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1.
J Robot Surg ; 18(1): 225, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38805107

ABSTRACT

General surgery residents should be proficiently trained in robotic surgery. However, there is currently no standardized robotic training curriculum. We aimed to evaluate two approaches to a robotic curriculum and how implementing a virtual reality (VR) simulation curriculum improves trainee robotic performance. From 2019 to 2022, two models of a robotic training curriculum were examined: an in-unit rotation (IUR) and a 2-week curriculum (2WR). The VR curriculum was completed using the da Vinci® Skill Simulator. The curriculum used a pre/post-test design. Residents completed a pre-test that consisted of 4 VR exercises (graded 0-100%) and 3 inanimate box trainer exercises (graded using modified Objective Structured Assessment of Technical Skills). Then, residents completed a VR curriculum of 23 modules. Following the curriculum, residents were given a post-test with the same pre-test exercises. Time necessary to complete the curriculum and compliance were recorded. Of the 11 residents who participated in the IUR, 4 completed the VR curriculum. Comparatively, 100% (n = 23) of residents in the 2WR completed the curriculum. Average time to complete the VR curriculum was 3.8 h. After completion of the 2WR curriculum, resident performance improved from pre-test to post-test: VR test scores increased (160% vs 223%, p < 0.001), OSATS scores increased (15.0 vs 21.0, p < 0.001), and time to complete inanimate exercises decreased (1083 vs 756 s, p = 0.001). Residents who mastered all modules had higher post-test VR scores (241% vs 214%, p = 0.024). General surgery residents demonstrated improved compliance with the 2WR. The VR curriculum improved resident robotic performance in both virtual and inanimate domains.


Subject(s)
Clinical Competence , Curriculum , General Surgery , Internship and Residency , Robotic Surgical Procedures , Virtual Reality , Internship and Residency/methods , Robotic Surgical Procedures/education , Humans , General Surgery/education , Simulation Training/methods
2.
Pediatr Gastroenterol Hepatol Nutr ; 27(3): 186-195, 2024 May.
Article in English | MEDLINE | ID: mdl-38818275

ABSTRACT

Purpose: Infantile colic diagnostic criteria were established by Rome IV. A universally accepted management remains to be established. We aimed to evaluate diagnostic criteria, management strategies, and perceived regional prevalence of infantile colic in Pakistan, as well as its effect on physicians and parents. Methods: A questionnaire was distributed amongst 1,256 physicians. Results: We received 800 replies. Wessel and Rome IV criteria were used by most physicians for diagnosis; however, the response "any infant who cries a lot" was selected by older physicians (48% of those over 60 years), physicians in rural areas (32%), physicians practicing in private clinics (27%), and general physicians (30%). Estimated prevalence of infantile colic ranges from 21-40%. Reassurance was the most widely recommended management strategy followed by herbal teas (51%), switching to a different formula (49%), probiotics (28%) and antibiotics (26%), discontinuation of breastfeeding (14%), elimination of dairy products from the breastfeeding mothers' diet (6%), and the administration of colic drops (1%). Most physicians considered the negative impact of colic on their personal lives and the parents as mild-to-moderate. Notably, 38% of percent of physicians routinely screened for maternal depression, and 45% of physicians were aware of the association between infantile colic and shaken baby syndrome. Conclusion: Most physicians in Pakistan diagnose and manage infantile colic according to the established guidelines. However, the guidelines pertaining to treatment planning are not followed. Educational efforts directed toward general physicians and doctors practicing in rural areas and clinics must be implemented to avoid unnecessary testing and treatment burden.

