Turbinate hypertrophy following COVID-19 infection masks choanal atresia in adult.

A 34-year-old female 4 weeks post COVID-19 infection was diagnosed with inferior turbinate hypertrophy and a deviated nasal septum. The patient underwent inferior turbinate bone resection and nasal septoplasty with minimal improvement in nasal obstruction. Upon reevaluation, unilateral choanal atresia was discovered. Subsequent repair of the choanal atresia resolved all complaints of nasal obstruction. This unique presentation of a missed diagnosis of choanal atresia contributes to the idea that a variety of conditions may precede and at times delay the discovery of choanal atresia in adults.

Targeted Disruption of the Inhibitor of DNA Binding 4 (Id4) Gene Alters Photic Entrainment of the Circadian Clock.

Inhibitor of DNA binding (Id) genes comprise a family of four helix-loop-helix (HLH) transcriptional inhibitors. Our earlier studies revealed a role for ID2 within the circadian system, contributing to input, output, and core clock function through its interaction with CLOCK and BMAL1. Here, we explore the contribution of ID4 to the circadian system using a targeted disruption of the Id4 gene. Attributes of the circadian clock were assessed by monitoring the locomotor activity of Id4-/- mice, and they revealed disturbances in its operation. Id4-mutant mice expressed a shorter circadian period length, attenuated phase shifts in responses to continuous and discrete photic cues, and an advanced phase angle of entrainment under a 12:12 light:dark cycle and under short and long photoperiods. To understand the basis for these properties, suprachiasmatic nucleus (SCN) and retinal structures were examined. Anatomical analysis reveals a smaller Id4-/- SCN in the width dimension, which is a finding consistent with its smaller brain. As a result of this feature, anterograde tracing in Id4-/- mice revealed retinal afferents innovate a disproportionally larger SCN area. The Id4-/- photic entrainment responses are unlikely to be due to an impaired function of the retinal pathways since Id4-/- retinal anatomy and function tested by pupillometry were similar to wild-type mice. Furthermore, these circadian characteristics are opposite to those exhibited by the Id2-/- mouse, suggesting an opposing influence of the ID4 protein within the circadian system; or, the absence of ID4 results in changes in the expression or activity of other members of the Id gene family. Expression analysis of the Id genes within the Id4-/- SCN revealed a time-of-day specific elevated Id1. It is plausible that the increased Id1 and/or absence of ID4 result in changes in interactions with bHLH canonical clock components or with targets upstream and/or downstream of the clock, thereby resulting in abnormal properties of the circadian clock and its entrainment.

Kasabach-Merritt-like phenomenon in a massive uterine leiomyoma presenting with chronic disseminated intravascular coagulation: A case report.

Kasabach-Merritt phenomenon is a process where the presence of vascular irregularity within a Kaposiform hemangioendothelioma or tufted angioma leads to constitutive coagulation factor activation and the development of chronic disseminated intravascular coagulation (DIC). A similar phenomenon has been seen in other tumors but has rarely been described. A 42-year-old woman presented to the hospital following the development of worsening easy bruising and bleeding. She was ultimately found to have a massive uterine fibroid that led to constitutive coagulation cascade activation and subsequent chronic DIC. Following resection, she had complete resolution of DIC and made a full recovery. Although rare, the development of unexplained chronic DIC in a woman should prompt evaluation for the presence of massive uterine fibroids.

Inhibitor of DNA binding 2 (Id2) Regulates Photic Entrainment Responses in Mice: Differential Responses of the Id2-/- Mouse Circadian System Are Dependent on Circadian Phase and on Duration and Intensity of Light.

