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1.
Arch Microbiol ; 206(4): 198, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38558101

ABSTRACT

Micro- plastics (MPs) pose significant global threats, requiring an environment-friendly mode of decomposition. Microbial-mediated biodegradation and biodeterioration of micro-plastics (MPs) have been widely known for their cost-effectiveness, and environment-friendly techniques for removing MPs. MPs resistance to various biocidal microbes has also been reported by various studies. The biocidal resistance degree of biodegradability and/or microbiological susceptibility of MPs can be determined by defacement, structural deformation, erosion, degree of plasticizer degradation, metabolization, and/or solubilization of MPs. The degradation of microplastics involves microbial organisms like bacteria, mold, yeast, algae, and associated enzymes. Analytical and microbiological techniques monitor microplastic biodegradation, but no microbial organism can eliminate microplastics. MPs can pose environmental risks to aquatic and human life. Micro-plastic biodegradation involves fragmentation, assimilation, and mineralization, influenced by abiotic and biotic factors. Environmental factors and pre-treatment agents can naturally degrade large polymers or induce bio-fragmentation, which may impact their efficiency. A clear understanding of MPs pollution and the microbial degradation process is crucial for mitigating its effects. The study aimed to identify deteriogenic microorganism species that contribute to the biodegradation of micro-plastics (MPs). This knowledge is crucial for designing novel biodeterioration and biodegradation formulations, both lab-scale and industrial, that exhibit MPs-cidal actions, potentially predicting MPs-free aquatic and atmospheric environments. The study emphasizes the urgent need for global cooperation, research advancements, and public involvement to reduce micro-plastic contamination through policy proposals and improved waste management practices.


Subject(s)
Microplastics , Water Pollutants, Chemical , Humans , Plastics , Biodegradation, Environmental , Industry , Microbiological Techniques
2.
J Orthop Trauma ; 38(6): 220-224, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38457751

ABSTRACT

OBJECTIVES: To determine if talar neck fractures with concomitant ipsilateral foot and/or ankle fractures (TNIFAFs) are associated with higher rates of avascular necrosis (AVN) compared with isolated talar neck fractures (ITNs). DESIGN: Retrospective cohort. SETTING: Single level I trauma center. PATIENT SELECTION CRITERIA: Skeletally mature patients who sustained talar neck fractures from January 2008 to January 2017 with at least 6-month follow-up. Based on radiographs at the time of injury, fractures were classified as ITN or TNIFAF and by Hawkins classification. OUTCOME MEASURES AND COMPARISONS: The primary outcome was the development of AVN based on follow-up radiographs, with secondary outcomes including nonunion and collapse. RESULTS: There were 115 patients who sustained talar neck fractures, with 63 (55%) in the ITN group and 52 (45%) in the TNIFAF group. In total, 63 patients (54.7%) were female with the mean age of 39 years (range, 17-85), and 111 fractures (96.5%) occurred secondary to high-energy mechanisms of injury. There were no significant differences in demographic or clinical characteristics between groups ( P > 0.05). Twenty-four patients (46%) developed AVN in the TNIFAF group compared with 19 patients (30%) in the ITN group ( P = 0.078). After adjusting for Hawkins classification and other variables, the odds of developing AVN was higher in the TNIFAF group compared with the ITN group [odds ratio, 2.43 (95% confidence interval, 1.01-5.84); ( P = 0.047)]. CONCLUSIONS: This study found a significantly higher likelihood of AVN in patients with talar neck fractures with concomitant ipsilateral foot and/or ankle fractures compared to those with isolated talar neck fractures after adjusting for Hawkins classification and other potential prognostic confounders. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Subject(s)
Ankle Fractures , Fractures, Bone , Osteonecrosis , Talus , Humans , Female , Male , Adult , Talus/injuries , Talus/diagnostic imaging , Retrospective Studies , Middle Aged , Ankle Fractures/complications , Ankle Fractures/surgery , Aged , Adolescent , Young Adult , Osteonecrosis/etiology , Fractures, Bone/complications , Fractures, Bone/diagnostic imaging , Aged, 80 and over , Risk Factors , Cohort Studies
3.
J Orthop Trauma ; 38(7): 358-365, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38506517

