bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of urinary tract infection and antimicrobial resistance patterns of uropathogens with biofilm forming capacity among outpatients in morogoro, Tanzania: a cross-sectional study
Authors: Mlugu Eulambius M. , Mohamedi Juma A. , Sangeda Raphael Z. , Mwambete Kennedy D.
Published: October 2023

Introduction

Urinary tract infection (UTI) is the second most common infectious disease affecting more than 150 million people globally annually. UropathogenicE. coli(UPEC), the predominant cause of UTI, can occur as a biofilm associated with antimicrobial resistance (AMR). There is a data gap on global AMR patterns from low-income settings, including Tanzania. Data on antimicrobial susceptibility patterns in relation to biofilm formation will help in the proper selection of antibiotics and the fight against AMR.

Methods

This analytical cross-sectional study was conducted among consecutively selected outpatients (n = 344) from January to May 2022 at Morogoro Regional Referal Hospital. Mid-stream urine samples were collected aseptically from symptomatic patients. A significant UTI was defined when more than 105colonies/ml of urine were recorded. Kirby Bauer’s disc diffusion method was used for antibiotics susceptibility patterns and a Congo Red Agar method was used to determine biofilm formation. Two-sided χ2 test or Fisher’s exact test, Cohen’s kappa coefficient and logistic regression were used for data analysis. A p-value < 0.05 was considered statistically significant.

Results

The prevalence of UTIs was 41% (141/344) and elders (>=60 years) had five times higher odds of having UTI as compared to adolescents (p < 0.001).E. coliwas the most predominant bacteria (47%; 66/141), which displayed moderate susceptibility against ciprofloxacin (59.1%) and nitrofurantoin (57.6%). A total of 72 (51%) of all isolated bacteria were multi-drug resistant. All isolated bacteria demonstrated high resistance (> 85%) against ampicillin and co-trimoxazole. In this study, 51.5% (34/66) were biofilm-formingE. coliand demonstrated relatively higher antibiotic resistance as compared to non-biofilm forming bacteria (p < 0.05).

Conclusion

We report high antibiotic resistance against commonly used antibiotics. Slightly more than half of the isolated bacteria were biofilm formingE. coli.A need to strengthen stewardship programs is urgently advocated.
Prevalence of Neurolathyrism and its associated factors in Grass pea cultivation areas of Dawunt District, North-eastern Ethiopia; 2022: a community based multilevel analysis
Authors: Bimerew Melaku , Gebremeskel Teshome , Beletew Biruk , Ayalneh Manay , Ayaliew Wondye , Wodaje Mulugeta
Published: October 2023

Introduction

: Neurolathyrism is an upper motor neuron disorder characterized by spastic paraparesis, which is caused by the prolonged over-consumption of grass pea. It is a devastating disease with great impacts on physical, social, mental, and economical health.

Objective

To determine the prevalence of neurolathyrism and its associated factors in grass pea cultivation areas of Dawunt wereda.

Methods

Community based cross-sectional study design was conducted from February 01- March 30, 2021 on 631 Households with a total of 3,350 individuals. Two-stage random sampling technique was used to select participants. Multilevel binary logistic regression was used to identify factors associated with neurolathyrism. Statistical significance was declared at p < 0.05; and AOR with 95% CI was used to interpret the results.

Results

The household and population level prevalence of neurolathyrism in Dawunt district were 9.2% (7.2–11.7%) and 2.4% (2.0-2.3.0%) respectively. Age (AOR = 7.4 ( 2.6–20.6)), male sex (AOR = 7.8 (3.9, 15.4)), and marital status (AOR = 4.0 (1.3–12.8)) were the individual level variables; family size (AOR = 12.6 (3.0-52.8)), annual grass pea production (AOR = 5.0 (2.3–11.0)), ever feeding only grass pea (AOR = 8.8(3.5–22.2)), ever feeding immature seeds of grass pea (AOR = 6.28 (2.80, 14.08)), high grass pea to other cereals mixing ratio (> 3:1) (AOR = 6.1 (1.1, 33.5)) were the household level variables found to have significant association with neurolathyrism.

Conclusion

The prevalence of neurolathyrism was found to be high. Ever feeding only grass pea, Grass pea to other cereals mixing ratio (using ratio of 1:1 or more), and Ever feeding immature grass pea seeds were the modifiable risk factors for neurolathyrism.
Strengthening quality in sexual, reproductive, maternal, and newborn health systems in low- and middle-income countries through midwives and facility mentoring: an integrative review
Authors: Anderson Rondi , Zaman Sojib Bin , Jimmy Abdun Naqib , Read Jonathan M , Limmer Mark
Published: October 2023

Background

There is an urgent global call for health systems to strengthen access to quality sexual, reproductive, maternal, newborn and adolescent health, particularly for the most vulnerable. Professional midwives with enabling environments are identified as an important solution. However, a multitude of barriers prevent midwives from fully realizing their potential. Effective interventions to address known barriers and enable midwives and quality sexual, reproductive, maternal, newborn and adolescent health are less well known. This review intends to evaluate the literature on (1) introducing midwives in low- and middle-income countries, and (2) on mentoring as a facilitator to enable midwives and those in midwifery roles to improve sexual, reproductive, maternal, newborn and adolescent health service quality within health systems.

