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1.
PLoS One ; 19(5): e0303902, 2024.
Article in English | MEDLINE | ID: mdl-38814974

ABSTRACT

BACKGROUND: To assess the attitudes of women towards intimate partner violence (IPV) in Guyana. METHODS: We used national data from the publicly available Multiple Indicator Cluster Survey (MICS) conducted in Guyana in 2019 for women aged 15 to 49 years. The prevalence of women who agreed that a husband is justified in beating his wife was analyzed. Respondent reasons included if she: "goes out without telling him", "neglects the children", "argues with him", "refuses sex with him", "burns the food", "has another partner", "stays out late/partying", "refuses to cook or clean", "overspends", and/or "he doesn't have access to her cellphone". Descriptive analyses were carried for all the variables. Logistic regression was used to identify factors associated with these 10 respondent reasons, separately and in combination. RESULTS: The overall prevalence of women's attitudes justifying IPV against women if there was a 'yes' response to any of the 10 reasons was 17.9% (95%CI: 16.6-19.3%), and varied from 2.7% if she "goes out without telling him", "burns the food", or "overspends" to 10.0% if she "has another partner". This prevalence ranged from 10.2% in urban areas to 19.3% in rural areas (p<0.001), and from 16.1% in coastal to 30.1% in interior areas (p<0.001). Similarly, 25.9% of women from the poorest household agreed that a husband has the right in beating his wife for any of the 10 reasons compared to 11.6% of the richest women (11.6%) (p<0.001). Rural place of residence, ethnicity, geographic region, level of education, wealth quintile, ever used of a computer, and frequency of listening to the radio were significant factors associated with women's attitudes justifying IPV against women (p<0.05). CONCLUSION: Over one-sixth of the respondents agreed that a husband was justified in committing IPV against women in Guyana. Public health programs focusing on geographic locations, ethnicity, and economic status must be implemented to change attitudes justifying IPV and reduce this significant public health challenge.


Subject(s)
Intimate Partner Violence , Humans , Female , Adult , Cross-Sectional Studies , Intimate Partner Violence/psychology , Intimate Partner Violence/statistics & numerical data , Adolescent , Middle Aged , Young Adult , Guyana/epidemiology , Male , Prevalence , Attitude , Surveys and Questionnaires , Rural Population
2.
Physiol Behav ; 276: 114474, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38272107

ABSTRACT

Nausea is an uncomfortable sensation that accompanies many therapeutics, especially diabetes treatments involving glucagon-like peptide-1 receptor (GLP1R) agonists. Recent studies in mice have revealed that GLP1R-expressing neurons in the area postrema play critical roles in nausea. Here, we characterized a ligand-conjugated saporin that can efficiently ablate GLP1R+ cells from humans, mice, and the Suncus murinus, a small animal model capable of emesis. This new tool provides a strategy to manipulate specific neural pathways in the area postrema in the Suncus murinus and may help elucidate roles of area postrema GLP1R+ neurons in emesis during therapeutics involving GLP1R agonists.


Subject(s)
Area Postrema , Glucagon-Like Peptide-1 Receptor , Animals , Humans , Mice , Glucagon-Like Peptide-1 Receptor/metabolism , Nausea , Neurons/metabolism , Vomiting/metabolism , Shrews
3.
J Hand Surg Am ; 49(1): 42-49, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37777934

ABSTRACT

Intramedullary fixation has long been popular for fracture fixation in the upper extremity from the shoulder through the carpus. Recently, intramedullary fixation in the hand has gained increasing interest, specifically in the metacarpals and phalanges, corresponding with the development of improved cannulated headless screw technology. Along with the advantages of increased operative speed and less surgical dissection, which can promote rapid healing, many benefits exist, supporting their use despite some drawbacks. This article reviews the background and biomechanics of intramedullary fixation with a specific focus on cannulated headless screws, describes the application and techniques of intramedullary screw fixation in the hand, and details the associated outcomes and costs for metacarpal fractures, phalangeal fractures, and interphalangeal joint arthrodesis.


