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1.
BMJ Open ; 13(2): e066990, 2023 02 20.
Article En | MEDLINE | ID: mdl-36806138

OBJECTIVE: Performance of maternal death surveillance and response (MDSR) relies on the system's ability to identify and notify all maternal deaths and its ability to review all maternal deaths by a committee. Unified definitions for indicators to assess these functions are lacking. We aim to estimate notification and review coverage rates in 30 countries between 2015 and 2019 using standardised definitions. DESIGN: Repeat cross-sectional surveys provided the numerators for the coverage indicators; United Nations (UN)-modelled expected country maternal deaths provided the denominators. SETTING: 30 low-income and middle-income countries responding to the Maternal Health Thematic Fund annual surveys conducted by the UN Population Fund between 2015 and 2019. OUTCOME MEASURES: Notification coverage rate ([Formula: see text]) was calculated as the proportion of expected maternal deaths that were notified at the national level annually; review coverage rate ([Formula: see text]) was calculated as the proportion of expected maternal deaths that were reviewed annually. RESULTS: The average annual [Formula: see text] for all countries increased from 17% in 2015 to 28% in 2019; the average annual [Formula: see text] increased from 8% to 13%. Between 2015 and 2019, 22 countries (73%) reported increases in the [Formula: see text]-with an average increase of 20 (SD 18) percentage points-and 24 countries (80%) reported increases in [Formula: see text] by 7 (SD 11) percentage points. Low values of [Formula: see text] contrasts with country-published review rates, ranging from 46% to 51%. CONCLUSION: MDSR systems that count and review all maternal deaths can deliver real-time information that could prompt immediate actions and may improve maternal health. Consistent and systematic documentation of MDSR efforts may improve national and global monitoring. Assessing the notification and review functions using coverage indicators is feasible, not affected by fluctuations in data completeness and reporting, and can objectively capture progress.


Maternal Death , Humans , Female , Cross-Sectional Studies , Developing Countries , Maternal Mortality , Poverty
2.
Health Promot Pract ; 24(4): 728-739, 2023 07.
Article En | MEDLINE | ID: mdl-35414293

BACKGROUND AND PURPOSE: There is growing interest in expanding healthy eating interventions in the retail setting. The purpose of this study was to evaluate the implementation of a successful 2-for-1 price incentive for fruits and vegetables (F&V), including frozen and canned, that took place in partnership with a large chain grocery retailer in Maine. Intervention Approach. A randomized controlled trial (RCT) pilot study was conducted in 2015-2016, followed by a larger RCT in 2016-2017, to assess whether a supermarket double-dollar F&V incentive increased purchases of these items. EVALUATION METHODS: A convergent, parallel mixed-methods design was used to examine barriers and facilitators to implementing the interventions, using six implementation outcomes: acceptability, adoption, appropriateness, feasibility, implementation fidelity, and perceived cost. RESULTS: The intervention was deemed highly acceptable, appropriate, and feasible by shoppers, retailers, and researchers. The F&V discount had a high rate of initial adoption. There was a moderate degree of fidelity, which improved over time based on lessons learned from the pilot and applied to the subsequent RCT. Specific costs associated with implementation from the research perspective are reported. Implications for Practice, Policy, and Research. Partnerships between academic researchers and retailers can be an effective model for improving healthful purchases among shoppers. These findings are relevant for investigators, public health advocates, and retailers interested in implementing similar grocery retail-based interventions.


Fruit , Vegetables , Humans , Motivation , Marketing , Diet, Healthy , Commerce
3.
Rev Esp Anestesiol Reanim (Engl Ed) ; 69(2): 105-108, 2022 02.
Article En | MEDLINE | ID: mdl-35177365

Vocal cord paralysis is a rare but severe complication after orotracheal intubation. The most common cause is traumatic, due to compression of the recurrent laryngeal nerve between the orotracheal tube cuff and the thyroid cartilage. Other possible causes are direct damage to the vocal cords during intubation, dislocation of the arytenoid cartilages, or infections, especially viral infections. It is usually due to a recurrent laryngeal nerve neuropraxia, and the course is benign in most patients. We present the case of a man who developed late bilateral vocal cord paralysis after pneumonia complicated with respiratory distress due to SARS-CoV-2 that required orotracheal intubation for 11 days. He presented symptoms of dyspnea 20 days after discharge from hospital with subsequent development of stridor, requiring a tracheostomy. Due to the temporal evolution, a possible contribution of the SARS-CoV-2 infection to the picture is pointed out.