ABSTRACT

OBJECTIVES: To determine whether scheduled low-dose, short-term ketorolac modulates cytokine concentrations in orthopaedic polytrauma patients. DESIGN: Secondary analysis of a double-blinded, randomized controlled trial. SETTING: Single Level I trauma center from August 2018 to October 2022. PATIENT SELECTION CRITERIA: Orthopaedic polytrauma patients between 18 and 75 years with a New Injury Severity Score greater than 9 were enrolled. Participants were randomized to receive 15 mg of intravenous ketorolac every 6 hours for up to 5 inpatient days or 2 mL of intravenous saline similarly. OUTCOME MEASURES AND COMPARISONS: Daily concentrations of prostaglandin E2 and interleukin (IL)-1a, IL-1b, IL-6, and IL-10. Clinical outcomes included hospital and intensive care unit length of stay, pulmonary complications, and acute kidney injury. RESULTS: Seventy orthopaedic polytrauma patients were enrolled, with 35 participants randomized to the ketorolac group and 35 to the placebo group. The overall IL-10 trend over time was significantly different in the ketorolac group ( P = 0.043). IL-6 was 65.8% higher at enrollment compared to day 3 ( P < 0.001) when aggregated over both groups. There was no significant treatment effect for prostaglandin E2, IL-1a, or IL-1b ( P > 0.05). There were no significant differences in clinical outcomes between groups ( P > 0.05). CONCLUSIONS: Scheduled low-dose, short-term, intravenous ketorolac was associated with significantly different mean trends in IL-10 concentration in orthopaedic polytrauma patients with no significant differences in prostaglandin E2, IL-1a, IL-1b, or IL-6 levels between groups. The treatment did not have an impact on clinical outcomes of hospital or intensive care unit length of stay, pulmonary complications, or acute kidney injury. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Cytokines , Ketorolac , Multiple Trauma , Humans , Male , Female , Middle Aged , Adult , Double-Blind Method , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Ketorolac/administration & dosage , Aged , Young Adult , Drug Administration Schedule , Adolescent
4.
J Orthop Trauma ; 38(7): 383-389, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38527088

ABSTRACT

OBJECTIVES: To compare radiographic and clinical outcomes in nonoperative management of humeral shaft fractures treated initially with coaptation splinting (CS) followed by delayed functional bracing (FB) versus treatment with immediate FB. DESIGN: Retrospective cohort study. SETTING: Academic Level 1 Trauma Center. PATIENT SELECTION CRITERIA: Patients with closed humeral shaft fractures managed nonoperatively with initial CS followed by delayed FB or with immediate FB from 2016 to 2022. Patients younger than 18 years and/or with less than 3 months of follow-up were excluded. OUTCOME MEASURES AND COMPARISONS: The primary outcome was coronal and sagittal radiographic alignment assessed at the final follow-up. Secondary outcomes included rate of failure of nonoperative management (defined as surgical conversion and/or fracture nonunion), fracture union, and skin complications secondary to splint/brace wear. RESULTS: Ninety-seven patients were managed nonoperatively with delayed FB (n = 58) or immediate FB (n = 39). Overall, the mean age was 49.9 years (range 18-94 years), and 64 (66%) patients were female. The immediate FB group had less smokers ( P = 0.003) and lower incidence of radial nerve palsy ( P = 0.025), with more proximal third humeral shaft fractures ( P = 0.001). There were no other significant differences in demographic or clinical characteristics ( P > 0.05). There were no significant differences in coronal ( P = 0.144) or sagittal ( P = 0.763) radiographic alignment between the groups. In total, 33 (34.0%) humeral shaft fractures failed nonoperative management, with 11 (28.2%) in the immediate FB group and 22 (37.9%) in the delayed FB group ( P = 0.322). There were no significant differences in fracture union ( P = 0.074) or skin complications ( P = 0.259) between the groups. CONCLUSIONS: This study demonstrated that nonoperative treatment of humeral shaft fractures with immediate functional bracing did not result in significantly different radiographic or clinical outcomes compared to treatment with CS followed by delayed functional bracing. Future prospective studies assessing patient-reported outcomes will further guide clinical decision making. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Subject(s)
Braces , Humeral Fractures , Splints , Humans , Female , Retrospective Studies , Male , Middle Aged , Adult , Aged , Humeral Fractures/therapy , Adolescent , Aged, 80 and over , Young Adult , Treatment Outcome
5.
Cureus ; 15(11): e49235, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38143712

