bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost-effectiveness analysis of dapagliflozin for the treatment of type 2 diabetes mellitus in Spain: results of the DECLARE-TIMI 58 study
Authors: Escobar Carlos , Morales Cristóbal , Capel Margarita , Simón Susana , Pérez-Alcántara Ferran , Pomares Elisenda
Published: February 2022

Background

The objective of this study was to carry out a cost-effectiveness analysis of dapagliflozin, as an add-on therapy to standard of care (SoC), for the treatment of type 2 diabetes mellitus (T2DM) in Spain, based on the results of the DECLARE-TIMI 58 trial.

Methods

A discrete event simulation model (Cardiff T2DM) based on the data observed in the DECLARE-TIMI 58 trial was adapted to the Spanish setting to estimate the costs and health outcomes of treatment with dapagliflozin in patients with T2DM who had or were at risk of atherosclerotic cardiovascular disease. Macrovascular events (hospitalization for heart failure, myocardial infarction, stroke, and unstable angina), end-stage renal disease and cardiovascular and non-cardiovascular mortality were modeled according to the survival equations of the DECLARE-TIMI 58 study. Microvascular events (blindness and ulcers) were estimated based on the risk equations of the UK Prospective Diabetes Study. The analysis was conducted from the Spanish National Health System perspective and the time horizon was 30 years. The results were evaluated in terms of cost per quality-adjusted life year (QALY) gained. Only direct health costs were included, and a 3% discount rate was applied to costs and health outcomes. Univariate and probabilistic sensitivity analyses (PSA) were made to assess the robustness of the results.

Results

In the main analysis, dapagliflozin was a dominant therapeutic option compared with placebo, with greater effectiveness (0.08 QALYs) and lower associated total costs per patient (€ -2,921). The univariate sensitivity analysis and the PSA confirmed the robustness of the results. The PSA showed the probability that dapagliflozin was a dominant alternative compared with placebo was 84.2% and that it was cost-effective of 92.1%, under a willingness-to-pay of € 20,000/QALY gained.

Conclusions

The analysis of data from the DECLARE-TIMI 58 trial shows that dapagliflozin would be a cost-effective option in Spain for the treatment of adult patients with T2DM, as an add-on therapy to SoC, compared with placebo.
Challenges, opportunities, and potential roles of the private primary care providers in tuberculosis and diabetes mellitus collaborative care and control: a qualitative study
Authors: Arini Merita , Sugiyo Dianita , Permana Iman
Published: February 2022

Introduction

The comorbidity of tuberculosis and diabetes mellitus (TB-DM) is a looming global co-epidemic problem. Despite the Indonesian Government’s ongoing effort to impose regulation for collaborative TB-DM management, the involvement of private primary care providers (PPCs) has not been considered before the COVID-19 pandemic. This study aimed to capture the PPCs’ existing practices and explore their challenges, opportunities, and potential roles in the collaborative TB-DM services and control.

Methods

A descriptive qualitative research design was used to collect data. Two Focus Group Discussions (FGDs) were conducted with 13 healthcare workers (HCWs) from different private clinics and eight private/solo general practitioners (GPs) from Yogyakarta City, Indonesia. We triangulated these data with data from FGDs of HCWs community health centers (CHCs) and in-depth interviews of three regional health regulators, five hospitals staff members, and a representative of national health insurance. The discussions were audio-recorded, transcribed verbatim, and subjected to thematic analysis.

Results

PPCs have not been initiated into the implementation of the collaborative TB-DM programme. The themes identified in this study were health system-related barriers, knowledge and perception of HCWs, lack of implementation of bi-directional screening, and needs of multisector role. The potential roles identified for PPCs include involvement in health promotion, bi-directional screening, patient referral, and data reporting according to the TB-DM programme indicators. However, more thorough improvement of PPCs’ capacity and logistic supplies are needed to provide comprehensive TB treatment.

Conclusion

Although PPCs’ involvement in implementing collaborative TB-DM services has yet to be considered, their potential role should not be neglected. Therefore, it is essential to increase their involvement by enhancing their capacity and improving the Public-Private Mix. PPCs’ engagement should be initiated and maintained to ensure the sustainability of the programme.
Terminology and descriptions of navigation and related practices for children with neurodisability and their families: a scoping review
Authors: Gardiner Emily , Wong Vivian , Lin Grace , Miller Anton R.
Published: February 2022

Background

Children with neurodisability (ND) represent a significant population with a demonstrated need for coordinated support. Patient navigation has a primary focus on: facilitating access to and connection amongst fragmented systems; as well as the provision of educational and emotional support. Given the distinct needs of children with ND and their families, programs built upon such core concepts could be of great benefit. The diversity of terminology encompassing navigation-related concepts and activities (e.g., care coordination, case management, family support), however, presents challenges to both practice and research. This scoping review examined the terminology and descriptions provided within published articles on navigation-type models for children with ND and their families.

Methods

The scoping review was conducted according to the Joanna Briggs Institute methodology. A preliminary search was completed on PubMed (NCBI), MEDLINE (Ovid) and CINAHL (EBSCO) to identify initial search terms, upon which a full search strategy was developed and executed in MEDLINE (Ovid) and CINAHL (EBSCO). After screening records according to our inclusion and exclusion criteria, a full-text review of relevant articles was conducted and data extracted using a researcher-developed tool. Under close supervision by the research team, study selection was primarily performed by one author.