Subject(s)
Finger Phalanges , Fractures, Bone , Hand Injuries , Metacarpal Bones , Humans , Fractures, Bone/surgery , Fracture Fixation, Internal/methods , Hand , Finger Phalanges/surgery , Metacarpal Bones/surgery , Metacarpal Bones/injuries , Arthrodesis
4.
Nonlinear Dynamics Psychol Life Sci ; 28(1): 19-54, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38153300

ABSTRACT

Posttraumatic Growth (PTG), characterized by newfound meaning, perspective, and purpose for trauma survivors, remains enigmatic in its nature. This state is thought to arise from the dynamic interplay of biopsychosocial factors; however, the nature of this interplay is unclear. This study aimed to investigate the intricate relationship between PTG and facial affect dynamics, shedding light on the complex interplay of biopsychosocial factors that underpin this transformative process. We conducted a comprehensive investigation involving 19 wildfire survivors who provided daily self-reported PTG ratings alongside smartphone videos analyzed using Automated Facial Affect Recognition (AFAR) software. Our findings revealed compelling evidence of self-organization within facial affect, as indicated by notably high mean R2 and shape parameter values (i.e., nonlinear indices indicative of structural integrity and flexibility). Further regression analyses unveiled a significant interaction between the degree of facial affect 'burstiness' and coping self-efficacy (CSE) on PTG. This interaction suggested that PTG development was a nuanced process intricately linked to the coherence of emotion patterns exhibited by individuals. These insights illuminate the multifaceted dynamics at play in the emergence of PTG and contribute to a broader understanding of its biopsychosocial foundations.


Subject(s)
Posttraumatic Growth, Psychological , Stress Disorders, Post-Traumatic , Humans , Adaptation, Psychological , Ecological Momentary Assessment , Facial Expression , Stress Disorders, Post-Traumatic/psychology
5.
Curr Biol ; 33(16): 3409-3422.e6, 2023 08 21.
Article in English | MEDLINE | ID: mdl-37506702

ABSTRACT

Bees are the most significant pollinators of flowering plants. This partnership began ca. 120 million years ago, but the uncertainty of how and when bees spread across the planet has greatly obscured investigations of this key mutualism. We present a novel analysis of bee biogeography using extensive new genomic and fossil data to demonstrate that bees originated in Western Gondwana (Africa and South America). Bees likely originated in the Early Cretaceous, shortly before the breakup of Western Gondwana, and the early evolution of any major bee lineage is associated with either the South American or African land masses. Subsequently, bees colonized northern continents via a complex history of vicariance and dispersal. The notable early absences from large landmasses, particularly in Australia and India, have important implications for understanding the assembly of local floras and diverse modes of pollination. How bees spread around the world from their hypothesized Southern Hemisphere origin parallels the histories of numerous flowering plant clades, providing an essential step to studying the evolution of angiosperm pollination syndromes in space and time.


Subject(s)
Fossils , Magnoliopsida , Bees/genetics , Animals , Phylogeny , Genomics , Magnoliopsida/genetics , South America
6.
J Pediatr ; 257: 113363, 2023 06.
Article in English | MEDLINE | ID: mdl-36828344
8.
Am J Dermatopathol ; 44(7): 469-477, 2022 Jul 01.
Article in English | MEDLINE | ID: mdl-35704910

ABSTRACT

OBJECTIVE: We sought to assess the clinicopathologic/immunophenotypical features in patients with lupus erythematosus tumidus (LET). METHODS: All skin biopsies diagnosed as LET in 16 years were retrieved from our pathology laboratory. Clinical charts were reviewed and immunohistochemical markers were performed. Subpopulations of cells in the infiltrates were studied, as well as the number/distribution of plasmacytoid dendritic cells (PDC), which were compared with two control groups: normal skin and discoid lupus erythematosus. Direct immunofluorescence was performed when available. RESULTS: We found 20 patients (11 men and 9 women; mean age 43.5 years); the mean evolution previous to diagnosis was 20.3 months. They all had erythematous, nonscarring urticarial-like plaques: 8 in the head region only, 8 in trunk/limbs only; both segments were affected in 2 patients; topography was unknown in 2. Except for 1 patient, no one developed systemic lupus erythematosus. A dense perivascular/periadnexal superficial-to-deep lymphocytic infiltrate and stromal mucin deposition were characterized histopathologically; interphase changes were absent. Immunophenotype supported an inflammatory profile. The differential count of CD123 + PDC in 10/20 cases of LET (n = 1180) was notably higher than 5 cases of discoid lupus erythematosus (n = 419) and 5 cases of normal skin (n = 38). No immune deposits were found in 2 cases. CONCLUSION: LET is a rare, peculiar form of cutaneous lupus erythematosus that only exceptionally evolves to systemic lupus erythematosus . Its clinical-pathologic/immunophenotypical features are very characteristic. The amount of CD123 + PDC is a very helpful feature among the criteria for its diagnosis and seems to be relevant in its pathogenesis.