ABSTRACT

Introduction Lower limb fractures frequently require immobilization with backslabs to promote healing. This study investigates a novel approach involving the incorporation of a single ridge to enhance backslab strength while maintaining cost-effectiveness. Objective The aim of this study was to assess the mechanical performance of ridged backslabs in comparison to traditional non-ridged backslabs, specifically focusing on their load-bearing capacity and cost-effectiveness when used in lower limb fractures. Methods This experimental study, conducted between January 2023 and June 2023, compares three groups of backslabs with varying layers (eight, ten, and twelve) that were fabricated, each consisting of four ridged and four non-ridged specimens. These backslabs, constructed from six-inch plaster of Paris rolls, were 190 cm in length. A three-point bending test was conducted on both groups using a Hounsfield H100KS Universal Testing Machine (Tinius Olsen Ltd., Redhill, UK), with a crosshead speed of 5 mm/min and a span distance of 190 mm between supports. Results Significant differences in mean maximum force endured were observed between the ten-layered and twelve-layered flat and ridged backslabs (p-values: 0.003 and 0.004, respectively). Ten-layered ridged backslabs exhibited a 56 N higher load-bearing capacity, while twelve-layered ridged backslabs withstood 73.9 N more force than their flat counterparts, underscoring the superior strength of ridged lower limb backslabs. Conclusion Ridged backslabs outperformed non-ridged backslabs in terms of strength when subjected to external forces. These findings support the potential adoption of ridged backslabs as a lightweight, cost-effective, and robust alternative for immobilization in lower limb fractures.

6.
Cureus ; 15(10): e46336, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37920624

ABSTRACT

INTRODUCTION: Femoral shaft fractures significantly impact children and families, posing a significant challenge for pediatric patients. The prevalence of limb shortening in femur shaft fractures treated with hip spica casting in our group, however, has not been the subject of many recent investigations. AIMS: By comparing the prevalence of limb shortening to various age groups and common pediatric injury patterns, this research seeks to close this information gap. METHODS: This research, which lasted six months and was done at the Orthopedics Unit of Khyber Teaching Hospital Peshawar, Pakistan, included 129 children with closed femur shaft fractures who were between the ages of one and six. Clinical assessments, radiological examinations, and hip spica casting, all supervised by experienced orthopedic surgeons, were carried out. Senior postgraduate trainees oversaw the study's findings. RESULTS: The results unveiled key insights into the study population. Among the findings, 33% (n=43) of the children were aged one to three years, while 67% (n=86) fell within the three to six years age range. Gender distribution revealed that 72% (n= 93) were male. In terms of mechanism, 22% (n=28) of fractures were attributed to road traffic accidents, 69% (n=89) were the result of falls, and 5% (n=12) were due to other causes. Notably, 19% (n=29) of the children exhibited limb shortening. CONCLUSION: This study contributes significantly to the understanding of femur shaft fractures in children, shedding light on their complex dynamics. The study enhances our understanding of pediatric femur shaft fractures. We found that 19% of children exhibited limb shortening, underscoring the need for targeted treatment strategies. These insights can significantly improve patient care and treatment protocols for this challenging condition, benefiting both children and their families.

7.
Cureus ; 15(4): e37616, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37069840

ABSTRACT

A 17-year-old boy presented during the COVID-19 pandemic in late 2021 with intractable fevers and hemodynamic instability with early gastrointestinal disturbances, resembling features of the pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. Our patient required intensive unit care for persistently worsening signs of cardiac failure; initial admission echocardiography demonstrated severe left ventricular dysfunction with an estimated ejection fraction of 27%. Treatment with intravenous IgG and corticosteroids showed a rapid improvement in symptoms, but further specialist cardiological input was required for heart failure in the coronary care unit. Substantial improvement in cardiac function was shown on echocardiography before discharge, initially to left ventricular ejection fraction (LVEF) 51% two days after the commencement of treatment and then to >55% four days later, and on cardiac MRI. An echocardiogram one month post-discharge was normal, and the patient reported complete resolution of heart failure symptoms by four months in addition to full restoration of functional status.