Results

Of the 2597 papers identified, 33 were included in the final review. From the included papers, a total of 49 terms were extracted, 20 of which were unique. Across the diversity of terminology observed, articles provided detailed and rich descriptions characterized by four central domains, namely: (i) what navigation-related resources, supports and services aim to facilitate and (ii) provide; (iii) descriptions of their intended outcomes; as well as (iv) guiding principles.

Conclusions

This scoping review addresses a gap in our knowledge related to the specification of patient navigation and related supports as applied to the specific context of children with ND and their families. Given the particular needs of this population, we propose an empirically-informed integrative model that synthesizes the findings from this scoping review. We suggest that this framework can be used as a guide to the mindful characterization of how supports aiming to connect children and families to needed service are termed and described within future research and in practice.
Use and exchange of knowledge in the introduction of hospital-based home rehabilitation after a stroke: barriers and facilitators in change management
Authors: Karlsson Margareta , Nordström Birgitta
Published: February 2022

Background

The purpose of the study was to contribute to research and practice on how the use and exchange of knowledge can facilitate change in health care, specifically methods supporting managers. The study also aimed to investigate barriers related to governance principles that may affect organizational ability to improve quality of care. To achieve the purpose, the study followed a project of hospital-based home rehabilitation after a stroke at a hospital in Norrbotten County, Sweden.

Methods

Seven individual interviews were performed to obtain information from the project members and the managers involved in the project. A group interview with the team and their immediate manager were conducted after the project ended. A thematic analysis was performed to identify and present patterns that formed the results of the study.

Results

The study shows how knowledge was identified, gathered, used, and disseminated in the project. The analysis pointed out how knowledge played an important role from two perspectives: in evidence-based practice in rehabilitation work and for change management. Knowledge exchange and learning across organizational boundaries increased the pace, efficiency, and effectiveness, but collaboration on knowledge, in the sense of joint activities based on a common purpose, only took place within the rehabilitation work. Furthermore, there were indications that governance principles, such as the distribution of financial responsibility and the requirements for official recommendations, influenced the pace of change.

Conclusions

It was shown that the exchange of knowledge and collaboration can facilitate change in health care, but that communication needs to be planned and prioritised. Readiness for change was the basis for the success of the project and for ensuring commitment among those involved. There is also a need for the management to understand how governance principles may affect the efficiency of change work.
Molecular action of larvicidal flavonoids on ecdysteroidogenic glutathione S-transferase Noppera-bo in Aedes aegypti
Authors: Inaba Kazue , Ebihara Kana , Senda Miki , Yoshino Ryunosuke , Sakuma Chisako , Koiwai Kotaro , Takaya Daisuke , Watanabe Chiduru , Watanabe Akira , Kawashima Yusuke , Fukuzawa Kaori , Imamura Riyo , Kojima Hirotatsu , Okabe Takayoshi , Uemura Nozomi , Kasai Shinji , Kanuka Hirotaka , Nishimura Takashi , Watanabe Kodai , Inoue Hideshi , Fujikawa Yuuta , Honma Teruki , Hirokawa Takatsugu , Senda Toshiya , Niwa Ryusuke
Published: February 2022

Background

Mosquito control is a crucial global issue for protecting the human community from mosquito-borne diseases. There is an urgent need for the development of selective and safe reagents for mosquito control. Flavonoids, a group of chemical substances with variable phenolic structures, such as daidzein, have been suggested as potential mosquito larvicides with less risk to the environment. However, the mode of mosquito larvicidal action of flavonoids has not been elucidated.

Results

Here, we report that several flavonoids, including daidzein, inhibit the activity of glutathioneS-transferase Noppera-bo (Nobo), an enzyme used for the biosynthesis of the insect steroid hormone ecdysone, in the yellow fever mosquitoAedes aegypti. The crystal structure of the Nobo protein ofAe. aegypti(AeNobo) complexed with the flavonoids and its molecular dynamics simulation revealed that Glu113 forms a hydrogen bond with the flavonoid inhibitors. Consistent with this observation, substitution of Glu113 with Ala drastically reduced the inhibitory activity of the flavonoids against AeNobo. Among the identified flavonoid-type inhibitors, desmethylglycitein (4′,6,7-trihydroxyisoflavone) exhibited the highest inhibitory activity in vitro. Moreover, the inhibitory activities of the flavonoids correlated with the larvicidal activity, as desmethylglycitein suppressedAe. aegyptilarval development more efficiently than daidzein.

Conclusion

Our study demonstrates the mode of action of flavonoids on theAe. aegyptiNobo protein at the atomic, enzymatic, and organismal levels.
Restricted spirometry and cardiometabolic comorbidities: results from the international population based BOLD study
Authors: Kulbacka-Ortiz Katarzyna , Triest Filip J. J. , Franssen Frits M. E. , Wouters Emiel F. M. , Studnicka Michael , Vollmer William M. , Lamprecht Bernd , Burney Peter G. J. , Amaral Andre F. S. , Vanfleteren Lowie E. G. W.
Published: February 2022

Background

Whether restricted spirometry, i.e. low Forced Vital Capacity (FVC), predicts chronic cardiometabolic disease is not definitely known. In this international population-based study, we assessed the relationship between restricted spirometry and cardiometabolic comorbidities.

