, mild cognitive impairment, and mild dementia. Proteomics, metabolomics, lipidomics, one-carbon metabolism, and neuroinflammation related molecules were analyzed at single-omic level with correlation and regression approaches. Multi-omics factor analysis was used to integrate all biological levels. Identified analytes were used to construct best predictive models of the presence of AD pathology and of cognitive decline with multifactorial regression analysis. Pathway enrichment analysis identified pathway alterations in AD.

Results

Multi-omics integration identified five major dimensions of heterogeneity explaining the variance within the cohort and differentially associated with AD. Further analysis exposed multiple interactions between single ‘omics modalities and distinct multi-omics molecular signatures differentially related to amyloid pathology, neuronal injury, and tau hyperphosphorylation. Enrichment pathway analysis revealed overrepresentation of the hemostasis, immune response, and extracellular matrix signaling pathways in association with AD. Finally, combinations of four molecules improved prediction of both AD (protein 14-3-3 zeta/delta, clusterin, interleukin-15, and transgelin-2) and cognitive decline (protein 14-3-3 zeta/delta, clusterin, cholesteryl ester 27:1 16:0 and monocyte chemoattractant protein-1).

Conclusions

Applying an integrative multi-omics approach we report novel molecular and pathways alterations associated with AD pathology. These findings are relevant for the development of personalized diagnosis and treatment approaches in AD.
The use of multimodal imaging in the evaluation of a patient with central retinal artery occlusion in the setting of asteroid hyalosis: a case report
Authors: Janetos Timothy M. , German Olga , Mirza Rukhsana
Published: April 2021

Background

A central retinal artery occlusion (CRAO) is an ophthalmic emergency due to its strong association with cerebrovascular and cardiovascular morbidity and mortality. A timely diagnosis is necessary but difficult in the setting of dense asteroid hyalosis, as typical fundoscopic findings can be obscured. We present a case where multimodal imaging in an eye with an obscured fundus could lead to timely diagnosis and management of CRAO in a patient with acute vision loss.

Case presentation

A 94-year-old Caucasian woman with a history of exudative macular degeneration presented to the retina clinic with acute vision loss in one eye over the course of an afternoon. The patient had dense asteroid hyalosis, and a direct retinal exam was not possible. Multimodal imaging suggested a CRAO diagnosis. The patient received digital ocular massage directly prior to undergoing fluorescein angiography (FANG), which confirmed the diagnosis. The patient was transported from clinic to the emergency room for an emergency stroke workup, which revealed a spontaneous echo in the left atrial appendage, and the patient was started on antiplatelet therapy. When she presented for follow-up within a week, the patient noted that her vision had improved at the time of digital ocular massage and continued to improve thereafter. Her FANG showed marked reperfusion of the retina, and she subsequently has completely regained her baseline visual acuity.

Conclusions

Multimodal imaging is useful in evaluating visual loss in patients with acute vision loss. In addition, ocular massage is a simple, low-risk intervention that may have benefit in the treatment of acute CRAO. Patients who present to ophthalmologists with an acute CRAO need an emergency referral for evaluation of cerebrovascular and cardiovascular comorbidities.
Community readiness for collecting stray dogs in Aradan County: a quantitative‐qualitative study
Authors: Kamalikhah Tahereh , Mirrezaei Somayeh , Rahimi Tahereh , Sabzmakan Leila , Ghobakhloo Safiye
Published: April 2021

Background

Paying more attention to free-roaming dogs’ population control seems to be necessary because of public health and environmental problems. The present study used the community readiness model to determine the readiness of Aradan County in terms of collecting stray dogs.

