Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 57
Filter
1.
Cureus ; 16(5): e60934, 2024 May.
Article in English | MEDLINE | ID: mdl-38910752

ABSTRACT

Introduction Diabetic foot complications leading to limb amputations pose a global health concern. Platelet-rich plasma (PRP) gel has emerged as a promising method for ulcer healing, leveraging the growth factors provided by autologous PRP to enhance tissue healing. Therefore, we aimed to assess the frequency of the success of PRP therapy in the treatment of non-healing diabetic foot ulcers. Methods This quasi-experimental study, conducted in Lahore, Pakistan, from April 2021 to October 2022, enrolled 80 eligible individuals with non-responsive diabetic foot ulcers using a consecutive sampling technique. Inclusion criteria involved patients of both genders, aged 45-75 years, with unhealed diabetic foot ulcers, and exclusion criteria considered factors such as recurrent ulcers at the same site, smoking, and immunosuppressive or anticoagulant drug therapy. Baseline demographic details, ulcer measurements using a scale, and AutoCAD (Autodesk, Inc., San Francisco, California, United States)-assisted quantification of ulcer base were recorded. Autologous PRP injections were administered following strict aseptic protocols, with dressing changes and assessments performed at specified intervals over four weeks. Treatment success, defined as >90% healing after four weeks, was the primary outcome. Data analysis utilized IBM SPSS Statistics for Windows, Version 26.0 (Released 2019; IBM Corp., Armonk, New York, United States), employing post-stratification chi-square and t-tests where appropriate for significant differences. Results The mean age of the patients was 60.40 ± 9.72 years, the mean duration of diabetes was 9.48 ± 2.21 years, and the mean ulcer duration was 11.41 ± 1.63 months. The treatment success rate was 63.7%. Age, gender, and disease duration showed no significant impact on treatment success. However, patients with a normal BMI and shorter ulcer duration exhibited a significantly higher success rate (p <0.001 and p = 0.002, respectively). Conclusions This study reaffirms the efficacy of PRP in treating non-healing diabetic foot ulcers, aligning with previous research. Despite a slightly lower success rate compared to literature reports, PRP remains a promising agent for managing diabetic foot ulcers.

2.
Biomedicines ; 11(6)2023 Jun 17.
Article in English | MEDLINE | ID: mdl-37371842

ABSTRACT

Work-related injuries are common. The cost of these injuries is around USD 176 billion to USD 350 billion a year. A significant number of work-related injuries involve nerve damage or dysfunction. Injuries may heal with full recovery of function, but those involving nerve damage may result in significant loss of function or very prolonged recovery. While many factors can predispose a person to suffer nerve damage, in most cases, it is a multifactorial issue that involves both intrinsic and extrinsic factors. This makes preventing work-related injuries hard. To date, no evidence-based guidelines are available to clinicians to evaluate work-related nerve dysfunction. While the symptoms range from poor endurance to cramping to clear loss of motor and sensory functions, not all nerves are equally vulnerable. The common risk factors for nerve damage are a superficial location, a long course, an acute change in trajectory along the course, and coursing through tight spaces. The pathophysiology of acute nerve injury is well known, but that of chronic nerve injury is much less well understood. The two most common mechanisms of nerve injury are stretching and compression. Chronic mild to moderate compression is the most common mechanism of nerve injury and it elicits a characteristic response from Schwann cells, which is different from the one when nerve is acutely injured. It is important to gain a better understanding of work-related nerve dysfunction, both from health and from regulatory standpoints. Currently, management depends upon etiology of nerve damage, recovery is often poor if nerves are badly damaged or treatment is not instituted early. This article reviews the current pathophysiology of chronic nerve injury. Chronic nerve injury animal models have contributed a lot to our understanding but it is still not complete. Better understanding of chronic nerve injury pathology will result in identification of novel and more effective targets for pharmacological interventions.

3.
Proc Natl Acad Sci U S A ; 120(15): e2206217120, 2023 04 11.
Article in English | MEDLINE | ID: mdl-37011198

ABSTRACT

RNA-binding protein (RBP) dysfunction is a fundamental hallmark of amyotrophic lateral sclerosis (ALS) and related neuromuscular disorders. Abnormal neuronal excitability is also a conserved feature in ALS patients and disease models, yet little is known about how activity-dependent processes regulate RBP levels and functions. Mutations in the gene encoding the RBP Matrin 3 (MATR3) cause familial disease, and MATR3 pathology has also been observed in sporadic ALS, suggesting a key role for MATR3 in disease pathogenesis. Here, we show that glutamatergic activity drives MATR3 degradation through an NMDA receptor-, Ca2+-, and calpain-dependent mechanism. The most common pathogenic MATR3 mutation renders it resistant to calpain degradation, suggesting a link between activity-dependent MATR3 regulation and disease. We also demonstrate that Ca2+ regulates MATR3 through a nondegradative process involving the binding of Ca2+/calmodulin to MATR3 and inhibition of its RNA-binding ability. These findings indicate that neuronal activity impacts both the abundance and function of MATR3, underscoring the effect of activity on RBPs and providing a foundation for further study of Ca2+-coupled regulation of RBPs implicated in ALS and related neurological diseases.