Methods

A total of 23,623 subjects (47.5% males, 19.0% current smokers, age: 55.1 ± 10.8 years) from five continents (33 sites in 29 countries) participating in the Burden of Obstructive Lung Disease (BOLD) study were included. Restricted spirometry was defined as post-bronchodilator FVC < 5th percentile of reference values. Self-reports of physician-diagnosed cardiovascular disease (CVD; heart disease or stroke), hypertension, and diabetes were obtained through questionnaires.

Results

Overall 31.7% of participants had restricted spirometry. However, prevalence of restricted spirometry varied approximately ten-fold, and was lowest (8.5%) in Vancouver (Canada) and highest in Sri Lanka (81.3%). Crude odds ratios for the association with restricted spirometry were 1.60 (95% CI 1.37–1.86) for CVD, 1.53 (95% CI 1.40–1.66) for hypertension, and 1.98 (95% CI 1.71–2.29) for diabetes. After adjustment for age, sex, education, Body Mass Index (BMI) and smoking, the odds ratios were 1.54 (95% CI 1.33–1.79) for CVD, 1.50 (95% CI 1.39–1.63) for hypertension, and 1.86 (95% CI 1.59–2.17) for diabetes.

Conclusion

In this population-based, international, multi-site study, restricted spirometry associates with cardiometabolic diseases. The magnitude of these associations appears unattenuated when cardiometabolic risk factors are taken into account.
The value of ROX index in predicting the outcome of high flow nasal cannula: a systematic review and meta-analysis
Authors: Junhai Zhen , Jing Yan , Beibei Cao , Li Li
Published: February 2022

Background

High flow nasal cannula (HFNC) therapy is widely employed in acute hypoxemic respiratory failure (AHRF) patients. However, the techniques for predicting HFNC outcome remain scarce.

Methods

PubMed, EMBASE, and Cochrane Library were searched until April 20, 2021. We included the studies that evaluated the potential predictive value of ROX (respiratory rate-oxygenation) index for HFNC outcome. This meta-analysis determined sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic score, diagnostic odds ratio (DOR), and pooled area under the summary receiver operating characteristic (SROC) curve.

Results

We assessed nine studies with 1933 patients, of which 745 patients experienced HFNC failure. This meta-analysis found that sensitivity, specificity, PLR, NLR, diagnostic score, and DOR of ROX index in predicting HFNC failure were 0.67 (95% CI 0.57–0.76), 0.72 (95% CI 0.65–0.78), 2.4 (95% CI 2.0–2.8), 0.46 (95% CI 0.37–0.58), 1.65(95% CI 1.37–1.93), and 5.0 (95% CI 4.0–7.0), respectively. In addition, SROC was 0.75 (95% CI 0.71–0.79). Besides, our subgroup analyses revealed that ROX index had higher sensitivity and specificity for predicting HFNC failure in COVID-19 patients, use the cut-off value > 5, and the acquisition time of other times after receiving HFNC had a greater sensitivity and specificity when compared to 6 h.

Conclusions

This study demonstrated that ROX index could function as a novel potential marker to identify patients with a higher risk of HFNC failure. However, the prediction efficiency was moderate, and additional research is required to determine the optimal cut-off value and propel acquisition time of ROX index in the future.

PROSPERO registration number: CRD42021240607.
Whole blood fatty acid profile of young subjects and adherence to the Mediterranean diet: an observational cohort study
Authors: Syrén Marie-Louise , Turolo Stefano , de Marco Erika Adalgisa , De Cosmi Valentina , Risé Patrizia , Marangoni Franca , Minoli Dario Guido , Manzoni Gianantonio , Agostoni Carlo
Published: February 2022

Background

Relatively little is known about the physiological whole blood fatty acid composition in young people. Likewise, few studies have addressed the question of correlations between Mediterranean diet (MedDiet) adherence and blood fatty acids in childhood.

Methods

The fatty acid profile in whole blood from subjects, 46 days-19 years old (n = 152), without acute, chronic, or inflammatory diseases was analysed by gas chromatography. Dietary data was extracted from a 24-h recall in a subgroup of subjects (n = 60) into a modified Diet Quality Index for Children (KIDMED) questionnaire to evaluate MedDiet adherence. The cohort was divided into three age groups: < 2, 2- < 10, and 10–19 years. Kruskal-Wallis test and Bonferroni post hoc test were used to check for age group fatty acid differences. For correlations, Spearman’s correlation coefficient and partial Spearman’s correlation coefficient were used.

Results

Linoleic acid, EPA, DHA, palmitic acid, and total saturated fatty acids were stable over age groups. Dihomo-gamma-linolenic acid (DGLA), arachidonic acid (AA), total polyunsaturated FAs (PUFA), and total omega-6 PUFA increased from age group < 2 years; alpha-linolenic acid, total omega-3 PUFA, oleic acid, and total monounsaturated FAs decreased. Adherence to the MedDiet was at low-medium level in 91.7% of the subjects. In the age group 2- < 10 yrs., the degree of adherence correlated positively with total MUFA and PUFA balance, negatively with total PUFA, total n6-PUFA, AA/DHA, AA/EPA, and n6/n3. Age did not influence the correlations as to PUFA balance and AA/EPA.