COVID-19 , Vocal Cord Paralysis , COVID-19/complications , Humans , Intubation, Intratracheal/adverse effects , Male , SARS-CoV-2 , Tracheostomy/adverse effects , Vocal Cord Paralysis/etiology
4.
Rev. esp. anestesiol. reanim ; 69(2): 105-108, Feb 2022.
Article Es | IBECS | ID: ibc-206709

La parálisis de cuerdas vocales es una complicación poco frecuente, aunque severa, tras una intubación orotraqueal. La causa más frecuente es la traumática, debido a la compresión del nervio laríngeo recurrente entre el maguito del tubo orotraqueal y el cartílago tiroides. Otras posibles causas son lesión directa de las cuerdas vocales durante la intubación, luxación de los cartílagos aritenoides e infecciones, sobre todo víricas. Suele deberse a una neuroapraxia del nervio laríngeo recurrente, y el curso es benigno en la mayoría de los pacientes. Presentamos el caso de un varón que desarrolló una parálisis de cuerdas vocales bilateral tras una neumonía complicada con distrés respiratorio por SARS-CoV-2 que requirió intubación orotraqueal durante 11 días. Presentó clínica de disnea a los 20 días del alta hospitalaria con desarrollo posterior de estridor, siendo necesaria la realización de una traqueostomía. Debido a la evoución temporal, se apunta una posible contribución de la infección por SARS-CoV-2 al cuadro.(AU)


Vocal cord paralysis is a rare but severe complication after orotracheal intubation. The most common cause is traumatic, due to compression of the recurrent laryngeal nerve between the orotracheal tube cuff and the thyroid cartilage. Other possible causes are direct damage to the vocal cords during intubation, dislocation of the arytenoid cartilages, or infections, especially viral infections. It is usually due to a recurrent laryngeal nerve neuropraxia, and the course is benign in most patients. We present the case of a man who developed late bilateral vocal cord paralysis after pneumonia complicated with respiratory distress due to SARS-CoV-2 that required orotracheal intubation for 11 days. He presented symptoms of dyspnea 20 days after discharge from hospital with subsequent development of stridor, requiring a tracheostomy. Due to the temporal evolution, a possible contribution of the SARS-CoV- 2 infection to the picture is pointed out.(AU)


Humans , Female , Aged , Vocal Cord Paralysis/diagnosis , Vocal Cord Paralysis/drug therapy , Intubation, Intratracheal , Pneumonia , Betacoronavirus , Pandemics , Inpatients , Pneumonia, Viral , Coronavirus Infections , Anesthesiology , Cardiopulmonary Resuscitation
6.
Ann R Coll Surg Engl ; 104(2): 125-129, 2022 Feb.
Article En | MEDLINE | ID: mdl-34730439

INTRODUCTION: In 2013, The Association of Coloproctology of Great Britain and Ireland (ACPGBI) issued a position statement regarding management of malignant polyps. We reviewed the management of endoscopically resected malignant colorectal polyps in a district general hospital to evaluate whether patients were being overtreated as per these guidelines. METHODS: All patients who underwent a complete, non-piecemeal endoscopic removal of a malignant polyp between October 2013 and September 2018 were studied. Polyps were risk stratified for residual disease and followed up as per the ACPGBI. Patients were divided into two groups based on management after polypectomy. Primary outcome measured was the presence of residual tumour or involved lymph nodes in the resection specimen. Secondary outcomes included complications and recurrence. RESULTS: Thirty-three patients were included: 21 in the non-operative group (NOG) and 12 in the operative group (OG). The ACPGBI risk score in the NOG varied between 1 and over 4 compared with the OG who all scored over 4. Two patients in the OG (16%) demonstrated residual disease. Five patients suffered a postoperative complication. No recurrences were noted in the OG and one in the NOG. CONCLUSION: Our findings against a backdrop of the available literature suggest that the risk of residual disease after malignant polypectomy may not be as high as stated by the ACPGBI. As a result, there is a risk of overtreating patients and exposing them to the significant complications of surgery if careful consideration is not exercised.


