bluuebunny/crossref_metadata_2025 huggingface dataset:
Adiponectin protects obesity-related glomerulopathy by inhibiting ROS/NF-κB/NLRP3 inflammation pathway
Authors: Xu Xiaohong , Huang Xiaolin , Zhang Liexiang , Huang Xiaoli , Qin Zihan , Hua Fei
Published: June 2021

Background

Adiponectin is an adipocytokine that plays a key regulatory role in glucose and lipid metabolism in obesity. The prevalence of obesity has led to an increase in the incidence of obesity-related glomerulopathy (ORG). This study aimed to identify the protective role of adiponectin in ORG.

Methods

Small-interfering RNA (siRNA) against the gene encoding adiponectin was transfected into podocytes. The oxidative stress level was determined using a fluorometric assay. Apoptosis was analyzed by flow cytometry. The expressions of podocyte markers and pyrin domain containing protein 3 (NLRP3) inflammasome-related proteins were measured by qRT-PCR, immunohistochemistry, and Western blot.

Results

Podocytes treated with palmitic acid (PA) showed downregulated expressions of podocyte markers, increased apoptosis, upregulated levels of NLRP3 inflammasome-related proteins, increased production of inflammatory cytokines (IL-18 and IL-1β), and induced activation of NF-κB as compared to the vehicle-treated controls. Decreased adiponectin expression was observed in the serum samples from high fat diet (HFD)-fed mice. Decreased podocin expression and upregulated NLRP3 expression were observed in the kidney samples from high fat diet (HFD)-fed mice. Treatment with adiponectin or the NLRP3 inflammasome inhibitor, MCC950, protected cultured podocytes against podocyte apoptosis and inflammation. Treatment with adiponectin protected mouse kidney tissues against decreased podocin expression and upregulated NLRP3 expression. The knockout of adiponectin gene by siRNA increased ROS production, resulting in the activation of NLRP3 inflammasome and the phosphorylation of NF-κB in podocytes. Pyrrolidine dithiocarbamate, an NF-κB inhibitor, prevented adiponectin from ameliorating FFA-induced podocyte injury and NLRP3 activation.

Conclusions

Our study showed that adiponectin ameliorated PA-induced podocyte injury in vitro and HFD-induced injury in vivo via inhibiting the ROS/NF-κB/NLRP3 pathway. These data suggest the potential use of adiponectin for the prevention and treatment of ORG.
Evaluating essential medicines for treating childhood cancers: availability, price and affordability study in Ghana
Authors: Mensah Kofi Boamah , Mensah Adwoa Bemah Boamah , Bangalee Varsha , Padayachee Neelaveni , Oosthuizen Frasia
Published: June 2021

Introduction

Access to childhood cancer medicines is a critical global health challenge. There is a lack of sufficient context-specific data in Ghana on access to essential medicines for treating childhood cancers. Here, we present an analysis of essential cancer medicine availability, pricing, and affordability using the pediatric oncology unit of a tertiary hospital as the reference point.

Method

Data on prices and availability of 20 strength-specific essential cancer medicines and eight non-cancer medicines were evaluated using the modified World Health Organization (WHO)/Health Action International method. Two pharmacies in the hospital and four private pharmacies around the hospital were surveyed. We assessed their median price ratio using the WHO international reference price guide. The number of days wages per the government daily wage salary was used to calculate the affordability of medicines.

Results

The mean availability of essential cancer medicines and non-cancer medicines at the hospital pharmacies were 27 and 38% respectively, and 75 and 84% respectively for private pharmacies. The median price ratio of cancer medicines was 1.85, and non-cancer medicines was 3.75. The estimated cost of medicines for treating a 30 kg child with Acute lymphoblastic leukaemia was GHȻ 4928.04 (US$907.56) and GHȻ 4878.00 (US$902.62) for Retinoblastoma, requiring 417 and 413-days wages respectively for the lowest-paid unskilled worker in Ghana.

Conclusion

The mean availability of cancer medicines at the public and private pharmacies were less than the WHO target of 80%. The median price ratio for cancer and non-cancer medicines was less than 4, yet the cost of medicines appears unaffordable in the local setting. A review of policies and the establishment of price control could improve availability and reduce medicines prices for the low-income population.
Correlation between body mass index and prostate volume in benign prostatic hyperplasia patients undergoing holmium enucleation of the prostate surgery
Authors: Batai Ken , Phung Michael , Bell Robert , Lwin Aye , Hynes Kieran A. , Price Elinora , Meiklejohn Karleen M. , Bracamonte Erika R. , Funk Joel T.
Published: June 2021

Background

Benign prostatic obstruction (BPO) due to benign prostatic hyperplasia (BPH) is a leading cause of morbidity in men over the age of 40. This study examined whether there was an association between body mass index (BMI) and pre-operative prostate volume and whether expression of two genes, alpha-2-macroglobulin (A2M) and transforming growth factor beta 3 (TGFB3), was correlated with BMI, pre-operative prostate volume, and age at surgery.

Methods

Medical records of patients who underwent holmium enucleation of the prostate surgery for treatment of BPO were retrospectively reviewed. Surgical specimens were obtained from formalin-fixed paraffin-embedded blocks, and expression of the targeted genes was quantified using a real time PCR approach. Linear regression analysis was performed to assess association between BMI and prostate volume adjusting for demographic characteristics and co-morbidity. Spearman’s correlation was used to examine whether gene expression was correlated with BMI, prostate volume, and age at surgery.

