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1.
J Infect Dis ; 2024 Feb 09.
Article in English | MEDLINE | ID: mdl-38332750

ABSTRACT

In Lusaka, Zambia, we introduced liver fine needle aspiration (FNA) into a research cohort of adults with treatment-naïve chronic hepatitis B virus (HBV) infection, with and without HIV coinfection, as well as with acute HBV infection. Over 117 enrollment and 47 longitudinal FNAs (at 1 year follow-up), we established participant acceptability and safety. We also demonstrated the quality of the material through single cell RNA sequencing of selected enrollment FNAs, which revealed a range of immune cells. This approach can drive new insights into HBV immunology, informing cure strategies, and can improve our understanding of HBV natural history in Africa.

2.
Pediatr Blood Cancer ; 71(5): e30931, 2024 May.
Article in English | MEDLINE | ID: mdl-38433307

ABSTRACT

Here we report efficacy, pharmacokinetics, and safety data obtained in treatment-naive, pediatric patients with newly diagnosed advanced MDS receiving azacitidine in the AZA-JMML-001 study. The primary endpoint was response rate (proportion of patients with complete response [CR], partial response [PR], or marrow CR, sustained for ≥4 weeks). Of the 10 patients enrolled, one had an unconfirmed marrow CR and none had confirmed responses after three cycles; the study was therefore closed after stage 1. Azacitidine was well tolerated. The lack of efficacy of azacitidine in pediatric patients with newly diagnosed advanced MDS highlights the need for effective new treatments in these patients.


Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Humans , Child , Azacitidine/adverse effects , Leukemia, Myeloid, Acute/drug therapy , Myelodysplastic Syndromes/drug therapy , Myelodysplastic Syndromes/diagnosis , Treatment Outcome , Hematopoietic Stem Cell Transplantation/adverse effects
3.
Brain ; 146(9): 3747-3759, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37208310

ABSTRACT

Molecular biomarkers for neurodegenerative diseases are critical for advancing diagnosis and therapy. Normal pressure hydrocephalus (NPH) is a neurological disorder characterized by progressive neurodegeneration, gait impairment, urinary incontinence and cognitive decline. In contrast to most other neurodegenerative disorders, NPH symptoms can be improved by the placement of a ventricular shunt that drains excess CSF. A major challenge in NPH management is the identification of patients who benefit from shunt surgery. Here, we perform genome-wide RNA sequencing of extracellular vesicles in CSF of 42 NPH patients, and we identify genes and pathways whose expression levels correlate with gait, urinary or cognitive symptom improvement after shunt surgery. We describe a machine learning algorithm trained on these gene expression profiles to predict shunt surgery response with high accuracy. The transcriptomic signatures we identified may have important implications for improving NPH diagnosis and treatment and for understanding disease aetiology.

4.
Neurosurg Focus ; 56(5): E7, 2024 05.
Article in English | MEDLINE | ID: mdl-38691863

ABSTRACT

OBJECTIVE: Contemporary management of sacral chordomas requires maximizing the potential for recurrence-free and overall survival while minimizing treatment morbidity. En bloc resection can be performed at various levels of the sacrum, with tumor location and volume ultimately dictating the necessary extent of resection and subsequent tissue reconstruction. Because tumor resection involving the upper sacrum may be quite destabilizing, other pertinent considerations relate to instrumentation and subsequent tissue reconstruction. The primary aim of this study was to survey the surgical approaches used for managing primary sacral chordoma according to location of lumbosacral spine involvement, including a narrative review of the literature and examination of the authors' institutional case series. METHODS: The authors performed a narrative review of pertinent literature regarding reconstruction and complication avoidance techniques following en bloc resection of primary sacral tumors, supplemented by a contemporary series of 11 cases from their cohort. Relevant surgical anatomy, advances in instrumentation and reconstruction techniques, intraoperative imaging and navigation, soft-tissue reconstruction, and wound complication avoidance are also discussed. RESULTS: The review of the literature identified several surgical approaches used for management of primary sacral chordoma localized to low sacral levels (mid-S2 and below), high sacral levels (involving upper S2 and above), and high sacral levels with lumbar involvement. In the contemporary case series, the majority of cases (8/11) presented as low sacral tumors that did not require instrumentation. A minority required more extensive instrumentation and reconstruction, with 2 tumors involving upper S2 and/or S1 levels and 1 tumor extending into the lower lumbar spine. En bloc resection was successfully achieved in 10 of 11 cases, with a colostomy required in 2 cases due to rectal involvement. All 11 cases underwent musculocutaneous flap wound closure by plastic surgery, with none experiencing wound complications requiring revision. CONCLUSIONS: The modern management of sacral chordoma involves a multidisciplinary team of surgeons and intraoperative technologies to minimize surgical morbidity while optimizing oncological outcomes through en bloc resection. Most cases present with lower sacral tumors not requiring instrumentation, but stabilizing instrumentation and lumbosacral reconstruction are often required in upper sacral and lumbosacral cases. Among efforts to minimize wound-related complications, musculocutaneous flap closure stands out as an evidence-based measure that may mitigate risk.