3.
Int J Comput Assist Radiol Surg ; 19(4): 757-766, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38386176

ABSTRACT

PURPOSE: Intracardiac transcatheter interventions allow for reducing trauma and hospitalization stays as compared to standard surgery. In the treatment of mitral regurgitation, the most widely adopted transcatheter approach consists in deploying a clip on the mitral valve leaflets by means of a catheter that is run through veins from a peripheral access to the left atrium. However, precise manipulation of the catheter from outside the body while copying with the path constraints imposed by the vessels remains challenging. METHODS: We proposed a path tracking control framework that provides adequate motion commands to the robotic steerable catheter for autonomous navigation through vascular lumens. The proposed work implements a catheter kinematic model featuring nonholonomic constraints. Relying on the real-time measurements from an electromagnetic sensor and a fiber Bragg grating sensor, a two-level feedback controller was designed to control the catheter. RESULTS: The proposed method was tested in a patient-specific vessel phantom. A median position error between the center line of the vessel and the catheter tip trajectory was found to be below 2 mm, with a maximum error below 3 mm. Statistical testing confirmed that the performance of the proposed method exhibited no significant difference in both free space and the contact region. CONCLUSION: The preliminary in vitro studies presented in this paper showed promising accuracy in navigating the catheter within the vessel. The proposed approach enables autonomous control of a steerable catheter for transcatheter cardiology interventions without the request of calibrating the intuitive parameters or acquiring a training dataset.


Subject(s)
Cardiology , Mitral Valve Insufficiency , Robotics , Humans , Catheters , Mitral Valve
4.
BMJ Case Rep ; 17(1)2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38176750

ABSTRACT

IgM monoclonal gammopathies such as IgM myeloma and Waldenström macroglobulinaemia are distinct haematological conditions; however, differentiating between these entities can often present as a challenge.In this review, we explore the challenging diagnosis and treatment of IgM myeloma in a patient presenting with unexplained macrocytic anaemia, elevated serum protein and IgM levels in the absence of t(11;14) and lytic bone lesions that are classically associated with the diagnosis of IgM myeloma. The diagnosis was established based on 40% monoclonal plasma cell population on a bone marrow biopsy, gain of 1q21 on fluorescence in situ hybridisation, cyclin D1 positivity and absence of MYD88 mutation.


Subject(s)
Multiple Myeloma , Waldenstrom Macroglobulinemia , Humans , Multiple Myeloma/pathology , Bone Marrow/pathology , Plasma Cells/pathology , Waldenstrom Macroglobulinemia/genetics , Immunoglobulin M
5.
Muscle Nerve ; 69(1): 103-114, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37929655

ABSTRACT

INTRODUCTION/AIMS: Prior studies have emphasized the role of inflammation in the response to injury and muscle regeneration, but little emphasis has been placed on characterizing the relationship between innate inflammation, pain, and functional impairment. The aim of our study was to determine the contribution of innate immunity to prolonged pain following muscle contusion. METHODS: We developed a closed-impact mouse model of muscle contusion and a macrophage-targeted near-infrared fluorescent nanoemulsion. Closed-impact contusions were delivered to the lower left limb. Pain sensitivity, gait dysfunction, and inflammation were assessed in the days and weeks post-contusion. Macrophage accumulation was imaged in vivo by injecting i.v. near-infrared nanoemulsion. RESULTS: Despite hindpaw hypersensitivity persisting for several weeks, disruptions to gait and grip strength typically resolved within 10 days of injury. Using non-invasive imaging and immunohistochemistry, we show that macrophage density peaks in and around the affected muscle 3 day post-injury and quickly subsides. However, macrophage density in the ipsilateral sciatic nerve and dorsal root ganglia (DRG) increases more gradually and persists for at least 14 days. DISCUSSION: In this study, we demonstrate pain sensitivity is influenced by the degree of lower muscle contusion, without significant changes to gait and grip strength. This may be due to modulation of pain signaling by macrophage proliferation in the sciatic nerve, upstream from the site of injury. Our work suggests chronic pain developing from muscle contusion is driven by macrophage-derived neuroinflammation in the peripheral nervous system.