Subject(s)
Lupus Erythematosus, Cutaneous , Lupus Erythematosus, Discoid , Lupus Erythematosus, Systemic , Adult , Female , Humans , Inflammation/pathology , Interleukin-3 Receptor alpha Subunit , Lupus Erythematosus, Cutaneous/pathology , Lupus Erythematosus, Discoid/pathology , Lupus Erythematosus, Systemic/pathology , Male , Skin/pathology
11.
Breast Cancer Res Treat ; 189(2): 533-539, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34196900

ABSTRACT

PURPOSE: Mutations in hereditary breast cancer genes play an important role in the risk for cancer. METHODS: Cancer susceptibility genes were sequenced in 664 unselected breast cancer cases from Guatemala. Variants were annotated with ClinVar and VarSome. RESULTS: A total of 73 out of 664 subjects (11%) had a pathogenic variant in a high or moderate penetrance gene. The most frequently mutated genes were BRCA1 (37/664, 5.6%) followed by BRCA2 (15/664, 2.3%), PALB2 (5/664, 0.8%), and TP53 (5/664, 0.8%). Pathogenic variants were also detected in the moderate penetrance genes ATM, BARD1, CHEK2, and MSH6. The high ratio of BRCA1/BRCA2 mutations is due to two potential founder mutations: BRCA1 c.212 + 1G > A splice mutation (15 cases) and BRCA1 c.799delT (9 cases). Cases with pathogenic mutations had a significantly earlier age at diagnosis (45 vs 51 years, P < 0.001), are more likely to have had diagnosis before menopause, and a higher percentage had a relative with any cancer (51% vs 37%, P = 0.038) or breast cancer (33% vs 15%, P < 0.001). CONCLUSIONS: Hereditary breast cancer mutations were observed among Guatemalan women, and these women are more likely to have early age at diagnosis and family history of cancer. These data suggest the use of genetic testing in breast cancer patients and those at high risk as part of a strategy to reduce breast cancer mortality in Guatemala.


Subject(s)
Breast Neoplasms , Genetic Predisposition to Disease , Germ-Line Mutation , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Breast Neoplasms/diagnosis , Breast Neoplasms/epidemiology , Breast Neoplasms/genetics , Female , Genes, BRCA2 , Germ Cells , Guatemala , Humans
12.
Am J Bot ; 108(5): 756-768, 2021 05.
Article in English | MEDLINE | ID: mdl-33988869

ABSTRACT

PREMISE: A subset of parasitic plants bear extremely reduced features and grow nearly entirely within their hosts. Until recently, most of these endoparasites were thought to represent a single clade united by their reduced morphology. Current phylogenetic understanding contradicts this assumption and indicates these plants represent distantly related clades, thus offering an opportunity to examine convergence among plants with this life history. METHODS: We sampled species from Apodanthaceae, Cytinaceae, Mitrastemonaceae, and Rafflesiaceae spanning a range of developmental stages. To provide a broader comparative framework, Santalaceae mistletoes with a similar lifestyle were also analyzed. Microtomography and microscopy were used to analyze growth patterns and the ontogeny of host-parasite vascular connections. RESULTS: Apodanthaceae, Cytinaceae, Mitrastemonaceae, and Rafflesiaceae species demonstrated a common development characterized by late cell differentiation. These species were also observed to form direct connections to host vessels and to cause severe alterations of host xylem development. Apodanthaceae and Rafflesiaceae species were additionally observed to form sieve elements, which connect with the host phloem. Endophytic Santalaceae species demonstrated a dramatically different developmental pattern, featuring early cell differentiation and tissue organization, and little effect on host anatomy and cambial activity. CONCLUSIONS: Our results illuminate two distinct developmental trajectories in endoparasites. One involves the retention of embryonic characteristics and late connection with host vessels, as demonstrated in species of Apodanthaceae, Cytinaceae, Mitrastemonaceae, and Rafflesiaceae. The second involves tissue specialization and early connection with host xylem, as exemplified by Santalaceae species. These differences are hypothesized to be related to the absence/presence of photosynthesis in these plants.