Subject(s)
Chordoma , Sacrum , Spinal Neoplasms , Humans , Chordoma/surgery , Chordoma/diagnostic imaging , Chordoma/pathology , Sacrum/surgery , Sacrum/diagnostic imaging , Spinal Neoplasms/surgery , Spinal Neoplasms/diagnostic imaging , Spinal Neoplasms/pathology , Male , Middle Aged , Female , Aged , Adult , Plastic Surgery Procedures/methods
5.
Arthroscopy ; 40(1): 34-44, 2024 01.
Article in English | MEDLINE | ID: mdl-37356505

ABSTRACT

PURPOSE: To quantify cellular senescence in supraspinatus tendon and subacromial bursa of humans with rotator cuff tears and to investigate the in vitro efficacy of the senolytic dasatinib + quercetin (D+Q) to eliminate senescent cells and alter tenogenic differentiation. METHODS: Tissue was harvested from 41 patients (mean age, 62 years) undergoing arthroscopic rotator cuff repairs. In part 1 (n = 35), senescence was quantified using immunohistochemistry and gene expression for senescent cell markers (p16 and p21) and the senescence-associated secretory phenotype (SASP) (interleukin [IL] 6, IL-8, matrix metalloproteinase [MMP] 3, monocyte chemoattractant protein [MCP] 1). Senescence was compared between patients <60 and ≥60 years old. In part 2 (n = 6) , an in vitro model of rotator cuff tears was treated with D+Q or control. D+Q, a chemotherapeutic and plant flavanol, respectively, kill senescent cells. Gene expression analysis assessed the ability of D+Q to kill senescent cells and alter markers of tenogenic differentiation. RESULTS: Part 1 revealed an age-dependent significant increase in the relative expression of p21, IL-6, and IL-8 in tendon and p21, p16, IL-6, IL-8, and MMP-3 in bursa (P < .05). A significant increase was seen in immunohistochemical staining of bursa p21 (P = .028). In part 2, D+Q significantly decreased expression of p21, IL-6, and IL-8 in tendon and p21 and IL-8 in bursa (P < .05). Enzyme-linked immunosorbent assay analysis showed decreased release of the SASP (IL-6, MMP-3, MCP-1; P = .002, P = .024, P < .001, respectively). Tendon (P = .022) and bursa (P = .027) treated with D+Q increased the expression of COL1A1. CONCLUSIONS: While there was an age-dependent increase in markers of cellular senescence, this relationship was not consistently seen across all markers and tissues. Dasatinib + quercetin had moderate efficacy in decreasing senescence in these tissues and increasing COL1A1 expression. CLINICAL RELEVANCE: This study reveals that cellular senescence may be a therapeutic target to alter the biological aging of rotator cuffs and identifies D+Q as a potential therapy.


Subject(s)
Rotator Cuff Injuries , Humans , Middle Aged , Rotator Cuff Injuries/drug therapy , Rotator Cuff Injuries/surgery , Dasatinib/pharmacology , Dasatinib/therapeutic use , Quercetin/pharmacology , Quercetin/therapeutic use , Matrix Metalloproteinase 3/genetics , Interleukin-6/metabolism , Interleukin-8 , Cellular Senescence
6.
Adv Physiol Educ ; 48(3): 661-669, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38695083

