Adaptation and validation of a TB stigma scale for adolescents in Lima, Peru.

BACKGROUND: TB-related stigma contributes to poor clinical outcomes and reduced wellbeing for affected individuals. Adolescents may be particularly susceptible to TB-related stigma due to their heightened sensitivity to peer acceptance, yet few studies have evaluated TB-related stigma in this group. Without a validated scale, it remains challenging to measure TB-related stigma in adolescents.METHODS: We adapted and validated the Van Rie TB Stigma Scale (VTSS) for adolescents on treatment for rifampicin-susceptible TB in Lima, Peru. The modified stigma scale was administered within a larger survey, which measured other psychosocial factors, including depression, adverse childhood experiences (ACEs), and social support. Data analysis included factor analysis, internal consistency, and convergent validity.RESULTS: From October 2020 to September 2021, 249 adolescents (individuals aged 10-19 years) completed the survey. Preliminary confirmatory factor analysis led to removal of two items. The final 10-item scale demonstrated good internal consistency (Cronbach's α = 0.82) and adequate model fit (χ²/df = 2.0; root mean square error of approximation: 0.06; comparative fit index: 0.94; Tucker-Lewis Index: 0.92: standardized root mean square residual: 0.05). Stigma was positively correlated with ACEs (γ = 0.13), depression (γ = 0.39), and suicidal ideation (γ = 0.27), and negatively correlated with social support (γ = -0.19).CONCLUSION: This adolescent TB stigma scale may serve as a practical tool to measure TB-related stigma and evaluate the impact of stigma-reduction interventions in adolescents.

Exploring the successful experience of time-restricted eating in overweight adults: A qualitative study.

Time-restricted eating (TRE) has gained popularity in recent years as a weight loss option. Although many studies have explored the effectiveness of fasting, few have investigated the successful implementation of this method. Therefore, the purpose of this study is to examine the successful and failed experiences of overweight adults who have implemented TRE for weight loss, in order to identify strategies for maintaining a favorable weight over time. The study utilized semi-structured interviews and followed Constructivist Grounded Theory to collect and analyze data. Data saturation was achieved through purposive and theoretical sampling of 30 overweight adults. The research confirms four stages in the process of weight loss using a TRE strategy, namely, preparation, adaptation, challenge, and maintenance. The findings revealed that the successful implementation of TRE and its maintenance over time require viewing TRE as a lifestyle rather than a tool for short-term weight loss, the development of specific action plans to overcome obstacles, and a positive attitude and self-belief as important sources of support. Based on the study's results, a guide has been provided for those who wish to use TRE as a dietary control method.

Clinical standards for drug-susceptible TB in children and adolescents.

BACKGROUND: These clinical standards aim to provide guidance for diagnosis, treatment, and management of drug-susceptible TB in children and adolescents.METHODS: Fifty-two global experts in paediatric TB participated in a Delphi consensus process. After eight rounds of revisions, 51/52 (98%) participants endorsed the final document.RESULTS: Eight standards were identified: Standard 1, Age and developmental stage are critical considerations in the assessment and management of TB; Standard 2, Children and adolescents with symptoms and signs of TB disease should undergo prompt evaluation, and diagnosis and treatment initiation should not depend on microbiological confirmation; Standard 3, Treatment initiation is particularly urgent in children and adolescents with presumptive TB meningitis and disseminated (miliary) TB; Standard 4, Children and adolescents should be treated with an appropriate weight-based regimen; Standard 5, Treating TB infection (TBI) is important to prevent disease; Standard 6, Children and adolescents should receive home-based/community-based treatment support whenever possible; Standard 7, Children, adolescents, and their families should be provided age-appropriate support to optimise engagement in care and clinical outcomes; and Standard 8, Case reporting and contact tracing should be conducted for each child and adolescent.CONCLUSION: These consensus-based clinical standards, which should be adapted to local contexts, will improve the care of children and adolescents affected by TB.

Growth, phase transition, and island motion of Au on Ge(111).