Conclusions

Increased FA proportions with age were seen in the n6-series of PUFA. The n3-FA species decreased or were stable. The vast majority of the subjects with dietary data, 92%, obtained a KIDMED score indicative of low-medium adherence to the MedDiet. The score correlated negatively with various n6-species, i.e. the MedDiet suppressed circulating n6-PUFA. Whole blood may be used to investigate FAs and MedDiet adherence correlations which may be applied in the study of health issues in childhood.
Chronic exposure to polystyrene microplastics induced male reproductive toxicity and decreased testosterone levels via the LH-mediated LHR/cAMP/PKA/StAR pathway
Authors: Jin Haibo , Yan Minghao , Pan Chun , Liu Zhenyu , Sha Xiaoxuan , Jiang Chengyue , Li Luxi , Pan Mengge , Li Dongmei , Han Xiaodong , Ding Jie
Published: February 2022

Background

Microplastics (MPs), which are smaller in size and difficult to degrade, can be easily ingested by marine life and enter mammals through the food chain. Our previous study demonstrated that following acute exposure to MPs, the serum testosterone content reduced and sperm quality declined, resulting in male reproductive dysfunction in mice. However, the toxic effect of long-term exposure to MPs at environmental exposure levels on the reproductive system of mammals remains unclear.

Results

In vivo, mice were given drinking water containing 100 μg/L and 1000 μg/L polystyrene MPs (PS-MPs) with particle sizes of 0.5 μm, 4 μm, and 10 μm for 180 consecutive days. We observed alterations in testicular morphology and reductions in testosterone, LH and FSH contents in serum. In addition, the viability of sperm was declined and the rate of sperm abnormality was increased following exposure to PS-MPs. The expression of steroidogenic enzymes and StAR was downregulated in testis tissues. In vitro, we used primary Leydig cells to explore the underlying mechanism of the decrease in testosterone induced by PS-MPs. First, we discovered that PS-MPs attached to and became internalized by Leydig cells. And then we found that the contents of testosterone in the supernatant declined. Meanwhile, LHR, steroidogenic enzymes and StAR were downregulated with concentration-dependent on PS-MPs. We also confirmed that PS-MPs decreased StAR expression by inhibiting activation of the AC/cAMP/PKA pathway. Moreover, the overexpression of LHR alleviated the reduction in StAR and steroidogenic enzymes levels, and finally alleviated the reduction in testosterone induced by PS-MPs.

Conclusions

PS-MPs exposure resulted in alterations in testicular histology, abnormal spermatogenesis, and interference of serum hormone secretion in mice. PS-MPs induced a reduction in testosterone level through downregulation of the LH-mediated LHR/cAMP/PKA/StAR pathway. In summary, our study showed that chronic exposure to PS-MPs resulted in toxicity of male reproduction under environmental exposure levels, and these potential risks may ring alarm bells of public health.

Graphical abstract
Looking good but tweeting bad? The social perception of orthodontic-related posts on Twitter and Instagram
Authors: Graf Isabelle , Kruse Teresa , Braumann Bert , Hoefer Karolin , Ehlebracht Daniel
Published: February 2022

Background

Social media plays a major role in the daily life of adolescents and has become highly interesting for healthcare research as well. The aim of this study was to explore the social perception of orthodontic-related posts on Twitter and Instagram by young adults.

Methods

401 orthodontic-related posts were collected during a 30-day period and categorized with regard to specific characteristics – their content and the social networking site (SNS) being used as well as the presence or absence of a selfie. In order to investigate the social perception of these posts, 42 young adults rated the emotional states of the SNS users using the Self-Assessment Manikin (SAM)-Tool. A total of 4211 poster-rater observations pertaining to the three SAMs dimensions pleasure, arousal and dominance were analyzed by using linear and multinomial logistic regression analyses.

Results

The investigated characteristics of the collected posts had significant effects on the perceived emotional state of the SNS users. Besides significant SNS-associated differences, there were also effects that were independent of the SNS being used: Receiving orthodontic appliances was more often associated with rather negative emotions (p < 0.001), while users who posted about the removal of such braces were more often perceived as joyful (p < 0.001). Interestingly, users whose posts contained selfies with visible braces were perceived as significantly more positive and stronger in comparison to users who did not post a picture of themselves (p < 0.05).

