bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of mTORC1‑dependent circulating protein levels with cataract formation: a mendelian randomization study
Authors: Cai Yingjun , Liu Kangcheng , Wu Pengfei , Yuan Ruolan , He Fei , Zou Jing
Published: October 2022

Background

The mechanistic target of rapamycin (mTOR) signal pathway plays a critical regulating role in the occurrence and development of cataract. However, the role of mTORC1 downstream proteins, including ribosomal protein S6K (RP-S6K), eukaryotic initiation factor 4E-binding protein (EIF4EBP), eukaryotic initiation factor 4G (EIF-4G), eukaryotic initiation factor 4E (EIF-4E), and eukaryotic initiation factor 4A (EIF-4A), in regulating cataract development is still unknown. Herein, we conducted a mendelian randomization (MR) study to understand the function of mTORC1 signaling in the process of cataract development.

Results

The causal estimate was evaluated with inverse-variance weighted (IVW) estimate, weighted median estimator, MR-Egger and MR robust adjusted profile score (MR. RAPS). The single-nucleotide polymorphisms (SNPs), P<5 × 10− 6 and r2<0.05, were selected to genetically predict the RP-S6K, EIF4EBP, EIF-4E, EIF-4A, and EIF-4G. We included a total of 26,758 cases and 189,604 controls in this MR study. The study revealed causal association between circulating EIF4EBP (OR 1.09, 95% confidence interval 1.03,1.16, P = 0.004), RP-S6K (OR 1.04, 95% confidence interval 1.01, 1.08, P = 0.02) and cataract formation with IVW estimate. Whereas after correcting outliers, MR robust adjusted profile score (MR. RAPS) shows consistent result with IVW for EIF4EBP (OR = 1.08, 95%CI:1.05–1.11, P = 0.007). The observation strengthened the confidence in the true causal associations. However, no association was found for circulating EIF-4E (OR 1.03, 95% confidence interval 0.97, 1.09, P = 0.31), EIF-4A (OR 1.02, 95% confidence interval 0.98, 1.07, P = 0.34), and EIF-4G (OR 1.02, 95% confidence interval 0.94, 1.01, P = 0.64) levels with cataract formation. No evidence of heterogeneity and unbalanced horizontal pleiotropy was detected.

Conclusion

The MR study suggests that EIF4EBP is a high-risk factor for cataract development. There may be a potential causal association between the mTORC1/EIF4EBP axis and cataract. This research highlights the potential mechanism for cataract development and a genetic target to prevent as well as treat cataracts.
Species diversity analysis of commercial Mantidis Ootheca samples contaminated by store pests based on DNA metabarcoding
Authors: Xu Liuwei , Zhang Xiaoying , Guo Hua , Yang Xia , Xing Zhimei , Yang Wenzhi , Zhang Jian , Tian Xiaoxuan
Published: October 2022

Mantidis Ootheca (Sangpiaoxiao, mantis egg case) is a typical multi-origin Chinese medicinal material. The Chinese Pharmacopoeia stipulates that the Mantidis Ootheca originates from three species of Mantis: Tenodera sinensis, Statilia maculate, and Hierodula patellifera. However, Mantidis Ootheca mainly relies on field collection, which leads to confusion of its actual origin in the market. As the clinical use of Mantidis Ootheca with unknown original mantis species will pose potential risks to drug safety, it is necessary to survey the commercially available Mantidis Ootheca origin species. However, as the egg case of Mantis, the morphological characters of Mantidis Ootheca are limited and usually cannot serve as accurate identification tool. DNA barcoding, which is widely used in taxonomic studies of animals, is severely affected by the impact of storage pests and DNA degradation. Thus, this study collected a total of 4580 Mantidis Ootheca and pooled separately Mantidis Ootheca samples according to 18 different sources as DNA samples to analyze the origin diversity of Mantidis Ootheca individuals contaminated by common store pests collected in in the market using DNA metabarcoding, and to provide a basis for quality control of Mantidis Ootheca. 37 Mantis ASVs and 9 Mantis MOTUs were identified through species delimitation, and the high-level intraspecific diversity was depicted as haplotype network plot. Besides Tenodera sinensis and Hierodula patellifera as genuine original mantis species defined in the Chinese Pharmacopoeia, Tenodera angustipennis was also the origin species of these Mantidis Ootheca samples.
Molecular characteristics of global β-lactamase-producing Enterobacter cloacae by genomic analysis
Authors: Hu Jincao , Li Jia , Liu Chang , Zhang Yan , Xie Hui , Li Chuchu , Shen Han , Cao Xiaoli
Published: October 2022

Objective

To analyze the characteristics of global β-lactamase-producing Enterobacter cloacae including the distribution of β-lactamase, sequence types (STs) as well as plasmid replicons.

Methods

All the genomes of the E. cloacae were downloaded from GenBank. The distribution of β-lactamase encoding genes were investigated by genome annotation after the genome quality was checked. The STs of these strains were analyzed by multi-locus sequence typing (MLST). The distribution of plasmid replicons was further explored by submitting these genomes to the genome epidemiology center. The isolation information of these strains was extracted by Per program from GenBank.