Colonic Polyps , Colorectal Neoplasms , Colonic Polyps/pathology , Colonic Polyps/surgery , Colonoscopy/adverse effects , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Endoscopy , Humans , Retrospective Studies , Risk Factors , United Kingdom/epidemiology
7.
Int J Tuberc Lung Dis ; 25(7): 573-578, 2021 07 01.
Article En | MEDLINE | ID: mdl-34183103

BACKGROUND: Despite decreasing incidence of TB in South Africa, people with TB continue to be missed by facility-based case-finding interventions, and agricultural workers suffer disproportionately from limited access to services. We implemented two community-based active case-finding strategies to engage agricultural workers and assessed the cost of these interventions.METHODS: We summarized costs for two interventions - one led by enrolled nurses and one by non-governmental organizations (NGOs) - from April 2017 to December 2019, and calculated cost per person reached by services, screened for TB, identified as having TB and started on TB treatment. We performed Mann-Kendall tests of monotonic trend and conducted a sensitivity analysis of intervention costs.RESULTS: The enrolled nurses-led implementation started 442 people on TB treatment at a cost of US$118 per person, with decreasing trend in costs over the implementation period (P = 0.005). The NGO-led intervention started 160 people on treatment at a cost of US$554 per person, with decreasing trend in costs over the implementation period (P = 0.004).CONCLUSION: Community-based case-finding strategies find TB patients who would be missed by the health system. These strategies should be scaled up to close the missing cases gap in South Africa and to meet UN targets for ending TB.


Farmers , Tuberculosis , Humans , South Africa/epidemiology , Tuberculosis/diagnosis , Tuberculosis/drug therapy , Tuberculosis/epidemiology
8.
BMC Musculoskelet Disord ; 22(1): 138, 2021 Feb 04.
Article En | MEDLINE | ID: mdl-33541314

BACKGROUND: Although telehealth is becoming more popular for delivery of care for individuals with musculoskeletal pain, to our knowledge telehealth has not been used to manage Achilles tendinopathy. This research aimed to explore the experience of participants and physiotherapists with gym-based exercise interventions for Achilles tendinopathy monitored via videoconference. METHODS: A qualitative, interpretive description design was performed using semi-structured interviews (8 participants) and a focus group (7 physiotherapists). Participants and physiotherapists were interviewed about their experiences of the use of telehealth during a gym-based exercise intervention incorporating different calf load parameters for Achilles tendinopathy. We employed an inductive thematic analysis approach to analyse the data. RESULTS: Three themes identified from both participants and physiotherapists included i) acceptability of telehealth; ii) enablers to adherence with telehealth; and iii) barriers to adherence with telehealth. Two extra themes arose from participants regarding adherence with gym-based exercise, including enablers to adherence with the exercise intervention, and barriers to adherence with the exercise intervention. Both participants and physiotherapists expressed overall satisfaction and acceptability of telehealth monitoring of gym-based exercise. CONCLUSION: Gym-based exercise intervention for Achilles tendinopathy involving weekly telehealth monitoring was acceptable to both participants and physiotherapists. Potential enablers and barriers were identified that may improve adherence to this type of intervention.


Achilles Tendon , Physical Therapists , Telemedicine , Tendinopathy , Exercise , Exercise Therapy , Humans , Tendinopathy/therapy
9.
Proc Nutr Soc ; 80(1): 29-36, 2021 02.
Article En | MEDLINE | ID: mdl-32684178

