bluuebunny/crossref_metadata_2025 huggingface dataset:
The heritability of body composition
Authors: Brener Avivit , Waksman Yarden , Rosenfeld Talya , Levy Sigal , Peleg Itai , Raviv Adi , Interator Hagar , Lebenthal Yael
Published: May 2021

Background

Physical growth during childhood and adolescence is influenced by both genetic and environmental factors. Heritability, the proportion of phenotypic variance explained by genetic factors, has been demonstrated for stature and weight status. The aim of this study was to explore the heritability of body composition.

Methods

A real-life, observational study of the children and adolescents referred to the Endocrine Unit in a tertiary medical center. In January 2018, body composition by means of bioimpedance analysis (BIA) was implemented as part of the standard intake assessment of subjects referred for endocrine consultation. The clinic BIA database was searched for subjects with the term “observation of growth” as the sole reason for referral. BIA of 114 triads of healthy subjects aged 5–18 years and their parents were analyzed. The BIA report included the following data: fat mass, fat percentage, truncal fat percentage and muscle mass. Calculated variables included: appendicular skeletal muscle mass (ASMM = the sum of muscle mass of four limbs), muscle-to-fat ratio [MFR = ASMM (kg)/fat mass (kg)] and sarcopenic index [(SI = ASMM(kg)/height (meter)²]. Data collection from medical files included pubertal stage and home address for socioeconomic position grading.

Results

There were sex differences in body composition parameters in both the prepubertal and pubertal subjects. The boys among the prepubertal subjects had a lower fat percentage on average than girls (p = 0.020). Among the adolescents, boys on average had lower fat percentage (p = 0.011), higher sarcopenic index (p = 0.021), and higher muscle-to-fat ratio (p < 0.001), than adolescent girls. Correlation analyses between body composition parameters of all participants revealed significant correlations in the sarcopenic index of prepubertal children and their parents (boys-fathers: r = 0.380, p = 0.050; boys-mothers: r = 0.435, p = 0.026; girls-fathers: r = 0.462, p = 0.012; girls-mothers: r = 0.365, p = 0.050) and adiposity indices (fat percentage, truncal fat percentage and muscle-to-fat ratio) of prepubertal boys and their mothers (r = 0.438, p = 0.025; r = 0.420, p = 0.033, and r = 0.478, p = 0.014, respectively). There were no associations between body composition parameters of adolescents and their parents. Socioeconomic position adversely affected fat percentage in adolescent girls and mothers.

Conclusions

Heritable body composition traits were demonstrated in childhood but not in adolescence, suggesting that environmental influence has a more telling effect during teenage years.
Patient satisfaction and survival of maxillary overdentures supported by four or six splinted implants: a systematic review with meta-analysis
Authors: Di Francesco Fabrizio , De Marco Gennaro , Capcha Estefani B. , Lanza Alessandro , Cristache Corina M. , Vernal Rolando , Cafferata Emilio A.
Published: May 2021

Background

Implant-supported overdentures offer enhanced mechanical properties, which lead to better patient satisfaction and survival rates than conventional dentures. However, it is unclear whether these satisfaction levels and survival rates depend on the number of implants supporting the overdenture. Therefore, this systematic review aimed to compare maxillary overdentures supported by four or six splinted implants in terms of patient satisfaction, implant survival, overdenture survival, and prosthodontic complications.

Methods

Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (PubMed), and EMBASE databases were systematically searched and complemented by hand searching from 2000 to 2019, employing a combination of specific keywords. Studies comparing the use of four versus six implants for supporting overdentures with at least one-year of follow-up after prosthesis installation and including ten fully edentulous patients were included. The risk of bias (RoB) was analyzed with Cochrane’s RoB 2 and Newcastle–Ottawa tools. Implants and prosthesis survival rates were analyzed by random-effects meta-analysis and expressed as risk ratios or risk differences, respectively, and by the non-parametric unpaired Fisher’s test.

Results

A total of 15 from 1865 articles were included, and reported follow-up times after implant placement ranged from 1 to 10 years. Irrespective of the number of implants used, high scores were reported by all studies investigating patient satisfaction. Meta-analysis and non-parametric Fisher’s test showed no statistical differences regarding the survival rate of implants (P = 0.34, P = 0.3) or overdentures (P = 0.74, P = 0.9) when using 4 versus 6 splinted implants to support overdentures, and no significant differences regarding prosthodontic complications were found between groups. Randomized studies presented high RoB and non-randomized studies presented acceptable quality.

Conclusions

Within the limits of this systematic review, we can conclude that the bar-supported overdenture on four implants is not inferior to the overdenture supported by six implants for rehabilitating the edentulous maxilla, in terms of patient satisfaction, survival rates of implants and overdentures, and prosthodontic complications.
Subgingival microbiome of deep and shallow periodontal sites in patients with rheumatoid arthritis: a pilot study
Authors: Lehenaff Ryanne , Tamashiro Ryan , Nascimento Marcelle M. , Lee Kyulim , Jenkins Renita , Whitlock Joan , Li Eric C. , Sidhu Gurjit , Anderson Susanne , Progulske-Fox Ann , Bubb Michael R. , Chan Edward K. L. , Wang Gary P.
Published: May 2021

Background

Subgingival microbiome in disease-associated subgingival sites is known to be dysbiotic and significantly altered. In patients with rheumatoid arthritis (RA), the extent of dysbiosis in disease- and health-associated subgingival sites is not clear.