Results

A total of 272 out of 276 strains were found to carry β-lactamase encoding genes. Among them, 23 varieties of β-lactamase were identified, blaCMH (n = 130, 47.8%) and blaACT (n = 126, 46.3%) were the most predominant ones, 9 genotypes of carbapenem-hydrolyzing β-lactamase (CHβLs) were identified with blaVIM (n = 29, 10.7%) and blaKPC (n = 24, 8.9%) being the most dominant ones. In addition, 115 distinct STs for the 272 ß-lactamase-carrying E. cloacae and 48 different STs for 106 CHβLs-producing E. cloacae were detected. ST873 (n = 27, 9.9%) was the most common ST. Furthermore, 25 different plasmid replicons were identified, IncHI2 (n = 65, 23.9%), IncHI2A (n = 64, 23.5%) and IncFII (n = 62, 22.8%) were the most common ones. Notably, the distribution of plasmid replicons IncHI2 and IncHI2A among CHβLs-producing strains were significantly higher than theat among non-CHβLs-producing strains (p < 0.05).

Conclusion

Almost all the E. cloacae contained β-lactamase encoding gene. Among the global E. cloacae, blaCMH and blaACT were main blaAmpC genes. BlaTEM and blaCTX-M were the predominant ESBLs. BlaKPC, blaVIM and blaNDM were the major CHβLs. Additionally, diversely distinct STs and different replicons were identified.
An extended 36-week oral esomeprazole improved long-term recurrent peptic ulcer bleeding in patients at high risk of rebleeding
Authors: Chiang Hsueh-Chien , Yang Er-Hsiang , Hu Huang-Ming , Chen Wei-Ying , Chang Wei-Lun , Wu Chung-Tai , Wu Deng-Chyang , Sheu Bor-Shyang , Cheng Hsiu-Chi
Published: October 2022

Background

Patients with Rockall scores ≥6 have an increased risk of long-term peptic ulcer rebleeding. This study was aimed toward investigating whether an extended course of oral esomeprazole up to 1 year decreased ulcer rebleeding in such patients.

Methods

We prospectively enrolled 120 patients with peptic ulcer bleeding and Rockall scores ≥6. After an initial 16-week oral proton pump inhibitor (PPI) treatment, patients were randomized to receive a 36-week course of oral twice-daily esomeprazole 20 mg (Group D, n = 60) or once-daily (Group S, n = 60). Thereafter, they were divided into the PPI-on-demand (n = 32) and PPI-discontinued (n = 77) subgroups. Our previous cohort with Rockall scores ≥6 served as the controls (Group C, n = 135); they received only an initial 8- to 16-week oral PPI. The primary and secondary outcomes were peptic ulcer rebleeding during the first year and the second year-and-thereafter, respectively.

Results

For the primary outcome, groups D and S comprised a higher proportion of rebleeding-free than Group C (P = 0.008 and 0.03, log-rank test). The competing-risks regression analysis confirmed that extended PPI use and American Society of Anesthesiologists classification were independent factors contributing to the primary outcome. For the secondary outcome, PPI-on-demand had a borderline higher proportion of rebleeding-free than Group C (P = 0.07, log-rank test); however, only the Rockall score was the independent factor.

Conclusions

An extended 36-week course of oral esomeprazole 20 mg, twice- or once-daily for patients with Rockall scores ≥6 reduced ulcer rebleeding during the first year, but the effect needed to be further validated when PPIs were shifted to on-demand or discontinued thereafter (NCT02456012, 28/05/2015).
Study protocol of a mixed method pragmatic quasi-experimental trial to evaluate the day activity services targeted at older home care clients in Finland
Authors: Ristolainen Hanna , Forma Leena , Hawkins Jemma , Tiilikainen Elisa
Published: October 2022

Background

In Finland, the ‘day activity service’ is targeted at older home care clients who are unable to participate in other available activities due to poor health or functional disabilities. The aim of the day activity service is to support home care client’s ability to live at home and to enhance their wellbeing and social inclusion. This mixed method study examines the effectiveness, cost-effectiveness and process of the day activity service.

Methods

The target sample size is 200 participants. The intervention group (n = 100) is composed of home care clients who begin to participate in the day activity service. The comparison group (n = 100) are home care clients who do not participate in the day activity service, and whose functioning and care needs are similar to the participants of the intervention group. The primary outcome is social inclusion (ESIS-scale). Secondary outcomes are loneliness (single item and De Jong Gierveld Loneliness Scale) and social care related quality of life (ASCOT). Baseline, three-month and six-month follow-up surveys are gathered from intervention and comparison group participants in order to compare outcomes between groups pre- and post-intervention.

Costs of health and social services, based on administrative data, and the costs of the intervention are utilized in examining the cost-effectiveness of the intervention with the above-described measurements. Qualitative data are collected by interviewing the intervention participants (n = 10) and professionals working at the day activity centres and older people’s services (4 focus groups) to explore the perceived outcomes and process of the intervention to find out how and why the intervention is effective or ineffective.

Discussion

The study seeks to produce a comprehensive understanding of the effectiveness, cost-effectiveness and implementation process of the day activity service.

Trial registration

ISRCTN13146087, Registration date 03/04/2022.
Sulbactam combined with tigecycline improves outcomes in patients with severe multidrug-resistant Acinetobacter baumannii pneumonia
Authors: Deng Yanling , Chen Lin , Yue Mingrui , Huang Xiaobo , Yang Yang , Yu Hua
Published: October 2022

Background

The purpose of this study was to review the treatment plan of patients with multidrug-resistant Acinetobacter baumannii (MDR-AB) pneumonia and analyze the factors associated with patient deaths and the medication regimen.