Subject(s)
Amyotrophic Lateral Sclerosis , Humans , Amyotrophic Lateral Sclerosis/metabolism , Calcium/metabolism , Calmodulin/genetics , Calmodulin/metabolism , Calpain/genetics , Calpain/metabolism , RNA-Binding Proteins/metabolism , Nuclear Matrix-Associated Proteins/metabolism
4.
Cureus ; 14(6): e26101, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35875307

ABSTRACT

Introduction Healthcare workers (HCWs) are the foundation of the response to a pandemic. Also termed as frontline workers, not only are they at a health risk but also suffer from emotional and psychological stress. Objective The objective of the study was to determine the emotional impact of novel coronavirus on healthcare workers. Methodology An online survey was completed by 239 HCWs from five different countries during the peak of the coronavirus disease 2019 (COVID-19) outbreak amidst the lockdown. Their feelings and concerns as well as the safety measures they adopted were identified. Results The response rate was 100%. Most of the respondents were 20-40 years old (85.36%) and working as doctors (73.22%); 44.77% were working at middle grade. The majority felt confused (19.67%), whereas others felt stressed/overworked (17.15%), unhappy (16.74%), scared (13.81%), nervous (13.39%), motivated (8.79%), and privileged (5.86%). A few felt pressurized to perform their duty (4.6%), and 69.87% felt that it was their moral obligation to continue their duty, whereas 13.39% felt administrative pressure for the same. Of the respondents, 53.97% feared transferring the disease to their family and friends, while others feared the lack of personal protective equipment (PPE) (13.39%). According to the majority of the respondents (25.94%), support from family and friends had them going through the crisis. The most common safety measure adopted by the HCWs was strict hand hygiene (43.51%). The HCWs (28.87%) felt that adequate and easy access to PPE would have helped them better during the pandemic. Conclusion Healthcare institutions are responsible for protecting HCWs or frontline workers during pandemics so they can continue with their duty. From our study, we have concluded that simple protective measures as uninterrupted and easy access to PPE would have helped HCWs deal with their stress and concerns.

5.
Surg Endosc ; 36(10): 7717-7721, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35175414

ABSTRACT

INTRODUCTION: Postoperative nausea and vomiting (PONV) is a common complication of general anesthesia that is further potentiated in an obese patient undergoing a bariatric procedure. Literature shows trials of myriad of drugs used alone or in combination, as a prophylaxis for this cohort of patients with varied benefits. OBJECTIVE: The objective of the study was to determine the effect of intravenous scopolamine prior to stapling in obese patients undergoing sleeve gastrectomy. METHODOLOGY: A prospective randomized controlled trial of consecutive patients with BMI > 35 kg/m2, undergoing laparoscopic sleeve gastrectomy (LSG) was performed after approval of the hospital's ethical committee, explanation of trial to the patients and obtaining a consent. Patients were randomized into two groups; patients receiving intravenous scopolamine just before firing first stapler (Group 1) and patients receiving placebo (Group 2). Primary outcome parameter was PONV. The secondary outcome parameters were use of rescue antiemetic and time to oral intake. RESULTS: In our study, out of 100 cases of patients undergoing LSG, 50 received scopolamine before stapling and 50 were assigned to the control group. There was no significant difference between the two groups in terms of PONV. The group receiving scopolamine had lesser use of rescue antiemetic but no difference in time to oral intake. CONCLUSION: We concluded that incidence of PONV in obese patients undergoing LSG is not affected by scopolamine. Further trials are needed to validate the results.


Subject(s)
Antiemetics , Postoperative Nausea and Vomiting , Antiemetics/therapeutic use , Double-Blind Method , Gastrectomy/adverse effects , Gastrectomy/methods , Humans , Obesity/complications , Obesity/surgery , Postoperative Nausea and Vomiting/drug therapy , Postoperative Nausea and Vomiting/etiology , Postoperative Nausea and Vomiting/prevention & control , Prospective Studies , Scopolamine/therapeutic use
6.
J Neurointerv Surg ; 14(3): 216-220, 2022 Mar.
Article in English | MEDLINE | ID: mdl-33758065