Methods

This study is a quantitative-qualitative research study conducted in Aradan County in Semnan Province of Iran. The semi-structured questionnaire uses the six dimensions of the Community Readiness Model as guideline, with 36 items used for the interview. The interviews lasted 45 to 100 minutes with 11 key members including the governor, prefect, mayor’s assistant, city council chairman, key trustees, officials responsible for environmental health network, officials responsible for environmentalism of the city, and governors of a rural district. In quantitative part two, assessors read the interviews carefully and assigned scores based on the rating-scale form suggested by the guideline itself for scoring each dimension. A qualitative directed content analysis with deductive approach was used for analyzing the collected qualitative data.

Results

The study involved 11 key members of Aradan County, all of whom were male. Most of the participants were over 40 years old and with five years of work experience (73.6 %). The mean score of each six dimensions in Aradan County were: Community efforts (4.78), Community knowledge of efforts (4.28), Leadership (4.90), Community climate (4.38), Community knowledge about the issue (4.20) and Resources related to the issue (3.29) respectively. Community readiness in Aradan County and Aradan City was generally estimated to be in the preplanning stage, whereas vague public awareness was found in the rural areas.

In the qualitative part, 870 initial open codes, 589 refund codes, 19 subcategories and 6 themes emerged, including (a) community efforts, (b) community knowledge of the efforts (c) leadership, (d) community climate, (e) community knowledge of the issue, and (f) resources related to the issue.

Conclusions

For improving the process of collecting the stray dogs, it is necessary to focus on holding educational sessions for the public to increase their partnership and justify the responsible organizations’ activities to collaborate and provide the necessary financial resources.
Combined effects of composting and antibiotic administration on cattle manure–borne antibiotic resistance genes
Authors: Keenum Ishi , Williams Robert K. , Ray Partha , Garner Emily D. , Knowlton Katharine F. , Pruden Amy
Published: April 2021

Background

Research is needed to delineate the relative and combined effects of different antibiotic administration and manure management practices in either amplifying or attenuating the potential for antibiotic resistance to spread. Here, we carried out a comprehensive parallel examination of the effects of small-scale (> 55 °C × 3 days) static and turned composting of manures from dairy and beef cattle collected during standard antibiotic administration (cephapirin/pirlimycin or sulfamethazine/chlortetracycline/tylosin, respectively), versus from untreated cattle, on “resistomes” (total antibiotic resistance genes (ARGs) determined via shotgun metagenomic sequencing), bacterial microbiota, and indicator ARGs enumerated via quantitative polymerase chain reaction. To gain insight into the role of the thermophilic phase, compost was also externally heated to > 55 °C × 15 days.

Results

Progression of composting with time and succession of the corresponding bacterial microbiota was the overarching driver of the resistome composition (ANOSIM; R = 0.424, p = 0.001, respectively) in all composts at the small-scale. Reduction in relative abundance (16S rRNA gene normalized) of total ARGs in finished compost (day 42) versus day 0 was noted across all conditions (ANOSIM; R = 0.728, p = 0.001), except when externally heated. Sul1, intI1, beta-lactam ARGs, and plasmid-associated genes increased in all finished composts as compared with the initial condition. External heating more effectively reduced certain clinically relevant ARGs (blaOXA, blaCARB), fecal coliforms, and resistome risk scores, which take into account putative pathogen annotations. When manure was collected during antibiotic administration, taxonomic composition of the compost was distinct according to nonmetric multidimensional analysis and tet(W) decayed faster in the dairy manure with antibiotic condition and slower in the beef manure with antibiotic condition.

Conclusions

This comprehensive, integrated study revealed that composting had a dominant effect on corresponding resistome composition, while little difference was noted as a function of collecting manure during antibiotic administration. Reduction in total ARGs, tet(W), and resistome risk suggested that composting reduced some potential for antibiotic resistance to spread, but the increase and persistence of other indicators of antibiotic resistance were concerning. Results indicate that composting guidelines intended for pathogen reduction do not necessarily provide a comprehensive barrier to ARGs or their mobility prior to land application and additional mitigation measures should be considered.
Management of sudden sensorineural hearing loss among primary care physicians in Canada: A survey study
Authors: Ng Benjamin , Crowson Matthew G. , Lin Vincent
Published: April 2021

Background

Sudden Sensorineural Hearing Loss (SSNHL) is a medical emergency requiring immediate attention as delayed treatment can lead to permanent and devastating consequences. Primary care physicians are likely the first to be presented with SSNHL and therefore have the crucial role of recognizing it and initiating timely and appropriate management. The aim of this study was to gain insight into the current knowledge and practice trends pertaining to the diagnosis and management of SSNHL among family physicians in Canada.