Subject(s)
Contusions , Pain , Mice , Animals , Macrophages , Contusions/diagnostic imaging , Muscles , Inflammation
6.
Mol Cancer Ther ; 23(3): 316-329, 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-37816504

ABSTRACT

Expression of the serine/threonine kinase never in mitosis gene A (NIMA)-related kinase 2 (NEK2) is essential for entry into mitosis via its role in facilitating centrosome separation. Its overactivity can lead to tumorigenesis and drug resistance through the activation of several oncogenic pathways, including AKT. Although the cancer-enabling activities of NEK2 are documented in many malignancies, including correlations with poor survival in myeloma, breast, and non-small cell lung cancer, little is known about the role of NEK2 in lymphoma. Here, in tumors from patients with diffuse large B-cell lymphoma (DLBCL), the most common, aggressive non-Hodgkin lymphoma, we found a high abundance of NEK2 mRNA and protein associated with an inferior overall survival. Using our recently developed NEK2 inhibitor, NBI-961, we discovered that DLBCL cell lines and patient-derived cells exhibit a dependency on NEK2 for their viability. This compromised cell fitness was directly attributable to efficient NEK2 inhibition and proteasomal degradation by NBI-961. In a subset of particularly sensitive DLBCL cells, NBI-961 induced G2/mitosis arrest and apoptosis. In contrast, an existing indirect NEK2 inhibitor, INH154, did not prevent NEK2 autophosphorylation, induce NEK2 proteasomal degradation, or affect cell viability. Global proteomics and phospho-proteomics revealed that NEK2 orchestrates cell-cycle and apoptotic pathways through regulation of both known and new signaling molecules. We show the loss of NEK2-sensitized DLBCL to the chemotherapy agents, doxorubicin and vincristine, and effectively suppressed tumor growth in mice. These studies establish the oncogenic activity of NEK2 in DLBCL and set the foundation for development of anti-NEK2 therapeutic strategies in this frequently refractory and relapse-prone cancer.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Lymphoma, Large B-Cell, Diffuse , Lymphoma , Humans , Animals , Mice , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , NIMA-Related Kinases/genetics , Cell Line, Tumor , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/genetics
7.
J Surg Oncol ; 129(1): 164-182, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38031870

ABSTRACT

Robotic surgery has experienced a dramatic increase in utilization across general surgery over the last two decades, including in surgical oncology. Although urologists and gynecologists were the first to show that this technology could be utilized in cancer surgery, the robot is now a powerful tool in the treatment of gastrointestinal, hepato-pancreatico-biliary, colorectal, endocrine, and soft tissue malignancies. While long-term outcomes are still pending, short-term outcomes have showed promise for this technologic advancement of cancer surgery.


Subject(s)
Laparoscopy , Neoplasms , Robotic Surgical Procedures , Surgical Oncology , Humans , Lymph Node Excision , Treatment Outcome
8.
Croat Med J ; 64(4): 256-264, 2023 Aug 31.
Article in English | MEDLINE | ID: mdl-37654037

ABSTRACT

AIM: To establish the pattern of antibiotic resistance and assess the frequency of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Salmonella Typhi and Salmonella Paratyphi among children with enteric fever. METHODS: This cross-sectional study was carried out in the Department of Pediatrics, Sharif Medical City Hospital, Lahore, from July 2020 to January 2021. The study involved patients aged between 0 to 15 years who attended our outpatient department or were admitted to the ward with the suspicion of typhoid fever. A convenience sample of patients with blood cultures positive for S. Typhi and S. Paratyphi was enrolled. RESULTS: Of the 105 participants, 70 (66.7%) were male. The mean age was 8.48±4.18 years, and the most affected age group was 6-10 years (n=46, 43.8%). Among the cultured organisms, 95 (90.5%) isolates were S. Typhi and 10 (9.5%) were S. Paratyphi A. Antibiotic resistance was highest against ampicillin (n=91, 86.7%), and all of the isolates were sensitive to imipenem and meropenem. Twenty-three (21.9%) cultured organisms were MDR and 54 (56.8%) were XDR. CONCLUSION: An alarming antibiotic drug resistance pattern was observed among children with enteric fever in Lahore. The lowest resistance was noted for azithromycin, meropenem, and imipenem. Our findings warrant the immediate implementation of tailored antibiotic stewardship and infection control strategies.