ABSTRACT

The COVID-19 pandemic and subsequent policies (e.g., social distancing, travel restrictions) challenged both organizers for and attendees of programs typically held in person. Many scientific training programs quickly adapted to virtual formats by incorporating digital assets developed for virtual learning and remote social engagement. At the outset, the value of continuing digital elements with future in-person events was unclear. To examine how virtual resources supported heterogeneous professional training programs, we reviewed survey data for a 14-year-old training program for scientific professionals titled "Isotope Tracers in Metabolic Research: Principles and Practice of Kinetic Analysis." We found a positive relationship between survey satisfaction and the postpandemic in-person program that included digital assets held in 2022 compared to prepandemic in-person programs. To better understand the postpandemic program satisfaction, we assessed the 2021 virtual course format and survey data. We found that although there was a desire to return to in-person programs, the digital assets and approaches were valued. In examining the individual programmatic elements in the 2022 in-person course, there was better "value and understandability" of lectures over previous in-person years. These findings highlight how incorporating new digital engagement strategies for professional development benefits even the most established programs in supporting heterogeneous learners.NEW & NOTEWORTHY We examined impact of leveraging digital assets to support virtual engagement for an in-person program. Using survey data of a 14-year-old program for scientific professionals, we compared pre- and postpandemic in-person programs. Through incorporating digital assets, we found increased survey satisfaction compared to prepandemic in-person programs. These findings highlight how incorporating new digital engagement strategies benefits even the most successful professional development programs.


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , Education, Distance/methods , SARS-CoV-2 , Pandemics , Curriculum , Physiology/education
7.
Folia Phoniatr Logop ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38981448

ABSTRACT

INTRODUCTION: Benign and malignant vocal fold lesions are growths that occur on the vocal folds. However, the treatments for these two types of lesions differ significantly. Therefore, it is imperative to use a multidisciplinary approach to properly recognize suspicious lesions. This study aims to determine the important acoustic characteristics specific to benign and malignant vocal fold lesions. METHODS: The acoustic model of voice quality was utilized to measure various acoustic parameters in 157 participants, including individuals with normal, benign, and malignant conditions. The study comprised 62 female and 95 male participants (43 ± 10 years). Voice samples were collected at the Shanghai Eye, Ear, Nose and Throat Hospital between May 2020 and July 2021.The acoustic variables of the participants were analyzed using Principal Component Analysis to present important acoustic characteristics that are specific to normal vocal folds, benign vocal fold lesions, and malignant vocal fold lesions. The similarities and differences in acoustic factors were also studied for benign conditions including Reinke's edema, polyps, cysts, and leukoplakia. RESULTS: Using the Principal Component Analysis method, the components that accounted for the variation in the data were identified, highlighting acoustic characteristics in the normal, benign, and malignant groups. The analysis indicated that coefficients of variation in root mean square energy were observed solely within the normal group. Coefficients of variation in pitch were found to be significant only in benign voices, while higher formant frequencies and their variability were identified as contributors to the acoustic variance within the malignant group. The presence of formant dispersion as a weighted factor in Principal Component Analysis was exclusively noted in individuals with Reinke's edema. The amplitude ratio between subharmonics and harmonics and its coefficients of variation were evident exclusively in the polyps group. In the case of voices with cysts, both pitch and coefficients of variation for formant dispersion were observed to contribute to variations. Additionally, higher formant frequencies and their coefficients of variation played a role in the acoustic variance among voices of patients with leukoplakia. CONCLUSION: Experimental evidence demonstrates the utility of the Principal Component Analysis method in the identification of vibrational alterations in the acoustic characteristics of voice affected by lesions. Furthermore, the Principal Component Analysis analysis has highlighted underlying acoustic differences between various conditions such as Reinke's edema, polyps, cysts, and leukoplakia. These findings can be used in the future to develop an automated malignant voice analysis algorithm, which will facilitate timely intervention and management of vocal fold conditions.

8.
PLoS Biol ; 18(2): e3000622, 2020 02.
Article in English | MEDLINE | ID: mdl-32108181

ABSTRACT

Circadian (daily) regulation of metabolic pathways implies that food may be metabolized differentially over the daily cycle. To test that hypothesis, we monitored the metabolism of older subjects in a whole-room respiratory chamber over two separate 56-h sessions in a random crossover design. In one session, one of the 3 daily meals was presented as breakfast, whereas in the other session, a nutritionally equivalent meal was presented as a late-evening snack. The duration of the overnight fast was the same for both sessions. Whereas the two sessions did not differ in overall energy expenditure, the respiratory exchange ratio (RER) was different during sleep between the two sessions. Unexpectedly, this difference in RER due to daily meal timing was not due to daily differences in physical activity, sleep disruption, or core body temperature (CBT). Rather, we found that the daily timing of nutrient availability coupled with daily/circadian control of metabolism drives a switch in substrate preference such that the late-evening Snack Session resulted in significantly lower lipid oxidation (LO) compared to the Breakfast Session. Therefore, the timing of meals during the day/night cycle affects how ingested food is oxidized or stored in humans, with important implications for optimal eating habits.