Results

A total of 278 patients were identified, including 62.9% European Americans (n = 175) and 27.7% Hispanic Americans (n = 77). BMI was significantly correlated with prostate volume (Spearman’s rho = 0.123, P = 0.045). In linear regression analysis, BMI was positively associated with prostate volume (β = 0.01, P = 0.004), while hyperlipidemia was negatively associated with prostate volume (β = −0.08, P = 0.02). A trend for a positive association was also observed for diabetes (β = 0.07, P = 0.099). In the race/ethnicity stratified analysis, age at surgery showed a trend for significantly positive association with prostate volume in European Americans (β = 0.005, P = 0.08), but not in Hispanic Americans. Expression of the A2M gene in the stroma was negatively correlated with age at surgery (P = 0.006). A2M expression in the gland was positively correlated with prostate volume among older men (Age ≥ 70, P = 0.01) and overweight men (BMI 25–30, P = 0.04). TGFB3 expression in the gland was positively correlated with BMI (P = 0.007) among older men.

Conclusions

This study demonstrated the positive correlation between BMI and prostate volume. Expression of TGFB3 and A2M was correlated with BMI, prostate volume, and age at surgery.
Access to, use, knowledge, and preferences for information technology and technical equipment among people with chronic obstructive pulmonary disease (COPD) in Sweden. A cross-sectional survey study
Authors: Sönnerfors Pernilla , Skavberg Roaldsen Kirsti , Ståhle Agneta , Wadell Karin , Halvarsson Alexandra
Published: June 2021

Background

The use of information technology can make pulmonary rehabilitation interventions in people with chronic obstructive pulmonary disease (COPD) more flexible and thereby has the potential to reach a larger proportion of the population. However, the success of using information technology in pulmonary rehabilitation is dependent on the end-user’s competence in information technology and access to the Internet. The aim was to describe the access to, and the use, knowledge, and preferences of information technology and technical equipment among people with COPD.

Methods

Telephone interviews were conducted using a standardised questionnaire on information technology and technical devises addressing the household, access to and usage of the Internet, contact with authorities, e-commerce, security, the workplace, digital competence, and disabilities. Questions were also posed regarding participants’ views on a future eHealth tool for COPD, appropriate content, and the potential likelihood for them to use an eHealth tool for exercise training.

Results

In total 137 persons agreed to participate, 17 dropped out resulting in 120 included participants (response rate 88%). The participants (86 women) were aged 51 to 92 years (mean: 72.5), and all severity grades of COPD according to GOLD A-D were represented. Over 90% had access to the Internet. Smartphones were used by 81%, and over 90% used apps. Participants had high knowledge of how to use the Internet, 91% had used the Internet during the last 3 months, 85% almost every day. The most common requests for a future eHealth tool for COPD were evidence-based and trustworthy information on COPD, (including medication, exercise training, inhalation and breathing techniques), communication (chat) with others and with health carers. Access to individually adjusted exercise training, and support, (motivation via prompts, chat rooms, digital information board) was also desired.

Conclusions

The present study showed that people with COPD in Sweden have high access and ability to use the Internet and information technology. They are frequent users and most of them take part in the digital society, even to a higher extent than the general population. The results show that the use of an eHealth tool could be a suitable strategy for people with COPD.
Navigating change – managers’ experience of implementation processes in disability health care: a qualitative study
Authors: Granberg Anette , Matérne Marie , Lundqvist Lars-Olov , Duberg Anna
Published: June 2021

Background

Effective implementation processes play a central role in health care organizations and affect the care of patients. Managers are pivotal in facilitating the use of new practices, but their experience and how it affects the implementation outcome are still largely unknown. In the field of disability health care in particular, managers experiences have scarcely been investigated. Therefore, the aim of this study is to explore managers’ experiences of the implementation process when transferring new practices into disability health care settings.

Methods

Semi-structured individual telephone interviews were conducted with managers at disability health care organizations in four administrative regions in central Sweden. A total of 23 managers with formal managerial responsibility from both public and private health care were strategically selected to be interviewed. The interviews were analysed using reflexive thematic analysis with an inductive approach.

Results

The analysis resulted in two themes about factors influencing the implementation process: firstly, Contextual factors set the agenda for what can be achieved, which highlighted aspects that hinder or enable the implementation process, such as internal and external conditions, the workplace culture, the employees and managers’ attitudes and openness to change: secondly, Leadership in the winds of change, which described the challenges of balancing managerial tasks with leading the change, and the importance of a leadership that involves the participation of the employees.

Conclusions

This study explored how and to what extent managers address and manage the implementation process and the many associated challenges. The findings highlight the importance of leadership support and organizational structure in order to transfer new practices into the work setting, and to encourage an organizational culture for leading change that promotes positive outcomes. We suggest that identifying strategies by focusing on contextual factors and on aspects of leadership will facilitate implementation processes.

Trial registration

The SWAN (Structured Water Dance Intervention) study was retrospectively registered on April 9, 2019 and is available online at ClinicalTrials.gov (ID: NCT03908801).
Acute fasciolosis in an alpaca: a case report
Authors: Hayes C. J. , O’Brien P. J. , Wolfe A. , Hoey S. , Chandler C. , Rhodes V. , Carty C. I. , Piras I. M. , Ryan E. G.
Published: June 2021

Background

The popularity of new world camelids, particularly alpacas, is growing rapidly in Ireland, presenting a clinical challenge to veterinary practitioners who may not have worked with these species previously. To the authors’ knowledge, the clinical course of a case of acute fasciolosis in an alpaca has not previously been reported, and fasciolosis has not been reported at all in alpacas in Ireland, making this case report a valuable addition to the current literature.