8.
Cureus ; 15(11): e49723, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38161861

ABSTRACT

By encompassing a wide range of best practices within the ever-changing realm of modern surgical care, this exhaustive narrative compendium attempts to unravel the complex tapestry of novel approaches to safe surgery. Within the context of a dynamic surgical environment, this research endeavors to illuminate and integrate state-of-the-art methods that collectively methodically improve patient safety. The narrative elucidates a diverse array of practices that seek to revolutionize the paradigm of safe surgery, emphasizing technological progress, patient-centric approaches, and global viewpoints. The combined effectiveness of these methods in fostering an all-encompassing culture of safety, improving surgical precision, and decreasing complications is revealed by the results obtained from their implementation. The recognition of the dynamic interplay among multiple components, including the active participation of patients, the integration of cutting-edge technologies, and the establishment of comprehensive quality improvement programs, is fundamental to this narrative. By their collective composition, these components support the notion that secure surgical practices are intricate and interrelated. The present synthesis functions as a fundamental resource for healthcare professionals, policymakers, and researchers, providing an enlightening examination of the current condition of secure surgical practices. By emphasizing the promotion of innovation, continuous development, and the utmost quality of patient care, it offers a strategic guide for navigating the complex terrain of safe surgery. In the ever-evolving landscape of surgical care, this narrative synthesis serves as a guiding principle for stakeholders striving to understand better and implement safe surgical procedures in various healthcare environments.

9.
JBJS Rev ; 10(12)2022 Dec 01.
Article in English | MEDLINE | ID: mdl-36480655

ABSTRACT

➢: Arthroscopic hip labral reconstruction is a complex procedure which is growing in use as indications, techniques, and surgical expertise advance. ➢: Graft selection is an important component of labral reconstruction based on relative advantages and disadvantages of available types of autografts and allografts. ➢: The ideal graft should mimic the native acetabular labrum form and function while also being affordable, readily available, and associated with low morbidity. ➢: High rates of patient satisfaction and positive patient-reported outcomes have been reported after labral reconstruction using several graft types.

10.
J Ayub Med Coll Abbottabad ; 34(Suppl 1)(3): S671-S677, 2022.
Article in English | MEDLINE | ID: mdl-36414588

ABSTRACT

Background: The incidence of maternal mortality and morbidity related to the termination of unwanted pregnancy in Pakistan is rising at an alarming rate. Instant Postpartum insertion of intrauterine contraceptive device (PPIUCD) is an effective contraceptive measure to reduce unexpected pregnancy and its associated complications in developing countries like Pakistan. Methods: The current study was conducted in a public sector hospital in Karachi with a total of 7314 pregnant women counselled for insertion of PPIUCD antenatally. Out of which 5682 women agreed to the insertion and 1632 refused the procedure, mostly due to unfamiliarity with PPIUCD insertion. PPIUCD was inserted within 48 hours of delivery in 1441 patients and they were followed for 6 months onwards. Results: Total postpartum insertions were 1441 which was found to be an effective measure with the continuation rate of 91% among 785 followed up cases. Postpartum IUCD insertion was found as an effective, satisfactory and convenient practice for the women of developing countries like Pakistan, to get an on-time appropriate contraceptive measure. Conclusion: : PPIUCD was found to have high retention and low expulsion rate and its efficacy can be improved further by proper training and skills of healthcare professionals. In this regard, appropriate strategies should be formulated and implemented at the statutory level by increasing social awareness and practice of using PPIUCD by health care providers to reduce undesired pregnancies.


Subject(s)
Intrauterine Devices , Female , Humans , Pregnancy , Contraception , Postpartum Period , Contraceptive Agents , Health Personnel
11.
J Shoulder Elb Arthroplast ; 6: 24715492221075446, 2022.
Article in English | MEDLINE | ID: mdl-35669620