Methods

We collected 1,823 qualified respiratory specimens that were culture-positive for MDR-AB. 166 patients confirmed to have hospital-acquired MDR-AB pneumonia were selected as the research subjects. The differing clinical characteristics and treatment interventions between the surviving group and death group within 28 days were analyzed.

Results

The mortality rate was high for those aged > 75 years (p = 0.001). Patients who underwent invasive catheter placement (p < 0.001) and mechanical ventilation (p = 0.046) had a higher mortality rate. Combination therapy with tigecycline can reduce the mortality rate (p < 0.001) of MDR-AB pneumonia in patients with carbapenem-resistant AB(CRAB). Combination therapy with sulbactam was shown to reduce the mortality rate (p < 0.001), and high-dose sulbactam (> 3 g/day) might be better than low-dose sulbactam (≤ 3 g/day).

Conclusion

Reducing the time of invasive catheter placement and mechanical ventilation in patients in the intensive care unit (ICU), antimicrobial treatment, combined with tigecycline and sulbactam, might help reduce the mortality rate in patients with severe MDR-AB hospital-acquired pneumonia.
Clinical handover communication at maternity shift changes and women's safety in Banjul, the Gambia: a mixed-methods study
Authors: Rickard Faith , Lu Fides , Gustafsson Lotta , MacArthur Christine , Cummins Carole , Coker Ivan , Wilson Amie , Mane Kebba , Manneh Kebba , Manaseki-Holland Semira
Published: October 2022

Background

Clinical handover is a vital communication process for patient safety; transferring patient responsibility between healthcare professionals (HCPs). Exploring handover processes in maternity care is fundamental for service quality, addressing continuity of care and maternal mortality.

Methods

This mixed-methods study was conducted in all three maternity hospitals in Banjul, The Gambia. Shift-to-shift maternity handovers were observed and compared against a standard investigating content and environment. Semi-structured interviews and focus group discussions with doctors, midwives and nurses explored handover experience.

Results

One hundred ten nurse/midwife shift-to-shift handovers were observed across all shift times and maternity wards; only 666 of 845 women (79%) were handed over. Doctors had no scheduled handover. Shift-leads alone gave/received handover, delayed [median 35 min, IQR 24–45] 82% of the time; 96% of handovers were not confidential and 29% were disrupted. Standardised guidelines and training were lacking.

A median 6 of 28 topics [IQR 5–9] were communicated per woman. Information varied significantly by time, high-risk classification and location. For women in labour, 10 [IQR 8–14] items were handed-over, 8 [IQR 5–11] for women classed ‘high-risk’, 5 [IQR 4–7] for ante/postnatal women (p < 0.001); > 50% had no care management plan communicated.

Twenty-one interviews and two focus groups were conducted. Facilitators and barriers to effective handover surrounding three health service factors emerged; health systems (e.g. absence of formalised handover training), organisation culture (e.g. absence of multidisciplinary team handover) and individual clinician factors (e.g. practical barriers such as transportation difficulties in getting to work).

Conclusion

Maternity handover was inconsistent, hindered by contextual barriers including lack of team communication and guidelines, delays, with some women omitted entirely. Findings alongside HCPs views demonstrate feasible opportunities for enhancing handover, thereby improving women's safety.
Homemade pin-hook for surgical treatment of posterior cruciate ligament avulsion fractures
Authors: Guo Qiang , Li Xiaoning , Tang Yifu , Huang Yuzhao , Luo Ling
Published: October 2022

Background

How to treat the posterior cruciate ligament (PCL) tibial insertion small and comminuted avulsion fracture is still challenging. Our study evaluated the clinical and radiological outcomes after ORIF of PCL tibial insertion avulsion fractures through the inverted L-shaped postero-medial approach using a homemade pin-hook.

Methods

Between January 2009 and December 2020, twenty-four patients with isolated PCL tibial insertion bony avulsion were enrolled. There were 16 males and 8 females. The age range was 18-48 (32.5 ± 9.3) years. The time from injury to surgery was 1-10 (4.4 ± 2.8) days. There were 11 cases in the left knee and 13 cases in the right knee. The patients received anticoagulant therapy to prevent thrombosis. Preoperative standard X-ray, computerized tomography (CT) and magnetic resonance imaging (MRI) were performed. According to the Meyers-McKeever classification, there were 8 cases of type II and 16 cases of type III.

Results

The operation time was 60-120 (89.6 ± 19.8) min. Postoperative follow-up ranged from 3 to 18 months. The average follow-up was 11.4 ± 4.3 months. In all patients, one or two homemade pin-hooks were used to fix different sizes of fracture segments. X-ray or CT scans taken after surgery revealed fracture union. The fractures healed in 9-16 (11.8 ± 1.7) weeks. At the last follow-up, the patients were able to fully straighten. The ROM (132.6° ± 3.9°), the Tegner-Lysholm score (96.2 ± 2.3) and the IKDC scores (95.5 ± 1.6) were all significantly improved compared with the preoperative values (77.5° ± 13.1°, 46.8 ± 8.9, 36.2 ± 7.9). The posterior drawer test was negative. The gastrocnemius muscle strength did not diminish. No internal fixation migration was observed during the follow-up. No neurovascular bundle- or hardware-related complications were reported.

