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1.
bioRxiv ; 2024 May 29.
Article in English | MEDLINE | ID: mdl-38854026

ABSTRACT

A major mechanism of insecticide resistance in insect pests is knock-down resistance (kdr) caused by mutations in the voltage-gated sodium channel (Vgsc) gene. Despite being common in most malaria Anopheles vector species, kdr mutations have never been observed in Anopheles funestus, the principal malaria vector in Eastern and Southern Africa. While monitoring 10 populations of An. funestus in Tanzania, we unexpectedly found resistance to DDT, a banned insecticide, in one location. Through whole-genome sequencing of 333 An. funestus samples from these populations, we found 8 novel amino acid substitutions in the Vgsc gene, including the kdr variant, L976F (L1014F in An. gambiae), in tight linkage disequilibrium with another (P1842S). The mutants were found only at high frequency in one region, with a significant decline between 2017 and 2023. Notably, kdr L976F was strongly associated with survivorship to the exposure to DDT insecticide, while no clear association was noted with a pyrethroid insecticide (deltamethrin). Further study is necessary to identify the origin and spread of kdr in An. funestus, and the potential threat to current insecticide-based vector control in Africa.

2.
Sci Rep ; 14(1): 12402, 2024 05 30.
Article in English | MEDLINE | ID: mdl-38811610

ABSTRACT

Evaluating the quality of isolated human islets before transplantation is crucial for predicting the success in treating Type 1 diabetes. The current gold standard involves time-intensive in vivo transplantation into diabetic immunodeficient mice. Given the susceptibility of isolated islets to hypoxia, we hypothesized that hypoxia present in islets before transplantation could indicate compromised islet quality, potentially leading to unfavorable outcomes. To test this hypothesis, we analyzed expression of 39 hypoxia-related genes in human islets from 85 deceased donors. We correlated gene expression profiles with transplantation outcomes in 327 diabetic mice, each receiving 1200 islet equivalents grafted into the kidney capsule. Transplantation outcome was post-transplant glycemic control based on area under the curve of blood glucose over 4 weeks. In linear regression analysis, DDIT4 (R = 0.4971, P < 0.0001), SLC2A8 (R = 0.3531, P = 0.0009) and HK1 (R = 0.3444, P = 0.0012) had the highest correlation with transplantation outcome. A multiple regression model of 11 genes increased the correlation (R = 0.6117, P < 0.0001). We conclude that assessing pre-transplant hypoxia in human islets via gene expression analysis is a rapid, viable alternative to conventional in vivo assessments. This approach also underscores the importance of mitigating pre-transplant hypoxia in isolated islets to improve the success rate of islet transplantation.


Subject(s)
Diabetes Mellitus, Experimental , Islets of Langerhans Transplantation , Islets of Langerhans , Humans , Animals , Islets of Langerhans Transplantation/methods , Mice , Islets of Langerhans/metabolism , Diabetes Mellitus, Experimental/therapy , Male , Diabetes Mellitus, Type 1/metabolism , Hypoxia/metabolism , Female , Cell Hypoxia , Middle Aged , Blood Glucose/metabolism
3.
Perioper Med (Lond) ; 13(1): 38, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38735972