Methods

An integrative systematic literature review was conducted, guided by the Population, Intervention, Comparison, Outcome framework. Articles were reviewed for quality and relevance using the Gough weight-of-evidence framework and themes were identified. A master table categorized articles by Gough score, methodology, country of focus, topic areas, themes, classification of midwives, and mentorship model. The World Health Organization health systems building block framework was applied for data extraction and analysis.

Results

Fifty-three articles were included: 13 were rated as high, 36 as medium, and four as low according to the Gough criteria. Studies that focused on midwives primarily highlighted human resources, governance, and service delivery while those focused on mentoring were more likely to highlight quality services, lifesaving commodities, and health information systems. Midwives whose pre-service education met global standards were found to have more efficacy. The most effective mentoring packages were comprehensive, integrated into existing systems, and involved managers.

Conclusions

Effectively changing sexual, reproductive, maternal, newborn and adolescent health systems is complex. Globally standard midwives and a comprehensive mentoring package show effectiveness in improving service quality and utilization.

Trial registration

The protocol is registered in PROSPERO (CRD42022367657).
Prevalence and characteristics of patients with upper urinary tract urothelial carcinoma having potential Lynch syndrome identified by immunohistochemical universal screening and Amsterdam criteria II
Authors: Tanabe Kenji , Nakanishi Yasukazu , Okubo Naoya , Matsumoto Shunya , Umino Yosuke , Kataoka Madoka , Yajima Shugo , Yoshida Teruhiko , Miyazaki Saori , Kuwata Takeshi , Ishii Genichiro , Watanabe Reiko , Masuda Hitoshi
Published: October 2023

Background

This study aimed to identify patients with upper urinary tract urothelial carcinoma (UTUC) having potential Lynch syndrome (pLS) by immunohistochemistry (IHC) of DNA mismatch repair gene-related proteins (MMRPs) and Amsterdam criteria II and explore their clinical characteristics.

Methods

We retrospectively collected the clinical data of 150 consecutive patients with UTUC who underwent surgical resection at our institution between February 2012 and December 2020, and immunohistochemistry (IHC) of four MMRPs (MLH1, MSH2, MSH6, and PMS2) on all UTUC specimens was performed. Patients who tested positive for Amsterdam criteria (AMS) II and/or IHC screening were classified as having pLS and others as non-pLS, and their characteristics were explored.

Results

In this study, 5 (3%) and 6 (4%) patients were positive for AMS II and IHC screening, respectively. Two patient were positive for both AMS II and IHC screening, resulting in 9 (6%) patients with pLS. The pLS group was predominantly female (67% vs. 36%; p = 0.0093) and had more right-sided tumors (100% vs. 43%; p = 0.0009) than the non-pLS group. Of the 6 patients who were positive for IHC screening, 4 showed a combined loss of MSH2/MSH6 (n = 3) and MLH1/PMS2 (n = 1). Other two patients showed single loss of MSH6 and PSM2.

Conclusions

AMS II and IHC screening identified pLS in 6% of patients with UTUC. The IHC screening-positive group tends to have relatively high rate of combined loss, but some patients have single loss. AMS II may overlook patients with LS, and a universal screening may be required for patients with UTUC as well as those with colorectal and endometrial cancer.
Effects of fasciatherapy versus fascial manipulation on pain, range of motion and function in patients with chronic neck pain
Authors: Batool Syeda Aiman , Shakil-ul-Rehman Syed , Tariq Zainab , Ikram Mehwish
Published: October 2023

Background

Neck pain is among the common musculoskeletal problem that hinders a person’s daily activities. Fascial tightness is a familiar cause of chronic neck pain that is often neglected and can further cause neck disability and a limited range of motion.

Objective

The purpose was to compare the effects of fascia therapy and fascial manipulation on pain, range of motion and function in patients with chronic neck pain.

Methods

A randomized clinical trial was conducted from February to August 2022 in the Riphah Rehabilitation Centre, Lahore, Pakistan. Fifty-two participants of both genders, aged 18–40 years with chronic neck pain of at least 3–6 months were included. Group A (n = 26) received fascia therapy along with a conventional physical therapy protocol of hot pack, strengthening and stretching, while group B (n = 26) received the fascial manipulation treatment with conventional physical therapy. All the participants were assessed at baseline and after 3 weeks (3 sessions per week). Numeric Pain Rating Scale (NPRS), Neck Disability Index (NDI) and Goniometer (range of motions) were the outcome measures. SPSS 25 was used for the data analysis and normality of the data through the Shaphiro-Wilk test (p > 0.05), and parametric tests were applied.

Results

The mean age of group A was 24.82 ± 2.64 years, and group B was 24.17 ± 2.20 years. The independent t-test result showed no significant difference (p ≥ 0.05) in all parameters except in cervical extension and right-side bending (p < 0.05). At the same time, the pair-wise comparison showed significant results (p < 0.05) for all outcome measures in both groups.

Conclusion

DBM fascia therapy improved cervical extension and side bending (right) more than the fascial manipulation group.It is concluded that DBM fascia therapy shows more improvement as compared to other group.

Trial registration number

This study was registered at ClinicalTrials.gov ID: NCT05272111 on 09/03/2022.
Assessment of micromotion at the bone-bone interface after coracoid and scapular-spine bone-block augmentation for the reconstruction of critical anterior glenoid bone loss—a biomechanical cadaver study
Authors: Youssef Yasmin , Heilemann Martin , Melcher Peter , Fischer Jean-Pierre , Schleifenbaum Stefan , Hepp Pierre , Theopold Jan
Published: October 2023

Background

Glenoid bone loss is among the most important risk factors for recurrent anterior shoulder instability, and a bony reconstruction is recommended in cases of critical bone loss (> 15%). The commonly used surgical techniques, including coracoid transfer, are associated with considerable complications. The aim of this study was to assess the motion at the glenoid-bone-block interface after coracoid and spina-scapula bone-block reconstruction of the anterior glenoid.