ABSTRACT

Background: Intraarticular corticosteroid injection is commonly used conservative treatment for glenohumeral osteoarthritis (OA). The purpose of this study was to investigate the clinical fate of symptomatic glenohumeral OA following intraarticular corticosteroid injection and to identify factors associated with undergoing shoulder arthroplasty. Methods: Glenohumeral OA patients who had undergone at least one glenohumeral corticosteroid injection from 2012 to 2017 were identified. Data for demographics, comorbidities, number of injections, severity of radiographic arthritis, and subsequent treatment were collected up to February 2020. Data were analyzed to compare between patients who had eventually undergone shoulder arthroplasty and those who had not. Results: A total of 311 shoulders (275 patients) were followed up for 3 to 8 years after the index injection. The mean age of patients was 64.7 years. There were 148 females, and 116 shoulders (37.3%) eventually underwent arthroplasty, 68 (21.9%) further injections only, 104 (33.4%) no further treatment, 14 (4.5%) a non-arthroplasty surgical procedure, and 9 (2.9%) were lost to follow up. Severity of radiographic arthritic changes, female sex, younger age, and nonsmoking status were found to be significantly associated with undergoing arthroplasty (p < 0.001, p = 0.014, p = 0.003, and p = 0.043, respectively). Conclusion: Approximately one third of glenohumeral OA patients who had received an intraarticular corticosteroid injection eventually elected to undergo shoulder arthroplasty within 3 to 8 years of the injection. High-grade arthritic changes in radiographs, female gender, and younger age were found to be independent factors associated with undergoing arthroplasty. This information may be useful in counseling patients about their future clinical course.Level of Evidence: Level III Retrospective comparative study.

12.
Am J Surg ; 223(2): 238-242, 2022 02.
Article in English | MEDLINE | ID: mdl-34274104

ABSTRACT

INTRODUCTION: Non-accidental trauma (NAT) affects 2 per 100,000 children annually in the US and may go unrecognized. The aim of this study to quantify the burden of NAT and to evaluate regional variations in mortality. METHODS: The Kids Inpatient Database (2000-2012) was queried for pediatric patients presenting with a diagnosis of NAT. Data was obtained on demographic, clinical and hospital-level characteristics. Primary outcome measure was mortality. Multivariable logistic regression models for age, sex, race/ethnicity, insurance status, income quartile, hospital volume, region (Northeast, South, West and Midwest), teaching status, and injury severity scores. RESULTS: NAT represented 1.92% (n = 15,999) of all trauma patients. Mortality rates were 3.98% for patients presenting with NAT. African American children had a higher likelihood of mortality compared to White children (OR[95%CI]:1.35[1.03-1.79]), however, this effect was not statistically significant for patients being treated at designated children's hospitals (OR[95%CI]:1.23(0.78-1.95) and urban facilities (OR[95%CI]:1.30[0.99-1.72]). Statistically significant regional variations in mortality, lost significance for patients treated at designated children's hospitals (p > 0.05). CONCLUSION: NAT has devastating consequences and is associated with a high mortality rate. Treatment at designated children's hospitals results in the loss of variation in mortality, resulting in diminished disparities and improved outcomes. These findings align with current trends towards the "regionalization of pediatric health care" and reflects the value of regional transfer centers that are.


Subject(s)
Child Abuse , Child , Child Abuse/diagnosis , Databases, Factual , Hospital Mortality , Hospitals, Pediatric , Humans , Infant , Injury Severity Score , Retrospective Studies , Trauma Centers
13.
Ann Med Surg (Lond) ; 70: 102774, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34603712

ABSTRACT

BACKGROUND: Dietetics today occupy a significant place in the field of research, helping to discover cardiovascular benefits of healthy diets and consumption of organic foods such as fruits, vegetables, legumes, nuts, and whole grains. One of the components of vegetable-based diet is chili pepper (CP) which has been found to affect all-cause mortality. METHODS: MEDLINE, EMBASE, Scopus, EBSCO, and Cochrane (Wiley) Central Register of Controlled Trials were searched from inception till January 9, 2020, identifying all relevant studies using keywords and truncations. Studies were included if (1) they were observational or randomized in nature (2) included patients consuming CP and (3) evaluated direct comparison between regular and rarely/never CP consumption. RESULTS: Our preliminary search yielded 6976 articles. Post exclusion and after full-text screening, four potential observational studies with a population of 570,762. Pooled analysis found reduced all-cause mortality in CP consumers compared to nonconsumers with a risk ratio (RR) of 0.75 [95% CI: 0.64-0.88; p = 0.0004; I 2 = 97%]. The RR for CVD, cancer related and CVA deaths were 0.74 [95% CI: 0.62-0.88; p = 0.0006, I 2 = 66%], 0.77 [95% CI: 0.71-0.84; p = 0.0001; I 2 = 49%] and 0.76 [95% CI: 0.36-1.60; p = 0.47; I2 = 93%], respectively. CONCLUSION: Statistically significant results of our analysis put forward a rationale indicating an association between lower risk of all-cause, cardiovascular and cancer related deaths and CP consumption.