Methods

8 RA and 10 non-RA subjects were recruited for this pilot study. All subjects received full oral examination and underwent collection of subgingival plaque samples from both shallow (periodontal health-associated, probing depth ≤ 3mm) and deep subgingival sites (periodontal disease-associated, probing depth ≥ 4 mm). RA subjects also had rheumatological evaluation. Plaque community profiles were analyzed using 16 S rRNA sequencing.

Results

The phylogenetic diversity of microbial communities in both RA and non-RA controls was significantly higher in deep subgingival sites compared to shallow sites (p = 0.022), and the overall subgingival microbiome clustered primarily according to probing depth (i.e. shallow versus deep sites), and not separated by RA status. While a large number of differentially abundant taxa and gene functions was observed between deep and shallow sites as expected in non-RA controls, we found very few differentially abundant taxa and gene functions between deep and shallow sites in RA subjects. In addition, compared to non-RA controls, the UniFrac distances between deep and shallow sites in RA subjects were smaller, suggesting increased similarity between deep and shallow subgingival microbiome in RA. Streptococcus parasanguinis and Actinomyces meyeri were overabundant in RA subjects, while Gemella morbillorum, Kingella denitrificans, Prevotella melaninogenica and Leptotrichia spp. were more abundant in non-RA subjects.

Conclusions

The aggregate subgingival microbiome was not significantly different between individuals with and without rheumatoid arthritis. Although the differences in the overall subgingival microbiome was driven primarily by probing depth, in contrast to the substantial microbiome differences typically seen between deep and shallow sites in non-RA patients, the microbiome of deep and shallow sites in RA patients were more similar to each other. These results suggest that factors associated with RA may modulate the ecology of subgingival microbiome and its relationship to periodontal disease, the basis of which remains unknown but warrants further investigation.
Let’s ask the patient – composition and validation of a questionnaire for patients’ feedback to medical students
Authors: Björklund Karin , Stenfors Terese , Nilsson Gunnar H. , Alinaghizadeh Hassan , Leanderson Charlotte
Published: May 2021

Background

Adequate communication and maintaining a patient-centered approach throughout patient encounters are important skills for medical students to develop. Feedback is often provided by clinical teachers. Patients are seldom asked to provide feedback to students that systematically addresses knowledge and skills regarding communication and patient-centeredness during an encounter. One way for patients to provide feedback to students is through a questionnaire; there is, however, a lack of such validated feedback questionnaires. This study aimed to compose and validate a feedback questionnaire for patients’ feedback to medical students regarding students’ ability to communicate and apply patient-centeredness in clinical practice.

Method

This study comprises (a) composition of the questionnaire and (b) validation of the questionnaire. The composition included (1) literature review, (2) selection and composition of items and construction of an item pool, (3) test of items’ content, and (4) test of the applicability of the questionnaire. The items originated from the Calgary-Cambridge Guide (Kurtz S, Silverman J, Benson J and Draper J, Acad Med 78:802-809, 2003), the ‘Swedish National Patient Survey’ (National Patient Survey, Primary Health Care, 2020), patient evaluation form by Braend et al. (Tidsskr Nor Laegeforen 126:2122–5, 2006), and additional developed items. The items were further developed after feedback from 65 patients, 22 students, eight clinical supervisors, and six clinical teachers. The validation process included 246 patients who provided feedback to 80 students. Qualitative content analysis and psychometric methods were used and exploratory factor analysis assessed internal validity. Cronbach’s alpha was used to test the reliability of the items.

Results

The process resulted in the 19-item ‘Patient Feedback in Clinical Practice’ (PFCP) questionnaire. Construct validity revealed two dimensions: consultational approach and transfer of information. Internal consistency was high. Thematic analysis resulted in three themes: ability to capture the personal agenda of the consultation, alignment with the consultation, and constructs and characteristics. Students reported that the PFCP questionnaire provided useful feedback that could facilitate their learning in clinical practice.

Conclusions

The results of this study indicate that the questionnaire is a valid, reliable, and internally consistent instrument for patients’ feedback to medical students. The participants found the questionnaire to be useful for the provision of feedback in clinical practice. However, further studies are required regarding the PFCP questionnaire applicability as a feedback tool in workplace learning.
Insured clients out-of-pocket payments for health care under the national health insurance scheme in Ghana
Authors: Akweongo Patricia , Aikins Moses , Wyss Kaspar , Salari Paola , Tediosi Fabrizio
Published: May 2021

Background

In 2003, Ghana implemented a National Health Insurance Scheme (NHIS) designed to promote universal health coverage and equitable access to health care. The scheme has largely been successful, yet it is confronted with many challenges threatening its sustainability. Out-of-pocket payments (OOP) by insured clients is one of such challenges of the scheme. This study sought to examine the types of services OOP charges are made for by insured clients and how much insured clients pay out-of-pocket.