Methods

Twelve cadaveric shoulders were tested. A 20% bone defect of the anterior glenoid was created, and the specimens were randomly assigned for glenoid augmentation using a coracoid bone block (n = 6) or a scapular spine bone block (n = 6). The glenoid-bone interface was cyclically loaded for 5000 cycles with a force of 170 N. The micromotion was tracked using an optical measurement system (GOM ARMIS) and was evaluated with the GOM Correlate Pro software.

Results

The most dominant motion component was medial irreversible displacement for the spina-scapula (1.87 mm; SD: 1.11 mm) and coracoid bone blocks (0.91 mm; SD: 0.29 mm) (n.s.). The most medial irreversible displacement took place during the first nine cycles. The inferior reversible displacement was significantly greater for spina-scapula bone blocks (0.28 mm, SD: 0.16 mm) compared to coracoid bone blocks (0.06 mm, SD: 0.10 mm) (p = 0.02).

Conclusions

The medial irreversible displacement is the dominant motion component in a bone-block reconstruction after a critical bone loss of the anterior glenoid. The spina-scapula and coracoid bone blocks are comparable in terms of primary stability and extent of motion. Thus, spina-scapula bone blocks may serve as alternatives in bony glenoid reconstruction from a biomechanical point of view.
The association between thyroid dysfunction, autoimmune thyroid disease, and rheumatoid arthritis disease severity
Authors: Yazdanifar Mohammad Amin , Bagherzadeh-Fard Mahsa , Habibi Mohammad Amin , Vahedian Mostafa , Bagherzadeh Mohammad , Masoumi Maryam
Published: October 2023

Background

Rheumatoid Arthritis (RA) and autoimmune thyroid disease (AITD) are the two most prevalent coexisting autoimmune diseases due to their similar pathogenesis. Considering the potential effect of AITD on the severity of RA disease, this study aimed to determine the association between thyroid dysfunction, anti-thyroid peroxidase (anti-TPO) positivity, AITD, and RA disease severity in the Iranian population.

Methods

Three hundred and fifty RA patients who presented to Shahid Beheshti tertiary care center, Qom, Iran, were included in this cross-sectional study. The data were collected through the patient’s medical records, interviews, physical examinations, and laboratory tests. The RA disease activity score in 28 joints for RA with erythrocyte sedimentation rate (DAS-28-ESR) was used to divide patients into three subgroups, remission (DAS-28-ESR ⩽ 2.6), mild-to-moderate (2.6 < DAS-28-ESR ⩽ 5.1), and severe disease activity (DAS-28-ESR > 5.1).

Results

Using the aforementioned method, 111, 96, and 138 patients were put into remission, mild-to-moderate, and severe disease activity groups, respectively. Anti-TPO antibody positivity rate was 2.93 times more prevalent among patients with severe disease compared to the remission subgroup (OR: 2.93; P-value < 0.001). Patients suffering from a more severe disease were almost 2.7 times more probable to have AITD (OR = 2.71; P-value < 0.001) and they were 82% more likely to have thyroid dysfunction compared to patients in remission (OR = 1.82; P-value = 0.006).

Conclusions

It was demonstrated that thyroid dysfunction, anti-TPO antibody positivity, and AITD were significantly more common among RA patients with more severe disease activity.
Development and validation of a case definition for problematic menopause in primary care electronic medical records
Authors: Pham Anh N.Q. , Cummings Michael , Yuksel Nese , Sydora Beate , Williamson Tyler , Garies Stephanie , Pilling Russell , Lindeman Cliff , Ross Sue
Published: October 2023

Background

Menopause is a normal transition in a woman’s life. For some women, it is a stage without significant difficulties; for others, menopause symptoms can severely affect their quality of life. This study developed and validated a case definition for problematic menopause using Canadian primary care electronic medical records, which is an essential step in examining the condition and improving quality of care.

Methods

We used data from the Canadian Primary Care Sentinel Surveillance Network including billing and diagnostic codes, diagnostic free-text, problem list entries, medications, and referrals. These data formed the basis of an expert-reviewed reference standard data set and contained the features that were used to train a machine learning model based on classification and regression trees. An ad hoc feature importance measure coupled with recursive feature elimination and clustering were applied to reduce our initial 86,000 element feature set to a few tens of the most relevant features in the data, while class balancing was accomplished with random under- and over-sampling. The final case definition was generated from the tree-based machine learning model output combined with a feature importance algorithm. Two independent samples were used: one for training / testing the machine learning algorithm and the other for case definition validation.

Results

We randomly selected 2,776 women aged 45–60 for this analysis and created a case definition, consisting of two occurrences within 24 months of International Classification of Diseases, Ninth Revision, Clinical Modification code 627 (or any sub-codes) OR one occurrence of Anatomical Therapeutic Chemical classification code G03CA (or any sub-codes) within the patient chart, that was highly effective at detecting problematic menopause cases. This definition produced a sensitivity of 81.5% (95% CI: 76.3-85.9%), specificity of 93.5% (91.9-94.8%), positive predictive value of 73.8% (68.3-78.6%), and negative predictive value of 95.7% (94.4-96.8%).