Conclusion

This research gives insights into the social perception of orthodontic-related posts on SNS. While users’ emotional states were perceived highly differential on both SNS, orthodontic-related content also revealed significant effects on social perception. Because selfies with visible braces were associated with positive feelings by young adults, a modern and SNS-related way of coping with a temporary supposed impairment like fixed orthodontic appliances might have been revealed through this research.
Patient safety assurance in the age of defensive medicine: a review
Authors: Shenoy Amrita , Shenoy Gopinath N. , Shenoy Gayatri G.
Published: February 2022

The definition of defensive medicine has evolved over time given various permutations and combinations. The underlying meaning, however, has persisted in its relevance towards two classifications, positive and negative defensive medicine. Positive defensive medicine is specific to overutilization, excessive testing, over-diagnosing, and overtreatment. Negative defensive medicine, on the contrary, is specific to avoiding, referring, or transferring high risk patients. Given the above bifurcation, the present research analyzes defensive medicine in the landscape of medical errors. In its specificity to medical errors, we consider the cognitive taxonomies of medical errors contextual to execution and evaluation slips and mistakes. We, thereafter, illustrate how the above taxonomy interclasps with five classifications of medical errors. These classifications are those that involve medical errors of operative, drug-related, diagnostic, procedure-related, and other types. This analytical review illustrates the nodular frameworks of defensive medicine. As furtherance of our analysis, this review deciphers the above nodular interconnectedness to these error taxonomies in a cascading stepwise sequential manner. This paper was designed to elaborate and to stress repeatedly that practicing defensive medicine entails onerous implications to physicians, administrators, the healthcare system, and to patients. Practicing defensive medicine, thereby, is far from adhering to those optimal healthcare practices that support quality of care metrics/milestones, and patient safety measures. As an independent standalone concept, defensive medicine is observed to align with the taxonomies of medical errors based on this paper’s diagrammatic and analytical inference.
Detoxification of a pyrolytic aqueous condensate from wheat straw for utilization as substrate in Aspergillus oryzae DSM 1863 cultivations
Authors: Kubisch Christin , Ochsenreither Katrin
Published: February 2022

Background

The pyrolytic aqueous condensate (PAC) formed during the fast pyrolysis of wheat straw contains a variety of organic carbons and might therefore potentially serve as an inexpensive substrate for microbial growth. One of its main components is acetic acid, which was recently shown to be a suitable carbon source for the filamentous fungusAspergillus oryzae. However, the condensate also contains numerous toxic compounds that inhibit fungal growth and result in a tolerance of only about 1%. Therefore, to enable the use of the PAC as sole substrate forA. oryzaecultivations, a pretreatment seems to be necessary.

Results

Various conditions for treatments with activated carbon, overliming, rotary evaporation and laccase were evaluated regarding fungal growth and the content of inhibitory model substances. Whereas the first three methods considerably increased the fungal tolerance to up to 1.625%, 12.5% and 30%, respectively, the enzymatic treatment did not result in any improvement. The optimum carbon load for the treatment with activated carbon was identified to be 10% (w/v) and overliming should ideally be performed at 100 °C and an initial pH of 12. The best detoxification results were achieved with rotary evaporation at 200 mbar as a complete removal of guaiacol and a strong reduction in the concentration of acetol, furfural, 2-cyclopenten-1-one and phenol by 84.9%, 95.4%, 97.7% and 86.2%, respectively, were observed.Subsequently, all possible combinations of the effective single methods were performed and rotary evaporation followed by overliming and activated carbon treatment proved to be most efficient as it enabled growth in 100% PAC shake-flask cultures and resulted in a maximum cell dry weight of 5.21 ± 0.46 g/L.

Conclusion

This study provides a comprehensive insight into the detoxification efficiency of a variety of treatment methods at multiple conditions. It was revealed that with a suitable combination of these methods, PAC toxicity can be reduced to such an extent that growth on pure condensate is possible. This can be considered as a first important step towards a microbial valorization of the pyrolytic side-stream withA. oryzae.
Gender-affirming hormone therapy induces specific DNA methylation changes in blood
Authors: Shepherd Rebecca , Bretherton Ingrid , Pang Ken , Mansell Toby , Czajko Anna , Kim Bowon , Vlahos Amanda , Zajac Jeffrey D. , Saffery Richard , Cheung Ada , Novakovic Boris
Published: February 2022

Background

DNA methylation is an epigenetic mark that is influenced by underlying genetic profile, environment, and ageing. In addition to X-linked DNA methylation, sex-specific methylation patterns are widespread across autosomal chromosomes and can be present from birth or arise over time. In individuals where gender identity and sex assigned at birth are markedly incongruent, as in the case of transgender people, feminization or masculinization may be sought through gender-affirming hormone therapy (GAHT). GAHT is a cornerstone of transgender care, yet no studies to date have investigated its effect on genome-wide methylation. We profiled genome-wide DNA methylation in blood of transgender women (n = 13) and transgender men (n = 13) before and during GAHT (6 months and 12 months into feminizing or masculinizing hormone therapy).

Results

We identified several thousand differentially methylated CpG sites (DMPs) (Δβ ≥ 0.02, unadjusted p value < 0.05) and several differentially methylated regions (DMRs) in both people undergoing feminizing and masculinizing GAHT, the vast majority of which were progressive changes over time. X chromosome and sex-specific autosomal DNA methylation patterns established in early development are largely refractory to change in association with GAHT, with only 3% affected (Δβ ≥ 0.02, unadjusted p value < 0.05). The small number of sex-specific DMPs that were affected by GAHT were those that become sex-specific during the lifetime, known as sex-and-age DMPs, including DMRs in PRR4 and VMP1 genes. The GAHT-induced changes at these sex-associated probes consistently demonstrated a shift towards the methylation signature of the GAHT-naïve opposite sex, and we observed enrichment of previously reported adolescence-associated methylation changes.