Using low energy electron microscopy, Au on Ge(111) is determined to follow a Stranski-Krastanov growth mode consisting of a single layer up to one monolayer (ML), followed by three-dimensional Au-Ge alloy droplets. Near 600 °C, we report the first observation of a reversible first-order phase transition that occurs from the (3 × 3)R30° phase to a (1 × 1) phase, which has a coverage of 0.367 ML. The transition gradually occurs through a coexistence region with a temperature range of about 2 °C and weakly depends on coverage, varying from 640 °C at 1 ML down to 580 °C at 0.8 ML. The phase transition is accompanied by phase fluctuations of small domains or the fluctuations of phase boundaries of large domains. At coverage >1 ML and above 250 °C, the 3D droplets move with stick-slip hopping behavior that has previously been explained by dissolution of Ge at step edges into the alloy droplet, which then comes to concentration and thermal equilibrium via the island motion.

Assessment of the efficacy of intra-articular platelet rich plasma treatment in an ACLT experimental model by dynamic contrast enhancement MRI of knee subchondral bone marrow and MRI T2∗ measurement of articular cartilage.

OBJECTIVE: The vascularization of subchondral bone plays a significant role in the progression of knee osteoarthritis (OA). Treatment with platelet-rich plasma (PRP) has positive effects on cartilage lesions. However, PRP's efficacy for subchondral bone marrow lesions and the relationship of these lesions to cartilage are still undiscovered. Therefore, our aims were first to longitudinally investigate the change in subchondral flow by dynamic contrast enhanced MRI and degeneration of cartilage by MRI T2∗ in an anterior cruciate transection rodent (ACLT) model, and second to examine changes in parameters after intra-articular PRP injection. DESIGN: A 32-week investigation in 18 rats allocated to sham-control, ACLT with normal saline injection (ACLT + NS), and ACLT with PRP injection groups ended with histological evaluation. Another rat was used as a donor of allogenic PRP. RESULTS: Compared to the sham-control group, the ACLT + NS group had higher subchondral blood volume A (0.051, 95% confidence interval: 0.009, 0.092) and lower venous washout kel (-0.030: -0.055, -0.005) from week 4; lower permeability kep from week 18 (-0.954: -1.339, -0.569); higher cartilage T2∗ values (1.803: 1.504, 2.102) reflecting collagen loss beginning at week 10. For the PRP treatment group, subchondral bone marrow A and cartilage T2∗ decreased from week 10. Histological results confirmed and were correlated with the MRI findings. CONCLUSION: Subchondral hyper-perfusion plays a vital role in the pathogenesis of OA and was associated with cartilage degeneration. The efficacy of PRP can be observed from reduced perfusion and MRI T2∗ values.

Uncovering reasons for treatment initiation delays among children with TB in Lima, Peru.

BACKGROUND: Timely diagnosis and treatment of pediatric tuberculosis (TB) is critical to reducing mortality but remains challenging in the absence of adequate diagnostic tools. Even once a TB diagnosis is made, delays in treatment initiation are common, but for reasons that are not well understood.METHODS: To examine reasons for delay post-diagnosis, we conducted semi-structured interviews with Ministry of Health (MoH) physicians and field workers affiliated with a pediatric TB diagnostic study, and caregivers of children aged 0-14 years who were diagnosed with pulmonary TB in Lima, Peru. Interviews were analyzed using systematic comparative and descriptive content analysis.RESULTS: We interviewed five physicians, five field workers and 26 caregivers with children who initiated TB treatment < 7 days after diagnosis (n = 15) or who experienced a delay of ≥7 days (n = 11). Median time in delay from diagnosis to treatment initiation was 26 days (range 7-117). Reasons for delay included: health systems challenges (administrative hurdles, medication stock, clinic hours), burden of care on families and caregiver perceptions of disease severity.CONCLUSION: Reasons for delay in treatment initiation are complex. Interventions to streamline administrative processes and tools to identify and support families at risk for delays in treatment initiation are urgently needed.

Antioxidant defense mechanisms and its dysfunctional regulation in the mitochondrial disease, Friedreich's ataxia.