Case presentation

A three-year-old male castrated huacaya alpaca was admitted to UCD Veterinary Hospital with a two-day history of colic and tenesmus. He had been treated with albendazole, dexamethasone and potentiated amoxycillin by the referring veterinary practitioner with no response. On initial clinical exam, sensitivity to abdominal palpation was the only abnormality. However, the alpaca proceeded to show abnormal lying positions, tenesmus and reduced faecal output over the next 24 h. A general blood panel demonstrated moderate anaemia, marked hyperglobulinaemia and moderately increased hepatocellular and hepatobiliary enzyme activity. Abdominal radiography revealed enlargement of the first forestomach compartment without evidence of gastrointestinal obstruction or peritonitis. An abdominal ultrasound exam revealed an elongated, heterogenous mass in the caudoventral abdomen that appeared to be contiguous with the liver. FNA of this mass revealed that it was in fact a liver lobe with biliary stasis and inflammation. Faecal sedimentation demonstrated Fasciola hepatica eggs. In spite of treatment with triclabendazole and supportive treatment including blood transfusion, the alpaca’s condition continued to deteriorate and he was euthanised. On post-mortem exam, acute fasciolosis was diagnosed.

Conclusions

The clinical presentation and course of a case of acute fasciolosis in an individual alpaca is described, including the results of a range of diagnostic tests that were carried out. The final diagnosis is supported by a description of post-mortem findings. This information will serve as a resource for veterinary practitioners involved in the diagnosis and treatment of similar cases.
The analgesic efficacy of extracorporeal shock wave combined with percutaneous vertebroplasty in the treatment of osteoporotic thoracolumbar compression fractures in postmenopausal women
Authors: Liu Xiaowei , Wang Hui , Zhang Yang , Wang Mingling , Qiu Yujin , Sun Xiaodong , Wang Sheng
Published: June 2021

Background

To explore the analgesic efficacy of extracorporeal shock wave (ESW) combined with percutaneous vertebroplasty (PVP) after reduction in overextension position in the treatment of osteoporotic thoracolumbar compression fractures in postmenopausal women.

Methods

The data of postmenopausal women with osteoporotic thoracolumbar compression fracture admitted in our department from January 2017 to October 2019 were analyzed retrospectively. They were divided into groups of unipedicular percutaneous kyphoplasty (U-PKP n = 21), bipedicular PKP (B-PKP n = 20), and ESW combined with PVP after reduction in overextension position (EP-PVP n = 18). The improvement of pain and vertebral height in three groups was compared.

Results

Postoperative compression rate and Cobb angle of vertebral fractures in the three groups were all lower than those before surgery, and the differences between pre-operation and post-operation were statistically significant (P < 0.05). The visual analog scale (VAS) and Oswestry dysfunction index (ODI) scores of the three groups decreased significantly after the operation (P < 0.05). The ODI scores of the EP-PVP group in the third months after the operation were significantly improved compared with the other two groups, and the difference was statistically significant (P < 0.05).

Conclusions

In our small-sample study, all three treatment schemes can treat osteoporotic compression fracture of thoracolumbar vertebrae in postmenopausal women, relieve pain, and improve quality of life. ESW combined with PVP after reduction in overextension position could achieve a good vertebral reduction rate and improve kyphosis, and may reduce the application of analgesic drugs.
Cellular and molecular mediators of lymphangiogenesis in inflammatory bowel disease
Authors: Ocansey Dickson Kofi Wiredu , Pei Bing , Xu Xinwei , Zhang Lu , Olovo Chinasa Valerie , Mao Fei
Published: June 2021

Background

Recent studies reporting the intricate crosstalk between cellular and molecular mediators and the lymphatic endothelium in the development of inflammatory bowel diseases (IBD) suggest altered inflammatory cell drainage and lymphatic vasculature, implicating the lymphatic system as a player in the occurrence, development, and recurrence of intestinal diseases. This article aims to review recent data on the modulatory functions of cellular and molecular components of the IBD microenvironment on the lymphatic system, particularly lymphangiogenesis. It serves as a promising therapeutic target for IBD management and treatment. The interaction with gut microbiota is also explored.

Main text

Evidence shows that cells of the innate and adaptive immune system and certain non-immune cells participate in the complex processes of inflammatory-induced lymphangiogenesis through the secretion of a wide spectrum of molecular factors, which vary greatly among the various cells. Lymphangiogenesis enhances lymphatic fluid drainage, hence reduced infiltration of immunomodulatory cells and associated-inflammatory cytokines. Interestingly, some of the cellular mediators, including mast cells, neutrophils, basophils, monocytes, and lymphatic endothelial cells (LECs), are a source of lymphangiogenic molecules, and a target as they express specific receptors for lymphangiogenic factors.