Sensing of nutrients by chemosensory cells in the gastrointestinal tract plays a key role in transmitting food-related signals, linking information about the composition of ingested foods to digestive processes. In recent years, a number of G protein-coupled receptors (GPCR) responsive to a range of nutrients have been identified. Many are localised to intestinal enteroendocrine (chemosensory) cells, promoting hormonal and neuronal signalling locally, centrally and to the periphery. The field of gut sensory systems is relatively new and still evolving. Despite huge interest in these nutrient-sensing GPCR, both as sensors for nutritional status and targets for preventing the development of metabolic diseases, major challenges remain to be resolved. However, the gut expressed sweet taste receptor, resident in L-enteroendocrine cells and responsive to dietary sweetener additives, has already been successfully explored and utilised as a therapeutic target, treating weaning-related disorders in young animals. In addition to sensing nutrients, many GPCR are targets for drugs used in clinical practice. As such these receptors, in particular those expressed in L-cells, are currently being assessed as potential new pathways for treating diabetes and obesity. Furthermore, growing recognition of gut chemosensing of microbial-produced SCFA acids has led further attention to the association between nutrition and development of chronic disorders focusing on the relationship between nutrients, gut microbiota and health. The central importance of gut nutrient sensing in the control of gastrointestinal physiology, health promotion and gut-brain communication offers promise that further therapeutic successes and nutritional recommendations will arise from research in this area.


Gastrointestinal Tract/metabolism , Intestinal Mucosa/metabolism , Nutrients/metabolism , Nutritional Physiological Phenomena/physiology , Signal Transduction/physiology , Enteroendocrine Cells/metabolism , Gastrointestinal Hormones/metabolism , Humans , Receptors, G-Protein-Coupled/metabolism
10.
Vaccine ; 38(33): 5278-5285, 2020 07 14.
Article En | MEDLINE | ID: mdl-32527598

OBJECTIVES: To map the integration of existing maternal tetanus immunization programmes within antenatal care (ANC) services for pregnant women in low- and middle-income countries (LMICs) and to identify and understand the challenges, barriers and facilitators associated with high performance maternal vaccine service delivery. DESIGN: A mixed methods, cross sectional study with four data collection phases including a desk review, online survey, telephone and face-to-face interviews and in country visits was undertaken between 2016 and 2018. Associations of different service delivery process components with protection at birth (PAB) and with country groups were established. PAB was defined as the proportion of neonates protected at birth against neonatal tetanus. Regression analysis and structural equation modelling was used to assess associations of different variables with maternal tetanus immunization coverage. Latent class analysis (LCA), was used to group country performance for maternal immunization, and to address the problem of multicollinearity. SETTING: LMICs. RESULTS: The majority of LMICs had a policy on recommended number of ANC visits, however most were yet to implement the WHO guidelines recommending eight ANC contacts. Countries that recommended > 4 ANC contacts were more likely to have high PAB > 90%. Passive disease surveillance was the most common form of disease surveillance performed but the maternal and neonatal morbidity and mortality indicators recorded differed between countries. The presence of user fees for antenatal care and maternal immunization was significantly associated with lower PAB (<90%). CONCLUSIONS: Recommendations include implementing the current WHO ANC guideline to facilitate increased opportunities for vaccination during each pregnancy. Improved utilisation of ANC services by increasing the demand side by increasing the quality of services, reducing any associated costs and supporting user fee exemptions, or the supply side can also enhance utilisation of ANC services which are positioned as an ideal platform for delivery of maternal vaccines.


Prenatal Care , Tetanus Toxoid , Cross-Sectional Studies , Developing Countries , Female , Humans , Immunization , Infant, Newborn , Pregnancy , Vaccination
11.
Int J Tuberc Lung Dis ; 24(6): 612-618, 2020 06 01.
Article En | MEDLINE | ID: mdl-32552992

SETTING: While South Africa has improved access to tuberculosis (TB) treatment and care, the 2015 treatment success rate for multidrug-resistant TB (MDR-TB) remains low, at 55%. Community-based TB treatment and care improves patient retention compared to the standard of care alone.OBJECTIVE: To assess the cost of a USAID-funded community-based TB model in Nelson Mandela Bay Health District (NMBHD), Eastern Cape Province, South Africa compared to the national standard of care alone.DESIGN: We estimated the cost of community-based DR-TB treatment and adherence support compared to the standard of care alone.RESULTS: Average overall costs were US$2827 lower per patient on the community-based model than the standard of care alone.CONCLUSION: The per-patient cost of the community-based model is lower than the standard of care alone. Assuming the costs and effects of a community-based model implemented in NMBHD were observed at a larger scale, implementing the model could reduce overall health system costs.