Methods

This was a descriptive cross-sectional health facility survey. A total of 2066 respondents were interviewed using structured questionnaires at the point of health care exit in the Ashanti, Northern and Central regions of Ghana. Health facilities of different levels were selected from 3 districts in each of the three regions. Data were collected between April and June 2018. Using Epidata and STATA Version 13.1 data analyses were done using multiple logistic regression and simple descriptive statistics and the results presented as proportions and means.

Results

Of all the survey respondents 49.7% reported paying out-of-pocket for out-patient care while 46.9% of the insured clients paid out-of-pocket. Forty-two percent of the insured poorest quintile also paid out-of-pocket. Insured clients paid for consultation (75%) and drugs (63.2%) while 34.9% purchased drugs outside the health facility they visited. The unavailability of drugs (67.9%) and drugs not covered by the NHIS (20.8%) at the health facility led to out-of-pocket payments. On average, patients paid GHS33.00 (USD6.6) out-of-pocket. Compared to the Ashanti region, patients living in the Northern region were 74% less at odds to pay out-of-pocket for health care.

Conclusion and recommendation

Insured clients of Ghana’s NHIS seeking health care in accredited health facilities make out-of-pocket payments for consultation and drugs that are covered by the scheme. The out-of-pocket payments are largely attributed to unavailability of drugs at the facilities while the consultation fees are charged to meet the administrative costs of services. These charges occur in disadvantaged regions and in all health facilities. The high reliance on out-of-pocket payments can impede Ghana’s progress towards achieving Universal Health Coverage and the Sustainable Development Goal 3, seeking to end poverty and reduce inequalities. In order to build trust and confidence in the NHIS there is the need to eliminate out-of-pocket payments for consultation and medicines by insured clients.
Relationship between satisfaction with mental health services, personal recovery and quality of life among service users with psychosis: a cross-sectional study
Authors: Skar-Fröding Regina , Clausen Hanne Kristin , Šaltytė Benth Jūratė , Ruud Torleif , Slade Mike , Sverdvik Heiervang Kristin
Published: May 2021

Background

Mental health policy internationally emphasizes patient centredness and personal recovery. This study investigated the relationship between satisfaction with mental health services among service users with psychosis in Norway, and personal recovery, perceived support for personal recovery, and quality of life.

Methods

Cross-sectional data were collected from 292 service users diagnosed with psychosis from 39 clinical sites across Norway. Satisfaction with services was assessed using the Client Satisfaction Questionnaire-8. A linear mixed model was estimated to explore the relationship between satisfaction with services and preselected covariates, and to control for confounding factors.

Results

A large majority of participants (89%) reported moderate-to-high levels of satisfaction. Satisfaction with services was positively associated with perceived support for personal recovery, but not with personal recovery or quality of life. In addition, service users under a Community Treatment Order (CTO) were significantly less satisfied than those who were not.

Conclusions

Satisfaction levels among service users were higher compared with similar, international studies. Those who feel supported in their personal recovery were more satisfied with the care they receive, which support the need for implementation of recovery-oriented practices for service users with psychosis. However, satisfaction with services was not related to service user-rated quality of life or level of personal recovery; thus, more follow-up studies are needed. The lower satisfaction of service users placed under CTOs shows the importance of targeted interventions to improve satisfaction with services among this group.

Trial registration

NCT03271242, date of registration: 5 sept. 2017.
Analysis of diverse factors influencing the health status as well as medical and health service utilization in the floating elderly of China
Authors: Fu Yuwei , Lin Weiwei , Yang Yuan , Du Ranran , Gao Dongping
Published: May 2021

Background

Based on the “China Migrants Dynamic Survey-Special investigation on Floating Elderly in 8 megacities in 2015”, the health status and the utilization of medical and health services in floating elderly were described and analyzed.

Objective

Scientific basis and critical suggestions are provided for improving the utilization level of medical and health services in the floating elderly and designing targeted health policies to improve their well-being.

Methods

The rank-sum test and Pearson χ2 test were used to compare the health status of floating elderly with different characteristics. Thereafter based on Andersen model, floating characteristics were added and binary logistic regression was used to explore the influencing factors of medical and health service utilization in the floating elderly.

Results

About 94.7% of the floating elderly were self-assessed as healthy/basically healthy. About 24.2% had hypertension or diabetes as diagnosed by the qualified doctors. About 7% suffered from diseases that required hospitalization. Only 28.6% of the floating elderly with hypertension or diabetes had visited a doctor for follow-up. In the case of minor ailments, only 48.7% decided to visit the clinics. Approximately 70.7% of the floating elderly had used in-patient services when they suffered from diseases requiring hospitalization.

Conclusion

The floating elderly were observed to be generally in good health but a high prevalence of hypertension or diabetes was observed among them. The cultivation of health awareness was found to be of great significance contributing to the improvement of the overall health level among the floating elderly. The basic medical insurance coverage was low, and the medical and health services were found to be severely underutilized. Adequate social support can promote the health of the floating elderly and improve their utilization of medical and health services. The floating reasons, scope and years of the elderly significantly affected their health status and the utilization rate of the basic public health services.
Joint effects of ethnic enclave residence and ambient volatile organic compounds exposure on risk of gestational diabetes mellitus among Asian/Pacific Islander women in the United States
Authors: Williams Andrew D. , Ha Sandie , Shenassa Edmond , Messer Lynne C. , Kanner Jenna , Mendola Pauline
Published: May 2021

Background

Asian/Pacific Islander (API) communities in the United States often reside in metropolitan areas with distinct social and environmental attributes. Residence in an ethnic enclave, a socially distinct area, is associated with lower gestational diabetes mellitus (GDM) risk, yet exposure to high levels of air pollution, including volatile organic compounds (VOCS), is associated with increased GDM risk. We examined the joint effects of ethnic enclaves and VOCs to better understand GDM risk among API women, the group with the highest prevalence of GDM.