Conclusion

The effective target of lymphangiogenesis is expected to provide novel therapeutic interventions for intestinal inflammatory conditions, including IBD, through both immune and non-immune cells and based on cellular and molecular mechanisms of lymphangiogenesis that facilitate inflammation resolution.
Ral GTPase is essential for actin dynamics and Golgi apparatus distribution in mouse oocyte maturation
Authors: Sun Ming-Hong , Hu Lin-Lin , Zhao Chao-Ying , Lu Xiang , Ren Yan-Ping , Wang Jun-Li , Cui Xiang-Shun , Sun Shao-Chen
Published: June 2021

Background

Ral family is a member of Ras-like GTPase superfamily, which includes RalA and RalB. RalA/B play important roles in many cell biological functions, including cytoskeleton dynamics, cell division, membrane transport, gene expression and signal transduction. However, whether RalA/B involve into the mammalian oocyte meiosis is still unclear. This study aimed to explore the roles of RalA/B during mouse oocyte maturation.

Results

Our results showed that RalA/B expressed at all stages of oocyte maturation, and they were enriched at the spindle periphery area after meiosis resumption. The injection of RalA/B siRNAs into the oocytes significantly disturbed the polar body extrusion, indicating the essential roles of RalA/B for oocyte maturation. We observed that in the RalA/B knockdown oocytes the actin filament fluorescence intensity was significantly increased at the both cortex and cytoplasm, and the chromosomes were failed to locate near the cortex, indicating that RalA/B regulate actin dynamics for spindle migration in mouse oocytes. Moreover, we also found that the Golgi apparatus distribution at the spindle periphery was disturbed after RalA/B depletion.

Conclusions

In summary, our results indicated that RalA/B affect actin dynamics for chromosome positioning and Golgi apparatus distribution in mouse oocytes.
Surgical site infection prevention and management in immunocompromised patients: a systematic review of the literature
Authors: Coccolini Federico , Improta Mario , Cicuttin Enrico , Catena Fausto , Sartelli Massimo , Bova Raffaele , de’ Angelis Nicola , Gitto Stefano , Tartaglia Dario , Cremonini Camilla , Ordonez Carlos , Baiocchi Gian Luca , Chiarugi Massimo
Published: June 2021

Background

Immunocompromised patients are at higher risk of surgical site infection and wound complications. However, optimal management in the perioperative period is not well established. Present systematic review aims to analyse existing strategies and interventions to prevent and manage surgical site infections and other wound complications in immunocompromised patients.

Methods

A systematic review of the literature was conducted.

Results

Literature review shows that partial skin closure is effective to reduce SSI in this population. There is not sufficient evidence to definitively suggest in favour of prophylactic negative pressure wound therapy. The use of mammalian target of rapamycin (mTOR) and calcineurin inhibitors (CNI) in transplanted patient needing ad emergent or undeferrable abdominal surgical procedure must be carefully and multidisciplinary evaluated. The role of antibiotic prophylaxis in transplanted patients needs to be assessed.

Conclusion

Strict adherence to SSI infection preventing bundles must be implemented worldwide especially in immunocompromised patients. Lastly, it is necessary to elaborate a more widely approved definition of immunocompromised state. Without such shared definition, it will be hard to elaborate the needed methodologically correct studies for this fragile population.
Who would benefit from open abdomen in severe acute pancreatitis?—a matched case-control study
Authors: Husu Henrik Leonard , Leppäniemi Ari Kalevi , Mentula Panu Juhani
Published: June 2021

Background

Selection of patients for open abdomen (OA) treatment in severe acute pancreatitis (SAP) is challenging. Treatment related morbidity and risk of adverse events are high; however, refractory abdominal compartment syndrome (ACS) is potentially lethal. Factors influencing the decision to initiate OA treatment are clinically important. We aimed to study these factors to help understand what influences the selection of patients for OA treatment in SAP.

Methods

A single center study of patients with SAP that underwent OA treatment compared with conservatively treated matched controls.

Results

Within study period, 47 patients treated with OA were matched in a 1:1 fashion with conservatively treated control patients. Urinary output under 20 ml/h (OR 5.0 95% CI 1.8-13.7) and ACS (OR 4.6 95% CI 1.4-15.2) independently associated with OA treatment. Patients with OA treatment had significantly more often visceral ischemia (34%) than controls (6%), P = 0.002. Mortality among patients with visceral ischemia was 63%. Clinically meaningful parameters predicting developing ischemia were not found. OA treatment associated with higher overall 90-day mortality rate (43% vs 17%, P = 0.012) and increased need for necrosectomy (55% vs 21%, P = 0.001). Delayed primary fascial closure was achieved in 33 (97%) patients that survived past OA treatment.

Conclusion

Decreased urine output and ACS were independently associated with the choice of OA treatment in patients with SAP. Underlying visceral ischemia was strikingly common in patients undergoing OA treatment, but predicting ischemia in these patients seems difficult.
Case report: a novel approach for the emergency repair of acute aortic rupture associated with congenital aortic Coarctation
Authors: Pu Xin , Wang Maozhou , Huang Xiaoyong , Zhang Hongjia , Huang Lianjun
Published: June 2021

Background

Congenital aortic coarctation (CoA) associated with aortic rupture is a rare but extremely lethal condition. In pregnant patients, the condition becomes very risky.

Case presentation

We presented a case of a pregnant (20 weeks gestation) patient with CoA associated with ruptured aortic pseudoaneurysm who was successfully rescued using a novel hybrid strategy.