Tuberculosis, Multidrug-Resistant , Tuberculosis , Health Care Costs , Humans , South Africa/epidemiology , Treatment Outcome , Tuberculosis/drug therapy , Tuberculosis/epidemiology , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiology
12.
Vaccine ; 38(33): 5268-5277, 2020 07 14.
Article En | MEDLINE | ID: mdl-32586763

OBJECTIVES: To examine the characteristics of existing maternal tetanus immunization programmes for pregnant women in low- and middle-income countries (LMICs) and to identify and understand the challenges, barriers and facilitators associated with maternal vaccine service delivery that may impact the introduction and implementation of new maternal vaccines in the future. DESIGN: A mixed methods, cross sectional study with four data collection phases including a desk review, online survey, telephone and face-to-face interviews and in country visits. SETTING: LMICs. RESULTS: The majority of countries (84/95; 88%) had a maternal tetanus immunization policy. Countries with high protection at birth (PAB) were more likely to report tetanus toxoid-containing vaccine (TTCV) coverage targets > 90%. Less than half the countries included in this study had a TTCV coverage target of > 90%. Procurement and distribution of TTCV was nearly always the responsibility of the Expanded Programme on Immunization (EPI), however planning and management of maternal immunization was often shared between EPI and Maternal, Newborn and Child Health (MNCH) programmes. Receipt of TTCV at the same time as the antenatal care visit correlated with high PAB. Most countries (81/95; 85%) had an immunization safety surveillance system in place although only 11% could differentiate an adverse event following immunization (AEFI) in pregnant and non-pregnant women. CONCLUSIONS: Recommendations arising from the MIACSA project to strengthen existing services currently delivering maternal tetanus immunization in LMICs include establishing and maintaining vaccination targets, clearly defining responsibilities and fostering collaborations between EPI and MNCH, investing in strengthening the health workforce, improving the design and use of existing record keeping for immunization, adjusting current AEFI reporting to differentiate pregnant women and endeavoring to integrate the provision of TTCV within ANC services where appropriate.


Developing Countries , Tetanus , Child , Cross-Sectional Studies , Female , Humans , Immunization , Infant, Newborn , Pregnancy , Prenatal Care , Tetanus/prevention & control , Vaccination
14.
Biochem Biophys Res Commun ; 525(4): 936-940, 2020 05 14.
Article En | MEDLINE | ID: mdl-32173534

Toll-like receptors (TLRs) play a key role in the recognition of microbes via detection of specific and conserved microbial molecular features. TLRs, mainly expressed in immune cells, interact with intestinal microbiome. Little is known about mechanism(s) of sensing of bacteria by the intestinal surface enteroendocrine cells (EECs). We show here that TLR9 is expressed by the EECs of proximal intestine in a range of species and is co-expressed with the satiety hormone cholecystokinin (CCK). CCK secreted in excess induces emesis (vomiting). Using an EEC model cell line, STC-1, we demonstrate that in response to the TLR9 agonist, DNA containing unmethylated CpG dinucleotide motifs, STC-1 cells secrete CCK and that this secretion is inhibited by specific inhibitors of TLR9. Exposure of STC-1 cells to heat-inactivated pathogenic bacteria, Escherichia coli O55/H7, Shigella flexneri 2457T, Salmonella typhimurium ST4/74, and non-pathogenic Lactobacillus amylovorus GRL1112, results to an increase in CCK secretion compared to untreated control. The magnitudes of CCK release are higher in response to pathogenic bacteria and lowest in response to the non-pathogenic L. amylovorus. The pathogenic strains not only have substantially bigger genomes than L. amylovorus, they also have significantly higher numbers/frequency of RR/CG/YY stimulatory CpG hexamers in their genomic DNA. Pathogen-induced excessive secretion of the gut hormone CCK, provoking emesis can serve as a protective mechanism against development of enteric infections.