ABSTRACT

BACKGROUND: The incidence of intracranial atherosclerotic disease (ICAD) in acute ischemic stroke treated with mechanical thrombectomy (MT) is not well defined, and its description may lead to improved stroke devices and rates of first pass success. METHODS: A retrospective study was performed on MT patients from 2012 to 2019 at a comprehensive stroke center using chart review and angiogram analysis. Angiograms at the time of MT were reviewed for ICAD, and location and severity were recorded. Patients with ICAD were divided according to ICAD location relative to the large vessel occlusion (LVO) site. Statistical analyses were performed on baseline demographics, comorbidities, MT procedure variables, outcome variables, and their association with ICAD. RESULTS: Of the 533 patients (mean age 70.4 (SD 13.20) years, 43.5% women), 131 (24.6%) had ICAD. There was no significant difference in favorable discharge outcomes (modified Rankin Scale score of 0-2; 23.8% ICAD vs 27.0% non-ICAD; p=0.82) or groin puncture to recanalization times (average 43.5 (range 8-181) min for ICAD vs 40.2 (4-204) min for non-ICAD; p=0.42). Patients with ICAD experienced a significantly higher number of passes (average 1.8 (range 1-7) passes for ICAD vs 1.6 (1-5) passes for non-ICAD; p=0.0059). Adjusting for age, ≥3 device passes, baseline National Institutes of Health Stroke Scale, rates of angioplasty only, rates of concurrent angioplasty and stenting, coronary artery disease and atrial fibrillation incidences, and time from emergency department arrival to recanalization, yielded no significant difference in rates of favorable outcomes between the two groups. CONCLUSION: Patients who underwent MT with underlying ICAD had similar rates of favorable outcomes as those without, but required a higher number of device passes.


Subject(s)
Intracranial Arteriosclerosis , Ischemic Stroke , Stroke , Aged , Female , Humans , Incidence , Intracranial Arteriosclerosis/diagnostic imaging , Intracranial Arteriosclerosis/epidemiology , Intracranial Arteriosclerosis/surgery , Male , Retrospective Studies , Stroke/diagnostic imaging , Stroke/epidemiology , Stroke/surgery , Thrombectomy/methods , Treatment Outcome
7.
Water Environ Res ; 93(12): 2931-2940, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34570384

ABSTRACT

In this current work, the performance of an aerobic granular sludge (AGS) for real textile wastewater was investigated based on system operational parameters evaluation. The study was performed for 90 days, and sampling was done once a week in which textile dyeing effluent from the textile mill was collected and subjected to laboratory-scale treatment. The samples from the inlet, the outlet of the wastewater plant, and within the bioreactor were collected at various concentrations of mixed liquid suspended solids (MLSS), and hydraulic retention remained the same in the investigated period of 53 h. The objective of this study was to analyze the AGS system performance assessment by evaluating the effect of different MLSS concentrations on chemical oxygen demand (COD), total suspended solids (TSS), and oil/grease removal from real-based textile water. The results showed that removal of organic material from the process water increases with an increase in MLSS concentration in the bioreactor and gradually shifts removal of COD from 91.2% to 94.5%. As the concentration of microorganisms in the reactor (aeration tank) increases, the degradation of waste organics in the wastewater increases as well. Moreover, the % removal of TSS (83.5% to 98%) and removal of oil/grease (62.5% to 76.4%) were also increased. These results ultimately suggest that the utilization of an activated sludge system can effectively treat complex and highly polluted denim textile wastewater to avoid secondary pollution posed by this industry. PRACTITIONER POINTS: The effectiveness of aerobic granular sludge was investigated for industrial textile effluent. The increase in MLSS results in increase of % COD removal efficiency to 94.5%. The AGS system can efficiently treat complicated and highly contaminated textile wastewater.


Subject(s)
Sewage , Textile Industry , Biological Oxygen Demand Analysis , Bioreactors , Textiles , Waste Disposal, Fluid , Wastewater
8.
J Biol Chem ; 297(3): 101003, 2021 09.
Article in English | MEDLINE | ID: mdl-34303705

ABSTRACT

Autophagy is an evolutionarily conserved pathway mediating the breakdown of cellular proteins and organelles. Emphasizing its pivotal nature, autophagy dysfunction contributes to many diseases; nevertheless, development of effective autophagy modulating drugs is hampered by fundamental deficiencies in available methods for measuring autophagic activity or flux. To overcome these limitations, we introduced the photoconvertible protein Dendra2 into the MAP1LC3B locus of human cells via CRISPR/Cas9 genome editing, enabling accurate and sensitive assessments of autophagy in living cells by optical pulse labeling. We used this assay to perform high-throughput drug screens of four chemical libraries comprising over 30,000 diverse compounds, identifying several clinically relevant drugs and novel autophagy modulators. A select series of candidate compounds also modulated autophagy flux in human motor neurons modified by CRISPR/Cas9 to express GFP-labeled LC3. Using automated microscopy, we tested the therapeutic potential of autophagy induction in several distinct neuronal models of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In doing so, we found that autophagy induction exhibited discordant effects, improving survival in disease models involving the RNA binding protein TDP-43, while exacerbating toxicity in neurons expressing mutant forms of UBQLN2 and C9ORF72 associated with familial ALS/FTD. These studies confirm the utility of the Dendra2-LC3 assay, while illustrating the contradictory effects of autophagy induction in different ALS/FTD subtypes.