Redox stress is associated with the pathogenesis of a wide variety of disease states. This can be amplified potentially through redox active iron deposits in oxidatively active organelles such as the mitochondrion. There are a number of disease states, including Friedreich's ataxia (FA) and sideroblastic anemia, where iron metabolism is dysregulated and leads to mitochondrial iron accumulation. Considering FA, which is due to the decreased expression of the mitochondrial protein, frataxin, this iron accumulation does not occur within protective storage proteins such as mitochondrial ferritin. Instead, it forms unbound biomineral aggregates composed of high spin iron(III), phosphorous and sulfur, which probably contributes to the observed redox stress. There is also a dysregulated response to the ensuing redox assault, as the master regulator of oxidative stress, nuclear factor erythroid 2-related factor-2 (Nrf2), demonstrates marked down-regulation. The dysfunctional response of Nrf2 in FA is due to multiple mechanisms including: (1) up-regulation of Keap1 that is involved in Nrf2 degradation; (2) activation of the nuclear Nrf2 export/degradation machinery via glycogen synthase kinase-3ß (Gsk3ß) signaling; and (3) inhibited nuclear translocation of Nrf2. More recently, increased microRNA (miRNA) 144 expression has been demonstrated to down-regulate Nrf2 in several disease states, including an animal model of FA. Other miRNAs have also demonstrated to be dysregulated upon frataxin depletion in vivo in humans and animal models of FA. Collectively, frataxin depletion results in multiple, complex responses that lead to detrimental redox effects that could contribute to the mechanisms involved in the pathogenesis of FA.

Treatment of dilated cardiomyopathy in a mouse model of Friedreich's ataxia using N-acetylcysteine and identification of alterations in microRNA expression that could be involved in its pathogenesis.

Deficient expression of the mitochondrial protein, frataxin, leads to a deadly cardiomyopathy. Our laboratory reported the master regulator of oxidative stress, nuclear factor erythroid 2-related factor-2 (Nrf2), demonstrates marked down-regulation after frataxin deletion in the heart. This was due, in part, to a pronounced increase in Keap1. To assess if this can be therapeutically targeted, cells were incubated with N-acetylcysteine (NAC), or buthionine sulfoximine (BSO), which increases or decreases glutathione (GSH), respectively, or the NRF2-inducer, sulforaphane (SFN). While SFN significantly (p < 0.05) induced NRF2, KEAP1 and BACH1, NAC attenuated SFN-induced NRF2, KEAP1 and BACH1. The down-regulation of KEAP1 by NAC was of interest, as Keap1 is markedly increased in the MCK conditional frataxin knockout (MCK KO) mouse model and this could lead to the decreased Nrf2 levels. Considering this, MCK KO mice were treated with i.p. NAC (500- or 1500-mg/kg, 5 days/week for 5-weeks) and demonstrated slightly less (p > 0.05) body weight loss versus the vehicle-treated KO. However, NAC did not rescue the cardiomyopathy. To additionally examine the dys-regulation of Nrf2 upon frataxin deletion, studies assessed the role of microRNA (miRNA) in this process. In MCK KO mice, miR-144 was up-regulated, which down-regulates Nrf2. Furthermore, miRNA screening in MCK KO mice demonstrated 23 miRNAs from 756 screened were significantly (p < 0.05) altered in KOs versus WT littermates. Of these, miR-21*, miR-34c*, and miR-200c, demonstrated marked alterations, with functional clustering analysis showing they regulate genes linked to cardiac hypertrophy, cardiomyopathy, and oxidative stress, respectively.

Performance of a household tuberculosis exposure survey among children in a Latin American setting.

OBJECTIVE: To evaluate the performance of a survey that quantifies the intensity of household tuberculosis (TB) exposure among children.METHODS: Children aged 0-14 years in Lima, Peru, with ≥1 signs and/or symptoms of TB and a history of contact with an adult TB patient were included. The 10-question survey was administered to caregivers and addressed sleep proximity, frequency of exposure, and infectiousness of the contact. Infection status was determined using tuberculin skin tests (TSTs). The exposure scale was evaluated for association with TST positivity using mixed-effects regression analyses.RESULTS: The exposure score was significantly associated with TST positivity (age-adjusted odds ratio [aOR] 1.14, 95%CI 1.02-1.28). We observed a stronger association with TST positivity in children aged ≤5 years; (aOR 1.23, 95%CI 1.07-1.41) and no association in children 6-14 years of age (aOR 0.99, 95%CI 0.82-1.20).CONCLUSION: This survey was easy to use and modestly successful in predicting TST positivity in children aged ≤5 years. It may be a useful resource for clinicians for diagnosing TB in children, and for national TB programs aiming to scale up preventive therapy initiatives.

Change in symptom clusters in head and neck cancer patients undergoing postoperative radiotherapy: A longitudinal study.