ID2 is a rhythmically expressed helix-loop-helix transcriptional repressor, and its deletion results in abnormal properties of photoentrainment. By examining parametric and nonparametric models of entrainment, we have started to explore the mechanism underlying this circadian phenotype. Id2-/- mice were exposed to differing photoperiods, and the phase angle of entrainment under short days was delayed 2 h as compared with controls. When exposed to long durations of continuous light, enhanced entrainment responses were observed after a delay of the clock but not with phase advances. However, the magnitude of phase shifts was not different in Id2-/- mice tested in constant darkness using a discrete pulse of saturating light. No differences were observed in the speed of clock resetting when challenged by a series of discrete pulses interspaced by varying time intervals. A photic phase-response curve was constructed, although no genotypic differences were observed. Although phase shifts produced by discrete saturating light pulses at CT16 were similar, treatment with a subsaturating pulse revealed a ~2-fold increase in the magnitude of the Id2-/- shift. A corresponding elevation of light-induced per1 expression was observed in the Id2-/- suprachiasmatic nucleus (SCN). To test whether the phenotype is based on a sensitivity change at the level of the retina, pupil constriction responses were measured. No differences were observed in responses or in retinal histology, suggesting that the phenotype occurs downstream of the retina and retinal hypothalamic tract. To test whether the phenotype is due to a reduced amplitude of state variables of the clock, the expression of clock genes per1 and per2 was assessed in vivo and in SCN tissue explants. Amplitude, phase, and period length were normal in Id2-/- mice. These findings suggest that ID2 contributes to a photoregulatory mechanism at the level of the SCN central pacemaker through control of the photic induction of negative elements of the clock.

Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease.

BACKGROUND: Senescent cells, which can release factors that cause inflammation and dysfunction, the senescence-associated secretory phenotype (SASP), accumulate with ageing and at etiological sites in multiple chronic diseases. Senolytics, including the combination of Dasatinib and Quercetin (D + Q), selectively eliminate senescent cells by transiently disabling pro-survival networks that defend them against their own apoptotic environment. In the first clinical trial of senolytics, D + Q improved physical function in patients with idiopathic pulmonary fibrosis (IPF), a fatal senescence-associated disease, but to date, no peer-reviewed study has directly demonstrated that senolytics decrease senescent cells in humans. METHODS: In an open label Phase 1 pilot study, we administered 3 days of oral D 100 mg and Q 1000 mg to subjects with diabetic kidney disease (N = 9; 68·7 ±â€¯3·1 years old; 2 female; BMI:33·9 ±â€¯2·3 kg/m2; eGFR:27·0 ±â€¯2·1 mL/min/1·73m2). Adipose tissue, skin biopsies, and blood were collected before and 11 days after completing senolytic treatment. Senescent cell and macrophage/Langerhans cell markers and circulating SASP factors were assayed. FINDINGS: D + Q reduced adipose tissue senescent cell burden within 11 days, with decreases in p16INK4A-and p21CIP1-expressing cells, cells with senescence-associated ß-galactosidase activity, and adipocyte progenitors with limited replicative potential. Adipose tissue macrophages, which are attracted, anchored, and activated by senescent cells, and crown-like structures were decreased. Skin epidermal p16INK4A+ and p21CIP1+ cells were reduced, as were circulating SASP factors, including IL-1α, IL-6, and MMPs-9 and -12. INTERPRETATION: "Hit-and-run" treatment with senolytics, which in the case of D + Q have elimination half-lives <11 h, significantly decreases senescent cell burden in humans. FUND: NIH and Foundations. ClinicalTrials.gov Identifier: NCT02848131. Senescence, Frailty, and Mesenchymal Stem Cell Functionality in Chronic Kidney Disease: Effect of Senolytic Agents.

The prevalence of disrespect and abuse during facility-based childbirth in urban Tanzania.