Conclusion

Our case definition for problematic menopause demonstrated high validity metrics and so is expected to be useful for epidemiological study and surveillance. This case definition will enable future studies exploring the management of menopause in primary care settings.
‘Whose role is it anyway?’ Experiences of community nurses in the delivery and support of oral health care for older people living at home: a grounded theory study
Authors: Mitchell Gary , Stark Patrick , Wilson Christine Brown , Tsakos Georgios , Brocklehurst Paul , Lappin Caroline , Quinn Barry , Holland Nicola , McKenna Gerry
Published: October 2023

Background

Older people who receive care at home are likely to require support with oral health care. Community nurses, who are also referred to as district or home care nurses, have an important role with this population. This is because they are the healthcare professionals who are most likely to encounter this population, who may also not be receiving regular dental care or oral health promotion. However, few studies have explored community nursing experiences in the delivery and support of oral healthcare for older people living at home.

Methods

A grounded theory approach was used to explore experiences of community nurses in the delivery and support of oral health care for older people living at home. Fifteen practising community nurses from the United Kingdom participated in one-to-one semi-structed interviews from May 2021 to December 2021. These interviews were audio-recorded, transcribed verbatim and analysed using constant comparative analysis. Ethical approval was obtained for this study prior to data collection.

Results

Four categories emerged from the data to support development of the core phenomena. These four categories were: (1) Education, in relation to what community nurses knew about oral health, (2) Practice, with regards to how community nurses delivered oral health care to older people in their own home, (3) Confidence, with consideration to the extent to which this supported or impeded community nurses in providing oral healthcare to older people and (4) Motivation, in terms of the extent to which community nurses thought they could or should influence future practice improvement in the area. The core category was (C) Uncertainty as it was both present and central across all four categories and related to community nursing understanding about their specific role, and the role of other professionals, with reference to oral health of their patients.

Conclusions

This study reveals community nurses' uncertainty in providing oral healthcare to older adults at home. Emphasising comprehensive and continuous oral health education can boost nurses' confidence in patient support. Interprofessional collaboration and clear role definitions with oral health professionals are crucial for improving oral health outcomes in this vulnerable population.
The most effective systemic treatment in dogs with sarcoptic mange: a critically appraised topic
Authors: Dumitrache Mirabela O. , Cadiergues Marie-Christine
Published: October 2023

Background

Sarcoptic mange is a common, pruritic parasitic skin disease of dogs. Due to its highly contagious character, it represents a potential veterinary and public health risk. Because of clinical similarity with other diseases, cross-antigenicity, and low sensitivity of available diagnostic methods, therapeutical trial is frequently used to confirm the disease. Considering the variety of available acaricidal molecules as well as the need to use the most effective treatment, the present paper reviews evidence comparing different types of systemic treatment of canine scabies.

Results

Analysis of the results showed that afoxolaner, fluralaner and sarolaner as well as several macrocyclic lactones such as selamectin, moxidectin and milbemycin oxime can lead to parasitological and clinical cure.

Conclusion

The similarity in the clinical and parasitological efficacy of these substances enhances the need for comparative studies, which could allow the identification of the most efficacious product.
Ex-vivo RNA expression analysis of vaccine candidate genes in COPD sputum samples
Authors: Brettoni Cecilia , Muzzi Alessandro , Rondini Simona , Weynants Vincent , Rossi Paccani Silvia
Published: October 2023

Background

Chronic obstructive pulmonary disease (COPD) is a lung disease characterised by airflow-limiting inflammation and mucus production. Acute exacerbations are a major cause of COPD-related morbidity and mortality and are mostly associated with bacterial or viral infections. A vaccine targeting non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat), the main bacteria associated with exacerbations, was tested in a Phase 2 trial. We assessed “ex-vivo” expression of vaccine candidate and housekeeping genes pd, pe, pilA, gapA, ompP6 of NTHi, and uspA2, parE, polA of Mcat in sputum samples of COPD patients and determined whether expression of the vaccine candidate genes pd, pe, pilA (NTHi) and uspA2 (Mcat) differed between stable and exacerbation samples.

Methods

A single-centre, prospective, observational cohort study was conducted where 123 COPD patients were seen on enrolment, followed monthly for 2 years, and reviewed after onset of acute exacerbations. We selected 69 patients with sputum samples positive for NTHi or Mcat by PCR during at least one stable and one exacerbation visit. mRNA was isolated from the sputum, and expression of NTHi and Mcat genes was analysed with RT-PCR. Statistical analyses compared mRNA concentrations between stable and exacerbation samples and in relationship to COPD severity and exacerbation frequency.

Results

The vaccine candidate genes were variably expressed in sputum samples, suggesting they are expressed in the lung. Absolute and relative expression of all NTHi vaccine candidate genes and Mcat uspA2 were similar between exacerbation and stable samples. Expression of pd and pilA was slightly associated with the number of exacerbations in the year before enrolment, and uspA2 with the disease severity status at enrolment.

Conclusions

The NTHi-Mcat vaccine candidate genes were expressed in sputum samples, and each gene had a specific level of expression. No statistically significant differences in gene expression were detectable between stable and exacerbation samples. However, the history of COPD exacerbations was slightly associated with the expression of pd, pilA and uspA2.