Subject(s)
Autophagy , Adaptor Proteins, Signal Transducing/genetics , Amyotrophic Lateral Sclerosis/genetics , Amyotrophic Lateral Sclerosis/therapy , Autophagy/drug effects , Autophagy-Related Proteins/genetics , C9orf72 Protein/genetics , CRISPR-Cas Systems , DNA-Binding Proteins/genetics , Drug Screening Assays, Antitumor , Frontotemporal Dementia/genetics , Frontotemporal Dementia/therapy , HEK293 Cells , High-Throughput Screening Assays , Humans , Luminescent Proteins/genetics , Microtubule-Associated Proteins/genetics , Models, Biological , Motor Neurons/metabolism , Mutation
9.
Int J Clin Pract ; 75(9): e14488, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34115438

ABSTRACT

OBJECTIVE: To evaluate the clinical and radiological outcomes of the Ilizarov fixator in the proximal and distal fractures of the tibia. MATERIALS AND METHODOLOGY: This retrospective study reviewed 59 patients having high-energy intra-articular proximal and distal tibia fractures associated with severe soft-tissue injury, who were managed surgically with an Ilizarov fixator. The functional outcome was evaluated by using the American Orthopaedic Foot and Ankle Society scoring system (AOFAS) and the Association for the Study and Application of the Method of Ilizarov (ASAMI) Italy scoring system for tibial plateau and plafond fractures respectively. RESULTS: The most common mode of injury was road traffic accidents. According to the Gustilo open fracture classification, there were 16 patients with grade-I and nine with grade II open fractures. The remaining had closed fractures. According to the Schatzker classification of plateau fractures, 20 were graded as type V and 15 as type VI. According to the AO classification of plafond fractures, 12 fractures were graded as Type-43C1, 5 as Type-43C2, and 7 as Type-43C3. There was delayed union in 11 proximal and four distal fractures, all of which achieved union without additional bone grafting. In proximal fractures, according to AOFAS, out of 35, 26 had an acceptable while nine had a fair result. In distal fractures, according to ASAMI, out of 24, 16 had an acceptable while five had fair results. There were 192/448 wires in 58 patients with pin site infection; all were superficial and settled. Posttraumatic joint arthrosis was noted in nineteen. CONCLUSIONS: The postoperative clinical and radiological outcome indicated that primary Ilizarov external fixator is a reliable minimal invasive surgery and definitive fixation method for high-energy intra-articular proximal and distal tibial fractures with compromised soft-tissue. It also offers early stabilisation and painless joint motion without a high rate of complications.


Subject(s)
Intra-Articular Fractures , Tibial Fractures , Adult , External Fixators , Humans , Intra-Articular Fractures/diagnostic imaging , Intra-Articular Fractures/surgery , Retrospective Studies , Tibia , Tibial Fractures/diagnostic imaging , Tibial Fractures/surgery , Treatment Outcome
10.
JMIR Rehabil Assist Technol ; 8(2): e25996, 2021 May 31.
Article in English | MEDLINE | ID: mdl-34057420

ABSTRACT

BACKGROUND: Cardiovascular diseases are a leading cause of death worldwide and result in significant economic costs to health care systems. The prevalence of cardiovascular conditions that require monitoring is expected to increase as the average age of the global population continues to rise. Although an accurate cardiac assessment can be performed at medical centers, frequent visits for assessment are not feasible for most people, especially those with limited mobility. Monitoring of vital signs at home is becoming an increasingly desirable, accessible, and practical alternative. As wearable devices are not the ideal solution for everyone, it is necessary to develop parallel and complementary approaches. OBJECTIVE: This research aims to develop a zero-effort, unobtrusive, cost-effective, and portable option for home-based ambient heart rate monitoring. METHODS: The prototype seat cushion uses load cells to acquire a user's ballistocardiogram (BCG). The analog signal from the load cells is amplified and filtered by a signal-conditioning circuit before being digitally recorded. A pilot study with 20 participants was conducted to analyze the prototype's ability to capture the BCG during five real-world tasks: sitting still, watching a video on a computer screen, reading, using a computer, and having a conversation. A novel algorithm based on the continuous wavelet transform was developed to extract the heart rate by detecting the largest amplitude values (J-peaks) in the BCG signal. RESULTS: The pilot study data showed that the BCG signals from all five tasks had sufficiently large portions to extract heart rate. The continuous wavelet transform-based algorithm for J-peak detection demonstrated an overall accuracy of 91.4% compared with electrocardiography. Excluding three outliers that had significantly noisy BCG data, the algorithm achieved 94.6% accuracy, which was aligned with that of wearable devices. CONCLUSIONS: This study suggests that BCG acquired through a seat cushion is a viable alternative to wearable technologies. The prototype seat cushion presented in this study is an example of a relatively accessible, affordable, portable, and unobtrusive zero-effort approach to achieve frequent home-based ambient heart rate monitoring.