Methods

We examined 9069 API births in the Consortium on Safe Labor (19 hospitals, 2002–2008). API ethnic enclaves were defined as areas ≥66th percentile for percent API residents, dissimilarity (geographic dispersal of API and White residents), and isolation (degree that API individuals interact with another API individual). High levels of 14 volatile organic compounds (VOC) were defined as ≥75th percentile. Four joint categories were created for each VOC: Low VOC/Enclave (reference group), Low VOC/No Enclave, High VOC/Enclave, High VOC/No Enclave. GDM was reported in medical records. Hierarchical logistic regression estimated odds ratios (OR) and 95% confidence intervals (95%CI) between joint exposures and GDM, adjusted for maternal factors and area-level poverty. Risk was estimated for 3-months preconception and first trimester exposures.

Results

Enclave residence was associated with lower GDM risk regardless of VOC exposure. Preconception benzene exposure was associated with increased risk when women resided outside enclaves [High VOC/No Enclave (OR:3.45, 95%CI:1.77,6.72)], and the effect was somewhat mitigated within enclaves, [High VOC/Enclave (OR:2.07, 95%:1.09,3.94)]. Risks were similar for 12 of 14 VOCs during preconception and 10 of 14 during the first trimester.

Conclusions

API residence in non-enclave areas is associated with higher GDM risk, regardless of VOC level. Ethnic enclave residence may mitigate effects of VOC exposure, perhaps due to lower stress levels. The potential benefit of ethnic enclaves warrants further study.
Therapeutic mechanisms of mesenchymal stem cells in acute respiratory distress syndrome reveal potentials for Covid-19 treatment
Authors: Wang Wendi , Lei Wei , Jiang Lina , Gao Siqi , Hu Shijun , Zhao Zi-Gang , Niu Chun-Yu , Zhao Zhen-Ao
Published: May 2021

The mortality rate of critically ill patients with acute respiratory distress syndrome (ARDS) is 30.9% to 46.1%. The emergence of the coronavirus disease 2019 (Covid-19) has become a global issue with raising dire concerns. Patients with severe Covid-19 may progress toward ARDS. Mesenchymal stem cells (MSCs) can be derived from bone marrow, umbilical cord, adipose tissue and so on. The easy accessibility and low immunogenicity enable MSCs for allogeneic administration, and thus they were widely used in animal and clinical studies. Accumulating evidence suggests that mesenchymal stem cell infusion can ameliorate ARDS. However, the underlying mechanisms of MSCs need to be discussed. Recent studies showed MSCs can modulate immune/inflammatory cells, attenuate endoplasmic reticulum stress, and inhibit pulmonary fibrosis. The paracrine cytokines and exosomes may account for these beneficial effects. In this review, we summarize the therapeutic mechanisms of MSCs in ARDS, analyzed the most recent animal experiments and Covid-19 clinical trial results, discussed the adverse effects and prospects in the recent studies, and highlight the potential roles of MSC therapy for Covid-19 patients with ARDS.
Combined detection of circulating tumor cells, α-fetoprotein heterogene-3 and α-fetoprotein in the early diagnosis of HCC for the prediction of efficacy, prognosis, recurrence after microwave ablation
Authors: Zhou Jian , Zhu Yue , Li Yi , Liu Kun , He Fei , Xu Sihuan , Li Xin , Li Li , Hu Junfang , Liu Yan
Published: May 2021

Background

Early diagnosis can significantly improve treatment outcomes for hepatocellular carcinoma (HCC) patients. Currently, the dosage of serum alpha fetoprotein (AFP) is widely used in the diagnosis of HCC, but this biomarker has low specificity and may cause false positive or false negative results. Thus, it’s necessary to find and validate other serum tumor markers that in association for AFP would increase the sensitivity and the specificity in the HCC diagnosis. This study investigated the predictive value of combined of AFP, AFP-L3, and Circulating tumor cells (CTCs).

Methods

A total of 105 patients with HCC after microwave ablation (MWA) were divided into non recurrence group, recurrence group, good prognosis (CR + PR group, CR: Complete remission, PR: Partial remission) and poor prognosis (SD + PD group, SD: Stable, PD: Progression). ROC curve was used to analyze the short-term efficacy, prognosis and clinical value of combined detection of the three indicators in predicting postoperative recurrence of HCC patients with MWA.

Results

The positive rate of serum CTCs, AFP-L3 and AFP combined detection in the diagnosis of HCC is higher than that of single index and two index detection. The AUC, sensitivity and specificity of serum CTCs, AFP-L3 and AFP combined detection was better than that of single index and two indexes in patients with HCC after MWA.