Subject(s)
Salmonella typhi , Typhoid Fever , Humans , Child , Male , Infant, Newborn , Infant , Child, Preschool , Adolescent , Female , Typhoid Fever/drug therapy , Typhoid Fever/epidemiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Salmonella paratyphi A , Meropenem , Pakistan/epidemiology , Cross-Sectional Studies , Tertiary Care Centers , Drug Resistance, Microbial , Imipenem
9.
J Pak Med Assoc ; 73(8): 1735-1737, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37697775

ABSTRACT

We report the anaesthetic management of a breast cancer patient, at a high risk for undergoing general anaesthesia, using a single-shot ultrasound-guided Erector Spinae Plane Block (ESPB) with monitored sedation. Targetted at T4, 20 mL of 0.375% bupivacaine provided complete surgical anaesthesia in 15 minutes. Concurrent sedation was administered with target controlled infusion of propofol with entropy monitoring throughout the procedure. The surgery lasted 90 minutes and the patient remained pain free and haemodynamically stable throughout. At the end of the surgery, the patient received 1 g of paracetamol intravenously, and did not require any further analgesics other than routinely administered paracetamol until her discharge from the hospital. On top of the successful execution of our plan, this case was especially interesting as her postoperative analgesia remained completely opioid-free.


Subject(s)
Anesthesia, Conduction , Breast Neoplasms , Nerve Block , Humans , Female , Breast Neoplasms/surgery , Acetaminophen , Ultrasonography, Interventional
10.
Cancers (Basel) ; 15(18)2023 Sep 12.
Article in English | MEDLINE | ID: mdl-37760488

ABSTRACT

Multiple myeloma (MM) induces dysfunctional bone marrow (BM) mesenchymal cells and neoangiogenesis. Pericytes and smooth muscle cells (SMCs) could detach from vessels and become cancer-associated fibroblasts. We found that the pericyte and SMC marker endothelin receptor type A (EDNRA) is overexpressed in whole MM bone biopsies; we sought to characterize its expression. EDNRA expression gradually increased with disease progression. High-risk MM patients had higher EDNRA expression than low-risk MM patients and EDNRA expression was highest in focal lesions. High EDNRA expression was associated with high expression of pericyte markers (e.g., RGS5, POSTN, and CD146) and the angiogenic marker FLT1. A single-cell analysis of unexpanded BM mesenchymal cells detected EDNRA expression in a subset of cells that coexpressed mesenchymal cell markers and had higher expression of proliferation genes. Immunohistochemistry revealed that the number of EDNRA+ cells in the interstitial BM increased as MM progressed; EDNRA+ cells were prevalent in areas near the MM focal growth. EDNRA+ cells were detached from CD34+ angiogenic cells and coexpressed RGS5 and periostin. Therefore, they likely originated from pericytes or SMCs. These findings identify a novel microenvironmental biomarker in MM and suggest that the presence of detached EDNRA+ cells indicates disrupted vasculature and increased angiogenesis.