Subject(s)
Circadian Rhythm/physiology , Lipid Metabolism/physiology , Meals/physiology , Body Mass Index , Breakfast , Carbohydrate Metabolism/physiology , Cross-Over Studies , Feeding Behavior/physiology , Female , Humans , Male , Middle Aged , Oxidation-Reduction , Pulmonary Gas Exchange/physiology , Sleep/physiology , Snacks
9.
Eur J Nutr ; 62(3): 1551-1559, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36469110

ABSTRACT

Vitamin B12 is an essential nutrient that is not made by plants; consequently, unfortified plant-based foods are not a reliable supply. Recent estimates suggest high rates of vitamin B12 deficiency among the vegetarian and vegan populations, particularly in pregnant women or women of child-bearing age who, for ethical and health reasons, are shifting towards higher consumption of plant-based foods in ever-increasing numbers. Vitamin B12 plays crucial metabolic roles across the life-course and in particular during pregnancy and in early development (first 1000 days of life). Evidence now implicates vitamin B12 deficiency with increased risk to a range of neuro, vascular, immune, and inflammatory disorders. However, the current UK recommended nutrient intake for vitamin B12 does not adequately consider the vitamin B12 deficit for those choosing a plant-based diet, including vegetarianism and in particular veganism, representing a hidden hunger. We provide a cautionary note on the importance of preventing vitamin B12 deficits for those individuals choosing a plant-based diet and the health professionals advising them.


Subject(s)
Diet , Vitamin B 12 , Humans , Female , Pregnancy , Diet, Vegetarian/adverse effects , Diet, Vegan , Vitamins
10.
Nature ; 546(7657): 221-226, 2017 06 07.
Article in English | MEDLINE | ID: mdl-28593964

ABSTRACT

The standard model of particle physics is our best description yet of fundamental particles and their interactions, but it is known to be incomplete. As yet undiscovered particles and interactions might exist. One of the most powerful ways to search for new particles is by studying processes known as flavour-changing neutral current decays, whereby a quark changes its flavour without altering its electric charge. One example of such a transition is the decay of a beauty quark into a strange quark. Here we review some intriguing anomalies in these decays, which have revealed potential cracks in the standard model-hinting at the existence of new phenomena.

11.
Neurosurg Focus ; 54(3): E2, 2023 03.
Article in English | MEDLINE | ID: mdl-36857788

ABSTRACT

OBJECTIVE: Management of Chiari malformation type I (CM-I) requires the functional restoration of an obstructed cisterna magna. In posterior fossa decompression with duraplasty (PFDD), various intradural pathologies are suggested to alter CSF flow at the craniocervical junction and require surgical correction. However, reports of the spectrum of intraoperative intradural findings and their nuances are scarce, especially those characterizing rarer findings pertaining to the vascular structures and vascular compression. METHODS: The authors conducted a retrospective cohort analysis of adults and children who underwent first-time PFDD for CM-I (2011-2021), with and without syringomyelia. The surgical reports and intraoperative videos were reviewed, and the frequency and nature of the intradural observations in regard to the tonsils, arachnoid, and vasculature were analyzed along with the clinical findings and surgical outcomes. RESULTS: All 180 patients (age range 1-72 years; median [interquartile range] 24 (14-38) years; 37% of patients were children < 21 years of age) exhibited multiple intradural findings, with a median of 7 distinct concurrent observations in each patient. Novel findings not previously reported included posterior inferior communicating artery (PICA) branches compressing the neural elements at the cervicomedullary junction (26.7%). Other common findings included arachnoid adhesions (92.8%), thickening (90.6%), webs at the obex (52.2%), tonsillar gliosis (57.2%), tonsillar hypertrophy (18.3%), adhesions obstructing the foramen of Magendie (FoM) (62.2%), PICA obstruction of the FoM (17.2%), and dural scarring (87.8%). Tonsillar gliosis and intertonsillar adhesions obstructing the FoM were more common in children than adults. Tonsillar gliosis and arachnoid webs were more common among syringomyelia patients. After multivariable adjustment, none of the observed findings were independently associated with syringomyelia, preoperative symptoms, or postoperative improvement. The vast majority of patients improved postoperatively. The complication rate was low: 1.2% of patients required revision PFDD at > 3 years postoperatively, 3.6% experienced other operative complications, and 0% had CSF leaks. CONCLUSIONS: The diversity of intradural findings and observations revealed in this study suggests that obstructive and compressive structural anomalies may be more common than previously reported among CM-I patients, both those patients with and those without syringomyelia and especially those with obstructive and compressive PICA branches. Although the authors cannot conclude that all these findings are necessarily pathological, further study may determine how they contribute to CM-I pathology and symptomatology in the setting of a compromised cisterna magna.