Subject(s)
Magnoliopsida , Mistletoe , Phloem , Phylogeny , Xylem
13.
Audiol Neurootol ; 26(3): 164-172, 2021.
Article in English | MEDLINE | ID: mdl-33434909

ABSTRACT

INTRODUCTION: When mapping cochlear implant (CI) patients with limited reporting abilities, the lowest electrical stimulus level that produces a stapedial reflex (i.e., the electrical stapedius reflex threshold [eSRT]) can be measured to estimate the upper bound of stimulation on individual or a subset of CI electrodes. However, eSRTs measured for individual electrodes or a subset of electrodes cannot be used to predict the global adjustment of electrical stimulation levels needed to achieve comfortable loudness sensations that can be readily used in a speech coding strategy. In the present study, eSRTs were measured for 1-, 4-, and 15-electrode stimulation to (1) determine changes in eSRT levels as a function of the electrode stimulation mode and (2) determine which stimulation mode eSRT levels best approximate comfortable loudness levels from patients' clinical maps. METHODS: eSRTs were measured with the 3 different electrical stimulation configurations in 9 CI patients and compared with behaviorally measured, comfortable loudness levels or M-levels from patients' clinical maps. RESULTS: A linear, mixed-effects, repeated-measures analysis revealed significant differences (p < 0.01) between eSRTs measured as a function of the stimulation mode. No significant differences (p = 0.059) were measured between 15-electrode eSRTs and M-levels from patients' clinical maps. The eSRTs measured for 1- and 4-electrode stimulation differed significantly (p < 0.05) from the M-levels on the corresponding electrodes from the patients' clinical map. CONCLUSION: eSRT profiles based on 1- or 4-electrode stimulation can be used to determine comfortable loudness level on either individual or a subset of electrodes, and 15-electrode eSRT profiles can be used to determine the upper bound of electrical stimulation that can be used in a speech coding strategy.


Subject(s)
Acoustic Impedance Tests/methods , Cochlear Implantation , Cochlear Implants , Reflex, Acoustic/physiology , Stapedius/physiopathology , Adolescent , Adult , Electric Stimulation/methods , Humans , Young Adult
14.
Neuroendocrinology ; 111(1-2): 70-86, 2021.
Article in English | MEDLINE | ID: mdl-31955161

ABSTRACT

BACKGROUND/AIMS: Furosemide is a loop diuretic widely used in clinical practice for the treatment of oedema and hypertension. The aim of this study was to determine physiological and molecular changes in the hypothalamic-neurohypophysial system as a consequence of furosemide-induced sodium depletion. METHODS: Male rats were sodium depleted by acute furosemide injection (10 and 30 mg/kg) followed by access to low sodium diet and distilled water for 24 h. The renal and behavioural consequences were evaluated, while blood and brains were collected to evaluate the neuroendocrine and gene expression responses. RESULTS: Furosemide treatment acutely increases urinary sodium and water excretion. After 24 h, water and food intake were reduced, while plasma angiotensin II and corticosterone were increased. After hypertonic saline presentation, sodium-depleted rats showed higher preference for salt. Interrogation using RNA sequencing revealed the expression of 94 genes significantly altered in the hypothalamic paraventricular nucleus (PVN) of sodium-depleted rats (31 upregulated and 63 downregulated). Out of 9 genes chosen, 5 were validated by quantitative PCR in the PVN (upregulated: Ephx2, Ndnf and Vwf; downregulated: Caprin2 and Opn3). The same genes were also assessed in the supraoptic nucleus (SON, upregulated: Tnnt1, Mis18a, Nr1d1 and Dbp; downregulated: Caprin2 and Opn3). As a result of these plastic transcriptome changes, vasopressin expression was decreased in PVN and SON, whilst vasopressin and oxytocin levels were reduced in plasma. CONCLUSIONS: We thus have identified novel genes that might regulate vasopressin gene expression in the hypothalamus controlling the magnocellular neurons secretory response to body sodium depletion and consequently hypotonic stress.