Methods

An 18-question survey targeting Canadian family physicians was marketed through two, physician-only discussion groups on the social media platform Facebook. Responses were collected between August 1st and December 22nd 2019 then aggregated and quantified.

Results

52 family physicians submitted responses. 94.2% ( n = 49) reported that in their practice, unilateral SSNHL warrants urgent referral to otolaryngology and 84.6% ( n = 44) reported that unilateral sudden-onset hearing loss warrants urgent referral for audiological testing. 73.1% of participants ( n = 38) reported that they would attempt to differentiate between conductive and sensorineural hearing loss if presented with unilateral, acute or sudden-onset hearing loss. 61.5% ( n = 32) would rely on tuning fork tests to inform management decisions, as compared to 94.2% ( n = 49) relying on case history and 88.5% ( n = 46) on otoscopy. 76.9% ( n = 40) would prescribe corticosteroids if presented with confirmed, unilateral SSNHL.

Conclusion

The majority of family physicians in the study would make appropriate referral and treatment decisions in the management of SSNHL, understanding it is a medical emergency. Tuning fork tests are under-utilized for informing management decisions compared to other means of differentiating conductive and sensorineural hearing loss. Further research is needed to understand why some family physicians do not prescribe corticosteroids for treatment of SSNHL, which may then identify any gaps in knowledge or inform improvements in clinical protocol.

Graphical Abstract
Neuropathological and behavioral characterization of aged Grn R493X progranulin-deficient frontotemporal dementia knockin mice
Authors: Frew Jonathan , Nygaard Haakon Berge
Published: April 2021

Frontotemporal lobar degeneration (FTLD) causes a spectrum of clinical presentations of frontotemporal dementia (FTD), including progressive changes in behavior, personality, executive function, and language. Up to 20% of familial FTLD cases are caused by progranulin (GRN) haploinsufficiency (FTD-GRN), with one of the most common causal variant being a nonsense mutation at arginine 493 (R493X). Recently, a genetic knockin FTD-GRNmouse model was generated bearing thisGrnR493Xmutation, at the analogous arginine in murineGrn. Aged, homozygousGrnR493Xmice (GrnR493X/R493X) have been shown to phenotypically replicate several neuropathological hallmarks previously demonstrated inGrnnull mice. We conducted a comprehensive neuropathological and behavioral assessment of 18 month oldGrnR493X/R493Xmice, observing a striking lysosomal dysfunction and thalamic neurodegeneration not previously described in this model, as well as a male-specific increase in generalized anxiety. These findings provide additional phenotypic markers of pathogenesis in agedGrnR493X/R493Xmice that will contribute to better defining mechanisms underlying FTD-GRN, and offer relevant outcome measures for preclinical efficacy testing of novel therapeutics that target nonsense mutations leading to this devastating disease.
Arsenic in the Pearl River Delta and its related waterbody, South China: occurrence and sources, a review
Authors: Luo Chen , Routh Joyanto , Luo Dinggui , Wei Lezhang , Liu Yu
Published: April 2021