Cholecystokinin/metabolism , Enteroendocrine Cells/metabolism , Enteroendocrine Cells/microbiology , Host-Pathogen Interactions/physiology , Toll-Like Receptor 9/metabolism , Animals , Cell Line , Female , Genome, Bacterial , Intestines/cytology , Male , Mice, Inbred C57BL , Swine , Toll-Like Receptors/metabolism
15.
Lymphology ; 53(4): 195-203, 2020.
Article En | MEDLINE | ID: mdl-33721925

Resistance exercise is deemed safe for women recovering from conventional breast cancer therapies but few clinicians are aware that dragon boat racing, as a form of resistive exercise, is available to the breast cancer community. The objectives of this study were to 1) increase clinician awareness of dragon boat racing (DBR) in breast cancer survivors as a community-based physical activity, and 2) evaluate quality of life (QOL) in breast cancer survivors with or without lymphedema who participate in DBR. This prospective, observational study surveyed 1,069 international breast cancer dragon boat racers from eight countries to compare function, activity, and participation in women with and without selfreported lymphedema using the Lymph-ICF questionnaire. Seventy-one percent of women (n=758) completed the questionnaires. Results revealed significantly higher Lymph-ICF scores in the lymphedema participants, signifying reduced QOL, when compared to the nonlymphedema participants (p<0.05), except for "go on vacation" for which no statistical difference was reported (p=0.20). International breast cancer survivors with lymphedema participating in DBR at an international competition had reduced function, limited activity, and restricted participation compared to participants without lymphedema. Clinicians should consider utilizing DBR as a community-based activity to support exercise and physical activity after a breast cancer diagnosis.


Breast Neoplasms , Cancer Survivors , Lymphedema , Breast Neoplasms/therapy , Female , Humans , Lymphedema/etiology , Prospective Studies , Quality of Life
16.
Article En, Es | MEDLINE | ID: mdl-33558055

Vocal cord paralysis is a rare but severe complication after orotracheal intubation. The most common cause is traumatic, due to compression of the recurrent laryngeal nerve between the orotracheal tube cuff and the thyroid cartilage. Other possible causes are direct damage to the vocal cords during intubation, dislocation of the arytenoid cartilages, or infections, especially viral infections. It is usually due to a recurrent laryngeal nerve neuropraxia, and the course is benign in most patients. We present the case of a man who developed late bilateral vocal cord paralysis after pneumonia complicated with respiratory distress due to SARS-CoV-2 that required orotracheal intubation for 11 days. He presented symptoms of dyspnea 20 days after discharge from hospital with subsequent development of stridor, requiring a tracheostomy. Due to the temporal evolution, a possible contribution of the SARS-CoV- 2 infection to the picture is pointed out.

17.
Br J Dermatol ; 182(1): 147-155, 2020 01.
Article En | MEDLINE | ID: mdl-31049933

BACKGROUND: The malignant mechanisms that control the development of cutaneous T-cell lymphoma (CTCL) are beginning to be identified. Recent evidence suggests that disturbances in specific intracellular signalling pathways, such as RAS-mitogen-activated protein kinase, T-cell receptor (TCR)-phospholipase C gamma 1 (PLCG1)-nuclear factor of activated T cells (NFAT) and Janus kinase (JAK)-signal transducer and activator of transcription (STAT), may play an essential role in the pathogenesis of CTCL. OBJECTIVES: To investigate the mechanisms controlling disease development and progression in mycosis fungoides (MF), the most common form of CTCL. METHODS: We collected 100 samples that were submitted for diagnosis of, or a second opinion regarding, MF between 2001 and 2018, 80% of which were in the early clinical stages of the disease. Formalin-fixed paraffin-embedded tissues were used for histological review and to measure the expression by immunohistochemistry of surrogate markers of activation of the TCR-PLCG1-NFAT, JAK-STAT and NF-κB pathways. Folliculotropism and large-cell transformation were also examined. RESULTS: NFAT and nuclear factor kappa B (NF-κB) markers showed a comparable activation status in early and advanced stages, while STAT3 activation was more frequent in advanced stages and was associated with large-cell transformation. Consistently with this observation, STAT3 activation occurred in parallel with MF progression in two initially MF-negative cases. A significant association of NFAT with NF-κB markers was also found, reflecting a common mechanism of activation in the two pathways. Genomic studies identified nine mutations in seven genes known to play a potential role in tumorigenesis in T-cell leukaemia/lymphoma, including PLCG1, JAK3 and STAT3, which underlies the activation of these key cell-survival pathways. A higher mutational allele frequency was detected in advanced stages. CONCLUSIONS: Our results show that STAT3 is activated in advanced cases and is associated with large-cell transformation, while the activation of NFAT and NF-κB is maintained throughout the disease. These findings could have important diagnostic and therapeutic implications. What's already known about this topic? Mycosis fungoides is characterized by a clonal expansion of T cells in the skin. The mechanisms controlling disease development and progression are not fully understood. What does this study add? An association of the nuclear factor of activated T cells and nuclear factor kappa B pathways was found, which could reflect a common mechanism of activation. These pathways were activated in early and advanced stages at the same level. Signal transducer and activator of transcription 3 activation was associated with large-cell transformation and was more frequent in advanced stages. A genomic analysis of cutaneous T-cell lymphoma-associated genes was performed. Nine mutations were detected. What is the translational message? These results could have important implications for the treatment of MF in the near future.