11.
JCI Insight ; 6(1)2021 01 11.
Article in English | MEDLINE | ID: mdl-33427209

ABSTRACT

RNA-binding proteins (RBPs) are essential factors required for the physiological function of neurons, muscle, and other tissue types. In keeping with this, a growing body of genetic, clinical, and pathological evidence indicates that RBP dysfunction and/or gene mutation leads to neurodegeneration and myopathy. Here, we summarize the current understanding of matrin 3 (MATR3), a poorly understood RBP implicated not only in ALS and frontotemporal dementia but also in distal myopathy. We begin by reviewing MATR3's functions, its regulation, and how it may be involved in both sporadic and familial neuromuscular disease. We also discuss insights gleaned from cellular and animal models of MATR3 pathogenesis, the links between MATR3 and other disease-associated RBPs, and the mechanisms underlying RBP-mediated disorders.


Subject(s)
Neuromuscular Diseases/genetics , Neuromuscular Diseases/physiopathology , Nuclear Matrix-Associated Proteins/genetics , Nuclear Matrix-Associated Proteins/physiology , RNA-Binding Proteins/genetics , RNA-Binding Proteins/physiology , Amyotrophic Lateral Sclerosis/genetics , Amyotrophic Lateral Sclerosis/physiopathology , Animals , Disease Models, Animal , Distal Myopathies/genetics , Distal Myopathies/physiopathology , Frontotemporal Dementia/genetics , Frontotemporal Dementia/physiopathology , Gene Expression Regulation , Humans , Mice, Knockout , Mutation , Nuclear Matrix-Associated Proteins/chemistry , Nuclear Matrix-Associated Proteins/deficiency , RNA-Binding Proteins/chemistry
12.
Mol Cell ; 79(3): 362-364, 2020 08 06.
Article in English | MEDLINE | ID: mdl-32763223

ABSTRACT

In this issue of Molecular Cell, Wang et al. (2020) investigate stress-induced nuclear condensates of the RNA-binding protein TDP-43, uncovering a protective function for these granules as well as an RNA-dependent mechanism for scaffolding them.


Subject(s)
Amyotrophic Lateral Sclerosis , RNA, Long Noncoding , DNA-Binding Proteins , Humans , RNA-Binding Proteins
13.
EMBO Rep ; 20(9): e47498, 2019 09.
Article in English | MEDLINE | ID: mdl-31347257

ABSTRACT

A CGG trinucleotide repeat expansion in the 5' UTR of FMR1 causes the neurodegenerative disorder Fragile X-associated tremor/ataxia syndrome (FXTAS). This repeat supports a non-canonical mode of protein synthesis known as repeat-associated, non-AUG (RAN) translation. The mechanism underlying RAN translation at CGG repeats remains unclear. To identify modifiers of RAN translation and potential therapeutic targets, we performed a candidate-based screen of eukaryotic initiation factors and RNA helicases in cell-based assays and a Drosophila melanogaster model of FXTAS. We identified multiple modifiers of toxicity and RAN translation from an expanded CGG repeat in the context of the FMR1 5'UTR. These include the DEAD-box RNA helicase belle/DDX3X, the helicase accessory factors EIF4B/4H, and the start codon selectivity factors EIF1 and EIF5. Disrupting belle/DDX3X selectively inhibited FMR1 RAN translation in Drosophila in vivo and cultured human cells, and mitigated repeat-induced toxicity in Drosophila and primary rodent neurons. These findings implicate RNA secondary structure and start codon fidelity as critical elements mediating FMR1 RAN translation and identify potential targets for treating repeat-associated neurodegeneration.