ABSTRACT

BACKGROUND: Duke Activity Status Index (DASI) is a widely used tool to assess functional capacity among patients, but there is no Sinhala version validated for patients in Sri Lanka. This study aimed to cross-culturally adapt and test the validity and reliability of the Sinhala version of DASI (DASI-S). METHODS: The translation and cross-cultural adaptation of the DASI questionnaire were conducted following the standard guidelines. It was pre-tested on ten pre-operative patients and further modified. The construct validity and reliability of DASI-S were evaluated by administering the modified final DASI-S, which comprised 12 items, along with the physical functioning sub-scale of the 36-item short-form health survey (SF-36), consisting of 10 items to eighty-one patients who were awaiting non-cardiac surgeries at university surgical wards, National Hospital of Sri Lanka (NHSL), and Colombo North Teaching Hospital (CNTH), Sri Lanka. Reliability was assessed through Cronbach alpha, while the validity was evaluated using factor analysis and Spearman's correlation. The ethical approval was obtained from the Ethics Review Committee, Faculty of Medicine, University of Colombo, Sri Lanka. RESULTS: The mean age of the participants was 46.2 (± 16.6) years and the majority were females (54.3%). The mean height, weight, and body mass index of the sample were 160.5 (± 9.6) cm, 60.3 (± 11.9) kg, and 23.4 (± 4.5) kgm-2 respectively. The Cronbach's alpha coefficient for the internal consistency of DASI-S was 0.861. The concurrent validity of DASI-S was substantiated by positively correlating (p < 0.01, rs = 0.466) with the physical sub-scale of SF-36. There was a significant difference (p < 0.01) in the total score of DASI-S between the two age groups. CONCLUSIONS: Sinhala version of the DASI appears to be a valid, reliable and easy-to-administer tool to assess functional capacity among patients who are awaiting non-cardiac surgeries.

4.
Parasit Vectors ; 17(1): 230, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38760849

ABSTRACT

BACKGROUND: Anopheles funestus is a leading vector of malaria in most parts of East and Southern Africa, yet its ecology and responses to vector control remain poorly understood compared with other vectors such as Anopheles gambiae and Anopheles arabiensis. This study presents the first large-scale survey of the genetic and phenotypic expression of insecticide resistance in An. funestus populations in Tanzania. METHODS: We performed insecticide susceptibility bioassays on An. funestus mosquitoes in nine regions with moderate-to-high malaria prevalence in Tanzania, followed by genotyping for resistance-associated mutations (CYP6P9a, CYP6P9b, L119F-GSTe2) and structural variants (SV4.3 kb, SV6.5 kb). Generalized linear models were used to assess relationships between genetic markers and phenotypic resistance. An interactive R Shiny tool was created to visualize the data and support evidence-based interventions. RESULTS: Pyrethroid resistance was universal but reversible by piperonyl-butoxide (PBO). However, carbamate resistance was observed in only five of the nine districts, and dichloro-diphenyl-trichloroethane (DDT) resistance was found only in the Kilombero valley, south-eastern Tanzania. Conversely, there was universal susceptibility to the organophosphate pirimiphos-methyl in all sites. Genetic markers of resistance had distinct geographical patterns, with CYP6P9a-R and CYP6P9b-R alleles, and the SV6.5 kb structural variant absent or undetectable in the north-west but prevalent in all other sites, while SV4.3 kb was prevalent in the north-western and western regions but absent elsewhere. Emergent L119F-GSTe2, associated with deltamethrin resistance, was detected in heterozygous form in districts bordering Mozambique, Malawi and the Democratic Republic of Congo. The resistance landscape was most complex in western Tanzania, in Tanganyika district, where all five genetic markers were detected. There was a notable south-to-north spread of resistance genes, especially CYP6P9a-R, though this appears to be interrupted, possibly by the Rift Valley. CONCLUSIONS: This study underscores the need to expand resistance monitoring to include An. funestus alongside other vector species, and to screen for both the genetic and phenotypic signatures of resistance. The findings can be visualized online via an interactive user interface and could inform data-driven decision-making for resistance management and vector control. Since this was the first large-scale survey of resistance in Tanzania's An. funestus, we recommend regular updates with greater geographical and temporal coverage.


Subject(s)
Anopheles , Insecticide Resistance , Insecticides , Malaria , Mosquito Vectors , Animals , Anopheles/genetics , Anopheles/drug effects , Insecticide Resistance/genetics , Tanzania/epidemiology , Mosquito Vectors/genetics , Mosquito Vectors/drug effects , Insecticides/pharmacology , Malaria/transmission , Malaria/epidemiology , Genetic Markers , Pyrethrins/pharmacology , Genotype , Mutation
5.
Int J Breast Cancer ; 2024: 2408355, 2024.
Article in English | MEDLINE | ID: mdl-38450330