Conclusions

The inverted L-shaped postero-medial approach with homemade pin-hook fixation for the treatment of PCL avulsion fractures produces acceptable clinical and radiological results. Moreover, the homemade pin-hook made of K-wires is affordable and reduces patient costs. It is a practical application and worth recommending, especially for community hospitals.
Simiao pill inhibits epithelial mesenchymal transition in a mouse model of chronic hyperuricemic nephropathy by inhibiting NLRP3 inflammasome activation
Authors: Shui Guangxing , Cai Zheyi , Wang Feng , Chen Ting , Huang Xueyuan , Cai Yun , Mi Xiuhua
Published: October 2022

Background

Simiao pill module (SMM), a traditional Chinese medicine formula, has been widely used to treat gout and gouty arthritis. The goal of this study was to investigate the effects of SMM on epithelial-mesenchymal transition (EMT) and activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome in a mouse model of potassium oxonate (PO)-induced chronic hyperuricemic nephropathy (HN).

Methods

Mice were randomly divided into the following four groups: control, HN model (PO), febuxostat (FEB)-treated (PO + FEB), and SMM-treated (PO + SMM) groups. Following 6 weeks of treatment, blood samples were collected and mice were sacrificed to collect kidney samples to study the biochemical parameters associated with renal function and histopathological changes associated with HN, respectively. The samples were analyzed for the expression of markers of EMT (collagen type 3, α-smooth muscle actin [α-SMA], fibronectin, vimentin and E-cadherin) and activation of NLRP3 inflammasome (NLRP3, apoptosis-associated speck-like protein [ASC], caspase-1, interleukin [IL]-1β, and IL-18).

Results

Our results showed that hyperuricemia, impaired kidney function, and renal pathological characteristics induced by PO treatment were improved following treatment with SMM and FEB. Additionally, treatment with SMM and FEB decreased the expression of vimentin, collagen 3, fibronectin, and α-SMA, and increased the expression of E-cadherin. Moreover, NLRP3 inflammasome activation, as assessed by the increased expression of NLRP3, ASC, and caspase-1, and secretion of IL-1β and IL-18, was inhibited by treatment with SMM and FEB.

Conclusion

These results suggest that SMM inhibited EMT and NLRP3 inflammasome activation in chronic HN mice, and the beneficial effect of SMM was compared with a standard drug, FEB.
Antiviral activity and mechanism of the antifungal drug, anidulafungin, suggesting its potential to promote treatment of viral diseases
Authors: Shen Shu , Zhang Yaxian , Yin Zhiyun , Zhu Qiong , Zhang Jingyuan , Wang Tiantian , Fang Yaohui , Wu Xiaoli , Bai Yuan , Dai Shiyu , Liu Xijia , Jin Jiayin , Tang Shuang , Liu Jia , Wang Manli , Guo Yu , Deng Fei
Published: October 2022

Background

The severe fever with thrombocytopenia syndrome disease (SFTS), caused by the novel tick-borne SFTS virus (SFTSV), was listed among the top 10 priority infectious disease by World Health Organization due to the high fatality rate of 5–30% and the lack of effective antiviral drugs and vaccines and therefore raised the urgent need to develop effective anti-SFTSV drugs to improve disease treatment.

Methods

The antiviral drugs to inhibit SFTSV infection were identified by screening the library containing 1340 FDA-approved drugs using the SFTSV infection assays in vitro. The inhibitory effect on virus entry and the process of clathrin-mediated endocytosis under different drug doses was evaluated based on infection assays by qRT-PCR to determine intracellular viral copies, by Western blot to characterize viral protein expression in cells, and by immunofluorescence assays (IFAs) to determine virus infection efficiencies. The therapeutic effect was investigated in type I interferon receptor defective A129 mice in vivo with SFTSV infection, from which lesions and infection in tissues caused by SFTSV infection were assessed by H&E staining and immunohistochemical analysis.

Results

Six drugs were identified as exerting inhibitory effects against SFTSV infection, of which anidulafungin, an antifungal drug of the echinocandin family, has a strong inhibitory effect on SFTSV entry. It suppresses SFTSV internalization by impairing the late endosome maturation and decreasing virus fusion with the membrane. SFTSV-infected A129 mice had relieving symptoms, reduced tissue lesions, and improved disease outcomes following anidulafungin treatment. Moreover, anidulafungin exerts an antiviral effect in inhibiting the entry of other viruses including SARS-CoV-2, SFTSV-related Guertu virus and Heartland virus, Crimean-Congo hemorrhagic fever virus, Zika virus, and Herpes simplex virus 1.

Conclusions

The results demonstrated that the antifungal drug, anidulafungin, could effectively inhibit virus infection by interfering with virus entry, suggesting it may be utilized for the clinical treatment of infectious viral diseases, in addition to its FDA-approved use as an antifungal. The findings also suggested to further evaluate the anti-viral effects of echinocandins and their clinical importance for patients with infection of viruses, which may promote therapeutic strategies as well as treatments and improve outcomes pertaining to various viral and fungal diseases.
Insecticidal effects of some selected plant extracts against Anopheles stephensi (Culicidae: Diptera)
Authors: Muhammed Merdya , Dugassa Sisay , Belina Merga , Zohdy Sarah , Irish Seth R. , Gebresilassie Araya
Published: October 2022

Background

The use of synthetic insecticides against mosquitoes may lead to resistance development and potential health hazards in humans and the environment. Consequently, a paradigm needs to shift towards the alternative use of botanical insecticides that could strengthen an insecticide resistance management programme. This study aimed to assess the insecticidal effects aqueous, hexane, and methanol crude leaf extracts of Calpurnia aurea, Momordica foetida, and Zehneria scabra on an insectary colony of Anopheles stephensi larvae and adults.