BACKGROUND: In many countries, rates of facility-based childbirth have increased substantially in recent years. However, insufficient attention has been paid to the acceptability and quality of maternal health services provided at facilities and, consequently, maternal health outcomes have not improved as expected. Disrespect and abuse during childbirth is increasingly being recognized as an indicator of overall poor quality of care and as a key barrier to achieving improved maternal health outcomes, but little evidence exists to describe the scope and magnitude of this problem, particularly in urban areas in low-income countries. METHODS: This paper presents findings from an assessment of the prevalence of disrespectful and abusive behaviors during facility-based childbirth in one large referral hospital in Dar es Salaam, Tanzania. Client reports of disrespect and abuse (D&A) were obtained through postpartum interviews immediately before discharge from the facility with 1914 systematically sampled women and from community follow-up interviews with 64 women four to six weeks post-delivery. Additionally, 197 direct observations of the labor, delivery, and postpartum period were conducted to document specific incidences of disrespect and abuse during labor and delivery, which we compared with women's reports. RESULTS: During postpartum interviews, 15 % of women reported experiencing at least one instance of D&A. This number was dramatically higher during community follow-up interviews, in which 70 % of women reported any experience of D&A. During postpartum interviews, the most common forms of D&A reported were abandonment (8 %), non-dignified care (6 %), and physical abuse (5 %), while reporting for all categories of D&A, excluding detention and non consented care, was above 50 % during community follow-up interviews. Evidence from direct observations of client-provider interactions during labor and delivery confirmed high rates of some disrespectful and abusive behaviors. CONCLUSIONS: This study is one of the first to quantify the prevalence of disrespect and abuse during facility-based childbirth in a large public hospital in an urban setting. The difference in respondent reports between the two time periods is striking, and more research is needed to determine the most appropriate methodologies for measuring this phenomenon. The levels and types of disrespect and abuse reported here represent fundamental violations of women's human rights and are symptomatic of failing health systems. Action is urgently needed to ensure acceptable, quality, and dignified care for all women.

Applying a participatory approach to the promotion of a culture of respect during childbirth.

Disrespect and abuse (D&A) during facility-based childbirth is a topic of growing concern and attention globally. Several recent studies have sought to quantify the prevalence of D&A, however little evidence exists about effective interventions to mitigate disrespect and abuse, and promote respectful maternity care. In an accompanying article, we describe the process of selecting, implementing, and evaluating a package of interventions designed to prevent and reduce disrespect and abuse in a large urban hospital in Tanzania. Though that study was not powered to detect a definitive impact on reducing D&A, the results showed important changes in intermediate outcomes associated with this goal. In this commentary, we describe the factors that enabled this effect, especially the participatory approach we adopted to engage key stakeholders throughout the planning and implementation of the program. Based on our experience and findings, we conclude that a visible, sustained, and participatory intervention process; committed facility leadership; management support; and staff engagement throughout the project contributed to a marked change in the culture of the hospital to one that values and promotes respectful maternity care. For these changes to translate into dignified care during childbirth for all women in a sustainable fashion, institutional commitment to providing the necessary resources and staff will be needed.

Mitigating disrespect and abuse during childbirth in Tanzania: an exploratory study of the effects of two facility-based interventions in a large public hospital.

BACKGROUND: There is emerging evidence that disrespect and abuse (D&A) during facility-based childbirth is prevalent in countries throughout the world and a barrier to achieving good maternal health outcomes. However, much work remains in the identification of effective interventions to prevent and eliminate D&A during facility-based childbirth. This paper describes an exploratory study conducted in a large referral hospital in Dar es Salaam, Tanzania that sought to measure D&A, introduce a package of interventions to reduce its incidence, and evaluate their effectiveness. METHODS: After extensive consultation with critical constituencies, two discrete interventions were implemented: (1) Open Birth Days (OBD), a birth preparedness and antenatal care education program, and (2) a workshop for healthcare providers based on the Health Workers for Change curriculum. Each intervention was designed to increase knowledge of patient rights and birth preparedness; increase and improve patient-provider and provider-administrator communication; and improve women's experience and provider attitudes. The effects of the interventions were assessed using a pre-post design and a range of tools: pre-post questionnaires for OBD participants and pre-post questionnaires for workshop participants; structured interviews with healthcare providers and administrators; structured interviews with women who gave birth at the study facility; and direct observations of patient-provider interactions during labor and delivery. RESULTS: Comparisons before and after the interventions showed an increase in patient and provider knowledge of user rights across multiple dimensions, as well as women's knowledge of the labor and delivery process. Women reported feeling better prepared for delivery and provider attitudes towards them improved, with providers reporting higher levels of empathy for the women they serve and better interpersonal relationships. Patients and providers reported improved communication, which direct observations confirmed. Additionally, women reported feeling more empowered and confident during delivery. Provider job satisfaction increased substantially from baseline levels, as did user reports of satisfaction and perceptions of care quality. CONCLUSIONS: Collectively, the outcomes of this study indicate that the tested interventions have the potential to be successful in promoting outcomes that are prerequisite to reducing disrespect and abuse. However, a more rigorous evaluation is needed to determine the full impact of these interventions.