Conclusions

This hybrid approach may be a life-saving bridging intervention in patients with CoA associated with devastating complications, such as ruptured aneurysms, especially with extremely narrowed access.
Congenital self-healing reticulohistiocytosis in a newborn: unusual oral and cutaneous manifestations
Authors: Rizzoli Alessandra , Giancristoforo Simona , Haass Cristina , De Vito Rita , Gaspari Stefania , Scapillati Eleonora , Diociaiuti Andrea , El Hachem May
Published: June 2021

Background

Congenital self-healing reticulohistiocytosis (CSHRH), also called Hashimoto-Pritzker disease, is a rare and benign variant of Langerhans cell histiocytosis, characterized by cutaneous lesions without extracutaneous involvement.

Case presentation

We present a case of CSHRH with diffuse skin lesions and erosions in the oral mucosa, present since birth and lasting for 2 months, and we perform a review of the literature on Pubmed in the last 10 years.

Conclusions

Our case confirm that lesions on oral mucosa, actually underestimated, may be present in patients with CSHRH. Patients affected by CSHRH require a close follow-up until the first years of life, due to the unpredictable course of Langerhans cell histiocytosis, in order to avoid missing diagnosis of more aggressive types of this disorder.
Dengue fever and insecticide resistance in Aedes mosquitoes in Southeast Asia: a review
Authors: Gan Soon Jian , Leong Yong Qi , bin Barhanuddin Muhammad Fakrul Hakim , Wong Siew Tung , Wong Shew Fung , Mak Joon Wah , Ahmad Rohani Binti
Published: June 2021

Dengue fever is the most important mosquito-borne viral disease in Southeast Asia. Insecticides remain the most effective vector control approach forAedesmosquitoes. Four main classes of insecticides are widely used for mosquito control: organochlorines, organophosphates, pyrethroids and carbamates. Here, we review the distribution of dengue fever from 2000 to 2020 and its associated mortality in Southeast Asian countries, and we gather evidence on the trend of insecticide resistance and its distribution in these countries since 2000, summarising the mechanisms involved. The prevalence of resistance to these insecticides is increasing in Southeast Asia, and the mechanisms of resistance are reported to be associated with target site mutations, metabolic detoxification, reduced penetration of insecticidesviathe mosquito cuticle and behavioural changes of mosquitoes. Continuous monitoring of the status of resistance and searching for alternative control measures will be critical for minimising any unpredicted outbreaks and improving public health. This review also provides improved insights into the specific use of insecticides for effective control of mosquitoes in these dengue endemic countries.

Graphical Abstract
Does methotrexate influence COVID-19 infection? Case series and mechanistic data
Authors: Schälter Fabian , Dürholz Kerstin , Bucci Laura , Burmester Gerd , Caporali Roberto , Figuereido Camille , Cobra Jaime Fogagnolo , Manger Bernhard , Zaiss Mario M. , Schett Georg
Published: June 2021

Background

To investigate whether methotrexate treatment may affect the susceptibility to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods

Clinical assessment of symptoms, SARS-CoV-2 RNA, and anti-SARS-CoV-2 IgG in an initial case series of four families and confirmatory case series of seven families, within which one family member developed coronavirus disease 19 (COVID-19) and exposed another family member receiving methotrexate treatment; experimental part with methotrexate treatment of mice and organoids followed by the assessment of mRNA and protein expression of the SARS-CoV-2 receptor angiotensin-converting enzyme (ACE)-2.

Results

In the initial case series, three of four women on a joint ski trip developed COVID-19, while the fourth woman, under treatment with methotrexate, remained virus-free. Two of the three diseased women infected their husbands, while the third husband treated with methotrexate remained virus-free. In addition, 7 other families were identified in a follow-up case series, in which one member developed COVID-19, while the other, receiving methotrexate, remained healthy. Experimentally, when mice were treated with methotrexate, ACE2 expression significantly decreased in the lung, in the intestinal epithelium, and in intestinal organoids.

Conclusion

These clinical and experimental data indicate that methotrexate has certain protective effects on SARS-CoV-2 infection via downregulating ACE2.
Evaluating the Chichewa version of the London Measure of Unplanned Pregnancy in Malawi: a validation update
Authors: Hall Jennifer A. , Stephenson Judith , Barrett Geraldine
Published: June 2021

Objective

To investigate the psychometric properties of the validated Chichewa version of the London Measure of Unplanned Pregnancy in a large representative community-based sample in Malawi, a low-income country. We collected data on pregnancy intention from a cohort of 4244 pregnant women in Malawi using the validated Chichewa version of the London Measure of Unplanned Pregnancy (LMUP). We evaluated the psychometric properties of the Chichewa LMUP using classical test theory and confirmatory factor analysis to re-assess the performance of items one and six, which had weaker performance in the original smaller, facility-based validation sample.

Results

The Chichewa version of the LMUP met all pre-set criteria for validation. There are now nine validations of the LMUP in different low-and-middle-income countries, confirming the validity and applicability of the LMUP in these settings.
Amnion epithelial cells are an effective source of factor H and prevent kidney complement deposition in factor H-deficient mice
Authors: Casiraghi Federica , Ordonez Pamela Yossenaidy Rodriguez , Azzollini Nadia , Todeschini Marta , Rottoli Daniela , Donadelli Roberta , Gramignoli Roberto , Benigni Ariela , Noris Marina , Remuzzi Giuseppe
Published: June 2021

Complement factor H (FH) is the main plasma regulator of the alternative pathway of complement. Genetic and acquired abnormalities in FH cause uncontrolled complement activation amplifying, with the consequent accumulation of complement components on the renal glomeruli. This leads to conditions such as C3 glomerulopathy (C3G) and atypical hemolytic uremic syndrome (aHUS). There is no effective therapy for these diseases. Half of the patients progress to end-stage renal disease and the condition recurs frequently in transplanted kidneys. Combined liver/kidney transplantation is a valid option for these patients, but the risks of the procedure and donor organ shortages hamper its clinical application. Therefore, there is an urgent need for alternative strategies for providing a normal FH supply. Human amnion epithelial cells (hAEC) have stem cell characteristics, including the capability to differentiate into hepatocyte-like cells in vivo.