11.
J Cardiothorac Surg ; 18(1): 252, 2023 Aug 24.
Article in English | MEDLINE | ID: mdl-37620956

ABSTRACT

OBJECTIVES: Performing wedge resection rather than lobectomy for primary lung cancer remains controversial. Recent studies demonstrate no survival advantage for non-anatomical resection compared to lobectomy in patients with early-stage lung cancer. The objective of this study was to investigate whether in patients with T1 tumours, non-anatomical wedge resection is associated with equivalent survival to lobectomy. METHODS: This was a retrospective cohort study of patients who underwent lung resection at the Lancashire Cardiac Centre between April 2005 and April 2018. Patients were subjected to multidisciplinary team discussion. The extent of resection was decided by the team based on British Thoracic Society guidelines. The primary outcome was overall survival. Propensity matching of patients with T1 tumours was also performed to determine whether differences in survival rates exist in a subset of these patients with balanced pre-operative characteristics. RESULTS: There were 187 patients who underwent non-anatomical wedge resection and 431 patients who underwent lobectomy. Cox modelling demonstrated no survival difference between groups for the first 1.6 years then a risk of death 3-fold higher for wedge resection group after 1.6 years (HR 3.14, CI 1.98-4.79). Propensity matching yielded 152 pairs for which 5-year survival was 66.2% for the lobectomy group and 38.5% for the non-anatomical wedge group (SMD = 0.58, p = 0.003). CONCLUSIONS: Non-anatomical wedge resection was associated with significantly reduced 5-year survival compared to lobectomy in matched patients. Lobectomy should remain the standard of care for patients with early-stage lung cancer who are fit enough to undergo surgical resection.


Subject(s)
Lung Neoplasms , Humans , Retrospective Studies , Lung Neoplasms/surgery , Heart , Thorax
12.
Surg Endosc ; 37(9): 7230-7237, 2023 09.
Article in English | MEDLINE | ID: mdl-37395804

ABSTRACT

INTRODUCTION: With the widespread adoption of minimally invasive surgery, there is a growing need for surgical residents to be trained by a procedure-specific curriculum. This study aimed to evaluate the technical performance and feedback of surgical residents undergoing the robotic and laparoscopic hepaticojejunostomy (HJ) and gastrojejunostomy (GJ) biotissue modules. METHODS: A total of 23 PGY-3 surgical residents participated in this study and performed the laparoscopic and robotic HJ and GJ drills, which were recorded and scored by two independent graders using the modified objective structured assessment of technical skills (OSATS). After completing each drill, all participants filled out the NASA Task Load Index (NASA-TLX), Borg Exertion Scale, and Edwards Arousal Rating Questionnaire. RESULTS: Twenty-two (95.7%) residents had already received fundamentals of laparoscopic surgery certification. Eighteen (78.3%) residents had robotic virtual simulation training and the median (range) number of robotic surgery console experience was 4 (0-30). In the HJ comparison of the six OSATS domains, the robotic system was superior in Gentleness (p = 0.031). In the GJ comparison, the robotic system was superior in Time and Motion (p < 0.001), Instrument Handling (p = 0.001), Flow of Operation (p = 0.002), Tissue Exposure (p = 0.013), and Summary (p < 0.001). Participants answered significantly higher demand scores for laparoscopy on all six facets of NASA-TLX for both HJ and GJ (p < 0.05). The Borg Level of Exertion was > 2 points higher for laparoscopic HJ and GJ (p < 0.001). Residents rated more Nervousness and Anxiety for laparoscopic compared to robotic (p < 0.05) HJ and GJ. Additionally, when asked to score preference for robotic and laparoscopic approach in terms of technique and ergonomics, residents scored robot as better (laparoscopy worse) for both HJ and GJ in both domains. CONCLUSIONS: The robotic surgical system provided a more favorable environment for trainees with less mental and physical burden for minimally invasive HJ and GJ curriculum.


Subject(s)
Internship and Residency , Laparoscopy , Robotic Surgical Procedures , Robotics , Simulation Training , Humans , Robotics/education , Robotic Surgical Procedures/education , Workload , Laparoscopy/methods , Curriculum , Clinical Competence , Simulation Training/methods
13.
Front Psychol ; 14: 1193411, 2023.
Article in English | MEDLINE | ID: mdl-37397287

ABSTRACT

Introduction: The quick pace of technological advancement and urbanization has led to a significant increase in waste production, severely damaging environmental quality and human health. The sorting of waste is a viable option to reduce environmental hazards and attain high recovery rates in the cities. This research extended the theory of planned behavior (TPB) by integrating information publicity (IP) and moral norms (MNs). Methods: A conceptual model has been developed to explore the predictors of waste-sorting intention of households. The data from 361 Pakistani households have been collected using the purposive sampling method and analyzed via PLS-SEM. Results and discussion: The study's results revealed that IP is important in creating awareness and establishing moral norms regarding waste sorting among households. The findings further confirm that MN, attitude (ATD), subjective norms (SNs), and perceived behavioral control (PBC) sequentially mediate between IP and WSI. The findings of the current study provides useful practical implications to the practitioners and academicians to combat environmental pollution.