ABSTRACT

Breast cancer (BC) stands as the most prevalent form of carcinoma among women, ranking as the second leading cause of cancer-related mortality in the female population. The objective of this study is to assess the expression of miR-10b and determine its diagnostic and prognostic significance in breast cancer patients across various disease stages. The investigation was carried out in Baghdad at the Oncology Teaching Hospital within Baghdad Medical City and the Oncology Unit at Al-Yarmouk Teaching Hospital. A total of 150 samples were included and divided into two groups: the blood group consisting of 90 samples (including control subjects, localized BC patients, and those with metastatic and locally advanced BC) and the tissue group comprising 60 samples (representing both benign and malignant BC cases). The study spanned from March 2022 to January 2023, with patients' ages ranging from 24 to 75 years. The primary focus of this investigation was to identify the gene expression of miRNA-10b in all sample types. This was achieved by measuring gene expression levels and normalizing them to the level of a housekeeping gene (U6), and quantification was carried out considering the ΔCt value and the fold change method (2-ΔΔCt). The results revealed an upregulated fold expression of miRNA-10b, particularly in locally advanced and metastatic BC, where the expression was significantly higher compared to the other groups, with a fold expression of 1.770 ± 0.1070. In localized breast cancer, the fold expression was 1.624 ± 0.064, and in malignant tissue, it measured 1.546 ± 0.06754, all relative to apparently healthy control subjects. In summary, our research provides compelling evidence supporting the classification of miRNA-10b as an oncogenic factor in BC. The central involvement of miRNA-10b in the tumorigenic processes of BC highlights its reference for developing novel targeted therapeutic interventions and detection biomarkers for BC treatment. Notably, elevated expression of miRNA-10b was observed in BC tissues, correlating with an unfavorable distant metastasis-free survival outcome.

6.
Neurogastroenterol Motil ; 36(5): e14774, 2024 May.
Article in English | MEDLINE | ID: mdl-38462678

ABSTRACT

BACKGROUND: Prokinetics are a class of pharmacological drugs designed to improve gastrointestinal (GI) motility, either regionally or across the whole gut. Each drug has its merits and drawbacks, and based on current evidence as high-quality studies are limited, we have no clear recommendation on one class or other. However, there remains a large unmet need for both regionally selective and/or globally acting prokinetic drugs that work primarily intraluminally and are safe and without systemic side effects. PURPOSE: Here, we describe the strengths and weaknesses of six classes of prokinetic drugs, including their pharmacokinetic properties, efficacy, safety and tolerability and potential indications.


Subject(s)
Gastrointestinal Agents , Gastrointestinal Motility , Humans , Gastrointestinal Motility/drug effects , Gastrointestinal Agents/therapeutic use , Gastrointestinal Agents/pharmacology , Gastroenterology , Gastrointestinal Diseases/drug therapy , Europe , Societies, Medical , United States
7.
Anaesthesia ; 79(3): 329, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37880920
8.
Am J Transplant ; 24(2): 177-189, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37813189

ABSTRACT

Present-day islet culture methods provide short-term maintenance of cell viability and function, limiting access to islet transplantation. Attempts to lengthen culture intervals remain unsuccessful. A new method was developed to permit the long-term culture of islets. Human islets were embedded in polysaccharide 3D-hydrogel in cell culture inserts or gas-permeable chambers with serum-free CMRL 1066 supplemented media for up to 8 weeks. The long-term cultured islets maintained better morphology, cell mass, and viability at 4 weeks than islets in conventional suspension culture. In fact, islets cultured in the 3D-hydrogel retained ß cell mass and function on par with freshly isolated islets in vitro and, when transplanted into diabetic mice, restored glucose balance similar to fresh islets. Using gas-permeable chambers, the 3D-hydrogel culture method was scaled up over 10-fold and maintained islet viability and function, although the cell mass recovery rate was 50%. Additional optimization of scale-up methods continues. If successful, this technology could afford flexibility and expand access to islet transplantation, especially single-donor islet-after-kidney transplantation.