Conclusions

Combined detection of AFP, AFP-L3, and CTCs can effectively make up for the shortcomings of the detection with single and pairwise indicators. It can’t only diagnose HCC in early, but also has a high clinical value of predicting the short-term efficacy, prognosis and recurrence of HCC patients after MWA treatment.
Impact of Gba2 on neuronopathic Gaucher’s disease and α-synuclein accumulation in medaka (Oryzias latipes)
Authors: Nakanishi Etsuro , Uemura Norihito , Akiyama Hisako , Kinoshita Masato , Masanori Sawamura , Taruno Yosuke , Yamakado Hodaka , Matsuzawa Shu-ichi , Takeda Shunichi , Hirabayashi Yoshio , Takahashi Ryosuke
Published: May 2021

Homozygous mutations in the lysosomal glucocerebrosidase gene, GBA1, cause Gaucher’s disease (GD), while heterozygous mutations in GBA1 are a strong risk factor for Parkinson’s disease (PD), whose pathological hallmark is intraneuronal α-synuclein (asyn) aggregates. We previously reported that gba1 knockout (KO) medaka exhibited glucosylceramide accumulation and neuronopathic GD phenotypes, including short lifespan, the dopaminergic and noradrenergic neuronal cell loss, microglial activation, and swimming abnormality, with asyn accumulation in the brains. A recent study reported that deletion of GBA2, non-lysosomal glucocerebrosidase, in a non-neuronopathic GD mouse model rescued its phenotypes. In the present study, we generated gba2 KO medaka and examined the effect of Gba2 deletion on the phenotypes of gba1 KO medaka. The Gba2 deletion in gba1 KO medaka resulted in the exacerbation of glucosylceramide accumulation and no improvement in neuronopathic GD pathological changes, asyn accumulation, or swimming abnormalities. Meanwhile, though gba2 KO medaka did not show any apparent phenotypes, biochemical analysis revealed asyn accumulation in the brains. gba2 KO medaka showed a trend towards an increase in sphingolipids in the brains, which is one of the possible causes of asyn accumulation. In conclusion, this study demonstrated that the deletion of Gba2 does not rescue the pathological changes or behavioral abnormalities of gba1 KO medaka, and GBA2 represents a novel factor affecting asyn accumulation in the brains.
Hypoxia-dependent drivers of melanoma progression
Authors: D’Aguanno Simona , Mallone Fabiana , Marenco Marco , Del Bufalo Donatella , Moramarco Antonietta
Published: May 2021

Hypoxia, a condition of low oxygen availability, is a hallmark of tumour microenvironment and promotes cancer progression and resistance to therapy. Many studies reported the essential role of hypoxia in regulating invasiveness, angiogenesis, vasculogenic mimicry and response to therapy in melanoma. Melanoma is an aggressive cancer originating from melanocytes located in the skin (cutaneous melanoma), in the uveal tract of the eye (uveal melanoma) or in mucosal membranes (mucosal melanoma). These three subtypes of melanoma represent distinct neoplasms in terms of biology, epidemiology, aetiology, molecular profile and clinical features.

In this review, the latest progress in hypoxia-regulated pathways involved in the development and progression of all melanoma subtypes were discussed. We also summarized current knowledge on preclinical studies with drugs targeting Hypoxia-Inducible Factor-1, angiogenesis or vasculogenic mimicry. Finally, we described available evidence on clinical studies investigating the use of Hypoxia-Inducible Factor-1 inhibitors or antiangiogenic drugs, alone or in combination with other strategies, in metastatic and adjuvant settings of cutaneous, uveal and mucosal melanoma.

Hypoxia-Inducible Factor-independent pathways have been also reported to regulate melanoma progression, but this issue is beyond the scope of this review.

As evident from the numerous studies discussed in this review, the increasing knowledge of hypoxia-regulated pathways in melanoma progression and the promising results obtained from novel antiangiogenic therapies, could offer new perspectives in clinical practice in order to improve survival outcomes of melanoma patients.
Macronutrient balance and micronutrient amounts through growth and development
Authors: Savarino Giovanni , Corsello Antonio , Corsello Giovanni
Published: May 2021

Nutrition is essential for human growth, particularly in newborns and children. An optimal growth needs a correct diet, in order to ensure an adequate intake of macronutrients and micronutrients. Macronutrients are the compounds that humans consume in largest quantities, mainly classified in carbohydrates, proteins and fats. Micronutrients are instead introduced in small quantities, but they are required for an adequate growth in the pediatric age, especially zinc, iron, vitamin D and folic acid. In this manuscript we describe the most important macro and micronutrients for children’s growth.
Comparison of culture-negative and culture-positive sepsis or septic shock: a systematic review and meta-analysis
Authors: Li Yuting , Guo Jianxing , Yang Hongmei , Li Hongxiang , Shen Yangyang , Zhang Dong
Published: May 2021

Background

Mortality and other clinical outcomes between culture-negative and culture-positive septic patients have been documented inconsistently and are very controversial. A systematic review and meta-analysis was performed to compare the clinical outcomes of culture-negative and culture-positive sepsis or septic shock.