Methods

Fresh leaves of C. aurea, M. foetida and Z. scabra were collected and dried, then separately ground to powder. Powdered leaves of test plants were extracted using sonication with aqueous, hexane, and methanol solvents. The extracts were concentrated, and a stock solution was prepared. For comparison, Temephos (Abate®) and control solutions (a mixture of water and emulsifier) were used as the positive and negative controls, respectively. Different test concentrations for the larvae and the adults were prepared and tested according to WHO (2005) and CDC (2010) guidelines to determine lethal concentration (LC) values. Mortality was observed after 24 h exposure. The statistical analyses were performed using Statistical Package for the Social Sciences (SPSS) software (Kruskal-Wallis test) and R software (a generalized linear model was used to determine LC50 and LC90 values of the extracts).

Results

The lowest LC50 values were observed in aqueous extracts of M. foetida followed by Z. scabra extract and C. aurea leaves at 34.61, 35.85, and 38.69 ppm, respectively, against the larvae. Larval mortality was not observed from the hexane extracts and negative control, while the standard larvicide (temephos) achieved 100% mortality. Further, the adulticidal efficacy was greatest for aqueous extract of Z. scabra with LC50 = 176.20 ppm followed by aqueous extract of C. aurea (LC50 = 297.75 ppm).

Conclusion

The results suggest that the leaf extracts of the three test plants have the potential of being used for the control of vector An. stephensi larvae and adult instead of synthetic mosquitocides. Further studies need to be conducted to identify the active ingredients and their mode of action.
House screening for malaria control: views and experiences of participants in the RooPfs trial
Authors: Jones Caroline , Matta A. , Pinder Margaret , D’Alessandro Umberto , Knudsen Jakob , Lindsay Steve W.
Published: October 2022

Background

The housing stock of rural sub-Saharan Africa is changing rapidly. With millions of new homes required over the coming decades, there is an opportunity to protect residents by screening homes from malaria mosquitoes. This study, undertaken in the Upper River Region of The Gambia, explores local perceptions of what a good house should provide for its inhabitants and responses to living in a house that has been modified as part of a randomized control trial designed to assess whether improved housing provided additional protection against clinical malaria in children (the RooPfs trial).

Methods

This descriptive, exploratory study was undertaken over 22 months using mixed-methods (informal conversations, observations, focus group discussions, photovoice, and a questionnaire survey) in a parallel convergent design. Analysis was conducted across the data sets using a framework approach. Following coding, the textual data were charted by a priori and emerging themes. These themes were compared with the quantitative survey results. The nature and range of views about housing and the RooPfs study modifications and the relationships among them were identified and described.

Results

The data were derived from a total of 35 sets of observations and informal conversations in 10 villages, 12 discussions with the photovoice photographers, 26 focus group discussions (across 13 villages) and 391 completed questionnaires. The study participants described a ‘good house’ as one with a corrugate-metal roof, cement walls (preferably cement block, but mud block covered with cement plaster was also an acceptable and cheaper substitute) and well-fitting doors. These features align with local perceptions of a modern house that provides social status and protection from physical harms. The RooPfs modifications were largely appreciated, although poor workmanship caused concerns that houses had become insecure. However, the long-term trusting relationship with the implementing institution and the actions taken to rectify problems provided reassurance and enhanced acceptability.

Conclusion

In developing housing to address population needs in Africa, attention should be paid to local perceptions of what is required to make a house secure for its inhabitants, as well as providing a healthy environment.
Scaling severe acute malnutrition treatment with community health workers: a geospatial coverage analysis in rural Mali
Authors: Charle-Cuéllar Pilar , Espí-Verdú Lidia , Goyanes Juan , Bunkembo Magloire , Samake Salimata , Traore Mamadou , Coulibaly Adama Balla , Landouré Aly , Diawara Fatou , Dougnon Abdias Ogobara , Vargas Antonio , López-Ejeda Noemí
Published: October 2022

Background

In 2015, the Ministry of Health in Mali included the treatment of severe acute malnutrition (SAM) into the package of activities of the integrated Community Case Management (iCCM). This paper aims to analyze the impact of including community health workers (CHWs) as treatment providers outside the Health Facilities (HFs) on the coverage of SAM treatment when scaling up the intervention in the three largest districts of the Kayes Region in Mali.

Methods

A baseline coverage assessment was conducted in August 2017 in the three districts before the CHWs started treating SAM. The end-line assessment was conducted one year later, in August 2018. Coverage was assessed by the standardized methodology called Semi-Quantitative Evaluation of Access and Coverage (SQUEAC). The primary outcome was treatment coverage and other variables evaluated were the geographical distribution of the HFs, CHW’s sites and overlapping between both health providers, the estimation of children with geographical access to health care and the estimation of children screened for acute malnutrition in their communities.