Subject(s)
Arnold-Chiari Malformation , Plastic Surgery Procedures , Syringomyelia , Adult , Child , Humans , Infant , Child, Preschool , Adolescent , Young Adult , Middle Aged , Aged , Gliosis , Retrospective Studies
12.
Neurosurg Focus ; 55(5): E2, 2023 11.
Article in English | MEDLINE | ID: mdl-37913544

ABSTRACT

OBJECTIVE: Studies have demonstrated the benefits of diversity in neurosurgery. However, recruitment of minoritized groups within the neurosurgical workforce consistently lags other surgical specialties. While racial and gender demographics of neurosurgical residents are well documented, there has been minimal exploration into the multidimensional nature of diversity. The current study will evaluate the longitudinal diversity changes in neurosurgery residency programs compared with other surgical fields with validated diversity indices. METHODS: Nationwide reports including data about resident physicians were obtained from the American Medical Association and the Association of American Medical Colleges for the academic years 2008-2021. Self-reported race, biological sex, and medical school affiliation were recorded for surgical residents in the 10 commonly recognized surgical fields. The Gini-Simpson Diversity Index was used to calculate the effective counts (ECs) of races, sexes, and medical school types for each field. A Composite Diversity Index (CDI) comprising the aforementioned diversity traits was used to calculate the percentage of characteristics upon which two randomly selected residents within each specialty would differ. CDIs were calculated for each field in every year from 2008 to 2021. Median CDIs were compared between fields using Kruskal-Wallis testing, and p values < 0.05 were deemed statistically significant. RESULTS: Plastic surgery had the highest median sex EC (1.92, interquartile range [IQR] 1.78-1.95), indicating greater diversity, while neurosurgery had the third lowest sex EC (1.40, IQR 1.35-1.41). All surgical fields examined had fewer than 3 races effectively represented among their residents, despite there being 8 races present. Neurosurgery ranked among the top fields in effective racial diversity (EC 2.17, IQR 2.09-2.21) and medical school type diversity (EC 1.25, IQR 1.21-1.26). There were statistically significant differences in the sex, race, and school ECs between surgical specialties. While neurosurgery had a relatively low median overall diversity (CDI = 32.7, IQR 32.0-34.6), there was a consistent longitudinal increase in CDI from 2015 to 2021. CONCLUSIONS: Neurosurgery resident physicians have become increasingly diverse in the past decade but are more homogenous than residents in other surgical fields. The continued use of diversity indices to more accurately track diversity progress over time may better inform leaders in the field of how they may best focus their equity and inclusion efforts.


Subject(s)
Internship and Residency , Neurosurgery , Specialties, Surgical , United States , Humans , Neurosurgery/education , Neurosurgical Procedures , Workforce
13.
Acta Neurochir (Wien) ; 165(2): 303-313, 2023 02.
Article in English | MEDLINE | ID: mdl-36529784