14.
Heart Lung Circ ; 29(11): 1668-1681, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32798049

ABSTRACT

Acute type A aortic dissection is a clinical emergency and is associated with significant morbidity and mortality rates if not managed promptly in specialised and high-volume centres. The mortality rate is increased by 1% for each hour delay in management; however, with advancement in clinical practice, diagnostic imaging and clinician awareness, this has been dramatically reduced to below 30% in most international centres. Not only timing of recognition of the pathology, but also other factors can significantly affect outcomes of such critical pathology. This includes, but is not limited to, age, extent of the pathology, existence of connective tissue disorders, hypertension, diabetes mellitus and surgeon experience. This narrative review will focus on current clinical practice and the evidence behind optimising each factor to minimise adverse outcomes in such high-risk cohort.


Subject(s)
Aortic Aneurysm, Thoracic/surgery , Aortic Dissection/surgery , Registries , Risk Assessment/methods , Vascular Surgical Procedures/methods , Acute Disease , Aortic Dissection/mortality , Aortic Aneurysm, Thoracic/mortality , Global Health , Humans , Risk Factors , Survival Rate/trends
15.
JAMA Neurol ; 77(6): 755-763, 2020 06 01.
Article in English | MEDLINE | ID: mdl-32202612

ABSTRACT

Importance: One major advantage of developing large, federally funded networks for clinical research in neurology is the ability to have a trial-ready network that can efficiently conduct scientifically rigorous projects to improve the health of people with neurologic disorders. Observations: National Institute of Neurological Disorders and Stroke Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) was established in 2011 and renewed in 2018 with the goal of being an efficient network to test between 5 and 7 promising new agents in phase II clinical trials. A clinical coordinating center, data coordinating center, and 25 sites were competitively chosen. Common infrastructure was developed to accelerate timelines for clinical trials, including central institutional review board (a first for the National Institute of Neurological Disorders and Stroke), master clinical trial agreements, the use of common data elements, and experienced research sites and coordination centers. During the first 7 years, the network exceeded the goal of conducting 5 to 7 studies, with 9 funded. High interest was evident by receipt of 148 initial applications for potential studies in various neurologic disorders. Across the first 8 studies (the ninth study was funded at end of initial funding period), the central institutional review board approved the initial protocol in a mean (SD) of 59 (21) days, and additional sites were added a mean (SD) of 22 (18) days after submission. The median time from central institutional review board approval to first site activation was 47.5 days (mean, 102.1; range, 1-282) and from first site activation to first participant consent was 27 days (mean, 37.5; range, 0-96). The median time for database readiness was 3.5 months (mean, 4.0; range, 0-8) from funding receipt. In the 4 completed studies, enrollment met or exceeded expectations with 96% overall data accuracy across all sites. Nine peer-reviewed manuscripts were published, and 22 oral presentations or posters and 9 invited presentations were given at regional, national, and international meetings. Conclusions and Relevance: NeuroNEXT initiated 8 studies, successfully enrolled participants at or ahead of schedule, collected high-quality data, published primary results in high-impact journals, and provided mentorship, expert statistical, and trial management support to several new investigators. Partnerships were successfully created between government, academia, industry, foundations, and patient advocacy groups. Clinical trial consortia can efficiently and successfully address a range of important neurologic research and therapeutic questions.


Subject(s)
Clinical Trials as Topic/organization & administration , National Institute of Neurological Disorders and Stroke (U.S.) , Nervous System Diseases/therapy , Neurology , Neurosciences , Humans , United States
17.
Eur J Pediatr ; 179(6): 865-874, 2020 Jun.
Article in English | MEDLINE | ID: mdl-31970487