Here, we administered hAEC into the livers of newborn Cfh−/− mice, which spontaneously developed glomerular complement deposition and renal lesions resembling human C3G. hAEC engrafted at low levels in the livers of Cfh−/− mice and produced sufficient human FH to prevent complement activation and glomerular C3 and C9 deposition. However, long-term engraftment was not achieved, and eventually hAEC elicited a humoral immune response in immunocompetent Cfh−/− mice.

hAEC cell therapy could be a valuable therapeutic option for patients undergoing kidney transplantation in whom post-transplant immunosuppression may protect allogeneic hAEC from rejection, while allogeneic cells provide normal FH to prevent disease recurrence.
Placental chorionic plate-derived mesenchymal stem cells ameliorate severe acute pancreatitis by regulating macrophage polarization via secreting TSG-6
Authors: Huang Qilin , Cheng Xiumei , Luo Chen , Yang Shuxu , Li Shuai , Wang Bing , Yuan Xiaohui , Yang Yi , Wen Yi , Liu Ruohong , Tang Lijun , Sun Hongyu
Published: June 2021

Background

Mesenchymal stem cells (MSCs) hold promising potential to treat systemic inflammatory diseases including severe acute pancreatitis (SAP). In our previous study, placental chorionic plate-derived MSCs (CP-MSCs) were found to possess superior immunoregulatory capability. However, the therapeutic efficacy of CP-MSCs on SAP and their underlying mechanism remain unclear.

Methods

The survival and colonization of exogenous CP-MSCs were observed by bioluminescence imaging and CM-Dil labeling in rodent animal models of SAP. The therapeutic efficacy of CP-MSCs on SAP rats was evaluated by pathology scores, the levels of pancreatitis biomarkers as well as the levels of inflammatory factors in the pancreas and serum. The potential protective mechanism of CP-MSCs in SAP rats was explored by selectively depleting M1 or M2 phenotype macrophages and knocking down the expression of TSG-6.

Results

Exogenous CP-MSCs could survive and colonize in the injured tissue of SAP such as the lung, pancreas, intestine, and liver. Meanwhile, we found that CP-MSCs alleviated pancreatic injury and systemic inflammation by inducing macrophages to polarize from M1 to M2 in SAP rats. Furthermore, our data suggested that CP-MSCs induced M2 polarization of macrophages by secreting TSG-6, and TSG-6 played a vital role in alleviating pancreatic injury and systemic inflammation in SAP rats. Notably, we found that a high inflammation environment could stimulate CP-MSCs to secrete TSG-6.

Conclusion

Exogenous CP-MSCs tended to colonize in the injured tissue and reduced pancreatic injury and systemic inflammation in SAP rats through inducing M2 polarization of macrophages by secreting TSG-6. Our study provides a new treatment strategy for SAP and initially explains the potential protective mechanism of CP-MSCs on SAP rats.
Temporal induction of Lhx8 by optogenetic control system for efficient bone regeneration
Authors: Huang Delan , Li Runze , Ren Jianhan , Luo Haotian , Wang Weicai , Zhou Chen
Published: June 2021

Background

The spatiotemporal regulation of essential genes is crucial for controlling the growth and differentiation of cells in a precise manner during regeneration. Recently, optogenetics was considered as a potent technology for sophisticated regulation of target genes, which might be a promising tool for regenerative medicine. In this study, we used an optogenetic control system to precisely regulate the expression of Lhx8 to promote efficient bone regeneration.

Methods

Quantitative real-time PCR and western blotting were used to detect the expression of Lhx8 and osteogenic marker genes. Alkaline phosphatase staining and alizarin red staining were used to detect alkaline phosphatase activity and calcium nodules. A customized optogenetic expression system was constructed to regulate Lhx8, of which the expression was activated in blue light but not in dark. We also used a critical calvarial defect model for the analysis of bone regeneration in vivo. Moreover, micro-computed tomography (micro-CT), three-dimensional reconstruction, quantitative bone measurement, and histological and immunohistochemistry analysis were performed to investigate the formation of new bone in vivo.

Results

During the osteogenic differentiation of BMSCs, the expression levels of Lhx8 increased initially but then decreased thereafter. Lhx8 promoted the early proliferation of BMSCs but inhibited subsequent osteogenic differentiation. The optogenetic activation of Lhx8 in BMSCs in the early stages of differentiation by blue light stimulation led to a significant increase in cell proliferation, thus allowing a sufficient number of differentiating BMSCs to enter the later osteogenic differentiation stage. Analysis of the critical calvarial defect model revealed that the pulsed optogenetic activation of Lhx8 in transplanted BMSCs over a 5-day period led to a significant increase in the generation of bone in vivo.