Subject(s)
Diuretics/pharmacology , Furosemide/pharmacology , Hypothalamo-Hypophyseal System/drug effects , Sodium/metabolism , Transcriptome/drug effects , Water-Electrolyte Balance/drug effects , Animals , Hypothalamo-Hypophyseal System/physiology , Male , Oxytocin/metabolism , Paraventricular Hypothalamic Nucleus/drug effects , Paraventricular Hypothalamic Nucleus/metabolism , Rats , Rats, Wistar , Time Factors , Transcriptome/physiology , Vasopressins/metabolism , Water-Electrolyte Balance/physiology
15.
BMC Public Health ; 20(1): 1771, 2020 Nov 23.
Article in English | MEDLINE | ID: mdl-33228642

ABSTRACT

BACKGROUND: Guaranteeing the sexual and reproductive health and rights (SRHR) of populations living in fragile and humanitarian settings is essential and constitutes a basic human right. Compounded by the inherent vulnerabilities of women in crises, substantial complications are directly associated with increased risks of poor SRHR outcomes for displaced populations. The migration of Venezuelans, displaced due to current economic circumstances, is one of the largest in Latin America's history. This study aims to provide an overview of the sexual and reproductive health (SRH) issues affecting migrant Venezuelan women in the state of Roraima, Brazil. METHODS: Face-to-face interviews were conducted from 24 to 30 November 2019. Data collection covered various issues involving access to and use of SRH services by 405 migrant Venezuelan women aged 18-49 years. The Minimum Initial Service Package readiness assessment tools, available from the Inter-Agency Working Group on Reproductive Health in Crises, were used in the data collection. RESULTS: Most commonly, the women reported unmet family planning needs. Of these, a significant proportion reported being unable to obtain contraceptive methods, particularly long-acting reversible contraceptives, either due to the woman's inability to access them or their unavailability at healthcare centres. Although a significant proportion of women were largely satisfied with the attention received at the maternity hospital, both before and during childbirth, 24.0% of pregnant or postpartum women failed to receive any prenatal or postnatal care. CONCLUSION: Meeting the essential SRHR needs of migrant Venezuelan women in Roraima, Brazil is a challenge that has yet to be fully addressed. Given the size of this migrant population, the Brazilian healthcare system has failed to adapt sufficiently to meet their needs; however, problems with healthcare provision are similar for migrants and Brazilian citizens. Efforts need to be encouraged not only in governmental health sectors, but also with academic, non-governmental and international organisations, including a coordinated approach to ensure a comprehensive SRHR response. Given the current high risks associated with the SARS-CoV-2 pandemic, meeting the SRHR needs of migrant populations has become more critical than ever.


Subject(s)
Maternal Health/statistics & numerical data , Transients and Migrants/statistics & numerical data , Brazil , Female , Health Services Needs and Demand , Humans , Pregnancy , Reproductive Health , Reproductive Rights , Sexual Health , Venezuela/ethnology
16.
Acta Trop ; 209: 105537, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32454033

ABSTRACT

Plasmodium vivax remains an important cause of malaria in South America and Asia, and analyses of the antibody immune response are being used to identify biomarker of parasite exposure. The IgG antibody naturally acquired predominantly occurs against targets on blood-stage parasites, including C-terminal of the merozoite surface protein 1 (MSP1-19). Epidemiological and immunological evidence has been showed that antibodies to malaria parasite antigens are lost in the absence of ongoing exposure. We describe the IgG antibody response in individuals living in an unstable malaria transmission area in Pará state, Amazon region, Brazil, where an epidemic of P. vivax malaria was recorded and monitored over time. As indicated by epidemiological data, the number of P. vivax-caused malaria cases decreased by approximately 90% after three years and the prevalence of IgG positive to PvMSP1-19 decreased significantly over time, in 2010 (93.4%), 2012 (78.3%), and 2013 (85.1%). Acquisition and decay of the IgG antibody against P. vivax MSP1-19 showed variability among individuals living in areas with recent circulating parasites, where the malaria epidemic was being monitored until transmission had been completely controlled. We also found that previous malaria episodes were associated with an increased in the IgG positivity . Our results showed epidemiological, spatial, temporal and individual variability. The understanding on dynamics of antibodies may have implications for the design of serosurveillance tools for monitoring parasite circulation, especially in a context with spatial and temporal changes in P. vivax malaria transmission.