Subject(s)
Diabetes Mellitus, Experimental , Islets of Langerhans Transplantation , Islets of Langerhans , Humans , Mice , Animals , Cell Culture Techniques , Hydrogels , Insulin , Cell Survival
9.
Cureus ; 15(7): e42286, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37609082

ABSTRACT

Introduction Musculoskeletal disorders (MSDs) have a tremendous impact on working people and are becoming a serious problem in the modern society. The healthcare system is regarded as having one of the most physically demanding jobs, and the risk of musculoskeletal injuries is high. Irrespective of their age, healthcare workers (HCWs) worldwide frequently experience shoulder and neck pain. In our study, we sought to understand what initiates shoulder and neck pain, such as stress or environmental factors, and what causes shoulder and neck discomfort among Saudi Arabian healthcare professionals. Methods A descriptive, cross-sectional study was conducted from 2022 to 2023, assessing shoulder and neck pain among healthcare workers in the central region of Saudi Arabia. An online survey was used, with 409 participants aged 20 or older. The questionnaire included socio-demographic data, Shoulder Pain and Disability Index (SPADI) questionnaire to measure shoulder pain and disability, neck Bournemouth questionnaire (NBQ) to assess neck pain, and quadruple visual analogue scale (QVAS) to measure the intensity of pain. Results Of the 409 HCWs, 56% were males, and 56.5% belonged to the age group of 20-30 years. The prevalence of high-intensity pain based on QVAS criteria was 29.3%. The mean percentage of neck pain (32.3%) was slightly higher than shoulder pain (31.8%). There was a significant association between the level of pain intensity in terms of the total score of NBQ, SPADI score, and its dimensions. It is interesting to know that HCWs with associated chronic diseases had higher scores in all three questionnaires (NBQ, SPADI, and QVAS). Conclusion High-intensity musculoskeletal pain was relatively high among HCWs. It was found that neck pain affected HCWs more than shoulder pain. Furthermore, an increased pain intensity in the shoulder and neck was more frequently seen in HCWs with chronic diseases. More studies are needed to determine the causes and risk factors for neck and shoulder pain to help improve the healthcare system and patient care.

10.
Malar J ; 22(1): 230, 2023 Aug 08.
Article in English | MEDLINE | ID: mdl-37553665

ABSTRACT

Anopheles mosquitoes present a major public health challenge in sub-Saharan Africa; notably, as vectors of malaria that kill over half a million people annually. In parts of the east and southern Africa region, one species in the Funestus group, Anopheles funestus, has established itself as an exceptionally dominant vector in some areas, it is responsible for more than 90% of all malaria transmission events. However, compared to other malaria vectors, the species is far less studied, partly due to difficulties in laboratory colonization and the unresolved aspects of its taxonomy and systematics. Control of An. funestus is also increasingly difficult because it has developed widespread resistance to public health insecticides. Fortunately, recent advances in molecular techniques are enabling greater insights into species identity, gene flow patterns, population structure, and the spread of resistance in mosquitoes. These advances and their potential applications are reviewed with a focus on four research themes relevant to the biology and control of An. funestus in Africa, namely: (i) the taxonomic characterization of different vector species within the Funestus group and their role in malaria transmission; (ii) insecticide resistance profile; (iii) population genetic diversity and gene flow, and (iv) applications of genetic technologies for surveillance and control. The research gaps and opportunities identified in this review will provide a basis for improving the surveillance and control of An. funestus and malaria transmission in Africa.


Subject(s)
Anopheles , Insecticides , Malaria , Humans , Animals , Malaria/epidemiology , Mosquito Vectors/genetics , Insecticides/pharmacology , Insecticide Resistance/genetics , Africa, Southern
11.
Heliyon ; 9(5): e16337, 2023 May.
Article in English | MEDLINE | ID: mdl-37305465

ABSTRACT

This paper examines the relationship between hotels' official ratings and customer review scores. Hotel ratings aim to provide an objective assessment of the hotel's quality and experience to potential customers. However, customer reviews frequently differ from official ratings. We use data on hotels in Dubai to explore their relationship and analyze their similarities and differences. Asymmetric information hampers demand in the hotel industry if ratings do not match the customers' views of quality. Furthermore, substantial discrepancies between the two measures provide competing interests for hotel managers to satisfy rating agencies' criteria or customers' preferences, reducing the hotels' efficiency and effectiveness in offering customers the best experience and value. Our findings show that, as expected, Star Rating primarily reflects hotel-related features. In contrast, customer review scores tend to appreciate features nearby in addition to hotel amenities. Also, some hotel amenities value differently in the customer review scores and Star Rating.