Trial registration NCT01360398 (https://www.clinicaltrials.gov)

Graphical abstract
Effect of predators on Anopheles arabiensis and Anopheles funestus larval survivorship in Homa Bay County Western Kenya
Authors: Orondo Pauline Winnie , Zhou Guofa , Ochwedo Kevin O. , Wang Xiaoming , Ondeto Benyl M. , Lee Ming-Chieh , Nyanjom Steven G. , Atieli Harrysone , Githeko Andrew K. , Kazura James W. , Yan Guiyun
Published: October 2023

Background

The rise of insecticide resistance against malaria vectors in sub-Saharan Africa has resulted in the need to consider other methods of vector control. The potential use of biological methods, including larvivorous fish, Bacillus thuringiensis israelensis (Bti) and plant shading, is sustainable and environmentally friendly options. This study examined the survivorship of Anopheles arabiensis and Anopheles funestus larvae and habitat productivity in four permanent habitat types in Homa Bay county, western Kenya.

Methods

Predator densities were studied in a laboratory setup while habitat productivity and larval survivorship was studied in field setup.

Results

Fish were observed as the most efficient predator (75.8% larval reduction rate) followed by water boatman (69%), and dragonfly nymph (69.5%) in predation rates. Lower predation rates were observed in backswimmers (31%), water beetles (14.9%), water spiders (12.2%), mayflies (7.3%), and tadpoles (6.9%). Increase in predator density in the field setup resulted in decreased Culex larval density. Larval and pupa age–specific distribution was determined and their survivorship curves constructed. Combined larvae (Stage I–IV) to pupa mortality was over 97% for An. arabiensis and 100% for An. funestus. The highest larval stage survival rate was from larval stages I to II and the lowest from larval stage IV to pupa. Stage-specific life tables indicated high mortality rates at every developmental stage, especially at the larval stage II and III.

Conclusion

Determination of the efficiency of various larval predators and habitat productivity will help with the correct identification of productive habitats and selection of complementary vector control methods through environmental management and/or predator introduction (for instance fish) in the habitats.
Evaluation of the novel three lipid indices for predicting five- and ten-year incidence of cardiovascular disease: findings from Kerman coronary artery disease risk factors study (KERCADRS)
Authors: Jafari Alireza , Najafipour Hamid , Shadkam Mitra , Aminizadeh Sina
Published: October 2023

Background

Data are limited on the relationship between cardiovascular disease (CVD) and the combinational indices of lipid accumulation product (LAP), triglyceride-glucose index (TyG), and visceral adiposity index (VAI). The association of these novel indices with the 5- and 10-year incidence of CVD was assessed.

Method

A total of 1888 and 1450 healthy adults aged between 15 and 75 years (out of the 5895 participants of the KERCADR study, 2012) were followed for five and ten years, respectively. Baseline LAP, TyG, and VAI were calculated and logistic regression models were used to assess their relationship with the incidence of CVD in the two follow-up periods. Also, the predictive performance of these three indices was analyzed using the area under ROC curve (AUC) for the development of CVD compared with traditional single indices.

Results

In the 5- and 10-year follow-ups, 399 and 476 CVD cases (21.1% and 32.8%) were documented, respectively. For the 5-year CVD risk, the adjusted odds ratio (AOR, 95% CI) was LAP (2.24 [1.44, 3.50]), VAI (1.58 [1.08, 2.33]), and TyG (1.57 [1.02, 2.42]). For the 10-year CVD risk, the AOR was LAP (1.61 [1.04, 2.49]), TyG (1.57 [1.02, 2.41]), and VAI (1.41 [0.96, 2.09]). In both periods and sexes, LAP had the best performance with the highest AUCs (0.644 and 0.651) compared to the other two indices and compared to the traditional single indices (e.g., BMI, LDL, etc.).

Conclusion

Overall LAP, TyG, and VAI were better CVD risk predictors compared to the traditional single risk factors, with LAP showing the strongest predictive power for the incidence of CVD.
Microvesicles from bone marrow-derived mesenchymal stem cells promote Helicobacter pylori-associated gastric cancer progression by transferring thrombospondin-2
Authors: Qi Cuihua , Shi Huiying , Fan Mengke , Chen Weigang , Yao Hailing , Jiang Chen , Meng Lingjun , Pang Suya , Lin Rong
Published: October 2023

Background

Our previous study found that bone marrow-derived mesenchymal stem cells (BMSCs) promote Helicobacter pylori (H pylori)-associated gastric cancer (GC) progression by secreting thrombospondin-2 (THBS2). Extracellular vesicles (EVs) are important carriers for intercellular communication, and EVs secreted by BMSCs have been shown to be closely related to tumor development. The aim of this study was to investigate whether BMSC-derived microvesicles (MVs, a main type of EV) play a role in H. pylori-associated GC by transferring THBS2.

Methods

BMSCs and THBS2-deficient BMSCs were treated with or without the supernatant of H. pylori for 12 h at a multiplicity of infection of 50, and their EVs were collected. Then, the effects of BMSC-derived MVs and THBS2-deficient BMSC-derived MVs on the GC cell line MGC-803 were assessed by in vitro proliferation, migration, and invasion assays. In addition, a subcutaneous xenograft tumor model, a nude mouse intraperitoneal metastasis model, and a tail vein injection metastasis model were constructed to evaluate the effects of BMSC-derived MVs and THBS2-deficient BMSC-derived MVs on GC development and metastasis in vivo.