Results

Treatment coverage increased in Kayes (28.7–57.1%) and Bafoulabé (20.4–61.1%) but did not in Kita (28.4–28.5%). The decentralization of treatment has not had the same impact on coverage in all districts, with significant differences. The geospatial analyses showed that Kita had a high proportion of overlap between HFs and/or CHWs 48.7% (39.2–58.2), a high proportion of children without geographical access to health care 70.4% (70.1–70.6), and a high proportion of children not screened for SAM in their communities 52.2% (51.9–52.5).

Conclusions

Working with CHWs in SAM increases treatment coverage, but other critical aspects need to be considered by policymakers if this intervention model is intended to be scaled up at the country level. To improve families’ access to nutritional health care, before establishing decentralized treatment in a whole region it must be considered the geographical location of CHWs. This previous assessment will avoid overlap among health providers and ensure the coverage of all unserved areas according to their population densities need.

Trial registration: ISRCTN registry with ID 1990746. https://doi.org/10.1186/ISRCTN14990746
Homes became the “everything space” during COVID-19: impact of changes to the home environment on children’s physical activity and sitting
Authors: Sheldrick Michael P. R. , Swindell Nils J. , Richards Amie B. , Fairclough Stuart J. , Stratton Gareth
Published: October 2022

Background

During the 2020 UK COVID-19 lockdown restrictions, children spent almost all of their time at home, which had a significant influence on their physical activity (PA) and sedentary behaviour. This study aimed to: 1) determine changes to the social and physical environment at home and children’s home-based sitting, PA, standing and sitting breaks as a result of the COVID-19 restrictions; and 2) examine associations between changes at home and children’s movement behaviours.

Methods

One hundred and two children had their PA and sitting, standing and sitting breaks at home objectively measured pre-COVID-19 and during the first COVID-19 lockdown (June-July 2020). Children’s parents (n = 101) completed an audit of their home physical environment and a survey on the home social environment at both time points. Changes in the home physical and social environment and behavioural outcomes were assessed using Wilcoxon signed ranked tests, paired t-tests, or chi-square. Repeated linear regression analyses examined associations between changes in homes and changes in the home-based behavioural outcomes.

Results

During COVID-19, households increased the amount of seated furniture and electronic media equipment at home. The number of books and PA equipment decreased and fewer parents enforced a screen-time rule. Children’s preference for physical activities and socialising at home decreased. Time at home and sitting at home increased during COVID-19, whilst PA, standing and sitting breaks decreased. Both MVPA and TPA were positively associated with child preference for PA, and negatively associated with attending school. Sitting was negatively associated with child preference for PA and child preference for socialising at home. Media equipment was negatively associated with sitting breaks, whilst PA equipment was positively associated with standing.

Conclusion

The COVID-19 restrictions forced children to spend almost all their time at home. Children’s PA, standing, and sitting breaks at home declined during the restrictions, while sitting increased. Mostly negative changes occurred in homes, some of which impacted children’s behaviours at home. To avoid the changes persisting post-lockdown, interventions are needed to reset and promote children’s PA and discourage prolonged sitting time.
Mediators of measurement-based care implementation in community mental health settings: results from a mixed-methods evaluation
Authors: Lewis Cara C. , Boyd Meredith R. , Marti C. Nathan , Albright Karen
Published: October 2022

Background

Tailored implementation approaches are touted as superior to standardized ones with the reasoning that tailored approaches afford opportunities to select strategies to resolve determinants of the local context. However, results from implementation trials on this topic are equivocal. Therefore, it is important to explore relevant contextual factors that function as determinants to evaluate if they are improved by tailoring and subsequently associated with changes in implementation outcomes (i.e., via statistical mediation) to better understand how tailoring achieves (or does not achieve) its effects. The present study examined the association between a tailored and standardized implementation approach, contextual factors that might mediate change, and a target implementation outcome in an initiative to implement measurement-based care (specifically the clinical integration of the Patient Health Questionnaire [PHQ-9] for depression) in a community mental health organization.

Methods

Using a cluster randomized control design, twelve community-based mental health clinics were assigned to a tailored or standardized implementation group. Clinicians completed a self-report battery assessing contextual factors that served as candidate mediators informed by the Framework for Dissemination at three time points: baseline, 5 months after active implementation support, and 10 months after sustainment monitoring. A subset of clinicians also participated in focus groups at 5 months. The routine use of the PHQ-9 (implementation outcome) was monitored during the 10-month sustainment period. Multi-level mediation analyses assessed the association between the implementation group and contextual factors and the association between contextual factors and PHQ-9 completion. Quantitative results were then elaborated by analyzing qualitative data from exemplar sites.

Results

Although tailored clinics outperformed standard clinics in terms of PHQ-9 completion at the end of active implementation, these group differences disappeared post sustainment monitoring. Perhaps related to this, no significant mediators emerged from our quantitative analyses. Exploratory qualitative analyses of focus group content emphasized the importance of support from colleagues, supervisors, and leadership when implementing clinical innovations in practice.

Conclusions

Although rates of PHQ-9 completion improved across the study, their sustained levels were roughly equivalent across groups and low overall. No mediators were established using quantitative methods; however, several partial quantitative pathways, as well as themes from the qualitative data, reveal fruitful areas for future research.