ABSTRACT

PURPOSE: Penetrating traumatic brain injury (pTBI) is an acute medical emergency with a high rate of mortality. Patients with survivable injuries face a risk of infection stemming from foreign body transgression into the central nervous system (CNS). There is controversy regarding the utility of antimicrobial prophylaxis in managing such patients, and if so, which antimicrobial agent(s) to use. METHODS: We reviewed patients with pTBI at our institution and performed a PRISMA systematic review to assess the impact of prophylactic antibiotics on reducing risk of CNS infection. RESULTS: We identified 21 local patients and 327 cases in the literature. In our local series, 17 local patients received prophylactic antibiotics; four did not. Overall, five of these patients (24%) developed a CNS infection (four and one case of intraparenchymal brain abscess and meningitis, respectively). All four patients who did not receive prophylactic antibiotics developed an infection (three with CNS infections; one superficial wound infection) compared to two of 17 (12%) patients who did receive prophylactic antibiotics. Of the 327 pTBI cases reported in the literature, 216 (66%) received prophylactic antibiotics. Thirty-eight (17%) patients who received antibiotics developed a CNS infection compared to 21 (19%) who did not receive antibiotics (p = 0.76). CONCLUSIONS: Although our review of the literature did not reveal any benefit, our institutional series suggested that patients with pTBI may benefit from prophylactic antibiotics. We propose a short antibiotic course with a regimen specific to cases with and without the presence of organic debris.


Subject(s)
Brain Injuries, Traumatic , Head Injuries, Penetrating , Wound Infection , Humans , Antibiotic Prophylaxis , Anti-Bacterial Agents/therapeutic use , Brain Injuries, Traumatic/drug therapy
14.
J Integr Neurosci ; 22(6): 143, 2023 Oct 23.
Article in English | MEDLINE | ID: mdl-38176935

ABSTRACT

This article presents evidence indicating that intracranial pressure (ICP) pulsatility, associated with the heartbeat and breathing, is not just a source of mechanical artefact in electrical recordings, but is "sensed" and plays a role in the brain's information processing. Patch-clamp recording of pressure-activated channels, and detection of Piezo2-protein channel expression in brain neurons, suggest that these channels provide neurons with an intrinsic resonance to ICP pulsatility, which acts to synchronize remote neural networks. Direct measurements in human patients indicate that heartbeat and breathing rhythms generate intracranial forces of tens of millinewtons, exceeding by orders of magnitude the localized forces shown by atomic force microscopy and optical tweezers to activate Piezo channels in isolated neocortical and hippocampal neurons. Additionally, many human touch and proprioceptors, which are also transduced by Piezo channels, show spiking that is phase-locked to heartbeat- and breathing-induced extracranial pressure pulsations. Finally, based on the observation that low-frequency oscillations modulate the phase and amplitude of high-frequency oscillations, body and brain oscillations are proposed to form a single hierarchical system in which the heartbeat is the basic frequency and scaling factor for all other oscillations. Together, these results support the idea that ICP pulsatility may be elemental in modulating the brain's electrical rhythmicity.


Subject(s)
Brain , Intracranial Pressure , Humans , Intracranial Pressure/physiology , Hippocampus , Cognition , Heart Rate
15.
World J Microbiol Biotechnol ; 39(10): 262, 2023 Jul 29.
Article in English | MEDLINE | ID: mdl-37507604

ABSTRACT

Tellurium is a super-trace metalloid on Earth. Owing to its excellent physical and chemical properties, it is used in industries such as metallurgy and manufacturing, particularly of semiconductors and - more recently - solar panels. As the global demand for tellurium rises, environmental issues surrounding tellurium have recently aroused concern due to its high toxicity. The amount of tellurium released to the environment is increasing, and microorganisms play an important role in the biogeochemical cycling of environmental tellurium. This review focuses on novel developments on tellurium transformations driven by microbes and includes the following sections: (1) history and applications of tellurium; (2) toxicity of tellurium; (3) microbial detoxification mechanisms against soluble tellurium anions including uptake, efflux and methods of reduction, and reduced ability to cope with oxidation stress or repair damaged DNA; and (4) the characteristics and applications of tellurium nanoparticles (TeNPs) produced by microbes. This review raises the awareness of microorganisms in tellurium biogeochemical cycling and the growing applications for microbial tellurium nanoparticles.