14.
Leuk Res ; 133: 107355, 2023 10.
Article in English | MEDLINE | ID: mdl-37499483

ABSTRACT

Bone marrow mesenchymal stem cells (MSCs) may have contrasting impacts on the progression of multiple myeloma (MM). Priming normal MSCs, by culturing them with MM cells, mimics the MSC-induced MM growth. We studied the contrasting effects of conditioned medium (CM) from unprimed or primed MSCs on growth of MM cells from newly diagnosed cases. We elucidated potential molecular pathways using global gene expression profiling and focused on the role of the mTOR2 component, RICTOR, as a novel mediator of dormancy in MM. Primed MSCs CM consistently increased proportions of proliferating cells and supported MM growth in 3-day (n = 20) and 10-day (n = 12) cultures, effects that were partially mediated through the IGF1 axis. In contrast, unprimed MSCs CM inhibited growth of MM cells in cases mainly from stages I/II MM. The genes most overexpressed in MM cells treated with primed MSCs CM were associated with cell cycle, DNA-damage repair, and proliferation; genes most overexpressed in MM cells treated with unprimed MSCs CM were associated with dormancy pathways including RICTOR (mTOR2 pathway), CXCR4, and BCL2. RICTOR protein level was induced by unprimed MSCs CM and was lower in KI67+ proliferating MM cells treated with primed MSCs CM. RICTOR was underexpressed in clinical relapse samples compared with baseline samples of the same patients. Inhibiting RICTOR expression in primary MM cells promoted their growth, and enforced expression of RICTOR in MM cell lines inhibited their growth. Our findings suggest that, after prolonged interactions with MM cells, bone marrow MSCs shift from MM-repressive to MM-permissive. AVAILABILITY OF DATA AND MATERIALS: Our institutional GEP data of MM cells from newly diagnosed patients used to show RICTOR expression have been deposited at Gene Expression Omnibus (GEO: GSE2658, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE2658).


Subject(s)
Mesenchymal Stem Cells , Multiple Myeloma , Humans , Multiple Myeloma/genetics , Multiple Myeloma/metabolism , Neoplasm Recurrence, Local/metabolism , Mesenchymal Stem Cells/metabolism , Transcription Factors/metabolism , Gene Expression Profiling , Cell Proliferation
15.
Sci Total Environ ; 896: 165308, 2023 Oct 20.
Article in English | MEDLINE | ID: mdl-37414186

ABSTRACT

Microplastics (MPs) have been recognized as prominent anthropogenic pollutants that inflict significant harm to marine ecosystems. Various approaches have been proposed to mitigate the risks posed by MPs. Gaining an understanding of the morphology of plastic particles can provide valuable insights into the source and their interaction with marine organisms, which can assist the development of response measures. In this study, we present an automated technique for identifying MPs through segmentation of MPs in microscopic images using a deep convolutional neural network (DCNN) based on a shape classification nomenclature framework. We used MP images from diverse samples to train a Mask Region Convolutional Neural Network (Mask R-CNN) based model for classification. Erosion and dilation operations were added to the model to improve segmentation results. On the testing dataset, the mean F1-score (F1) of segmentation and shape classification was 0.7601 and 0.617, respectively. These results demonstrate the potential of proposed method for the automatic segmentation and shape classification of MPs. Furthermore, by adopting a specific nomenclature, our approach represents a practical step towards the global standardization of MPs categorization criteria. This work also identifies future research directions to improve accuracy and further explore the possibilities of using DCNN for MPs identification.