Trial registration

Standardized
versus tailored implementation of measurement-based care for depression. ClinicalTrials.gov
NCT02266134, first posted on October
16, 2014
Anterior cruciate ligament injury and its postoperative outcomes are not associated with polymorphism in COL1A1 rs1107946 (G/T): a case–control study in the Middle East elite athletes
Authors: Mirghaderi Seyed Peyman , Salimi Maryam , Kheirollahi Majid , Mortazavi Seyed Mohammad Javad , Akbari-Aghdam Hossein
Published: October 2022

Background

It is unclear what role COL1A1 polymorphisms play in anterior cruciate ligament (ACL) injury pathophysiology. The present study investigated the relationship between COL1A1-1997 guanine (G)/thymine (T) (rs1107946) polymorphism and ACL injury. Moreover, the possible effect of this polymorphism on the postoperative outcomes of ACL reconstruction surgery was evaluated.

Methods

This prospective case–control study was performed on 200 young professional men with an ACL tear who underwent arthroscopic ACL reconstruction surgery. Moreover, 200 healthy athletes without a history of tendon or ligament injury who were matched with the case group were selected as the control group. DNA was extracted from the leukocytes of participants, and the desired allele was genotyped. Clinical outcomes were collected for the case group before and one year after surgery.

Results

The genotype distribution was in accordance with the Hardy–Weinberg principle. In the ACL injury group, the G allele frequency was non-significantly higher than the healthy controls, with an odds ratio [95% CI] of 1.08 [0.79–1.47] (P = 64). We did not find a significant difference between the genotype of individuals—GG, GT, and TT—in the case and control groups (P > 0.05). Clinical outcomes of the ACL tear group were significantly improved in terms of preoperative values. However, none of them were significantly different between the three genotypes (GG, GT, and TT).

Conclusion

According to the findings of the present investigation, single-nucleotide polymorphism (SNP) at COL1A1 rs1107946 (G/T) was not a predisposing genetic factor for ACL injury in a young professional male athlete population in the Middle East. Furthermore, patients' responses to treatment were not different between distinct genotypes.

Level of evidence III.
Genomic characteristics of two breast malignant phyllodes tumors during pregnancy and lactation identified through whole-exome sequencing
Authors: Lei Ting , Shen Mengjia , Deng Xu , Shi Yongqiang , Peng Yan , Wang Hui , Chen Tongbing
Published: October 2022

Background

The genomic landscape of breast malignant phyllodes tumors (PTs) is not well defined, especially pregnancy-related malignant PTs. To clarify this topic, whole-exome next-generation sequencing (NGS) was performed on tumor samples and paired normal breast tissues from two pregnancy-related malignant PTs, followed by a functional analysis of the genetic alterations.

Methods

DNA from malignant PT samples and matched normal breast tissues of both patients were subjected to molecular profiling. NGS of the whole-exome was performed in a commercial molecular pathology laboratory. Predictive tools were used to estimate genetic variation in somatic and germline genes.

Results

In total, 29 somatic genomic alterations and 18 germline alterations were found in both patients. In Patient 1, 12 aberrations were identified in the tumor tissue, and 9 alterations were identified in matched normal breast tissue. One pathogenic variant in tumor suppressor genes (TP53) was detected in patient 1. In Patient 2, 18 and 10 variants were found in the tumor and matched normal breast tissue, respectively. In Patient 2, pathogenic alterations were identified in two tumor suppressor genes (PTENandTP53).PTENandTP53may be potential drug targets. The functional predictive tools showed that genes of unknown significance for PTs, includingFCHO1in Patient 1, andLRP12andPKMin Patient 2, were pathogenic. Several genes, includingFCHO1,LRP12andPKM, were shown for the first time to be altered in malignant PTs. A potentially pathogenic germline variant inPRF1, was detected in Patient 1.

Conclusion

Our study first demonstrated somatic and germline gene alterations in two malignant PTs during pregnancy and lactation. These two PTs shared major genetic events, includingTP53mutation, which commonly occurs in malignant PTs; additionally, we identified two potential genes for targeted therapy,TP53andPTEN. One germline mutation inPRF1was also detected. These results provide clues regarding tumor pathogenesis and precision therapy development.
Lactobacillus crispatus M247 oral administration: Is it really an effective strategy in the management of papillomavirus-infected women?
Authors: Dellino Miriam , Cascardi Eliano , Laganà Antonio Simone , Di Vagno Giovanni , Malvasi Antonio , Zaccaro Rosanna , Maggipinto Katia , Cazzato Gerardo , Scacco Salvatore , Tinelli Raffaele , De Luca Alessandro , Vinciguerra Marina , Loizzi Vera , Daniele Antonella , Cicinelli Ettore , Carriero Carmine , Genco Chiara Antonia , Cormio Gennaro , Pinto Vincenzo
Published: October 2022

Background

Recent studies have shown the importance of the microbiota in women's health. Indeed, the persistence of Human Papilloma Virus (HPV)-related lesions in patients with dysbiosis can be the antechamber to cervical cancer. The aim of this study was to evaluate whether long term administration of oral Lactobacillus crispatus can restore eubiosis in women with HPV infections and hence achieve viral clearance.

Methods

In total, 160 women affected by HPV infections were enrolled at the Department of Gynecological Obstetrics of “San Paolo” Hospital, Italy between February 2021 and February 2022. The women were randomly assigned to two groups, one in treatment with oral Lactobacillus crispatus M247 (group 1, n = 80) versus the control group, that hence only in follow-up (Group 2, n = 80).