Lymphoma, T-Cell, Cutaneous , Mycosis Fungoides , NF-kappa B , NFATC Transcription Factors , STAT3 Transcription Factor , Skin Neoplasms , Humans , Mycosis Fungoides/genetics , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/metabolism , Skin Neoplasms/genetics , T-Lymphocytes/metabolism
18.
Clin Neurophysiol ; 131(1): 167-176, 2020 01.
Article En | MEDLINE | ID: mdl-31794958

OBJECTIVE: Essential tremor (ET) prominently affects the upper-limbs during voluntary movements, but can also affect the lower-limbs, head, and chin. Although deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of thalamus improves both clinical ratings and quantitative measures of tremor, no study has quantified effects of DBS on tremor across multiple body parts. Our objective was to quantify therapeutic effects of DBS across multiple body parts in ET. METHODS: We performed quantitative assessment of tremor in ET patients who had DBS for at least one year. We assessed tremor on and off VIM-stimulation using triaxial accelerometers on the upper-limbs, lower-limbs, head and chin during seated and standing tasks. RESULTS: VIM-DBS significantly reduced tremor, but there was no statistical difference in degree of tremor reduction across the measured effectors. Compared to healthy controls, ET patients treated with DBS showed significantly greater tremor power (4-8 Hz) across all effectors during seated and standing tasks. CONCLUSIONS: VIM-DBS reduced tremor in ET patients. There was no significant difference in the degree of tremor reduction across the measured effectors. SIGNIFICANCE: This study provides new quantitative evidence that VIM-DBS is effective at reducing tremor across multiple parts of the body.


Deep Brain Stimulation/methods , Essential Tremor/therapy , Ventral Thalamic Nuclei/physiology , Acceleration , Accelerometry/instrumentation , Aged , Aged, 80 and over , Case-Control Studies , Chin/physiopathology , Essential Tremor/physiopathology , Female , Hand/physiopathology , Head/physiopathology , Humans , Leg/physiopathology , Male , Middle Aged , Sitting Position , Standing Position
19.
Oncol Rep ; 42(1): 103-114, 2019 Jul.
Article En | MEDLINE | ID: mdl-31180539