Methods

We searched the PubMed, Cochrane and Embase databases for studies from inception to the 1st of January 2021. We included studies involving patients with sepsis or septic shock. All authors reported our primary outcome of all-cause mortality and clearly compared culture-negative versus culture-positive patients with clinically relevant secondary outcomes (ICU length of stay, hospital length of stay, mechanical ventilation requirements, mechanical ventilation duration and renal replacement requirements). Results were expressed as odds ratio (OR) and mean difference (MD) with accompanying 95% confidence interval (CI).

Results

Seven studies including 22,655 patients were included. The primary outcome of this meta-analysis showed that there was no statistically significant difference in the all-cause mortality between two groups (OR = 0.95; 95% CI, 0.88 to 1.01; P = 0.12; Chi-2 = 30.71; I2 = 80%). Secondary outcomes demonstrated that there was no statistically significant difference in the ICU length of stay (MD = − 0.19;95% CI, − 0.42 to 0.04; P = 0.10;Chi-2 = 5.73; I2 = 48%), mechanical ventilation requirements (OR = 1.02; 95% CI, 0.94 to 1.11; P = 0.61; Chi2 = 6.32; I2 = 53%) and renal replacement requirements (OR = 0.82; 95% CI, 0.67 to 1.01; P = 0.06; Chi-2 = 1.21; I2 = 0%) between two groups. The hospital length of stay of culture-positive group was longer than that of the culture-negative group (MD = − 3.48;95% CI, − 4.34 to − 2.63; P < 0.00001;Chi-2 = 1.03; I2 = 0%). The mechanical ventilation duration of culture-positive group was longer than that of the culture-negative group (MD = − 0.64;95% CI, − 0.88 to − 0.4; P < 0.00001;Chi-2 = 4.86; I2 = 38%).

Conclusions

Culture positivity or negativity was not associated with mortality of sepsis or septic shock patients. Furthermore, culture-positive septic patients had similar ICU length of stay, mechanical ventilation requirements and renal replacement requirements as those culture-negative patients. The hospital length of stay and mechanical ventilation duration of culture-positive septic patients were both longer than that of the culture-negative patients. Further large-scale studies are still required to confirm these results.
Production of the biocommodities butanol and acetone from methanol with fluorescent FAST-tagged proteins using metabolically engineered strains of Eubacterium limosum
Authors: Flaiz Maximilian , Ludwig Gideon , Bengelsdorf Frank R. , Dürre Peter
Published: May 2021

Background

The interest in using methanol as a substrate to cultivate acetogens increased in recent years since it can be sustainably produced from syngas and has the additional benefit of reducing greenhouse gas emissions. Eubacterium limosum is one of the few acetogens that can utilize methanol, is genetically accessible and, therefore, a promising candidate for the recombinant production of biocommodities from this C1 carbon source. Although several genetic tools are already available for certain acetogens including E. limosum, the use of brightly fluorescent reporter proteins is still limited.

Results

In this study, we expanded the genetic toolbox of E. limosum by implementing the fluorescence-activating and absorption shifting tag (FAST) as a fluorescent reporter protein. Recombinant E. limosum strains that expressed the gene encoding FAST in an inducible and constitutive manner were constructed. Cultivation of these recombinant strains resulted in brightly fluorescent cells even under anaerobic conditions. Moreover, we produced the biocommodities butanol and acetone from methanol with recombinant E. limosum strains. Therefore, we used E.limosum cultures that produced FAST-tagged fusion proteins of the bifunctional acetaldehyde/alcohol dehydrogenase or the acetoacetate decarboxylase, respectively, and determined the fluorescence intensity and product concentrations during growth.

Conclusions

The addition of FAST as an oxygen-independent fluorescent reporter protein expands the genetic toolbox of E. limosum. Moreover, our results show that FAST-tagged fusion proteins can be constructed without negatively impacting the stability, functionality, and productivity of the resulting enzyme. Finally, butanol and acetone can be produced from methanol using recombinant E.limosum strains expressing genes encoding fluorescent FAST-tagged fusion proteins.
Effects of a neuromuscular training program using external focus attention cues in male athletes with anterior cruciate ligament reconstruction: a randomized clinical trial
Authors: Ghaderi Mohamad , Letafatkar Amir , Thomas Abbey C. , Keyhani Sohrab
Published: May 2021

Background

Athletes who have undergone anterior cruciate ligament (ACL) reconstruction often exhibit persistent altered biomechanics and impaired function. Neuromuscular training programs appear to be effective for reducing high-risk landing mechanics and preventing primary ACL injuries; however, there have been few attempts to examine their effects in athletes who have undergone ACL reconstruction. The purpose of our study was to examine the effects of a neuromuscular training program that emphasizes external focus of attention cuing on biomechanics, knee proprioception, and patient-reported function in athletes who had undergone ACL reconstruction and completed conventional post-operative rehabilitation.

Methods

Twenty-four male athletes who had undergone primary, unilateral, hamstring autograft ACL reconstruction and completed conventional post-operative rehabilitation were randomly allocated to an experimental group (n = 12) who took part in an 8-week neuromuscular training program or a control group (n = 12) who continued a placebo program. The neuromuscular training program included lower extremity strengthening and plyometric exercises, balance training, and movement pattern re-training. Biomechanics during single-leg landing, knee proprioception, and patient-reported function were assessed before and after the 8-week training period.