Results

BMSC-derived MVs could be readily internalized by MGC-803 cells. BMSC-derived MVs after H. pylori treatment significantly promoted their proliferation, migration and invasion in vitro (all P < 0.05) and promoted tumor development and metastasis in a subcutaneous xenograft tumor model, a nude mouse intraperitoneal metastasis model, and a tail vein injection metastasis model in vivo (all P < 0.05). The protein expression of THBS2 was significantly upregulated after H. pylori treatment in BMSC-derived MVs (P < 0.05). Depletion of the THBS2 gene reduces the tumor-promoting ability of BMSC-MVs in an H. pylori infection microenvironment both in vitro and in vivo.

Conclusion

Overall, these findings indicate that MVs derived from BMSCs can promote H. pylori-associated GC development and metastasis by delivering the THBS2 protein.
TRPA1 promotes cisplatin-induced acute kidney injury via regulating the endoplasmic reticulum stress-mitochondrial damage
Authors: Deng Fei , Zhang Heping , Zhou Wei , Ma Shijie , Kang Yuwei , Yang Wei , Zhao Liangbin , Qin Wei
Published: October 2023

Background

Cisplatin is a widely used and effective chemotherapeutic agent against cancer. However, nephrotoxicity is one of the most common side effects of cisplatin, and it can proceed to acute kidney injury (AKI). Studies have reported that activation of transient receptor potential ankyrin-1 (TRPA1) mediates cisplatin-induced renal tubular cytotoxic injury. The aim of this study was to investigate the mechanism of TRPA1 in promoting cisplatin-induced AKI through modulation of the endoplasmic reticulum stress (ERS)-mitochondrial damage.

Methods

A cisplatin-induced HK-2 cell model in vitro and mouse model in vivo were established. The mechanism of TRPA1 promotes AKI was elucidated by H&E staining, TUNEL staining, transmission electron microscope (TEM), immunofluorescence, CCK-8 viability assays, flow cytometry, Western blotting, JC-1 assay, and enzyme linked immunosorbent assay (ELISA).

Result

In vivo and in vitro, HC-030031 reduced cisplatin-induced Scr and BUN level elevations; improved cisplatin-induced renal tissue injury, apoptosis, and mitochondrial dysfunction; elevated the reduced ERS-associated proteins glucose-regulated protein 78 (GRP78), glucose-regulated protein 75 (GRP75), and C/EBP homologous protein (CHOP) levels induced by cisplatin; reduced the elevated optic atrophy 1 (OPA1), mito-fusion 1 (MFN1), and mito-fusion 2 (MFN2) protein levels, and elevated phospho-dynamin-related protein 1 (p-DRP1) and mitochondrial fission factor (MFF) protein levels. HC-030031 also reduced the mitochondria-associated endoplasmic reticulum membrane (MAM) structure. In addition, TRPA1 agonists also decreased cell proliferation, increased apoptosis, and triggered mitochondrial dysfunction and calcium overload in HK-2 cells via modulation of MAM. ERS inhibitors and GRP75 inhibitors reversed these changes caused by TRPA1 agonists.

Conclusion

Our findings suggest that TRPA1 enhances cisplatin-induced AKI via modulation of ERS and mitochondrial damage.
Inhibition of adult hippocampal neurogenesis induced by postoperative CD8 + T-cell infiltration is associated with cognitive decline later following surgery in adult mice
Authors: Li Xiaowei , Wang Hong , Zhang Qidi , Sun Xiaobin , Zhang Mengyuan , Wang Gongming
Published: October 2023

Background

Some patients show persistent cognitive decline for weeks, months or even years after surgery, which seriously affects their long-term prognosis and quality of life. However, most previous basic studies have focused mainly on the mechanisms of early postoperative cognitive decline, whereas cognitive decline in the longer term after surgery is less well-understood. The subgranular zone of the dentate gyrus exhibits life-long neurogenesis, supporting hippocampus-dependent learning and memory.

Main text

The aim of this study was to investigate whether adult hippocampal neurogenesis (AHN) involves in cognitive decline later following surgery and to further explore the roles of CD8 + T lymphocytes infiltrating the hippocampal parenchyma after surgery in this pathological process. Cognitive function was examined in adult mice that underwent laparotomy combined with partial hepatectomy, and the results showed that cognitive decline persisted in mice who underwent surgery during the first postoperative month, even though there was a trend toward continuous improvement over time. Significantly decreased numbers of DCX + cells, BrdU + cells, and BrdU + /DCX + cells were observed on day 8 after surgery, and a significantly decreased number of NeuN + /BrdU + cells was observed on day 28 after surgery, which indicated inhibition of AHN. After surgery, T lymphocytes, the majority of which were CD8 + T cells, infiltrated the hippocampus and secreted Interferon-γ (IFN-γ). Depletion of CD8 + T cells could inhibit the increase of IFN-γ synthesis, improve hippocampal neurogenesis, and improve postoperative cognitive function. Hippocampal microinjection of IFN-γ neutralizing antibody or adeno-associated virus to knock down IFN-γ receptor 1 (IFNGR1) could also partially attenuate the inhibition of AHN and improve postoperative cognitive function.

Conclusions

These results demonstrate that postoperative infiltration of CD8 + T cells into the hippocampus and subsequent secretion of IFN-γ contribute to the inhibition of AHN and cognitive decline later following surgery.
Effect of sonification types in upper-limb movement: a quantitative and qualitative study in hemiparetic and healthy participants
Authors: Peyre Iseline , Roby-Brami Agnès , Segalen Maël , Giron Alain , Caramiaux Baptiste , Marchand-Pauvert Véronique , Pradat-Diehl Pascale , Bevilacqua Frédéric
Published: October 2023

Background

Movement sonification, the use of real-time auditory feedback linked to movement parameters, have been proposed to support rehabilitation. Nevertheless, if promising results have been reported, the effect of the type of sound used has not been studied systematically. The aim of this study was to investigate in a single session the effect of different types of sonification both quantitatively and qualitatively on patients with acquired brain lesions and healthy participants.