Disrespect and abuse during childbirth in Tanzania: are women living with HIV more vulnerable?

INTRODUCTION: HIV-related stigma and discrimination and disrespect and abuse during childbirth are barriers to use of essential maternal and HIV health services. Greater understanding of the relationship between HIV status and disrespect and abuse during childbirth is required to design interventions to promote women's rights and to increase uptake of and retention in health services; however, few comparative studies of women living with HIV (WLWH) and HIV-negative women exist. METHODS: Mixed methods included interviews with postpartum women (n = 2000), direct observation during childbirth (n = 208), structured questionnaires (n = 50), and in-depth interviews (n = 18) with health care providers. Bivariate and multivariate regressions analyzed associations between HIV status and disrespect and abuse, whereas questionnaires and in-depth interviews provided insight into how provider attitudes and workplace culture influence practice. RESULTS: Of the WLWH and HIV-negative women, 12.2% and 15.0% reported experiencing disrespect and abuse during childbirth (P = 0.37), respectively. In adjusted analyses, no significant differences between WLWH and HIV-negative women's experiences of different types of disrespect and abuse were identified, with the exception of WLWH having greater odds of reporting non-consented care (P = 0.03). None of the WLWH reported violations of HIV confidentiality or attributed disrespect and abuse to their HIV status. Provider interviews indicated that training and supervision focused on prevention of vertical HIV transmission had contributed to changing the institutional culture and reducing HIV-related violations. CONCLUSIONS: In general, WLWH were not more likely to report disrespect and abuse during childbirth than HIV-negative women. However, the high overall prevalence of disrespect and abuse measured indicates a serious problem. Similar institutional priority as has been given to training and supervision to reduce HIV-related discrimination during childbirth should be focused on ensuring respectful maternity care for all women.

Program ratings do not predict negative content in commercials on children's channels.

OBJECTIVE: The aim of this study was to determine the presence of negative content in commercials airing on 3 children's channels (Disney Channel, Nickelodeon, and Cartoon Network). METHOD: The 1681 commercials were coded with a reliable coding system and content comparisons were made. RESULTS: Although the majority of the commercials were coded as neutral, negative content was present in 13.5% of commercials. This rate was significantly more than the predicted value of zero and more similar to the rates cited in previous research examining content during sporting events. The rate of negative content was less than, but not significantly different from, the rate of positive content. Thus, our findings did not support our hypothesis that there would be more commercials with positive content than with negative content. Logistic regression analysis indicated that channel, and not rating, was a better predictor of the presence of overall negative content and the presence of violent behaviors. Commercials airing on the Cartoon Network had significantly more negative content, and those airing on Disney Channel had significantly less negative content than the other channels. Within the individual channels, program ratings did not relate to the presence of negative content. CONCLUSION: Parents cannot assume the content of commercials will be consistent with the program rating or label. Pediatricians and psychologists should educate parents about the potential for negative content in commercials and advocate for a commercials rating system to ensure that there is greater parity between children's programs and the corresponding commercials.

Sedation and antihistamines: an update. Review of inter-drug differences using proportional impairment ratios.

BACKGROUND: The use of antihistamines (AHs) has been associated with cognitive and psychomotor impairments, largely caused by the sedative properties of many of these drugs. Due to the ambulant nature of the population using AHs, it is important to evaluate these effects using standardised methodology and psychometric tests. A previous extensive review of the literature collated the results of studies of H(1) receptor antagonists to determine the extent to which a particular AH produced impairments on a battery of psychometric tests by calculating a proportional impairment ratio for each AH. OBJECTIVE: In light of a number of major studies published following the previous review, and the development of the second and new-generation AHs, the present review aims to add to the database and update the review, using the same methodology. RESULTS AND CONCLUSION: The newer generation AHs appear to be the least impairing, and the first generation, as expected, appear to be the most impairing. There are also differences within the AH drug generations. The review highlights the necessity to consider the sedating potential of AHs, along with other factors such as efficacy, when prescribing AHs to ambulant patients.