Conclusions

Lhx8 plays a critical role in balancing proliferation and osteogenic differentiation in BMSCs. The optogenetic activation of Lhx8 expression at early stage of BMSCs differentiation led to better osteogenesis, which would be a promising strategy for precise bone regeneration.
SOX9 inactivation affects the proliferation and differentiation of human lung organoids
Authors: Li Lian , Feng Jianqi , Zhao Shanshan , Rong Zhili , Lin Ying
Published: June 2021

Background

The regulation of the transcription factor sex-determining region Y-box transcription factor 9 (SOX9) in lung development has been described in mouse, but the same principles apply to human lung development is unknown due to a lack of appropriate experimental approaches and models.

Methods

Here, we used gene editing technology to inactivate SOX9 in human embryonic stem cells that were then induced to differentiate into lung organoids to investigate the role of SOX9 in human lung epithelium development.

Results

Complete knockout of the transactivation domain of SOX9 by gene editing resulted in indels in both alleles of SOX9. SOX9−/− hESCs could be induced to differentiate into lung progenitor organoids. In vitro long-term expansion showed that SOX9 inactivation did not affect the differentiation of pulmonary epithelial cells, but promoted apoptosis and reduced proliferative capacity in the organoids. When lung progenitor organoids were transplanted under the kidney capsule of immunodeficient mice, expression of the club cell marker secretoglobin family 1A member 1 (SCGB1A1) was detected in SOX9−/− transplants but was absent in wild-type (WT) transplants. The maturation of goblet cells was also affected by SOX9 inactivation, as evidenced by the presence of mucin 5 AC (MUC5AC) in the cytoplasm of SOX9−/− grafts as compared to WT grafts in which most MUC5AC was secreted into the lumen. In vivo lung orthotopic transplantations showed that SOX9 inactivation had a limited effect on the differentiation of alveolar cells and lung regeneration in injured mice.

Conclusions

SOX9 modulates the proliferative capacity of lung epithelium but is not an indispensable transcription factor in the regulation of human lung epithelium development.
Engineering and characterization of human β-defensin-3 and its analogues and microcin J25 peptides against Mannheimia haemolytica and bovine neutrophils
Authors: Dhingra Harpreet , Kaur Kamaljit , Singh Baljit
Published: June 2021

Mannheimia haemolytica-induced bovine respiratory disease causes loss of millions of dollars to Canadian cattle industry. Current antimicrobials are proving to be ineffective and leave residues in meat. Antimicrobial peptides (AMPs) may be effective against M. haemolytica while minimizing the risk of drug residues. Cationic AMPs can kill bacteria through interactions with the anionic bacterial membrane. Human β-Defensin 3 (HBD3) and microcin J25 (MccJ25) are AMPs with potent activity against many Gram-negative bacteria. We tested the microbicidal activity of wild-type HBD3, three HBD3 peptide analogues (28 amino acid, 20AA, and 10AA) derived from the sequence of natural HBD3, and MccJ25 in vitro against M. haemolytica. Three C-terminal analogues of HBD3 with all cysteines replaced with valines were manually synthesized using solid phase peptide synthesis. Since AMPs can act as chemoattractant we tested the chemotactic effect of HBD3, 28AA, 20AA, and 10AA peptides on bovine neutrophils in Boyden chamber. Minimum bactericidal concentration (MBC) assay showed that M. haemolytica was intermediately sensitive to HBD3, 28AA and 20AA analogues with an MBC of 50 µg/mL. The 10AA analogue had MBC 6.3 µg/mL which is likely a result of lower final inoculum size. MccJ25 didn’t have significant bactericidal effect below an MBC < 100 µg/mL. Bovine neutrophils showed chemotaxis towards HBD3 and 20AA peptides (P < 0.05) but not towards 28AA analogue. Co-incubation of neutrophils with any of the peptides did not affect their chemotaxis towards N-formyl-l-methionyl-l-leucyl-phenylalanine (fMLP). The data show that these peptides are effective against M. haemolytica and are chemotactic for neutrophils in vitro.
Mental health in the Republic of The Gambia
Authors: Kretzschmar Imogen , Nyan Ousman , Mendy Ann Marie , Janneh Bamba
Published: June 2021

The Republic of The Gambia, on the west coast of Africa, is a narrow enclave into Senegal (which surrounds the nation on three sides), with a coastline on the Atlantic Ocean, enclosing the mouth of the River Gambia. The smallest country on mainland Africa, The Gambia covers 11 295 km2 and has a population of 1705 000. There are five major ethnic groups: Mandinka, Fula, Wolof, Jola and Sarahuleh. Muslims represent 95% of the population. English is the official language but a miscellany of minor languages are also spoken (Serere, Aku, Mandjago, etc.). The Gambia has a history steeped in trade, with records of Arab traders dating back to the ninth century, its river serving as an artery into the continent, reaching as far as Mauritania. Indeed, as many as 3 million slaves were sold from the region during the trans-Atlantic slave trade. The Gambia gained independence from the UK in 1965 and joined the Commonwealth of Nations.
Summary of the 12 Most Common Cancers in the CancerLinQ Discovery (CLQD) Database
Authors: Potter Danielle M. , Riffon Mark F. , Manning Brittany , Taylor Aliki , Emmas Cathy , Kabadi Shaum , Jiang Miao , Miller Robert S.
Published: June 2021

PURPOSE

In 2014, the ASCO developed CancerLinQ (CLQ), a health technology platform for oncology. The CLQ Discovery (CLQD) database was created to make data available for research and this paper provides a summary of this database.