Subject(s)
Nanoparticles , Trace Elements , Tellurium/chemistry
16.
Cerebellum ; 21(4): 592-605, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35334077

ABSTRACT

Semi-structured interviews of patient accounts and caregiver, or informant, perspectives are a beneficial resource for patients suffering from diseases with complex symptomatology, such as cerebellar ataxia. The aim of this study was to identify, quantify, and compare the ways in which cerebellar ataxia patients' and informants' quality of life had changed as a result of living with ataxia. Using a semi-structured interview, responses were collected from patients and informants regarding motor, cognitive, and psychosocial variables. Responses were also collected from patients and informants to open-ended questions that were subsequently categorized into 15 quality of life themes that best represented changes experienced by the patients and informants. Ataxia patients and informants agreed as to the severity of posture/gait, daily activities/fine motor tasks, speech/feeding/swallowing, and oculomotor/vision impairment. It was also demonstrated that severity ratings for specific motor-related functions strongly correlated with corresponding functions within the International Cooperative Ataxia Rating Scale (ICARS), and that this interview identified frequency associations between motor impairments and specific psychosocial difficulties, which could be useful for prognostic purposes. Overall, the information obtained from this study characterized the symptoms and challenges to ataxia patients and their caregivers, which could serve as a useful educational resource for those affected by ataxia, clinicians, and researchers.


Subject(s)
Cerebellar Ataxia , Ataxia , Cerebellar Ataxia/diagnosis , Gait/physiology , Humans , Quality of Life , Self Report
17.
Curr Urol Rep ; 23(9): 195-201, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36057019

ABSTRACT

PURPOSE OF REVIEW: This article evaluates the historical influences, current use, surgical techniques, and recent evidence on outcomes for cystectomy performed for benign indications. RECENT FINDINGS: At the population level, cystectomy for benign indications has similar perioperative morbidity to radical cystectomy for cancer. Postoperative patient satisfaction is high and functional outcomes appear good, including sexual function. Patient regret about diversion choice is low provided decisions are well informed. Cystectomy is important both as a primary procedure for benign disease and as an adjunct to primary urinary diversion. Early morbidity remains high but long-term results are encouraging. Further studies are needed to guide patient decision-making, to help inform diversion choice, and to understand the long-term impact of surgery and diversion choice on quality of life.


Subject(s)
Urinary Bladder Neoplasms , Urinary Diversion , Cystectomy/methods , Humans , Quality of Life , Urinary Bladder , Urinary Bladder Neoplasms/surgery , Urinary Diversion/methods
18.
J Mol Cell Cardiol ; 156: 33-44, 2021 07.
Article in English | MEDLINE | ID: mdl-33781820

ABSTRACT

Phosphorylation of cardiac myosin binding protein-C (cMyBP-C) regulates cardiac contraction through modulation of actomyosin interactions mediated by the protein's amino terminal (N')-region (C0-C2 domains, 358 amino acids). On the other hand, dephosphorylation of cMyBP-C during myocardial injury results in cleavage of the 271 amino acid C0-C1f region and subsequent contractile dysfunction. Yet, our current understanding of amino terminus region of cMyBP-C in the context of regulating thin and thick filament interactions is limited. A novel cardiac-specific transgenic mouse model expressing cMyBP-C, but lacking its C0-C1f region (cMyBP-C∆C0-C1f), displayed dilated cardiomyopathy, underscoring the importance of the N'-region in cMyBP-C. Further exploring the molecular basis for this cardiomyopathy, in vitro studies revealed increased interfilament lattice spacing and rate of tension redevelopment, as well as faster actin-filament sliding velocity within the C-zone of the transgenic sarcomere. Moreover, phosphorylation of the unablated phosphoregulatory sites was increased, likely contributing to normal sarcomere morphology and myoarchitecture. These results led us to hypothesize that restoration of the N'-region of cMyBP-C would return actomyosin interaction to its steady state. Accordingly, we administered recombinant C0-C2 (rC0-C2) to permeabilized cardiomyocytes from transgenic, cMyBP-C null, and human heart failure biopsies, and we found that normal regulation of actomyosin interaction and contractility was restored. Overall, these data provide a unique picture of selective perturbations of the cardiac sarcomere that either lead to injury or adaptation to injury in the myocardium.