12.
J Crit Care ; 77: 154326, 2023 10.
Article in English | MEDLINE | ID: mdl-37186999

ABSTRACT

BACKGROUND/OBJECTIVES: Thiamine plays a pivotal role in energy metabolism. The aim of the study was to determine serial whole blood TPP concentrations in critically ill patients receiving chronic diuretic treatment before ICU admission and to correlate TPP levels with clinically determined serum phosphorus concentrations. SUBJECTS/METHODS: This observational study was performed in 15 medical ICUs. Serial whole blood TPP concentrations were measured by HPLC at baseline and at days 2, 5 and 10 after ICU admission. RESULTS: A total of 221 participants were included. Of these, 18% demonstrated low TPP concentrations upon admission to the ICU, while 26% of participants demonstrated low levels at some point during the 10-day study period. Hypophosphatemia was detected in 30% of participants at some point during the 10-day period of observation. TPP levels were significantly and positively correlated with serum phosphorus levels at each time point (P < 0.05 for all). CONCLUSIONS: Our results show that 18% of these critically ill patients exhibited low whole blood TPP concentrations on ICU admission and 26% had low levels during the initial 10 ICU days, respectively. The modest correlation between TPP and phosphorus concentrations suggests a possible association due to a refeeding effect in ICU patients requiring chronic diuretic therapy.


Subject(s)
Critical Illness , Thiamine Pyrophosphate , Humans , Prospective Studies , Critical Illness/therapy , Intensive Care Units , Diuretics/therapeutic use
13.
Stem Cell Reports ; 18(3): 618-635, 2023 03 14.
Article in English | MEDLINE | ID: mdl-36868230

ABSTRACT

Progenitor cells capable of self-renewal and differentiation in the adult human pancreas are an under-explored resource for regenerative medicine. Using micro-manipulation and three-dimensional colony assays we identify cells within the adult human exocrine pancreas that resemble progenitor cells. Exocrine tissues were dissociated into single cells and plated into a colony assay containing methylcellulose and 5% Matrigel. A subpopulation of ductal cells formed colonies containing differentiated ductal, acinar, and endocrine lineage cells, and expanded up to 300-fold with a ROCK inhibitor. When transplanted into diabetic mice, colonies pre-treated with a NOTCH inhibitor gave rise to insulin-expressing cells. Both colonies and primary human ducts contained cells that simultaneously express progenitor transcription factors SOX9, NKX6.1, and PDX1. In addition, in silico analysis identified progenitor-like cells within ductal clusters in a single-cell RNA sequencing dataset. Therefore, progenitor-like cells capable of self-renewal and tri-lineage differentiation either pre-exist in the adult human exocrine pancreas, or readily adapt in culture.


Subject(s)
Diabetes Mellitus, Experimental , Methylcellulose , Humans , Adult , Mice , Animals , Pancreas , Pancreatic Ducts , Stem Cells
14.
J Vasc Access ; : 11297298231160573, 2023 Mar 20.
Article in English | MEDLINE | ID: mdl-36941769