The Pearl River Delta (PRD) is a densely populated special economic zone in South China where rapid development since the late 1990s coincided with an increase of many environmental problems in recent years. One of these concerns is the high concentration of arsenic (As; up to 300 μg/L in groundwater) that has been documented in the PRD. Likewise, in surface water and soils, As levels are comparatively higher than in other places in China. Arsenic is discharged from various geogenic sources and anthropogenic activities along the river courses before it drains into the Pearl River Estuary. In general, relatively low As concentrations in the river are due to the limited input from weathering of parent rocks. In contrast, where mining is an important industry, As levels in the surroundings are higher, exceeding the national and international standards for drinking water and soil. The presence of sulfide ores and mining operations, such as extraction of heavy metals and disposal of mine tailings, are most likely responsible for the sharp increase of As above background levels in several tributaries draining into the Pearl River. Besides, in the middle and lower reaches of the tributaries, other anthropogenic sources, e.g., industrial effluents and domestic sewage discharge play an important role in increasing As levels. Finally, rice cultivated in the contaminated areas accumulates As and poses a health risk to the local people in the watershed.
Validity of the French version of Catquest-9SF and use of an electronic notepad for entering patient-reported outcome measures
Authors: Katz Gregory , Rouquette Alexandra , Lignereux François , Mourgues Thierry , Weber Michel , Lundström Mats
Published: April 2021

Background

The Catquest-9SF questionnaire is a patient reported outcome measure that quantifies the visual benefits from cataract surgery. The purpose of this study was to translate and adapt the Catquest-9SF questionnaire for France, to assess its psychometric properties via Rasch analysis, and to assess its validity when completed using an electronic notepad.

Methods

The Catquest-9SF questionnaire was translated following the guidelines of the International Society for Pharmacoeconomics and Outcomes Research. Catquest-9SF and clinical data were collected from patients before and after routine cataract surgery. All questionnaire data were collected via an electronic notepad. Rasch analysis was performed to assess psychometric properties, and sensitivity to change was analysed for patients with complete paired pre- and post-operative questionnaires.

Results

A complete filled-in preoperative questionnaire was obtained for 848 patients. Rasch analysis showed good precision (person separation: 2.32, person reliability: 0.84), ordered category probability curves, no item misfit, and unidimensionality. The respondents were slightly more able than the level of item difficulty (targeting: −1.12 logits). Sensitivity was analysed on 211 paired questionnaires, and the postoperative questionnaires showed a clear ceiling effect. The effect size was 2.6. The use of an electronic notepad for completing the questionnaire worked out very well after some adjustments.

Conclusions

The French version of Catquest-9SF has good psychometric properties and is suitable for use in French-speaking patients. The use of the Catquest-9SF questionnaire in an electronic format showed good validity.
Endodontic remnants are found more than other radiopacities in proposed implant sites
Authors: Marzook Hamdy A. M. , Yousef Eman A. , Elgendy Abeer A.
Published: April 2021

Background

Foreign bodies may be a cause of concern in dental implant failure.

Purpose

The aim of the present study was to assess the occurrence and to evaluate the types of radiopacities in dental extraction sites using cone beam computed tomography (CBCT).

Materials and methods

The incidence, location, and types of radiopacities were evaluated in 180 CBCT scans.

Results

Different radiopaque structures could be noted in 84 scans. Foreign bodies and remaining roots were frequently seen. Most of the radiopacities were attributed to remaining endodontic filling in upper and lower jaws in 25 scans in different locations. Remaining roots could be detected in 20 scans. Focal and diffuse radiopaque bony lesions were observed in 16 scans. Tissue response in the form of radiolucency could be seen more with endodontic foreign bodies. Tissue reactions to radiopaque filling remnants were seen in 6.11% of cases.