Conclusion

We provide evidence for GAHT inducing a unique blood methylation signature in transgender people. This study advances our understanding of the complex interplay between sex hormones, sex chromosomes, and DNA methylation in the context of immunity. We highlight the need to broaden the field of ‘sex-specific’ immunity beyond cisgender males and cisgender females, as transgender people on GAHT exhibit a unique molecular profile.
Gene-driving management practices in the dromedary husbandry systems under arid climatic conditions in Algeria
Authors: Harek Derradji , El Mokhefi M’hamed , Ikhlef Hacene , Bouhadad Rachid , Sahel Hocine , Djellout Noreddine , Arbouche Fodil
Published: February 2022

Changes in socio-economics, demography, politics, and climate in arid and semi-arid regions in recent decades have led to profound transformations in livestock practices, particularly in the management of local animal resources. The dromedaryCamelus dromedariushas always played an important role in human life history in Algeria; it provides a substantial contribution in protein production such as milk and meat, and it is used as means of transportation by local populations. It is well-adapted to arid environments and has a satisfactory potential for food production that enables economic security to locals, especially in the context of climate change. This paper adds supplementary yet valuable information to the current knowledge on camel genetic diversity related to different management practices. Genetic and phenotypic variations and the underlying management practices are studied to understand differences between breeds, for a better resource management. The survey of 277 camel breeders across the Algerian desert revealed a genetic diversity in terms of breeds driven by four pastoral practices. According to coat colour and morphological aspect, the camel population “Tergui” corresponds to three breeds, namely Mahri with 53.13% of the population, Marouki (43.22%), and the single-ecotype Azerghaf (3.65%). Mahri is a mixture of Amelal and Abahou ecotypes that are being outnumbered by Marouki’s ecotypes (Atelagh and Alemlagh). This biodiversity is under real threat because of the behaviour of pastoral societies that pushes breeders to turn to breeds with a high market value. Several useful conservation methods, including the use of modern farming systems, could be positively used and/or improved, in order to protect the genetic variety and help breeders realize a good living out of rearing camels.
Indwelling time of peripherally inserted central catheters and incidence of bloodstream infections in haematology patients: a cohort study
Authors: Caris M. G. , de Jonge N. A. , Punt H. J. , Salet D. M. , de Jong V. M. T. , Lissenberg-Witte B. I. , Zweegman S. , Vandenbroucke-Grauls C. M. J. E. , van Agtmael M. A. , Janssen J. J. W. M.
Published: February 2022

Background

We aimed to assess whether longer indwelling time of peripherally inserted central catheters (PICC) increases risk of central line associated bloodstream infections (CLABSI) in haematology patients.

Methods

Multicentre retrospective cohort study among haematology patients receiving PICCs between 2013 and 2015. Occurrence of CLABSI based on CDC definitions was assessed. We calculated incidence rates, determined risk factors for CLABSI and used Poisson regression models to assess the risk of developing CLABSI as a function of PICC dwell time. We compared diagnoses and treatment characteristics between 2013–2015 and 2015–2020.

Results

455 PICCs placed in 370 patients were included, comprising 19,063 catheter days. Median indwelling time was 26 days (range 0–385) and CLABSI incidence was 4.0 per 1000 catheter days, with a median time to CLABSI of 33 days (range 18–158). Aplastic anaemia (AA) was associated with an increased risk of CLABSI; patients undergoing autologous stem cell transplantation (SCT) were less likely to develop CLABSI. In the unadjusted analysis, PICCs with an indwelling time of 15–28 days, 29–42 days, 43–56 days and > 56 days each had an increased CLABSI incidence rate ratio of 2.4 (1.2–4.8), 2.2 (0.95–5.0), 3.4 (1.6–7.5) and 1.7 (0.9–3.5), respectively, compared to PICCs in place for < 15 days. However, after adjusting for AA and SCT, there was no significant difference in incidence rates between dwell times (p 0.067).

Conclusions

Our study shows that risk of CLABSI does not appear to increase with longer PICC indwelling time. Routine replacement of PICCs therefore is unlikely to prevent CLABSI in this population.
The Association of Traumatic Brain Injury, post-traumatic stress disorder, and criminal recidivism
Authors: Lattimore Pamela K. , Richardson Nicholas J. , Ferguson Pamela L. , Pickelsimer E. Elisabeth
Published: February 2022

Background

The purpose of the study was to assess the prevalence of traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) and to determine whether TBI or PTSD is associated with an increase in general or violent criminal recidivism among a representative sample of released prisoners.

In-person interviews were conducted with a stratified random sample of individuals incarcerated with the South Carolina Department of Corrections approximately 90 days prior to the prisoners’ releases. In addition to a variety of items and scales, respondents were screened for TBI and were asked whether they had received a current diagnosis of PTSD. Data were merged with arrest data that provided measures of past criminal involvement and indicators of post-release recidivism (arrest). Arrests were coded as “general” for any arrest charge and “violent” for any violent offense charge.

Results

Survival analyses indicate that neither TBI nor PTSD predicts time to general recidivism. PTSD (p < 0.01) and age at first arrest (p < 0.01) are significant predictors for violent recidivism and TBI is non-significant at p = 0.09. Results from the negative binomial models indicate that TBI (p < 0.05) and PTSD (p < 0.05) are significantly associated with more post-release violent arrests, but not general arrests.