Subject(s)
Ataxia/metabolism , DEAD-box RNA Helicases/metabolism , Drosophila Proteins/metabolism , Eukaryotic Initiation Factors/metabolism , Fragile X Mental Retardation Protein/metabolism , Fragile X Syndrome/metabolism , Tremor/metabolism , Animals , Ataxia/genetics , Cells, Cultured , DEAD-box RNA Helicases/genetics , Drosophila Proteins/genetics , Drosophila melanogaster , Eukaryotic Initiation Factors/genetics , Female , Fragile X Mental Retardation Protein/genetics , Fragile X Syndrome/genetics , HEK293 Cells , HeLa Cells , Humans , Immunoprecipitation , Male , Phenotype , Reverse Transcriptase Polymerase Chain Reaction , Tremor/genetics
14.
Cell Rep ; 27(4): 1133-1150.e8, 2019 04 23.
Article in English | MEDLINE | ID: mdl-31018129

ABSTRACT

The majority of individuals with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) exhibit neuronal cytoplasmic inclusions rich in the RNA binding protein TDP43. Even so, the relation between the RNA binding properties of TDP43 and neurodegeneration remains obscure. Here, we show that engineered mutations disrupting a salt bridge between the RNA recognition motifs of TDP43 interfere with RNA binding and eliminate the recognition of native TDP43 substrates. The same mutations dramatically destabilize TDP43, alter its subcellular localization, and abrogate TDP43-dependent neurodegeneration. Worms harboring homologous TDP-1 mutations phenocopy knockout strains, confirming the necessity of salt bridge residues for TDP43 function. Moreover, the accumulation of functional TDP43, but not RNA binding-deficient variants, disproportionately affects transcripts encoding ribosome and oxidative phosphorylation components. These studies demonstrate the significance of the salt bridge in sustaining TDP43 stability and RNA binding properties, factors that are crucial for neurodegeneration arising from TDP43 deposition in ALS and FTD.


Subject(s)
DNA-Binding Proteins/chemistry , DNA-Binding Proteins/metabolism , Mutation , Neurodegenerative Diseases/pathology , RNA/metabolism , Salts/chemistry , Animals , Caenorhabditis elegans , Female , Humans , Male , Neurodegenerative Diseases/genetics , Neurodegenerative Diseases/metabolism , Protein Aggregates , Protein Stability , RNA/chemistry , RNA, Mitochondrial/chemistry , RNA, Mitochondrial/metabolism , RNA, Ribosomal/chemistry , RNA, Ribosomal/metabolism , Rats
15.
Saudi J Kidney Dis Transpl ; 30(1): 151-152, 2019.
Article in English | MEDLINE | ID: mdl-30804276

ABSTRACT

In regions where tuberculosis (TB) is endemic, up to 15% of kidney transplant recipients develop Mycobacterium tuberculosis infections (TBI), typically with an increased risk of disseminated disease and allograft loss. To reduce these risks, donors and recipients with latent TB usually receive isoniazid (INH) prophylaxis. However, it is unclear whether latent TB in donors justifies routine prophylaxis of recipients. At our institution, donors and recipients with latent infection receive INH prophylaxis, and those who do not have latent infections are not routinely treated. We retrospectively analyzed the records of 269 living donor kidney transplant recipient and donor pairs in order to determine the risk of posttransplant TB in those whose kidneys were obtained from living donors with latent TB. Three recipients (1.1%) developed active TB, three, 11, and 12 months after transplantation. Neither donors nor recipients in these pairs had evidence of latent TB before transplantation. Of the 224 pairs with complete data, 24 transplant recipients with negative tuberculin skin test received organs from living donors with evidence of latent TB. None developed active TB, and kidney function one and three years later was preserved. Our findings suggest that routine use of prophylaxis in recipients without latent TB who receive organs from positive donors might not add additional benefit.


Subject(s)
Antibiotic Prophylaxis/statistics & numerical data , Kidney Transplantation/adverse effects , Latent Tuberculosis , Tuberculosis , Adult , Antitubercular Agents/therapeutic use , Creatine/blood , Female , Humans , Isoniazid/therapeutic use , Latent Tuberculosis/drug therapy , Latent Tuberculosis/prevention & control , Living Donors/statistics & numerical data , Male , Retrospective Studies , Transplant Recipients/statistics & numerical data , Treatment Outcome , Tuberculosis/drug therapy , Tuberculosis/epidemiology , Tuberculosis/prevention & control , Tuberculosis/transmission
16.
Elife ; 72018 07 17.
Article in English | MEDLINE | ID: mdl-30015619

ABSTRACT

Abnormalities in nucleic acid processing are associated with the development of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Mutations in Matrin 3 (MATR3), a poorly understood DNA- and RNA-binding protein, cause familial ALS/FTD, and MATR3 pathology is a feature of sporadic disease, suggesting that MATR3 dysfunction is integrally linked to ALS pathogenesis. Using a rat primary neuron model to assess MATR3-mediated toxicity, we noted that neurons were bidirectionally vulnerable to MATR3 levels, with pathogenic MATR3 mutants displaying enhanced toxicity. MATR3's zinc finger domains partially modulated toxicity, but elimination of its RNA recognition motifs had no effect on survival, instead facilitating its self-assembly into liquid-like droplets. In contrast to other RNA-binding proteins associated with ALS, cytoplasmic MATR3 redistribution mitigated neurodegeneration, suggesting that nuclear MATR3 mediates toxicity. Our findings offer a foundation for understanding MATR3-related neurodegeneration and how nucleic acid binding functions, localization, and pathogenic mutations drive sporadic and familial disease.