ABSTRACT

To assess the efficacy of double phototherapy in managing neonatal jaundice compared to single phototherapy in infants with different birth weight and gestational age. CENTRAL, PubMed, clinicaltrials.gov, and gray literature sources were searched from date of inception of these databases till August 2019. Primary outcome was decline of total serum bilirubin (TSB) per hour. Ten studies were eligible. Our meta-analysis showed significant difference between double phototherapy versus single phototherapy in decline of TSB per hour in preterm infants (standardized mean difference [SMD] = 2.28 [0.79-3.76], p = 0.003) and a significant decrease in TSB levels at 24 h of phototherapy in infants with birth weight ≥ 1500 g (mean difference [MD] = - 61.70 µmol/L, [- 107.96, - 15.43], p = <0.001).Conclusion: Double phototherapy is effective in reducing TSB in infants of different gestational ages and birth weights with the most important finding regarding preterm infants, who are more susceptible to kernicterus.What is Known:• Double phototherapy has shown to be more efficacious than single phototherapy in treating neonatal jaundice.• Double phototherapy efficacy on neonates with different gestational ages and birth weights still remain ambiguous in treating neonatal jaundice.What is New:• The results of this meta-analysis show that double phototherapy is effective in reducing TSB in infants of different gestational ages and birth weights with the most important finding regarding preterm infants, who are more susceptible to kernicterus.


Subject(s)
Jaundice, Neonatal/therapy , Phototherapy/methods , Bilirubin/blood , Biomarkers/blood , Humans , Infant, Newborn , Jaundice, Neonatal/blood , Jaundice, Neonatal/diagnosis , Treatment Outcome
18.
PLoS One ; 13(3): e0192145, 2018.
Article in English | MEDLINE | ID: mdl-29554088

ABSTRACT

Vision impairment from corneal fibrosis is a common consequence of irregular corneal wound healing after injury. Intermediate-conductance calmodulin/calcium-activated K+ channels 3.1 (KCa3.1) play an important role in cell cycle progression and cellular proliferation. Proliferation and differentiation of corneal fibroblasts to myofibroblasts can lead to corneal fibrosis after injury. KCa3.1 has been shown in many non-ocular tissues to promote fibrosis, but its role in corneal fibrosis is still unknown. In this study, we characterized the expression KCa3.1 in the human cornea and its role in corneal wound healing in vivo using a KCa3.1 knockout (KCa3.1-/-) mouse model. Additionally, we tested the hypothesis that blockade of KCa3.1 by a selective KCa3.1 inhibitor, TRAM-34, could augment a novel interventional approach for controlling corneal fibrosis in our established in vitro model of corneal fibrosis. The expression of KCa3.1 gene and protein was analyzed in human and murine corneas. Primary human corneal fibroblast (HCF) cultures were used to examine the potential of TRAM-34 in treating corneal fibrosis by measuring levels of pro-fibrotic genes, proteins, and cellular migration using real-time quantitative qPCR, Western blotting, and scratch assay, respectively. Cytotoxicity of TRAM-34 was tested with trypan blue assay, and pro-fibrotic marker expression was tested in KCa3.1-/-. Expression of KCa3.1 mRNA and protein was detected in all three layers of the human cornea. The KCa3.1-/- mice demonstrated significantly reduced corneal fibrosis and expression of pro-fibrotic marker genes such as collagen I and α-smooth muscle actin (α-SMA), suggesting that KCa3.1 plays an important role corneal wound healing in vivo. Pharmacological treatment with TRAM-34 significantly attenuated corneal fibrosis in vitro, as demonstrated in HCFs by the inhibition TGFß-mediated transcription of pro-fibrotic collagen I mRNA and α-SMA mRNA and protein expression (p<0.001). No evidence of cytotoxicity was observed. Our study suggests that KCa3.1 regulates corneal wound healing and that blockade of KCa3.1 by TRAM-34 offers a potential therapeutic strategy for developing therapies to cure corneal fibrosis in vivo.


Subject(s)
Cornea/metabolism , Corneal Diseases/metabolism , Disease Models, Animal , Intermediate-Conductance Calcium-Activated Potassium Channels/metabolism , Animals , Cell Differentiation/drug effects , Cell Differentiation/genetics , Cell Proliferation/drug effects , Cell Proliferation/genetics , Cells, Cultured , Cornea/drug effects , Cornea/pathology , Corneal Diseases/drug therapy , Corneal Diseases/genetics , Fibroblasts/metabolism , Fibrosis , Gene Expression/drug effects , Humans , Intermediate-Conductance Calcium-Activated Potassium Channels/antagonists & inhibitors , Intermediate-Conductance Calcium-Activated Potassium Channels/genetics , Mice, Inbred C57BL , Mice, Knockout , Molecular Targeted Therapy/methods , Myofibroblasts/metabolism , Pyrazoles/pharmacology , Wound Healing/drug effects , Wound Healing/genetics
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