METHODS

This study described the clinical and demographic characteristics of the 12 most common cancers in the CLQD database. We included patients with a new malignant tumor diagnosis between January 1, 2013, and December 31, 2018, of the following cancers: breast, lung and bronchus, prostate, colon and rectum, melanoma of the skin, bladder, non-Hodgkin lymphoma, kidney and renal pelvis, uterus, leukemia, pancreas, and thyroid. Patients with an in-situ diagnosis were excluded. Summary statistics and Kaplan-Meier survival estimates were calculated for each tumor.

RESULTS

From 2013 to 2018, 491,360 patients were diagnosed with the study tumors. Breast cancer (139,506) was the most common, followed by lung and bronchus (70,959), prostate (63,303), and colon and rectum (53,504). The median age at diagnosis (years) was 61, 68, 68, and 64 in breast, lung and bronchus, prostate, and colon and rectum cohorts, respectively. Compared to the SEER 5-year overall survival estimates for several tumor types were higher in the CLQD database, possibly because of incomplete mortality capture in electronic health records.

CONCLUSION

This paper presents the first description of the CLQD database since its inception. CLQ will continue to evolve over time, and the breadth and depth of this data asset will continue to grow. ASCO and CLQ's long-term goal is to improve the quality of patient care and create a sustainable database for oncology researchers. These results demonstrate that CLQ built a scalable database that can be used for oncology research.
High Peak Inspiratory Pressures After a Change of Heat and Moisture Exchangers: A Case Series
Authors: Dewasurendra Anusari M. , McHugh Stephen M.
Published: June 2021

Elevated peak inspiratory pressures (PIPs) cause harm via hypoventilation, barotrauma, and hemodynamic instability. Heat and moisture exchangers (HMEs) are used during mechanical ventilation to prevent heat loss, dehydration of airway mucosa, and accumulation of dried secretions. Multiple reports detail sudden HME occlusions causing increased PIPs. We describe 4 cases of gradually increasing PIPs from progressive HME obstruction that occurred within 6 months of an institutional change to a newer model. HME obstruction should be considered when PIPs are elevated. Alternative heat and moisture preservation strategies should be contemplated, as HMEs increase airflow resistance and add another point of possible malfunction.
Exercise, programmed cell death and exhaustion of cardiomyocyte proliferation in aging zebrafish
Authors: Murphy Lindsay B. , Santos-Ledo Adrian , Dhanaseelan Tamilvendhan , Eley Lorraine , Burns David , Henderson Deborah J. , Chaudhry Bill
Published: June 2021

Exercise may ameliorate the eventual heart failure inherent in human aging. In this study, we use zebrafish to understand how aging and exercise affect cardiomyocyte turnover and myocardial remodelling. We show that cardiomyocyte proliferation remains constant throughout life but that onset of fibrosis is associated with a late increase in apoptosis. These findings correlate with decreases in voluntary swimming activity, critical swimming speed (Ucrit), and increases in biomarkers of cardiac insufficiency. The ability to respond to severe physiological stress is also impaired with age. Although young adult fish respond with robust cardiomyocyte proliferation in response to enforced swimming, this is dramatically impaired in older fish and served by a smaller proliferation-competent cardiomyocyte population. Finally, we show that these aging responses can be improved through increased activity throughout adulthood. However, despite improvement in Ucrit and the proliferative response to stress, the size of the proliferating cardiomyocyte population remained unchanged. The zebrafish heart models human aging and reveals the important trade-off between preserving cardiovascular fitness through exercise at the expense of accelerated fibrotic change.
Distortion or magnification? An in vitro cone-beam CT study of dimensional changes of objects with different compositions
Authors: Coelho-Silva Fernanda , Gaêta-Araujo Hugo , Rosado Lucas P. Lopes , Freitas Deborah Queiroz , Haiter-Neto Francisco , de-Azevedo-Vaz Sergio Lins
Published: June 2021

Objectives:

To assess whether dimensional changes occur as shape distortion (unevenly), contraction or magnification (evenly) in cone beam computed tomography (CBCT) considering materials, anatomical regions and metal artefact reduction algorithms.

Methods:

Four cylinders of amalgam (Am), cobalt-chromium (Co-Cr), gutta-percha (Gu), titanium (Ti) and zirconium (Zi) were inserted inside a polymethylmethacrylate phantom in anterior and posterior regions for acquisitions in Picasso Trio and OP300 with MAR enabled and disabled. Two observers measured the dimensions of each cylinder in three axes: Y (height), Z (antero posterior diameter) and X (latero-lateral diameter). Repeated measures ANOVA with Tukey post-hoc test compared the data (α = 5%).

Results:

Shape distortion occurred for all materials in anterior region of Picasso Trio without MAR (p < 0.05). With MAR enabled, Gu and Ti contracted (p ≥ 0.05), while the others showed distortion (p < 0.05). In posterior region, all materials distorted in both MAR conditions (p < 0.05), except Gu, which magnified without MAR (p ≥ 0.05) and contracted unevenly with MAR (p < 0.05). In anterior region of OP300, all materials magnified without MAR, (p ≥ 0.05) and had shape distortion with MAR (p < 0.05). In posterior region, only Am showed magnification without MAR (p ≥ 0.05), while all materials presented shape distortion with MAR (p < 0.05).

Conclusion:

Dimensional changes of high-density materials in CBCT can be either a magnification, a contraction or a distortion; the last condition is the most prevalent. Furthermore, changes differ considering material, anatomical region and MAR condition.