Subject(s)
Antibodies, Protozoan/blood , Antigens, Protozoan/immunology , Immunoglobulin G/blood , Malaria, Vivax/immunology , Merozoite Surface Protein 1/immunology , Plasmodium vivax/immunology , Adolescent , Adult , Aged , Antibodies, Protozoan/immunology , Brazil/epidemiology , Child , Child, Preschool , Female , Humans , Malaria, Vivax/transmission , Male , Middle Aged , Young Adult
17.
Int Forum Allergy Rhinol ; 10(4): 521-525, 2020 04.
Article in English | MEDLINE | ID: mdl-32104979

ABSTRACT

BACKGROUND: Patients undergoing endoscopic resection of neoplasms with both sinonasal and skull base involvement can develop chronic rhinosinusitis (CRS) after treatment and may occasionally benefit from additional endoscopic sinus surgery (ESS). We investigate risk factors and outcomes associated with revision ESS (rESS) after endoscopic skull-base surgery (SBS) for neoplasms with combined sinonasal and skull base involvement. METHODS: A retrospective review of patients with neoplasms with both sinonasal and skull base involvement who underwent endoscopic resection at a single tertiary care academic institution from 2004 through 2017 was performed. Eighty-three patients were included. Main outcome measures included incidence and timing of revision surgery, Lund-Mackay (LM) scores, and 22-item Sino-Nasal Outcome Test (SNOT-22) scores. RESULTS: rESS was performed in 21 (25%) cases, 15 (18%) of which were due to CRS. Time between initial resection and rESS was an average of 42 months (range, 6 to 142 months). Pre-SBS and post-SBS LM scores were not significantly different (5.0 vs 4.7, p = 0.640), although pre-SBS and post-SBS SNOT-22 scores showed significant improvement (32.6 vs 24.5, p = 0.030). Malignant pathology correlated with need for rESS (odds ratio [OR] 5.07, p = 0.04), as well as treatment including chemotherapy (OR 5.10, p = 0.003) and radiation (OR 4.15, p = 0.013). CONCLUSION: A significant proportion of patients develop clinically significant sinusitis after endoscopic SBS for neoplasms with combined sinonasal and skull base involvement and may benefit from rESS. Intervention occurred, on average, 3.5 years after initial tumor resection. Malignant pathology, radiation therapy, and chemotherapy correlate with need for rESS.


Subject(s)
Paranasal Sinuses , Rhinitis , Chronic Disease , Endoscopy , Humans , Incidence , Paranasal Sinuses/diagnostic imaging , Paranasal Sinuses/surgery , Retrospective Studies , Rhinitis/epidemiology , Rhinitis/surgery , Risk Factors , Skull Base/diagnostic imaging , Skull Base/surgery , Treatment Outcome
18.
Int Forum Allergy Rhinol ; 10(2): 265-270, 2020 02.
Article in English | MEDLINE | ID: mdl-32086998

ABSTRACT

BACKGROUND: Ketotifen is a second-generation noncompetitive H1-antihistamine and mast-cell stabilizer. It is commonly used to treat or prevent allergic conjunctivitis, asthma, chronic urticaria, anaphylaxis, mast-cell, and other allergic-type disorders. However, it has never been studied in aspirin-exacerbated respiratory disease (AERD), an aggressive phenotype of chronic rhinosinusitis with nasal polyps, where the mast cell plays a prominent role its pathogenesis. METHODS: Human sinonasal epithelial cells were grown at an air-liquid interface (ALI). Ketotifen powder was dissolved in saline to make 4 test solutions at 1.04, 2.08, 10.4, and 20.8 µg/mL. Control (saline) or ketotifen solution was added apically to ALI cultures from tissue of 5 unique patients, and ciliary beat frequency (CBF) changes were recorded. Lactate dehydrogenase was measured at 24 and 48 hours to estimate long-term cellular toxicity. RESULTS: Apical application of ketotifen at all concentrations was neither ciliotoxic nor ciliostimulatory, with no change in CBF over a period of 15 minutes after application. Cellular toxicity for all concentrations at 24 and 48 hours after application was <3% and <7%, respectively, that of lysed cultures. CONCLUSION: Topical application of ketotifen to an in vitro model of sinonasal epithelium is safe, as evaluated by CBF and lactate dehydrogenase. Ketotifen is neither ciliotoxic nor ciliostimulatory, and no long-term cellular toxicity was observed. Ketotifen may have promise as a topical nasal rinse in the treatment of AERD.