Methods

An experimental setup enabling arm sonification was developed using three different categories of sonification (direct sound modulation, musical interaction, and soundscape). Simple moving forward movements performed while sliding on a table with both arms were investigated with all participants. Quantitative analysis on the movement timing were performed considering various parameters (sound condition, affected arm and dominance, sonification categories). Qualitative analysis of semi-structured interviews were also conducted, as well as neuropsychological evaluation of music perception.

Results

For both the patient and healthy groups (15 participants each), average duration for performing the arm movement is significantly longer with sonification compared to the no-sound condition (p < 0.001). Qualitative analysis of semi-structured interviews revealed different aspects of motivational and affective aspects of sonification. Most participants of both groups preferred to complete the task with sound (29 of 30 participants), and described the experience as playful (22 of 30 participants). More precisely, the soundscape (nature sounds) was the most constantly preferred (selected first by 14 of 30 participants).

Conclusion

Overall, our results confirm that the sonification has an effect on the temporal execution of the movement during a single-session. Globally, sonification is welcomed by the participants, and we found convergent and differentiated appreciations of the different sonification types.
Growth patterns of young achondroplasia patients in Korea and predictability of neurosurgical procedures
Authors: Lee Jong Seok , Shim Youngbo , Cho Tae-Joon , Kim Seung-Ki , Ko Jung Min , Phi Ji Hoon
Published: October 2023

Background

Achondroplasia is an autosomal dominant disorder mainly affecting bony growth, typically resulting in markedly short stature. From a neurosurgical viewpoint, patients sometimes develop spinal cord compression at the narrowed foramen magnum and hydrocephalus. This study aims to construct growth references for height, weight, and head circumference (HC) of young achondroplasia patients in Korea and to evaluate the predictability of the necessity and timing of neurosurgical procedures through growth patterns.

Methods

Growth data were collected from achondroplasia patients who visited our institution between January 2002 and August 2022. First, we constructed percentile growth curves of height, weight, and HC for the patients under 3 years of age with the generalized additive model for location, scale, and shape (GAMLSS). Second, the growth patterns of the patients with hydrocephalus who underwent neurosurgical procedures such as foramen magnum decompression (FMD) and ventriculoperitoneal (VP) shunt were analyzed.

Results

There were 125 achondroplasia patients, including 67 males and 58 females. Among 125 patients, 46 underwent FMD, and 5 underwent VP shunt. As short stature and macrocephaly were typical characteristics of achondroplasia, the height of achondroplasia was lower than that of the general population, and HC in achondroplasia showed accelerated growth postnatally. There were no significant changes in HC in hydrocephalus patients before they underwent neurosurgical procedures. The influence of hydrocephalus on the growth patterns of HC in achondroplasia seemed insignificant.

Conclusion

Growth references for height, weight, and HC in young achondroplasia patients were constructed. It is the first report of growth patterns of achondroplasia in Korea. Unlike other pediatric patients, the diagnosis of hydrocephalus and the necessity of neurosurgical procedures are hard to be predicted with HC in achondroplasia. Neuroimaging should be considered for achondroplasia patients with neurological symptoms.
The lyophilized chloroplasts store synthetic DARPin G3 as bioactive encapsulated organelles
Authors: Ehsasatvatan Maryam , Kohnehrouz Bahram Baghban
Published: October 2023

Background

The high cost of fermentation, purification, cold storage and transportation, short shelf life, and sterile delivery methods of biopharmaceuticals, is a matter for producers and consumers as well. Since the FDA has now approved plant cells for large-scale, cost-effective biopharmaceutical production, the isolation and lyophilization of transplastomic chloroplasts can cover concerns about limitations. DARPins are engineered small single-domain proteins that have been selected to bind to HER2 with high affinity and specificity. HER2 is an oncogene involved in abnormal cell growth in some cancers and the target molecule for cancer immunotherapy.

Results

In this study, we reported the prolonged stability and functionality of DARPin G3 in lyophilized transplastomic tobacco leaves and chloroplasts. Western blot analysis of lyophilized leaves and chloroplasts stored at room temperature for up to nine months showed that the DARPin G3 protein was stable and preserved proper folding. Lyophilization of leaves and isolated chloroplasts increased DARPin G3 protein concentrations by 16 and 32-fold, respectively. The HER2-binding assay demonstrated that the chloroplast-made DARPin G3 can maintain its stability and binding activity without any affinity drop in lyophilized leaf materials throughout this study for more than nine months at room temperature.