Results

Athletes in the experimental group demonstrated increased trunk, hip, and knee flexion angles and decreased knee abduction, internal rotation angles and knee valgus during landing following the intervention. Further, the experimental group decreased their peak knee extension and abduction moments and vertical ground reaction force on landing post-intervention. International Knee Documentation Committee questionnaire (IKDC) scores increased in the experimental group following training. The control group demonstrated no changes in any variable over the same time period.

Conclusions

Neuromuscular training with external focus of attention cueing improved landing biomechanics in patients after ACL reconstruction. Neuromuscular training programs beneficially mitigate second ACL injury risk factors and should be emphasized during and after traditional post-operative rehabilitation.

Trial registration

Current Controlled Trials using the IRCT website with ID number of, IRCT20180412039278N1 “Prospectively registered” at 21/12/2018.
Migraine and stress—an exploratory cross-country study of external stress factors
Authors: van Staveren Irene
Published: May 2021

Objective

The data collected by the Global Burden of Disease 2016 project indicate that migraine ranks second in high-income countries with very competitive and flexible labour markets, and first in low- and middle-income countries suffering from civic unrest and conflict. This raises the question whether external stress factors may be correlated with migraine years lived with disability per 100,000 inhabitants (YLD). The objective of this exploratory study is to test the hypothesis that external stress factors are correlated with the prevalence and severity of migraine at the country level. The analysis uses two country groups: developed and developing countries. For the first group, the proxy variables for stress are labour productivity and unemployment rate. For the second group, the proxy variables measure conflict-related deaths and share of migrant/refugee population.

Results

The results show a positive relationship between the stress variables on the one hand and migraine YLD on the other hand for both country groups. Almost all results are statistically significant at p < 0.01. These exploratory findings suggest that societal stress factors may be potential candidates for modifiable factors for the prevalence and/or severity of migraine at the country level.
Conducting epigenetics research with refugees and asylum seekers: attending to the ethical challenges
Authors: Taki Faten , de Melo-Martin Inmaculada
Published: May 2021

An increase in global violence has forced the displacement of more than 70 million people, including 26 million refugees and 3.5 asylum seekers. Refugees and asylum seekers face serious socioeconomic and healthcare barriers and are therefore particularly vulnerable to physical and mental health risks, which are sometimes exacerbated by immigration policies and local social discriminations. Calls for a strong evidence base for humanitarian action have encouraged conducting research to address the barriers and needs of refugees and asylum seekers. Given the role of epigenetics factors to mediate the effect of psychological and environmental exposures, epigenetic modifications have been used as biomarkers for life adversity and disease states. Therefore, epigenetic research can be potentially beneficial to address some of the issues associated with refugees and asylum seekers. Here, we review the value of previous and ongoing epigenetic studies with traumatized populations, explore some of the ethical challenges associated with epigenetic research with refugees and asylees and offer suggestions to address or mitigate some of these challenges. Researchers have an ethical responsibility to implement strategies to minimize the harms and maximize the short and long-term benefits to refugee and asylee participants.
Examining a stepped-care telehealth program for parents of young children with autism: a proof-of-concept trial
Authors: Wainer Allison L. , Arnold Zachary E. , Leonczyk Caroline , Valluripalli Soorya Latha
Published: May 2021

Background

Intervention during the first years of life for children with autism spectrum disorder (ASD) may have the strongest impact on long-term brain development and functioning. Yet, barriers such as a shortage of trained professionals contribute to significant delays in service. The goal of this proof-of-concept study was to explore strategies that support timely and equitable deployment of ASD-specific interventions.

Methods

This 15-week, randomized proof-of-concept study explored the acceptability of a digital parent mediated intervention online reciprocal imitation training (RIT; a naturalistic developmental behavioral intervention) and compared it to a treatment as usual (TAU) control on parent and child outcomes. Eligible children were between 18 and 60 months, met the cutoff for ASD on the Autism Diagnostic Observation Schedule-2nd Edition and demonstrate significant social imitation deficits. Primary outcomes include the acceptability of RIT (Scale of Treatment Perceptions) and the feasibility of the Online RIT digital intervention (online RIT attributes). Secondary outcomes included parent fidelity (RIT parent fidelity form) and parental self-efficacy (Early Intervention Parenting Self-Efficacy Scale). Exploratory outcome measures included child social communication (Social Communication Checklist), child imitation skills (Unstructured Imitation Assessment), and family quality of life (Beach Center Family Quality of Life Scale).

Results

Twenty participants were randomized in a 1:1 fashion. The acceptability and feasibility of RIT and the Online RIT digital intervention were rated highly. Among the secondary outcomes, there were significant group differences in parent fidelity (p < .001) and self-efficacy (p = .029). On exploratory outcomes, there were group differences in child social communication (p = .048). There were no significant group differences in imitation ability (p = .05) or family quality of life (p = .22).

Limitations

There are several limitations with this study, including the small sample size as well as lack of data on enactment and website engagement. This study was not able to address questions related to which variables predict program engagement and treatment response, which will be critical for determining which families may benefit from such a stepped-care delivery model.