Subject(s)
Anti-Allergic Agents/pharmacology , Histamine H1 Antagonists/pharmacology , Ketotifen/pharmacology , Administration, Topical , Cells, Cultured , Cilia/drug effects , Cilia/physiology , Epithelial Cells/drug effects , Epithelial Cells/physiology , Humans , L-Lactate Dehydrogenase/metabolism , Therapeutic Irrigation
19.
J Vitreoretin Dis ; 4(2): 125-135, 2020 Mar 01.
Article in English | MEDLINE | ID: mdl-34308094

ABSTRACT

PURPOSE: Nonproliferative (NPDR) and proliferative diabetic retinopathy (PDR) without diabetic macular edema (DME) affect millions of individuals living with diabetes throughout the world. There is increasing data on various management strategies for such patients, but there is limited consensus on how the data should be adopted into clinical practice. METHODS: This literature review and editorial presents and synthesizes the current evidence for various management paradigms for NPDR and PDR without DME. RESULTS: Retina specialists are an integral member of the diabetes management team, and should encourage patients on the importance of glycemic and cardiovascular optimization for both systemic and retinopathy risk factor reduction. The diabetic retinopathy severity scale (DRSS) is now an approvable endpoint for clinical trials in the United States, therefore becoming more clinically relevant. For PDR without DME, the Diabetic Retinopathy Study (DRS) and the Early Treatment Diabetic Retinopathy Study (ETDRS) established the standard of care with panretinal photocoagulation (PRP). Laser parameters have since evolved to include less intense and earlier intervention. Studies have recently demonstrated that anti-vascular endothelial growth factor (VEGF) treatment of PDR is effective at regressing neovascularization and improving DRSS levels in many patients. Further evidence is required to determine optimal treatment frequency, duration, and retreatment criteria, in the real world. There are concerns for adverse events in patients being lost to follow up during anti-VEGF treatment. For NPDR without DME, the standard of care has been a wait-and-watch approach. Data within the DRS and the ETDRS suggest that PRP for severe NPDR can be an option for select patients as well. Multiple clinical trials have now demonstrated that anti-VEGF treatment can improve the DRSS score in NPDR. Further studies are required to assess whether this positively affects long-term visual outcomes, and whether the benefits outweigh the risks in the real world for routine use. CONCLUSIONS: There is cumulative evidence demonstrating the efficacy of various treatment options for NPDR and PDR without DME. Currently, patients would most likely benefit from thoughtful management strategies that are tailored to the individual patient.

20.
Int Forum Allergy Rhinol ; 9(9): 1046-1053, 2019 09.
Article in English | MEDLINE | ID: mdl-31314958

ABSTRACT

BACKGROUND: Primary sinonasal mucoepidermoid carcinoma (SN-MEC) is a malignancy arising from seromucinous glands of the nasal cavity and paranasal sinuses. Given its rarity, few large-scale studies have been performed. In this study we describe the incidence and determinants of survival of patients with SN-MEC leveraging the National Cancer Database (NCDB). METHODS: This was a retrospective, population-based cohort study of patients diagnosed with SN-MEC between 2004 and 2012 within the NCDB. The main outcome measure was overall survival (OS). RESULTS: A total of 164 patients were identified. The cohort was composed of 47.6% males. Mean age at diagnosis was 59.7 years. The maxillary sinus was the most common primary site, accounting for 45.7% of cases. Eleven percent of patients presented with nodal disease, whereas 2.1% had distant metastases. Stage IV disease was seen in 30.4% of cases. A total of 79.8% of the patients underwent surgery, 61.0% received radiation therapy, and 15.1% had chemotherapy. OS at 1, 2, and 5 years was 83%, 77.0%, and 57%, respectively. On multivariate analysis, Medicaid insurance status (hazard ratio [HR], 7.29; 95% confidence interval [CI], 1.74-30.57), advanced tumor size (HR, 4.94; 95% CI, 1.19-20.5), and advanced nodal disease (N1: HR, 9.48; 95% CI, 1.66-54.23; N2B: HR, 19.3; 95% CI, 1.07-350.64) were associated with worse OS. CONCLUSION: Mucoepidermoid carcinoma is the most common salivary gland malignancy but a rare sinonasal malignancy, with 5-year survival for SN-MEC approximating 50%. A significant proportion of patients present with advanced disease. Both socioeconomic factors and tumor characteristics are associated with survival.


Subject(s)
Carcinoma, Mucoepidermoid/epidemiology , Paranasal Sinus Neoplasms/epidemiology , Population Groups , Adult , Aged , Carcinoma, Mucoepidermoid/diagnosis , Carcinoma, Mucoepidermoid/mortality , Cohort Studies , Databases, Factual , Female , Humans , Incidence , Male , Middle Aged , Neoplasm Staging , Paranasal Sinus Neoplasms/diagnosis , Paranasal Sinus Neoplasms/mortality , Paranasal Sinuses , Prognosis , Retrospective Studies , Risk Factors , Survival Analysis
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