Subject(s)
Cell Nucleus/metabolism , Neurotoxins/toxicity , Nuclear Matrix-Associated Proteins/metabolism , Nucleic Acids/metabolism , RNA-Binding Proteins/metabolism , Animals , Cell Nucleus/drug effects , Cell Survival , HEK293 Cells , Humans , Models, Biological , Mutant Proteins/metabolism , Mutation/genetics , Nerve Degeneration/pathology , Neurons/drug effects , Neurons/metabolism , Nuclear Matrix-Associated Proteins/chemistry , Nuclear Matrix-Associated Proteins/genetics , Protein Binding , Protein Stability , RNA Recognition Motif , RNA-Binding Proteins/chemistry , RNA-Binding Proteins/genetics , Rats , Rats, Long-Evans , Solubility , Zinc Fingers
17.
J Vasc Interv Neurol ; 9(4): 54-58, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28702121

ABSTRACT

BACKGROUND: The proximity of the femoral nerve to the femoral artery renders it vulnerable to injury during transfemoral percutaneous catheterization (TPC) procedures. OBJECTIVE: To determine the incidence of femoral nerve injury in patients undergoing cardiac catheterization in a nationally representative inpatient database. METHODS: We analyzed data released annually from the Nationwide Inpatient Sample. We pooled data from 2002 to 2010 and, using the ICD-9-CM procedure codes, identified patients who underwent TPC. We subsequently identified occurrences of femoral nerve injury in this cohort. Baseline characteristics, comorbid conditions, in-hospital complications, and discharge outcomes-including mortality, mild disability, and moderate-to-severe disability-were compared between patients with femoral neuralgia and those without. RESULTS: Of the 15,894,201 patients who underwent percutaneous catheterization procedures, 597 (3.8 per 100,000 procedures) developed femoral nerve injury. The incidence of femoral nerve injury was higher in women: 57% versus 39%, p < 0.004. Patients with coexisting congestive heart failure or coagulopathy had a non-significant increase in the incidence of femoral nerve injury. There was no in-hospital mortality among patients who developed femoral nerve injury, but the rate of discharge to nursing facilities was higher in this cohort: 17% versus 6%, p < 0.001. After adjusting for age, gender, presence of congestive heart failure, and coagulopathy, femoral nerve injury during percutaneous catheterization procedures was independently associated with moderate-to-severe disability at discharge (odds ratio 2.3; 95% confidence interval 1.4-3.8; p < 0.001). CONCLUSION: Femoral nerve injury is a rare complication of percutaneous catheterization procedures that may increase the likelihood of moderate-to-severe disability at patient's discharge.

18.
J Vasc Interv Neurol ; 9(3): 45-50, 2017 Jan.
Article in English | MEDLINE | ID: mdl-28243351

ABSTRACT

BACKGROUND: The risk of catheter-based angiograms alone (non-therapeutic angiogram that does not lead to therapeutic intervention) in acute ischemic stroke patients who are considered for endovascular treatment is not well studied. METHODS: We compared the rates of neurological deterioration within 24 h; symptomatic intracranial hemorrhage (ICH) within 30 h; acute kidney injury (AKI) and major non-ICH within five days; and functional independence (defined by modified Rankin scale of 0-2) at three months among subjects who underwent a non-therapeutic catheter-based angiogram with subjects who did not undergo catheter-based angiogram in a multicenter clinical trial. Logistic regression analyses was performed to adjust for age, baseline Alberta stroke program early CT score (ASPECTS) strata (0-7 and 8-10), and baseline National Institutes of Health Stroke Scale (NIHSS) score strata (≤9, 10-19, and ≥20). RESULTS: Compared with subjects who did not undergo any catheter-based angiogram (n = 222), 89 subjects who underwent a non-therapeutic catheter-based angiogram had similar adjusted rates of neurological deterioration [odds ratio (OR) = 1; 95% confidence interval (CI) 0.4-2.3; p = 1] and symptomatic ICH (OR = 0.4; 95% CI 0.1-1.8; p = 0.2). There was no difference in the adjusted rates of AKI, or non-ICH between the two groups. The rate of functional independence at three months was significantly higher among the patients who received a catheter-based angiogram (OR = 2; 95% CI 1.1-3.5; p = 0.016) after adjusting for potential confounders. CONCLUSION: Non-therapeutic catheter-based angiograms in acute ischemic stroke patients who are being considered for endovascular treatment do not adversely affect patient outcomes.