Conclusions

Overall, the Online RIT program delivered in a stepped-care format shows strong acceptability and holds promise as an innovative delivery model.

Trial registration ClinicalTrials.gov, NCT04467073. Registered 10 July 2020- Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04467073
Application of the topological sensitivity method to the reconstruction of plasma equilibrium domain in a tokamak
Authors: Abdelwahed Mohamed , Chorfi Nejmeddine , Hassine Maatoug , Kallel Imen
Published: May 2021

The topological sensitivity method is an optimization technique used in different inverse problem solutions. In this work, we adapt this method to the identification of plasma domain in a Tokamak. An asymptotic expansion of a considered shape function is established and used to solve this inverse problem. Finally, a numerical algorithm is developed and tested in different configurations.
The NIDA clinical trials network: evolving, expanding, and addressing the opioid epidemic
Authors: Tai Betty , Dobbins Ronald , Blackeney Quandra , Liu David , Moran Landhing
Published: May 2021

Over the past two decades, the National Drug Abuse Treatment Clinical Trials Network (CTN), a program of the National Institute on Drug Abuse (NIDA), has expanded from the initial six Nodes to 16 Nodes, as a nationwide consortium of research scientists and treatment providers working together to improve care for substance use in the nation’s communities. Encompassing both specialty care programs and general medical settings, the Network has become a unique resource for expertise on clinically focused research, bridging the gap between research and treatment delivery. Over 22 years, the CTN has completed 101 studies, resulting in 650 publications. In response to the opioid epidemic, a CTN task force generated a comprehensive list of research priorities in the areas of prevention, treatment, knowledge dissemination, and workforce training, to form the basis of the Network’s opioid portfolio. The Network’s opioid portfolio currently includes five main categories of studies: (1) large multi-site studies; (2) studies aimed at closing the treatment gap; (3) expansion of ongoing studies to improve service delivery and implementation; (4) studies to explore the use of substance use data in electronic health record systems; (5) training and dissemination projects to expand the research/health care provider workforce. With funding from the Helping to End Addiction Long-Term InitiativeSM (HEAL), the CTN established five new Nodes, which, along with the pre-existing Nodes, are distributed in every region of the nation and engage researchers and clinicians in areas that have been among the hardest hit by the opioid epidemic. Through this expanded network and its commitment to developing personalized, evidence-based treatments, the CTN is poised to address and provide solutions for the ongoing epidemic of opioid use and addiction.
Phase II Study of Maintenance Rucaparib in Patients With Platinum-Sensitive Advanced Pancreatic Cancer and a Pathogenic Germline or Somatic Variant in BRCA1, BRCA2, or PALB2
Authors: Reiss Kim A. , Mick Rosemarie , O'Hara Mark H. , Teitelbaum Ursina , Karasic Thomas B. , Schneider Charles , Cowden Stacy , Southwell Traci , Romeo Janae , Izgur Natallia , Hannan Zain M. , Tondon Rashmi , Nathanson Katherine , Vonderheide Robert H. , Wattenberg Max M. , Beatty Gregory , Domchek Susan M.
Published: May 2021

PURPOSE

Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi), is approved as maintenance therapy for patients with advanced pancreatic cancer (PC) and a germline BRCA1 or BRCA2 pathogenic variant (PV). This investigator-initiated, single-arm phase II study assessed the role of the PARPi rucaparib as maintenance therapy in advanced PC with germline or somatic PV in BRCA1, BRCA2, or PALB2.

PATIENTS AND METHODS

Eligible patients had advanced PC; germline (g) or somatic (s) PVs in BRCA1, BRCA2, or PALB2, and received at least 16 weeks of platinum-based chemotherapy without evidence of platinum resistance. Chemotherapy was discontinued and patients received rucaparib 600 mg orally twice a day until progression. The primary end point was the progression-free survival (PFS) rate at 6 months (PFS6). Secondary end points included safety, ORR, disease control rate, duration of response, and overall survival.

RESULTS

Of 46 enrolled patients, 42 were evaluable (27 g BRCA2, seven g BRCA1, six g PALB2, and two s BRCA2). PFS6 was 59.5% (95% CI, 44.6 to 74.4), median PFS was 13.1 months (95% CI, 4.4 to 21.8), and median overall survival was 23.5 months (95% CI, 20 to 27). The PFS at 12 months was 54.8%. ORR of the 36 patients with measurable disease was 41.7% (3 complete responses; 12 partial responses; 95% CI, 25.5 to 59.2), and disease control rate was 66.7% (95% CI, 49.0 to 81.4). Median duration of response was 17.3 months (95% CI, 8.8 to 25.8). Responses occurred in patients with gBRCA2 (41%, 11 out of 27), gPALB2 (50%, 3 out of 6), and sBRCA2 (50%, 1 out of 2). No new safety signals were noted.

CONCLUSION

Maintenance rucaparib is a safe and effective therapy for platinum-sensitive, advanced PC with a PV in BRCA1, BRCA2, or PALB2. The finding of efficacy in patients with g PALB2 and s BRCA2 PVs expands the population likely to benefit from PARPi beyond g BRCA1/ 2 PV carriers.