16.
Mol Med ; 29(1): 92, 2023 Jul 06.
Article in English | MEDLINE | ID: mdl-37415117

ABSTRACT

BACKGROUND: Diabetic nephropathy (DN) is a major complication of diabetes mellitus. Clinical reports indicate that smoking is a significant risk factor for chronic kidney disease, and the tobacco epidemic exacerbates kidney damage in patients with DN. However, the underlying molecular mechanisms remain unclear. METHOD: In the present study, we used a diabetic mouse model to investigate the molecular mechanisms for nicotine-exacerbated DN. Twelve-week-old female mice were injected with streptozotocin (STZ) to establish a hyperglycemic diabetic model. After four months, the control and hyperglycemic diabetic mice were further divided into four groups (control, nicotine, diabetic mellitus, nicotine + diabetic mellitus) by intraperitoneal injection of nicotine or PBS. After two months, urine and blood were collected for kidney injury assay, and renal tissues were harvested for further molecular assays using RNA-seq analysis, real-time PCR, Western blot, and immunohistochemistry. In vitro studies, we used siRNA to suppress Grem1 expression in human podocytes. Then we treated them with nicotine and high glucose to compare podocyte injury. RESULT: Nicotine administration alone did not cause apparent kidney injury, but it significantly increased hyperglycemia-induced albuminuria, BUN, plasma creatinine, and the kidney tissue mRNA expression of KIM-1 and NGAL. Results from RNA-seq analysis, real-time PCR, Western blot, and immunohistochemistry analysis revealed that, compared to hyperglycemia or nicotine alone, the combination of nicotine treatment and hyperglycemia significantly increased the expression of Grem1 and worsened DN. In vitro experiments, suppression of Grem1 expression attenuated nicotine-exacerbated podocyte injury. CONCLUSION: Grem1 plays a vital role in nicotine-exacerbated DN. Grem1 may be a potential therapeutic target for chronic smokers with DN.


Subject(s)
Diabetes Mellitus, Experimental , Diabetic Nephropathies , Hyperglycemia , Humans , Mice , Female , Animals , Diabetic Nephropathies/genetics , Diabetic Nephropathies/chemically induced , Up-Regulation , Nicotine/adverse effects , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Experimental/chemically induced , Hyperglycemia/genetics , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/metabolism
17.
Front Immunol ; 14: 1148209, 2023.
Article in English | MEDLINE | ID: mdl-37266425

ABSTRACT

Inflammation contributes to many chronic conditions. It is often associated with circulating pro-inflammatory cytokines and immune cells. GLP-1 levels correlate with disease severity. They are often elevated and can serve as markers of inflammation. Previous studies have shown that oxytocin, hCG, ghrelin, alpha-MSH and ACTH have receptor-mediated anti-inflammatory properties that can rescue cells from damage and death. These peptides have been studied well in the past century. In contrast, GLP-1 and its anti-inflammatory properties have been recognized only recently. GLP-1 has been proven to be a useful adjuvant therapy in type-2 diabetes mellitus, metabolic syndrome, and hyperglycemia. It also lowers HbA1C and protects cells of the cardiovascular and nervous systems by reducing inflammation and apoptosis. In this review we have explored the link between GLP-1, inflammation, and sepsis.