Conclusions

TBI and PTSD were found to predict violent offending but not general criminal behavior. These findings demonstrate the need for prison officials to identify individuals with a history of TBI and PTSD and to develop appropriate interventions that could be provided during incarceration to reduce the post-release likelihood of violence.
Phytochemical screening, antimycobacterial activity and acute toxicity of crude extracts of selected medicinal plant species used locally in the treatment of tuberculosis in Uganda
Authors: Oloya Benson , Namukobe Jane , Ssengooba Willy , Afayoa Mathias , Byamukama Robert
Published: February 2022

Background

Tuberculosis (TB) is one of the leading causes of death globally, and the rise in drug-resistant forms of TB has become a significant threat. Subsequently, it is crucial to explore new, effective and safe anti-TB agents. This study aimed at conducting phytochemical screening, antimycobacterial activity, and acute toxicity of the selected plant species’ crude extracts to assess their toxicological potentials and efficacies against TB.

Methods

The aqueous and methanol/dichloromethane (DCM) (1:1) extracts of each selected plant species were subjected to phytochemical screening and antimycobacterial activity using microplate alamar blue assay. For acute toxicity, a single dose (2000 mg/kg) of the aqueous extracts was orally administered to each animal following the Organization for Economic Cooperation and Development (OECD) guidelines No. 425 and then observed for 14 days. The animals were closely observed on the general behavior and clinical signs of toxicity, and body weights were recorded. After the termination of the experiment, hematological, biochemical, and histopathological analyses were performed.

Results

The extracts contained alkaloids, flavonoids, tannins, saponins, steroids, terpenoids, resins, cardiac glycosides, phenolic compounds, and coumarins. Aqueous extracts showed moderate to weak activity against the susceptible (H37Rv) M. tuberculosis strain and weak activity against the MDR-TB strain with Minimum Inhibitory Concentrations (MIC μg/mL) ranging from 293.0–2344.0 and 1172.0–4688.0, respectively. Methanol/DCM extracts showed significant to moderate activity against the susceptible TB strain and moderate to weak activity against the MDR-TB strain with MIC (μg/mL) ranging from 98.0–586.0 and 293.0–781.0, respectively. One mortality was recorded from the A. coriaria treated group following the acute toxicity tests, but the LD50 of all the extracts was estimated to be above 2000 mg/kg. Histopathological analyses did not show any significant lesions in the examined organs except those from the A. coriaria treated group.

Conclusion

Phytochemical screening of the extracts revealed the presence of alkaloids, tannins, saponins, flavonoids, steroids, terpenoids, resins, cardiac glycosides, phenolic compounds, and coumarins. All the methanol/DCM extracts of the plant species studied have promising antimycobacterial activity. The selected plant extracts studied exhibited low acute toxicity levels except for A. coriaria and could be safe for formulations into herbal products.
Determination of virulence and genetic variability of three Spodoptera littoralis nucleopolyhedrovirus isolates from Egypt
Authors: Yasser Norhan , Sayed Samy , Ghanem Nashwa , Thabit Amal , Abdelal Aziza , Elmenofy Wael , Osman Engy
Published: February 2022

Background

The genetic diversity is naturally occurring in baculovirus population, which may affect the potency of the bio-agent. The Spodoptera littoralis nucleopolyhedrovirus is a promising bio-control agent that can be used to control the cotton leafworm, S. littoralis in Egypt. This study described the virulence and genetic variability of 3 S. littoralis nucleopolyhedrovirus isolates named Cab2, P2 and P3 previously recovered from diseased S. littoralis larvae of cabbage, pepper and eggplant cultivation fields.

Results

The viral genomic DNA restriction analysis using PstI and ScaI endonucleases showed identical Pst1 restriction pattern of 10 fragments in both Cab2 and P3 isolates, while there are 7 extra fragments present in P2 isolate of about 25, 19.8, 15, 14, 11, 9 and 6.7 (kbp). On the other hand, the restriction pattern using ScaI revealed 10 common fragments in all three isolates, in addition to an extra marker fragment of about 25 kb in P3 isolate absent in both P2 and Cab3 isolates. The phylogenetic analysis of the partial nucleotide sequence of the polyhedrin gene confirmed an extensive degree of co-linearity among the genomes of the 3 tested isolates, with pairwise sequence identities of 97.04% with S. littoralis nucleopolyhedrovirus isolate A26-5 (Acc. No. AY706717). The median lethal concentration (LC50) value revealed that Cab2 had the best virulence toward the first instar of S. littoralis larvae with LC50 value of 1.59 × 104 Obs/ml compared to the virulence recorded by P3 and P2 which were 1.23 × 106 and 2.7 × 104 OBs/ml, respectively. The median survival time (LT50) value of Cab2 isolate was the highest speed of treated larval mortality with 120 hpi compared to P2 and P3, which recorded 132 hpi for both isolates.