Results

After a median follow-up of 12 months (range 10–30 months), the likelihood of resolving HPV-related cytological anomalies was higher in patients in treatment with the long term oral probiotic (group 1) versus the group that perfom only follow-up (group 2) (60.5% vs. 41.3%, p = 0.05). Total HPV clearance was shown in 9.3% of patients undergoing only follow-up compared to 15.3% of patients in the group taking long term oral Lactobacillus crispatus M247 (p = 0.34). However, the percentage of HPV-negative patients, assessed with the HPV-DNA test, documented at the end of the study period was not significantly different from the control group.

Conclusions

Despite the limitations of our analysis, we found a higher percentage of clearance of PAP-smear abnormalities in patients who took long term oral Lactobacillus crispatus M247 than in the control group. Larger studies are warranted, but we believe that future research should be aimed in this direction.

Trial registration This study is retrospectively registered.
HER3 in cancer: from the bench to the bedside
Authors: Gandullo-Sánchez Lucía , Ocaña Alberto , Pandiella Atanasio
Published: October 2022

The HER3 protein, that belongs to the ErbB/HER receptor tyrosine kinase (RTK) family, is expressed in several types of tumors. That fact, together with the role of HER3 in promoting cell proliferation, implicate that targeting HER3 may have therapeutic relevance. Furthermore, expression and activation of HER3 has been linked to resistance to drugs that target other HER receptors such as agents that act on EGFR or HER2. In addition, HER3 has been associated to resistance to some chemotherapeutic drugs. Because of those circumstances, efforts to develop and test agents targeting HER3 have been carried out. Two types of agents targeting HER3 have been developed. The most abundant are antibodies or engineered antibody derivatives that specifically recognize the extracellular region of HER3. In addition, the use of aptamers specifically interacting with HER3, vaccines or HER3-targeting siRNAs have also been developed. Here we discuss the state of the art of the preclinical and clinical development of drugs aimed at targeting HER3 with therapeutic purposes.
Novel sensing probe using Terbium-sensitized luminescence and 8-hydroxyquinoline for determination of prucalopride succinate: green assessment with Complex-GAPI and analytical Eco-Scale
Authors: Elshahed Mona S. , Toubar Safaa S. , Ashour Azza A. , El-Eryan Rasha Th.
Published: October 2022

A highly sensitive spectrofluorimetric method is developed for the determination of prucalopride succinate (PRU). The method depends on lanthanide-sensitized luminescence due to complex formation between the drug and terbium chloride (Tb+3) which is enhanced by the addition of 8 hydroxyquinoline (8HQ) and phosphate buffer (0.02 M, pH 3.2). The calibration curve was constructed over the linear range 10–300 ng/mL after excitation at 226 nm and measuring the emission of the ternary complex at 544 nm. The method was validated according to ICH Q2 (R1) guidelines and showed a good recovery ± RSD of 100.41% ± 1.26, the limits of detection and quantitation were found to be 2.81 and 8.53 ng/mL, respectively. The proposed method was successfully applied for the determination of the drug marketed tablet dosage form and the results were in good agreement with the reference method. Also, the method greenness was evaluated according to Complex-GAPI and analytical Eco-Scale.
G6PD promotes cell proliferation and dexamethasone resistance in multiple myeloma via increasing anti-oxidant production and activating Wnt/β-catenin pathway
Authors: Li Rui , Ke Mengying , Qi Mingming , Han Zhenru , Cao Yuhao , Deng Zhendong , Qian Jinjun , Yang Ye , Gu Chunyan
Published: October 2022

Background

Glucose-6-phosphate dehydrogenase (G6PD) as the rate-limiting enzyme in the pentose phosphate pathway (PPP) is well-established as an aberrantly expressed protein in numerous clinical diseases; however, its role in cancer, specifically in multiple myeloma (MM) remains elusive.

Methods

In this study, serum metabolites in 70 normal people and 70 newly diagnosed MM patients were analyzed using untargeted metabolomics and the results were verified using ELISA. The survival analysis of multiple clinical datasets was performed to identify a potential target gene in MM. The oncogenic role of G6PD was investigated using lentivirus-based overexpression or knockdown of G6PD using RNAi or an inhibitor in vitro, and in a xenograft mouse model in vivo. The mechanisms of induced Dexamethasone (Dexa)-resistance of G6PD were further explored using the above established MM cell lines in vitro.

Results

Based on the screening of potential genes, PPP was shown to be involved in the occurrence of MM, which was evidenced by the differential expression of serum metabolites of G6P and Dehydroepiandrosterone sulfate (DHEAS, the more stable sulfate ester form of an endogenously uncompetitive G6PD inhibitor known as DHEA). Elevated G6PD promoted MM cell proliferation. Mechanistically, high G6PD expression enhanced enzymatic generation of the antioxidant NADPH via the PPP and decreased the production of reactive oxygen species (ROS), thus inducing the proliferation and Dexa resistance in MM cells. Furthermore, canonical Wnt/β-catenin signaling also participated in regulating G6PD-induced drug resistance and cellular redox levels of ROS. Intriguingly, DHEA treatment could enhance the sensitivity of MM cells to Dexa primarily through augmenting cellular oxidative stress.

Conclusions

Our data demonstrate that G6PD enhances the generation of the enzymatic anti-oxidant NADPH and decreases ROS generation, thereby promoting resistance to Dexa-induced apoptosis via the enzymatic PPP and non-enzymatic Wnt/β-catenin signaling pathway in MM. Targeting G6PD to harness cellular redox may serve as a promising novel strategy for the management of MM.