Subject(s)
Diabetes Mellitus, Type 2 , Glucagon-Like Peptide 1 , Humans , Glucagon-Like Peptide 1/therapeutic use , Glucagon-Like Peptide 1/metabolism , Diabetes Mellitus, Type 2/drug therapy , Peptides/therapeutic use , Inflammation/drug therapy , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use
18.
Clin Lung Cancer ; 24(5): e179-e186, 2023 07.
Article in English | MEDLINE | ID: mdl-37217388

ABSTRACT

BACKGROUND: Historically, limited stage Small Cell Lung Cancer (SCLC) has been treated with concurrent chemoradiation (CRT). While current NCCN guidelines recommend consideration of lobectomy in node-negative cT1-T2 SCLC, data regarding the role of surgery in very limited SCLC is lacking. METHODS: Data from the National VA Cancer Cube were compiled. A total of 1,028 patients with pathologically confirmed stage I SCLC were studied. Only 661 patients that either received surgery or CRT were included. Interval-censored Weibull and Cox proportional hazard regression models were used to estimate median overall survival (OS) and hazard ratio (HR), respectively. Two survival curves were compared by a Wald test. Subset analysis was performed based on the location of the tumor in the upper vs. lower lobe as delineated by ICD-10 codes C34.1 and C34.3. RESULTS: Four-hundred and forty-six patients received concurrent CRT; while 223 underwent treatment that contained surgery (93 surgery only, 87 surgery/chemo, 39 surgery/chemo/radiation and 4 surgery/radiation). The median OS for the surgery-inclusive treatment was 3.87 years (95% CI 3.21-4.48) while median OS for the CRT cohort was 2.45 years (95% CI 2.17-2.74). HR of death for surgery-inclusive treatment when compared to CRT is 0.67 (95% CI 0.55-0.81; P < .001). Subset analysis based on the location of the tumor in both the upper or lower lobes showed improved survival with surgery as compared to CRT regardless of the location. HR for the upper lobe was 0.63 (95% CI 0.50-0.80; P < .001) and lower lobe 0.61 (95% CI 0.42-0.87; P = .006). Multivariable regression analysis accounting for age and ECOG-PS shows a HR 0.60 (95% CI 0.43-0.83; P = .002) favoring surgery. CONCLUSIONS: Surgery was used in less than a third of patients with stage I SCLC who received treatment. Surgery-inclusive multimodality treatment was associated with a longer overall survival as compared to chemoradiation, independent of age, performance status or tumor location. Our study suggests a more expansive role for surgery in stage I SCLC.


Subject(s)
Lung Neoplasms , Small Cell Lung Carcinoma , Humans , Small Cell Lung Carcinoma/surgery , Lung Neoplasms/surgery , Neoplasm Staging , Chemoradiotherapy , Combined Modality Therapy
19.
J Pak Med Assoc ; 73(5): 1043-1047, 2023 May.
Article in English | MEDLINE | ID: mdl-37218231

ABSTRACT

Objective: To assess upper-to-lower body segment ratio and arm span to height difference in children. METHODS: The descriptive, cross-sectional study was conducted in schools of the Raiwind area near Lahore, Pakistan, from November 2021 to May 2022, after approval from the ethics review committee of the Sharif Medical and Dental College, Lahore. The sample comprised children aged 3-14 years whose height fell between the 3rd and 97th centiles on the Centers for Disease Control and Prevention height-for-age chart. Data was analysed using SPSS 23. RESULTS: Of the 1,836 children, 906(49.3%) were boys with mean age 8.45±3.02 years, mean height 132.54±17.78cm and mean weight 32.0±13.72kg. Besides, there were 930(50.7%) girls with mean age 8.26±3.21 years, mean height 130.41±18.03cm and mean weight 31.09±13.88kg. The mean upper-to-lower body segment ratio in boys was 1.06±0.15 at age 3 years, 0.96±0.08 at age 7 and 0.94±0.08 at age 10. The mean upper-to-lower body segment ratio in girls was 1.08±0.08 at age 3 years, 0.98±0.07 at age 7, and 0.92±0.10 at age 10. The mean arm span to height difference in boys was -1.81±5.83 and in girls -4.09±5.77. Conclusion: Upper-to-lower body segment ratio and arm span to height difference may help paediatricians in the evaluation of disproportionate short stature.


Subject(s)
Arm , Body Height , Male , Female , Humans , Child , Child, Preschool , Cross-Sectional Studies , Pakistan , Body Weight
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