ABSTRACT

BACKGROUND: In haemodialysis patients with exhausted autogenous options, prosthetic arteriovenous grafts (AVGs) are frequently utilised as tertiary vascular access. However, the prosthetic nature of AVGs precipitates an increased risk of infection which may translate to excess morbidity and life-threatening complications. The current evidence remains divided on the optimal treatment strategy for arteriovenous graft infections (AVGi) with arguments for conservative management by antibiotics, salvaging with graft revision or total/subtotal excision. To address this gap, we assessed the outcomes of AVGi patients treated in our institution, developing an AVGi severity classification model and a proposed treatment algorithm to guide AVGi management. METHODS: We conducted a single centre retrospective review of outcomes of patients with AVGi managed either by sole antibiotics therapy, graft revision or surgical excision between June 2016 and May 2021. Outcomes of AVGi patients across differing treatment groups were compared, including 1-year mortality, 6-month and 1-year functional vascular access. We also analysed the outcomes of tunnelled haemodialysis lines (THL), which were used as a temporary vascular access in several AVGi patients in our study. RESULTS: A total of 34 AVGi patients were managed within that time frame and included in the study (5 conservatively management by antibiotics, 5 graft revisions and 24 surgical excision) with a mean age of 60.4 ± 14.4 years (67.6% males). Overall 1-year mortality was 14.7%. A 6-month functional vascular access status across the three groups stood at 60%, 60% and 10% while 1-year functional vascular access status was 60%, 75% and 42% respectively. CONCLUSIONS: When clinically appropriate, conservative management by antibiotics or salvage/graft revision can present as prudent AVGi treatment options. The adoption of our proposed severity classification system and treatment algorithm provides a more thorough objective assessment of the infection and helps guide the clinical decision-making process.

15.
Noncoding RNA ; 9(2)2023 Mar 17.
Article in English | MEDLINE | ID: mdl-36960965

ABSTRACT

miRNAs are critical for pancreas development and function. However, we found that there are discrepancies regarding pancreatic miRNA abundance in published datasets. To obtain a more relevant profile that is closer to the true profile, we profiled small RNAs from human islets cells, acini, and four rodent pancreatic cell lines routinely used in diabetes and pancreatic research using a bias reduction protocol for small RNA sequencing. In contrast to the previous notion that miR-375-3p is the most abundant pancreatic miRNA, we found that miR-148a-3p and miR-7-5p were also abundant in islets. In silico studies using predicted and validated targets of these three miRNAs revealed that they may work cooperatively in endocrine and exocrine cells. Our results also suggest, compared to the most-studied miR-375, that both miR-148a-3p and miR-7-5p may play more critical roles in the human pancreas. Moreover, according to in silico-predicted targets, we found that miR-375-3p had a much broader target spectrum by targeting the coding sequence and the 5' untranslated region, rather than the conventional 3' untranslated region, suggesting additional unexplored roles of miR-375-3p beyond the pancreas. Our study provides a valuable new resource for studying miRNAs in pancreata.

16.
JCO Glob Oncol ; 9: e2200221, 2023 03.
Article in English | MEDLINE | ID: mdl-36921242

ABSTRACT

PURPOSE: To examine cancer patients' perspectives on the impact of COVID-19 on teleoncology in Nigeria. METHODS: Data from a multicenter survey conducted at 15 outpatient clinics to 1,097 patients with cancer from April and July 2020 were analyzed. The study outcome was telemedicine, defined as patients who reported their routine follow-up visits were converted to virtual visits because of COVID-19 (coded yes/no). Covariates included patient age, ethnicity, marital status, income, cancer treatment, service disruption, and cancer diagnosis/type. Stata/SE.v.17 (StataCorp, College Station, TX) was used to perform chi-square and logistic regression analyses. P values ≤ .05 were considered statistically significant. RESULTS: The majority of the 1,097 patients with cancer were female (65.7%) and age 55 years and older (35.0%). Because of COVID-19, 12.6% of patients' routine follow-ups were converted to virtual visits. More patients who canceled/postponed surgery (17.7% v 7.5%; P ≤ .001), radiotherapy (16.9% v 5.3%; P ≤ .001), and chemotherapy (22.8% v 8.5%; P ≤ .001), injection chemotherapy (20.6% v 8.7%; P ≤ .001) and those who reported being seen less by their doctor/nurse (60.3% v 11.4%; P ≤ .001) reported more follow-up conversions to virtual visits. In multivariate analyses, patients seen less by their doctors/nurses were 14.3 times more likely to have their routine follow-ups converted to virtual visits than those who did not (odds ratio, 14.33; 95% CI, 8.36 to 24.58). CONCLUSION: COVID-19 caused many patients with cancer in Nigeria to convert visits to a virtual format. These conversions were more common in patients whose surgery, radiotherapy, chemotherapy, and injection chemotherapy treatments were canceled or postponed. Our findings suggest how COVID-19 affects cancer treatment services and the importance of collecting teleoncological care data in Nigeria.