Conclusions

Foreign body remnants, mostly of endodontic fillings, were frequently seen in CBCT in upper and lower jaws. Evidence of tissue reactions to extraction remnants could be found. Endodontic filling remnants could be seen more in the upper jaw. Thorough examination of implant site for the presence of endodontic foreign body remnants should be stressed. Debridement of the extraction socket should be done carefully in endodontically treated teeth.
Impact of a clinical pharmacist on ultrasound-guided venous thromboembolism screening in hospitalized COVID-19 patients: a pilot prospective study
Authors: Gillespie Laura , Khan Rashid Z. , Stillson John E. , Bunch Connor M. , Shariff Faisal Salim , Speybroeck Jacob , Grisoli Anne , Schmidt Meredith Wierman , Phyu Htay , Jablonski Jason , Wells Byars , Fulkerson Daniel H. , Oancea Lyndsay , Leiser Abraham , Walsh Mark
Published: April 2021

Background

The recognition, prevention and treatment of venous thromboembolism (VTE) remains a major challenge in the face of the recent COVID-19 pandemic which has been associated with significant cardiovascular, renal, respiratory and hematologic complications related to hypercoagulability. There has been little literature thus far on the utility of screening ultrasound and the role of the clinical pharmacist in treating these patients.

Methods

We present a prospective pilot program of thirty-one consecutive COVID-19 patients who were provided four extremity screening ultrasounds for VTE on admission. This was coordinated by a clinical pharmacist as part of a multidisciplinary approach. Quantitative and qualitative data were recorded with the goal of describing the utility of the clinical pharmacist in ultrasound screening. Data collected include demographics, information on clinical symptoms or signs at presentation, and laboratory and radiologic results during the hospitalization from each individual electronic medical record.

Results

Nine of the thirty-one patients presented with VTE. Of the nine patients, there were twenty-two total clotted vessels, all of which were asymptomatic. The clinical pharmacist, as the coordinator for a multidisciplinary COVID-19 associated coagulopathy management team, drafted a screening and treatment protocol for anticoagulation prophylaxis and therapy of VTE after ultrasound findings.

Conclusion

VTE screening of hospitalized COVID-19 patients reveals a significant number of asymptomatic VTEs and justifies diagnostic, prophylactic, and treatment measures coordinated by a clinical pharmacist.
Methodological Considerations for Furthering the Understanding of Constraints in Applied Sports
Authors: Browne Peter , Sweeting Alice J. , Woods Carl T. , Robertson Sam
Published: April 2021

Commonly classified as individual, task or environmental, constraints are boundaries which shape the emergence of functional movement solutions. In applied sport, an ongoing challenge is to improve the measurement, analysis and understanding of constraints to key stakeholders. Methodological considerations for furthering these pursuits should be centred around an interdisciplinary approach. This integration of methodology and knowledge from different disciplines also encourages the sharing of encompassing principles, concepts, methods and data to generate new solutions to existing problems. This narrative review discusses how a number of rapidly developing fields are positioned to help guide, support and progress an understanding of sport through constraints. It specifically focuses on examples from the fields of technology, analytics and perceptual science. It discusses how technology is generating large quantities of data which can improve our understanding of how constraints shape the movement solutions of performers in training and competition environments. Analytics can facilitate new insights from numerous and complex data through enhanced non-linear and multivariate analysis techniques. The role of the perceptual sciences is discussed with respect to generating outputs from analytics that are more interpretable for the end-user. Together, these three fields of technology, analytics and perceptual science may enable a more comprehensive understanding of constraints in sports performance.
Self-management advice, exercise and foot orthoses for plantar heel pain: the TREADON pilot and feasibility randomised trial
Authors: Chesterton Linda S. , Thomas Martin J. , Hendry Gordon , Chen Ying , Goddin David , Halliday Nicola , Lawton Sarah A. , Lewis Martyn , Mallen Christian D. , Menz Hylton B. , Foster Nadine E. , Roddy Edward
Published: April 2021

Background

Plantar heel pain (PHP) is common and impacts negatively on physical function and quality of life. Initial treatment usually comprises analgesia and self-management advice (SMA), with referral to a physiotherapist or podiatrist recommended only when symptoms persist. Systematic reviews highlight limitations of existing evidence for the effectiveness of exercises and orthoses. The objective of the TREADON pilot and feasibility trial was to inform the design of a future main trial to compare the clinical and cost-effectiveness of self-management advice (SMA), individualised exercises and foot orthoses for PHP.