19.
J Neurosurg ; 127(2): 270-277, 2017 Aug.
Article in English | MEDLINE | ID: mdl-27611208

ABSTRACT

OBJECTIVE Recent studies have found an underutilization of in-hospital procedures in treatments of Hispanic patients admitted with coronary artery disease in states along the US-Mexico border ("border states"). The purpose of this study was to determine any treatment disparities between patients treated for subarachnoid hemorrhage (SAH) in border and nonborder states and whether this disparity was associated with differential hospital charges. METHODS Using the National (Nationwide) Inpatient Sample, the authors retrieved data of Hispanic and non-Hispanic patients who were admitted in 2011 for SAH in a border state (California, Arizona, New Mexico, and Texas) or nonborder state (the remaining 46 US states). The authors determined the rates of use of endovascular coiling and surgical clipping treatments, hospital charges, and outcomes according to the patients' demographics and treatment in border or nonborder states. RESULTS In total, 18,368 patients were admitted with SAH in the selected time period, including 2310 Hispanic patients (12.6%). Of these patients, 1525 were admitted in a border state and 785 in a nonborder state. In border states, rates of surgical treatment significantly differed between patients of Hispanic (21.9%) and non-Hispanic (14.0%) origin (p = 0.02). In particular, Hispanic patients were more likely to undergo surgical clipping than were non-Hispanic patients. In the nonborder states, the rates of surgical treatment were similar for Hispanic and non-Hispanic patients (14.0% vs 15.6%, p = 0.6). Hispanic patients with SAH were billed significantly higher in-hospital charges in border states than in nonborder states ($219,260 and $192,418 [US dollars], respectively, p < 0.001). CONCLUSIONS Use of surgical treatments for Hispanic patients with SAH residing in border states has a unique pattern, which significantly increases in-hospital charges in this patient population.


Subject(s)
Health Care Costs/statistics & numerical data , Healthcare Disparities/statistics & numerical data , Hispanic or Latino , Subarachnoid Hemorrhage/economics , Subarachnoid Hemorrhage/therapy , Arizona , California , Female , Humans , Male , Middle Aged , New Mexico , Retrospective Studies , Texas
20.
Am J Obstet Gynecol ; 216(4): 409.e1-409.e6, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27956201

ABSTRACT

BACKGROUND: The incidence of pregnancy in advanced age among women is increasing because of the availability of assisted reproduction, although the long-term health consequences are not known. OBJECTIVE: The purpose of this study was to determine the effect of pregnancy in advanced age on the occurrence of cardiovascular events in a large cohort of postmenopausal women. STUDY DESIGN: We analyzed the data for 72,221 women aged 50-79 years who were enrolled in the observational arm of the Women's Health Initiative study. We determined the effect of pregnancy in advanced age (last pregnancy at age ≥40 year) on the risk of ischemic stroke, hemorrhagic stroke, myocardial infarction, and cardiovascular death over a mean period (±standard deviation) of 12±1 years using Cox Proportional Hazards analysis after adjusting for potential confounders. RESULTS: A total of 3306 of the 72,221 participants (4.6%) reported pregnancy in advanced age. Compared with pregnancy in normal age, the rates of ischemic stroke (3.8% vs 2.4%), hemorrhagic stroke (1.0% vs 0.5%), and cardiovascular death (3.9% vs 2.3%) were significantly higher among women with pregnancy in advanced age. In multivariate analysis, women with pregnancy in advanced age were 50% more likely to experience a hemorrhagic stroke (hazard ratio, 1.5; 95% confidence interval, 1.0-2.1) after adjustment for age, race/ethnicity, congestive heart failure, systolic blood pressure, atrial fibrillation, alcohol use, and cigarette smoking. There was no significant difference in the risk of ischemic stroke, myocardial infarction, and cardiovascular death among women with pregnancy in advanced age after adjustment for potential confounders. CONCLUSION: Women with pregnancy at an advanced age have a higher risk for hemorrhagic stroke in the postmenopausal period.


Subject(s)
Maternal Age , Postmenopause , Stroke/epidemiology , Adult , Aged , Cardiovascular Diseases/mortality , Female , Humans , Middle Aged , Multivariate Analysis , Pregnancy , Proportional Hazards Models , United States/epidemiology
SELECTION OF CITATIONS
SEARCH DETAIL