Subject(s)
COVID-19 , Neoplasms , Humans , Female , Male , Middle Aged , Outpatients , Neoplasms/therapy , Ambulatory Care Facilities , Ethnicity
17.
Am J Physiol Endocrinol Metab ; 324(4): E347-E357, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36791324

ABSTRACT

Thrombospondin-1 (TSP1) is a secreted protein minimally expressed in health but increased in disease and age. TSP1 binds to the cell membrane receptor CD47, which itself engages signal regulatory protein α (SIRPα), and the latter creates a checkpoint for immune activation. Individuals with cancer administered checkpoint-blocking molecules developed insulin-dependent diabetes. Relevant to this, CD47 blocking antibodies and SIRPα fusion proteins are in clinical trials. We characterized the molecular signature of TSP1, CD47, and SIRPα in human islets and pancreata. Fresh islets and pancreatic tissue from nondiabetic individuals were obtained. The expression of THBS1, CD47, and SIRPA was determined using single-cell mRNA sequencing, immunofluorescence microscopy, Western blot, and flow cytometry. Islets were exposed to diabetes-affiliated inflammatory cytokines and changes in protein expression were determined. CD47 mRNA was expressed in all islet cell types. THBS1 mRNA was restricted primarily to endothelial and mesenchymal cells, whereas SIRPA mRNA was found mostly in macrophages. Immunofluorescence staining showed CD47 protein expressed by ß cells and present in the exocrine pancreas. TSP1 and SIRPα proteins were not seen in islets or the exocrine pancreas. Western blot and flow cytometry confirmed immunofluorescent expression patterns. Importantly, human islets produced substantial quantities of secreted TSP1. Human pancreatic exocrine and endocrine tissue expressed CD47, whereas fresh islets displayed cell surface CD47 and secreted TSP1 at baseline and in inflammation. These findings suggest unexpected effects on islets from agents that intersect TSP1-CD47-SIRPα.NEW & NOTEWORTHY CD47 is a cell surface receptor with two primary ligands, soluble thrombospondin-1 (TSP1) and cell surface signal regulatory protein alpha (SIRPα). Both interactions provide checkpoints for immune cell activity. We determined that fresh human islets display CD47 and secrete TSP1. However, human islet endocrine cells lack SIRPα. These gene signatures are likely important given the increasing use of CD47 and SIRPα blocking molecules in individuals with cancer.


Subject(s)
CD47 Antigen , Neoplasms , Humans , CD47 Antigen/genetics , CD47 Antigen/metabolism , Macrophages/metabolism , Neoplasms/metabolism , Receptors, Cell Surface/metabolism , Thrombospondins/metabolism , Thrombospondins/therapeutic use , Thrombospondin 1/genetics , Thrombospondin 1/metabolism
18.
Int J Surg Case Rep ; 104: 107922, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36801763

ABSTRACT

INTRODUCTION: ACL reconstruction is needed to restore the stability and biomechanics properties of the injured knee joints in order to reproduce the function of the native ACL. The single-bundle (SB) and double-bundle (DB) techniques are most commonly used to reconstruct the injured ACL. However, its superiority upon each other is still controversial. PRESENTATION OF CASE: This study presented a case series of six patients underwent ACL reconstruction, consisted of three patients with SB ACL reconstruction and three patients with DB ACL reconstruction with further T2 mapping for joint instability evaluation. Only two DB patients showed consistent decreased value in every follow-up. DISCUSSION: ACL tear can generate joint instability. Joint instability is resulted from two mechanisms of relative cartilage overloading. First, there is an abnormal load distribution due to shifting of the center of pressure of the tibiofemoral force, resulting in increased stresses on the articular cartilage of the knee joint. There is also an increase of translation between articular surfaces, resulting in increased shear stresses on the articular cartilage. A trauma of knee joint causes cartilage damage and increased oxidative and metabolic stress of chondrocytes, resulting in chondrocyte senescence acceleration. CONCLUSION: This case series showed inconsistent results to determine either SB or DB has a better outcome in joint instability, thus further larger studies are needed.