Subject(s)
Carrier Proteins/genetics , Myocardial Contraction/genetics , Myocardium/metabolism , Protein Interaction Domains and Motifs , Animals , Carrier Proteins/chemistry , Carrier Proteins/metabolism , Heart/diagnostic imaging , Magnetic Resonance Imaging , Mice , Mice, Transgenic , Myocytes, Cardiac/metabolism , Phosphorylation , Sarcomeres/metabolism
19.
Int J Obes (Lond) ; 45(9): 2016-2027, 2021 09.
Article in English | MEDLINE | ID: mdl-34079069

ABSTRACT

BACKGROUND/OBJECTIVES: The worldwide prevalence of obesity, metabolic syndrome and type 2 diabetes (T2D) is reaching epidemic proportions that urge the development of new management strategies. Totum-63 is a novel, plant-based polyphenol-rich active principle that has been shown to reduce body weight, fasting glycemia, glucose intolerance, and fatty liver index in obese subjects with prediabetes. Here, we investigated the effects and underlying mechanism(s) of Totum-63 on metabolic homeostasis in insulin-resistant obese mice. METHODS: Male C57Bl6/J mice were fed a high-fat diet for 12 weeks followed by supplementation with Totum-63 for 4 weeks. The effects on whole-body energy and metabolic homeostasis, as well as on tissue-specific inflammation and insulin sensitivity were assessed using a variety of immunometabolic phenotyping tools. RESULTS: Totum-63 decreased body weight and fat mass in obese mice, without affecting lean mass, food intake and locomotor activity, and increased fecal energy excretion and whole-body fatty acid oxidation. Totum-63 reduced fasting plasma glucose, insulin and leptin levels, and improved whole-body insulin sensitivity and peripheral glucose uptake. The expression of insulin receptor ß and the insulin-induced phosphorylation of Akt/PKB were increased in liver, skeletal muscle, white adipose tissue (WAT) and brown adipose tissue (BAT). Hepatic steatosis was also decreased by Totum-63 and associated with a lower expression of genes involved in fatty acid uptake, de novo lipogenesis, inflammation, and fibrosis. Furthermore, a significant reduction in pro-inflammatory macrophages was also observed in epidydimal WAT. Finally, a potent decrease in BAT mass associated with enhanced tissue expression of thermogenic genes was found, suggesting BAT activation by Totum-63. CONCLUSIONS: Our results show that Totum-63 reduces inflammation and improves insulin sensitivity and glucose homeostasis in obese mice through pleiotropic effects on various metabolic organs. Altogether, plant-derived Totum-63 might constitute a promising novel nutritional supplement for alleviating metabolic dysfunctions in obese people with or without T2D.


Subject(s)
Body Composition/drug effects , Inflammation/drug therapy , Obesity/drug therapy , Plant Extracts/pharmacology , Polyphenols/pharmacology , Animals , Body Composition/physiology , Disease Models, Animal , Inflammation/prevention & control , Insulin Resistance/physiology , Mice , Mice, Inbred C57BL/metabolism
20.
Cerebellum ; 20(2): 222-245, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33123963

ABSTRACT

The cerebellum recognizes sequences from prior experiences and uses this information to generate internal models that predict future outcomes in a feedforward manner [Front Hum Neurosci 8: 475, 2014; Cortex 47: 137-44, 2011; Cerebellum 7: 611-5, 2008; J Neurosci 26: 9107-16, 2006]. This process has been well documented in the motor domain, but the cerebellum's role in cognitive sequencing, within the context of implicit versus explicit processes, is not well characterized. In this study, we tested individuals with cerebellar ataxia and healthy controls to clarify the role of the cerebellum sequencing using variations on implicit versus explicit and motor versus cognitive demands across five experiments. Converging results across these studies suggest that cerebellar feedforward mechanisms may be necessary for sequencing in the implicit domain only. In the ataxia group, rhythmic tapping, rate of motor learning, and implicit sequence learning were impaired. However, for cognitive sequencing that could be accomplished using explicit strategies, the cerebellar group performed normally, as though they shifted to extra-cerebellar mechanisms to compensate. For example, when cognitive and motor functions relied on cerebellar function simultaneously, the ataxia group's motor function was unaffected, in contrast to that of controls whose motor performance declined as a function of cognitive load. These findings indicated that the cerebellum is not critical for all forms of sequencing per se. Instead, it plays a fundamental role for sequencing within the implicit domain, whether functions are motor or cognitive. Moreover, individuals with cerebellar ataxia are generally able to compensate for cognitive sequencing when explicit strategies are available in order to preserve resources for motor function.


Subject(s)
Cerebellar Ataxia/physiopathology , Cerebellum/physiology , Learning/physiology , Adult , Aged , Female , Humans , Male , Middle Aged
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