Conclusions

Although all three S. littoralis nucleopolyhedrovirus isolates showed considered genotypic variation and insecticidal activity against S. littoralis larvae, the variant Cab2 showed the highest virulence and speed mortality against the first instar larvae of S. littoralis. The new variant proved to possess promising insecticidal properties for the development of virus-based biopesticide for the control of S. littoralis population in Egypt.
SOP: thrombolysis in ischemic stroke under oral anticoagulation therapy
Authors: Kermer Pawel , Schellinger Peter D. , Ringleb Peter A. , Köhrmann Martin
Published: February 2022

Introduction

Based on demographical trends and the expected worldwide increase in the number of individuals with atrial fibrillation, the rate of patients who are on oral anticoagulation therapy for secondary prevention of stroke rises continuously. Despite correct drug intake and good adherence to the respective medication, recurrent ischemic stroke still occurs in ~ 3% of patients. The question how to deal with such patients with regard to intravenous thrombolysis with rt-PA within the 4.5 h time window is of great relevance for daily clinical routine. However, international guidelines can be considered heterogenous or do even lack recommendations on this topic especially in light of available reversal agents. Therefore, we provide this SOP.

Comments

Beyond the identification of acute stroke patients on oral anticoagulation therapy, the type of medication, time since last intake, renal function and laboratory exams as well as the availability of reversal agents have to be considered before rt-PA application and potential endovascular therapy. Treatment on a Stroke Unit or Neuro-ICU is certainly recommended in any of those patients.

Conclusions

This standardized operating procedure was designed to guide stroke physicians through questions on eligibility for rt-PA treatment in patients with acute ischemic stroke who are on approved oral anticoagulation therapy thereby increasing the number of patients benefitting from thrombolysis and minimizing door-to-needle times.
Association between vitamin D and ear disease: a meta-analysis and systematic review
Authors: Salamah Marzouqi , Alghamdi Abdullah , Mania Khalid , Almahyawi Rawan , Alsubaie Haya , Alfarghal Mohamad , Algarni Mohammed
Published: February 2022

Background

Vitamin D deficiency is a suggested cause and risk factor for various ear diseases. This review assessed the role of vitamin D in ear diseases such as otitis media (OM); this study aimed to assess potential relationships between serum vitamin D level and OM risk; and determined the usefulness of vitamin D supplementation for ear disease prevention and treatment.

Material and methods

This systematic review searched the PubMed, EMBASE, Google Scholar, Web of Science, and the Cochrane Database for studies on vitamin D deficiency as a risk factor for ear diseases. A total of 55 articles were screened based on their titles. The abstracts were then reviewed to identify the 11 articles analyzed in the present study.

Results

Statistical heterogeneity was observed among the 11 studies for subgroup analysis of plasma vitamin D level according to disease type (acute otitis media [AOM], P < 0.00001; chronic otitis media [COM], P = 0.00001) and age (≤ 5 years, P < 0.00001; > 5 years, P < 0.00001). Heterogeneity was also observed in the frequency of participants with sufficient plasma vitamin D levels according to disease type (AOM, P < 0.00001; COM, P = 0.00001) and age (≤ 5 years, P < 0.00001; > 5 years, P = 0.003; I2 = 70%: substantial heterogeneity).

Conclusion

Vitamin D deficiency is common in otolaryngology patients, for which supplementation showed promising results. Vitamin D deficiency was associated with the etiopathology of ear diseases in adults and children. We recommend empirical supplementation of vitamin D in otolaryngology patients and further studies investigating this supplementation.
Challenges in Access to New Therapeutic Agents: Marginalized Patients With Cancer in Pakistan and the Need for New Guidelines
Authors: Aziz Zeba , Naseer Hafsa , Altaf Anjum
Published: February 2022

PURPOSE

Cancer care disparities persist among the medically underserved patients with cancer in Pakistan. To determine the access that marginalized patients with cancer have to chemotherapy and newer targeted agents in Pakistan approved by essential medicine list 2017, the barriers that patients face in getting such access, the implications of the barriers for the effectiveness of treatment, and ways of overcoming those barriers, with particular attention to breast cancer (BC), diffuse large B-cell lymphoma (DLBCL), and chronic myeloid leukemia (CML), need to be addressed.

METHODS

A cross-sectional survey of 28 private and public cancer centers targeting more than 50% of patients with cancer for year 2018 was conducted with focus on access to optimal therapy for BC, DLBCL, and CML. To assess the impact of socioeconomic status on the effectiveness of treatment, patients were categorized into three main income groups—low, middle, and high according to gross domestic product per capita on the basis of which some patients were categorized as economically marginalized. Differences in quality of care in public and private sector hospitals were assessed by optimal delivery and completion of chemotherapy on the basis of international guidelines. Access to optimal dose and timings of targeted therapies were determined.

RESULTS

In our marginalized patients, 30%-40% received optimal basic chemotherapy for BC and DLBCL. Less than 10% of patients with human epidermal growth factor receptor 2–positive BC completed 17 cycles of trastuzumab within 12 months. For DLBCL, hardly any patients received concurrent rituximab with chemotherapy for six cycles. Dose delays, modifications, and abandonment of treatment occurred in approximately 50% of the marginalized patients. In patients with CML, the compliance to imatinib/nilotinib was 85%.

CONCLUSION

Significant barriers exist in providing optimal basic and targeted therapies to our indigent patients despite government funding and availability of access programs.