Chondrosarcomas are malignant bone tumors refractory to chemotherapy and radiation treatment; thus, novel therapeutic strategies are required. Proline­rich polypeptide 1 (PRP­1) has previously demonstrated antitumor properties in chondrosarcoma. To further investigate the role of PRP­1 in chondrosarcoma cells, its effects on cancer stem cell (CSC) populations were determined by analyzing aldehyde dehydrogenase (ALDH) activity, an established marker of CSCs, in association with regulation of the Wnt/ß­catenin signaling. A significant decrease in ALDHhigh CSCs was observed following treatment of chondrosarcoma JJ012 cells with PRP­1. For RT2 profiler PCR array analysis of Wnt/ß­catenin signaling genes, cells were sorted into: i) Bulk JJ012 cells; ii) ALDHhigh cells sorted from untreated JJ012 cells (ALDHhigh­untreated); and iii) ALDHlow cells sorted from PRP­1­treated JJ012 cells (ALDHlow­PRP­1). The expression levels of Wnt/ß­catenin signaling genes were determined to be downregulated in the ALDHhigh­untreated cells and upregulated in ALDHlow­PRP­1 cells when compared to the bulk JJ012 cells. Additionally, two important oncogenes involved in this pathway, MMP7 and CCND2, were found to be downregulated in the ALDHlow­PRP­1 cells. Immunocytochemistry demonstrated the localization of ß­catenin in the nuclei of the PRP­1­treated cells. Western blotting indicated increased ß­catenin expression in the ALDHlow­PRP­1 cells compared with the bulk JJ012 cells. Analysis of the cytoplasmic and nuclear fractions of cells treated with increasing concentrations of PRP­1 and ß­catenin nuclear translocation inhibitor CGP57380, suggested the nuclear translocation of ß­catenin following PRP­1 treatment. In addition, treatment of JJ012 cells with a specific ALDH inhibitor, diethylaminobenzaldehyde, and PRP­1 resulted in a significant decrease in cytoplasmic ß­catenin protein expression. This indicated that ALDH inactivation may be associated with the nuclear translocation of ß­catenin. Derivation of sarcomas from mesenchymal stem cells via inactivation of the Wnt pathway has been previously documented. The findings of the present study support the notion that Wnt/ß­catenin activation may serve a differential role in sarcomas, limiting tumor progression in association with decreased CSC activity.


Aldehyde Dehydrogenase/metabolism , Antimicrobial Cationic Peptides/pharmacology , Bone Neoplasms/metabolism , Chondrosarcoma/metabolism , Neoplastic Stem Cells/metabolism , Wnt Signaling Pathway/drug effects , Aniline Compounds/pharmacology , Bone Neoplasms/drug therapy , Bone Neoplasms/genetics , Cell Line, Tumor , Cell Nucleus/metabolism , Chondrosarcoma/drug therapy , Chondrosarcoma/genetics , Cytoplasm/metabolism , Down-Regulation , Gene Expression Regulation, Neoplastic/drug effects , Gene Regulatory Networks/drug effects , Humans , Neoplastic Stem Cells/drug effects , Purines/pharmacology , beta Catenin/metabolism
20.
Int J Tuberc Lung Dis ; 23(2): 140-146, 2019 02 01.
Article En | MEDLINE | ID: mdl-30621813

SETTING: The tuberculous infection control strategy, FAST (Find cases Actively, Separate safely and Treat effectively), recommends prompt initiation of likely effective anti-tuberculosis treatment informed by Xpert® MTB/RIF results.OBJECTIVE: To describe FAST implementation at Quang Nam Provincial TB and Lung Disease Hospital (QNH), Tam Ky, Viet Nam, using time to initiation of effective TB treatment as a process measure. DESIGN: Hospital logs were used to calculate the time to likely effective treatment in patients with pulmonary TB (PTB) hospitalised during the study period. RESULTS: Between 1 January and 31 December 2016, of 858 patients treated for PTB, 493 (57.5%) received likely effective treatment. The median time to likely effective treatment was 3 days (interquartile range 2.0-6.0), with 213 (43.2%) patients receiving likely effective treatment within 2 days. Of 81 patients receiving likely effective treatment for drug-susceptible TB with a positive Xpert result as their initial in-patient diagnostic test, 64 (79.0%) received likely effective treatment within 2 days compared with 10 (5.7%) who were initially smear-negative then found to be Xpert-positive (P < 0.0001). CONCLUSIONS: A 'time to' process measure of the FAST tuberculous infection control strategy indicates delays in the initiation of likely effective anti-tuberculosis treatment in a resource-limited hospital. Expanding access to Xpert may speed time to likely effective treatment.


Antitubercular Agents/administration & dosage , Process Assessment, Health Care , Tuberculosis, Pulmonary/diagnosis , Humans , Sputum/microbiology , Time Factors , Time-to-Treatment , Treatment Outcome , Tuberculosis, Pulmonary/drug therapy , Vietnam
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