Methods

This was a four-arm randomised feasibility and pilot trial with 12-week follow-up. Adults aged ≥ 18 years with PHP were identified from primary care by general practice consultation, retrospective general practice medical record review or a population survey. Participants were randomised to either (i) SMA, (ii) SMA plus individualised exercises (SMA-exercises), (iii) SMA plus prefabricated foot orthoses (SMA-orthoses) or (iv) SMA plus combined individualised exercises and prefabricated foot orthoses (SMA-combined). Feasibility outcomes were recruitment; retention; intervention adherence, credibility and satisfaction; performance of three potential primary outcome measures (pain numeric rating scale (NRS), Foot Function Index-pain subscale (FFI-pain), Manchester Foot Pain and Disability Index-pain subscale (MFPDI-pain)); and parameters for informing the main trial sample size calculation.

Results

Eighty-two participants were recruited. All three identification methods met the target number of participants. Retention at 12 weeks was 67%. All interventions were successfully delivered as per protocol. Adherence (range over 12 weeks 64–100%) and credibility (93%) were highest in the SMA-combined arm. Satisfaction with treatment was higher for the three clinician-supported interventions (SMA 29%, SMA-exercises 72%, SMA-orthoses 71%, SMA-combined 73%). Responsiveness (baseline to 12 weeks) was higher for FFI-pain (standardised response mean 0.96) and pain NRS (1.04) than MFPDI-pain (0.57). Conservative sample size parameter estimates for standard deviation were pain NRS 2.5, FFI-pain 25 and MFPDI-pain 4, and baseline-outcome correlations were 0.5–0.6, 0.4 and < 0.3, respectively.

Conclusions

We demonstrated the feasibility of conducting a future main randomised clinical trial comparing the clinical and cost-effectiveness of SMA, exercises and/or foot orthoses for PHP.

Trial registration number

ISRCTN 12160508. Prospectively registered 5th July 2016.
Natural bio-based monomers for biomedical applications: a review
Authors: Birajdar Mallinath S. , Joo Haejin , Koh Won-Gun , Park Hansoo
Published: April 2021

In recent years, synthetic and semi-synthetic polymer materials have been widely used in various applications. Especially concerning biomedical applications, their biocompatibility, biodegradability, and non-toxicity have increased the interest of researchers to discover and develop new products for the well-being of humanity. Among the synthetic and semi-synthetic materials, the use of natural bio-based monomeric materials presents a possible novel avenue for the development of new biocompatible, biodegradable, and non-toxic products. The purpose of this article is to review the information on the role of natural bio-based monomers in biomedical applications. Increased eco-friendliness, biocompatibility, biodegradability, non-toxicity, and intrinsic biological activity are some of the attributes which make itaconic, succinic, citric, hyaluronic, and glutamic acids suitable potential materials for biomedical applications. Herein, we summarize the most recent advances in the field over the past ten years and specifically highlight new and interesting discoveries in biomedical applications.

Graphical abstract

Natural origin acid-based bio-monomers for biomedical applications
The use of HEPES-buffer in the production of gallium-68 radiopharmaceuticals – time to reconsider strict pharmacopoeial limits?
Authors: le Roux Jannie , Kleynhans Janke , Rubow Sietske
Published: April 2021

HEPES (4-(2-hydroxyethyl) piperazine-1-ethanesulfonic acid) is a buffer that is used in the radiolabelling of gallium-68 compounds. The beneficial effects of HEPES on molar activity in bioconjugates have been well described. Current strict regulations on the HEPES content in radiopharmaceuticals limit its use when intended for parenteral administration.

This short communication summarizes data from the literature on the toxicity of HEPES in dogs after intravenous infusion and the subsequent use in humans. We also highlight the use of HEPES in an FDA labelled intravenous drug formulation. Regulatory institutions may consider this data to review current strict limits.