19.
Cureus ; 15(1): e33816, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36819308

ABSTRACT

Bifurcation of the femur is a rare congenital orthopedic anomaly that is usually accompanied by tibial agenesis. Femoral bifurcation has been a part of the Gollop-Wolfgang complex criteria, which also include the tibia and fibula deformities with or without other variant abnormalities. Approximately 200 cases have been reported worldwide. This article presents a case of isolated bilateral distal femur bifurcation in a three-and-a-half-year-old girl who presented with abnormal gait and bilateral knee contractures. Extensive studies were performed to aid an appropriate diagnosis and treatment plan, including clinical history, physical examination, laboratory, and other investigations. After multiple consultations from different specialties, a gradual deformity correction was suggested as a treatment of choice. To our knowledge, there is a paucity of reported cases in the medical literature. Further research and case reporting are essential to better define the pathogenesis, prognosis, and treatment of such conditions.

20.
J Vasc Access ; 24(4): 660-665, 2023 Jul.
Article in English | MEDLINE | ID: mdl-34538194

ABSTRACT

BACKGROUND: Maintaining patent access is essential for haemodialysis dependent end stage renal failure patients. The COVID-19 pandemic has significantly affected surgical and interventional radiology services worldwide. We aimed to review the impact COVID-19 has caused to the management of acute dialysis access thrombosis. METHODS: We conducted a single centre retrospective review of outcomes of patients with arteriovenous fistula and arteriovenous graft thrombosis between March and May 2020, which coincided with the first peak of the COVID-19 pandemic in London, and a similar period in the previous year, March-May 2019. Outcomes in both cohorts of patients were compared, including attempts at salvage, salvage success, 1-month patency rates after salvage and subsequent surgery on the same access. We also analysed the use of tunnelled haemodialysis lines (THL), either due to failed salvage attempts or when salvage was not attempted. RESULTS: There was a similar incidence of access thrombosis in both periods (26 cases in 2019, 38 in 2020). There were 601 patients dialysing via an arteriovenous fistula or graft in 2019, and 568 patients in 2020. Access salvage, when attempted, had similar success rates and 1-month patency (salvage success 74% vs 80%, p = 0.39; 1-month patency 55% vs 62%, p = 0.69). The proportion of patients where access salvage was not attempted and a THL inserted was significantly higher in 2020 compared to 2019 (32% vs 4%, p = 0.007). There were more patients who subsequently had surgery to salvage or revise the same access in 2019 compared to 2020 (62% vs 13%, p < 0.001). CONCLUSIONS: During the peak of the COVID-19 pandemic, there were fewer attempts at access salvage. This was a conscious decision due to increased pressure on the healthcare system, access to emergency interventional radiology or operative theatres and the perceived risk/benefit ratio of access salvage. The long-term effects of this change in practice remain unknown.


Subject(s)
Arteriovenous Fistula , Arteriovenous Shunt, Surgical , COVID-19 , Thrombosis , Humans , Arteriovenous Fistula/etiology , Arteriovenous Shunt, Surgical/adverse effects , COVID-19/epidemiology , Graft Occlusion, Vascular/diagnostic imaging , Graft Occlusion, Vascular/etiology , Graft Occlusion, Vascular/therapy , Pandemics , Renal Dialysis , Retrospective Studies , Thrombosis/diagnostic imaging , Thrombosis/etiology , Thrombosis/therapy , Treatment Outcome , Vascular Patency
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