Conclusion

Lyophilization of chloroplasts expressing DARPin G3 would further reduce costs and simplify downstream processing, purification, and storage. Compressed packages of lyophilized chloroplasts were much more effective than lyophilized transplastomic leaves considering occupied space and downstream extraction and purification of DARPin G3 after nine months. These methods facilitate any relevant formulation practices for these compounds to meet any demand-oriented needs.
GET_PANGENES: calling pangenes from plant genome alignments confirms presence-absence variation
Authors: Contreras-Moreira Bruno , Saraf Shradha , Naamati Guy , Casas Ana M. , Amberkar Sandeep S. , Flicek Paul , Jones Andrew R. , Dyer Sarah
Published: October 2023

Crop pangenomes made from individual cultivar assemblies promise easy access to conserved genes, but genome content variability and inconsistent identifiers hamper their exploration. To address this, we define pangenes, which summarize a species coding potential and link back to original annotations. The protocol get_pangenes performs whole genome alignments (WGA) to call syntenic gene models based on coordinate overlaps. A benchmark with small and large plant genomes shows that pangenes recapitulate phylogeny-based orthologies and produce complete soft-core gene sets. Moreover, WGAs support lift-over and help confirm gene presence-absence variation. Source code and documentation: https://github.com/Ensembl/plant-scripts.
Mobile phone text messaging plus motivational interviewing versus usual care: study protocol for a randomized controlled trial to evaluate effects on breastfeeding, child health, and survival outcomes, among women living with HIV (MTI-MI)
Authors: Zunza Moleen , Thabane Lehana , Kuhn Louise , Els Christine , Cotton Mark F. , Young Taryn
Published: October 2023

Background

Many infants in low-resourced settings at high risk of infectious disease morbidity and death are deprived of the immunological and nutritional benefits of breast milk, through an attenuated duration of breast milk exposure. South Africa has one of the lowest exclusive breastfeeding rates in Africa, with 8% of infants under 6 months of age. We assume that breastfeeding is sustained among women living with HIV receiving weekly text messages and motivational interviewing and that this contributes to improved infant health outcomes.

Objectives

(1) To evaluate the effectiveness of a combined intervention of mobile phone text messaging and motivational interviewing in promoting (a) exclusive breastfeeding and (b) any form of breastfeeding, until 6 months of child age, compared to usual care, among mothers living with HIV. (2) To evaluate the effectiveness of a combined intervention on (a) reduction in all-cause hospitalization and mortality rates and (b) improvements in infant linear growth, compared to usual care, among HIV-exposed infants aged 0–6 months.

Methods

We are conducting a clinical trial to determine whether text messaging plus motivational interviewing prolongs breastfeeding and improves infant health outcomes. We are recruiting 275 women living with HIV and their HIV-exposed infants at birth and randomly assign study interventions for 6 months.

Statistical methods

Breastfeeding rates are compared between the study groups using a standard proportion test and binomial regression. Survival endpoints are presented using Kaplan–Meier survival curves and compared between the study groups using the Cox proportional-hazards regression model. The count endpoint is analysed using the Poisson random-effects model and mean cumulative function. We use mixed linear regression models to assess the evolution of infant growth over time. The maximum likelihood method will be used to handle missing data.

Discussion

The study findings may facilitate decision-making on (1) whether implementation of the breastfeeding policy achieved the desired outcomes, (2) interventions needed to sustain breastfeeding, and (3) whether the interventions do have an impact on child health.

Trial registration

ClinicalTrials.gov NCT05063240. Pan African Clinical Trial Registry PACTR202110870407786. Oct. 1, 2021.
Alterations in gut microbiome and metabolite profile of patients with Schistosoma japonicum infection
Authors: Zhou Chen , Li Junhui , Guo Chen , Zhou Zhaoqin , Yang Zhen , Zhang Yu , Jiang Jie , Cai Yu , Zhou Jie , Xia Meng , Ming Yingzi
Published: October 2023

Background

Schistosoma infection is a significant public health issue, affecting over 200 million individuals and threatening 700 million people worldwide. The species prevalent in China is Schistosoma japonicum. Recent studies showed that both gut microbiota and metabolome are closely related to schistosomiasis caused by S. japonicum, but clinical study is limited and the underlying mechanism is largely unclear. This study aimed to explore alterations as well as function of gut microbiota and metabolite profile in the patients with S. japonicum infection.

Methods

This study included 20 patients diagnosed with chronic schistosomiasis caused by S. japonicum, eight patients with advanced schistosomiasis caused by S. japonicum and 13 healthy volunteers. The fresh feces of these participators, clinical examination results and basic information were collected. 16S ribosomal RNA gene sequencing was used to investigate gut microbiota, while ultraperformance liquid chromatography-mass spectrometry (UHPLC-MS) was applied to explore the metabolome of patients in different stages of schistosomiasis.

Results

The study found that gut microbiota and metabolites were altered in patients with different stages of S. japonicum infection. Compared with healthy control group, the gut microbial diversity in patients with chronic S. japonicum infection was decreased significantly. However, the diversity of gut microbiota in patients with chronic schistosomiasis was similar to that in patients with advanced schistosomiasis. Compared with uninfected people, patients with schistosomiasis showed decreased Firmicutes and increased Proteobacteria. As disease progressed, Firmicutes was further reduced in patients with advanced S. japonicum infection, while Proteobacteria was further increased. In addition, the most altered metabolites in patients with S. japonicum infection were lipids and lipid-like molecules as well as organo-heterocyclic compounds, correlated with the clinical manifestations and disease progress of schistosomiasis caused by S. japonicum.

Conclusions

This study suggested that the gut microbiota and metabolome altered in patients in different stages of schistosomiasis, which was correlated with progression of schistosomiasis caused by S. japonicum. This inter-omics analysis may shed light on a better understanding of the mechanisms of the progression of S. japonicum infection and contribute to identifying new potential targets for the diagnosis and prognosis of S. japonicum infection. However, a large sample size of validation in clinic is needed, and further study is required to investigate the underlying mechanism.