PURPOSE: Research on symptom clusters is a newly emerging field in oncology; however, little evidence regarding symptom clusters in head and neck cancer (HNC) is currently available. To clarify this under-researched area, we investigated symptom clusters among patients with HNC treated with surgery and postoperative radiotherapy. We also examined the pattern of symptom clusters throughout the treatment course. METHOD: A convenience sample of 100 patients with HNC was recruited in the Ear, Nose, and Throat unit of a medical center in Taiwan. Before undergoing postoperative radiotherapy, patients were asked to complete the MD Anderson Symptom Inventory and a demographic sheet. Patients completed the same inventory questionnaire at week 1, 2, 3, 4, 5, and 6 of radiotherapy. RESULT: Two symptom clusters were observed, and they were stable throughout the course of radiotherapy. Cluster 1, the HNC-specific cluster, comprised the symptoms of pain, dry mouth, lack of appetite, sleep disturbance, fatigue, drowsiness, distress, and sadness. Cluster 2, the gastrointestinal cluster, included nausea, vomiting, numbness, shortness of breath, and difficulty remembering. CONCLUSION: This study advanced our knowledge of symptom clusters in patients with HNC. The results are expected to contribute to the development of appropriate assessment and nursing interventions targeting multiple symptoms that may coexist in postoperative radiotherapy.

Growth kinetics of Kr nano structures encapsulated by graphene.

Graphene can acquire salient properties by the intercalated nano structures, and to functionalize the graphene as designed, understanding the growth kinetics of the nano structures is a prerequisite. In that regards, Kr atoms are selectively intercalated just below the surface graphene of C(0001) by the incidence of low energy Kr ions. The growth kinetics of the encapsulated Kr nano structures is investigated by both scanning tunneling microscopy and molecular dynamics simulations. The intercalation proceeds via defect sites, such as surface vacancies. At room temperature, the thermal diffusion of intercalated Kr is almost frustrated by the strain field of the encapsulating graphene layers, and the growth of Kr nano structures proceeds via the transient mobility of both the intercalating Kr atoms and previously intercalated Kr atoms that are mobilized by collision with the incident Kr ions. At the elevated temperatures where thermal diffusion becomes effective, some Kr nano structures disappear, releasing pressurized Kr atoms, while others coalesce to form blisters via the delamination of the adjacent graphene. Some of the larger blisters explode to leave craters of varying depths at the surface. In contrast to growth on the substrate, the growth of each encapsulated nano structure depends significantly on extrinsic variables, such as surface vacancies and local topography around the nano structure, that affect the Kr diffusion and limit the maximal Kr pressure.

Monomeric M2e antigen in VesiVax® liposomes stimulates protection against type a strains of influenza comparable to liposomes with multimeric forms of M2e.

Given the interest in the ectodomain of the matrix 2 (M2e) channel protein as a target for development of a universal influenza vaccine, we examined the role of the antigen configuration of M2e in generating a protective immune response. A series of M2e mutations and a truncated M2e segment were prepared as a means of controlling the formation of monomer, dimer, and higher order multimeric forms of M2e. Each of these M2e peptides was incorporated into a liposome-based vaccine technology platform previously shown to stimulate a protective response to influenza A infection using M2e as a mixture of monomers, dimers and multimers (L-M2e1-HD/MPL). Our results using these modified forms of M2e produced 90-100% survival following lethal challenge with H1N1 (A/PR/8/34) in both inbred BALB/c and outbred Swiss Webster mice vaccinated with a truncated monomeric form of the M2 protein, M2e1-15 in liposomes. These observations show that a tetrameric configuration is not required to elicit significant protection when the M2e antigen is formulated in immunogenic liposomes and further, that the first 15 amino acids of M2e likely play a primary role in providing the protective immune response.

Growth and motion of liquid alloy droplets of Au on Ge(110).

The growth of low-dimensional nanostructures of Au on Ge(110) and their temperature-induced motion were observed with Low Energy Electron Microscopy (LEEM). Ge(110) was dosed with 0.5-4 ML of Au and heated to 850°C. Above 500°C, liquid AuGe eutectic alloy islands grew on the surface. Islands were 0.3-3.0µm in width, 1-10µm in length, and elongated in the [11¯0] direction. Above 600°C, islands began moving with speeds of 0.1-1.0µm/s, absorbing smaller stationary islands upon collision and increasing in size to more than 100µm in width. A temperature gradient of ∼0.017°C/µm across the sample results in a gradient in the Ge concentration across the islands, inducing their movement in the direction of increasing temperature. Optical microscopy confirmed that the large islands moved from the cooler edges of the sample towards its hotter center. The mechanism for motion of the droplets is discussed, and the island velocities fit well to a model for diffusion-driven motion of the liquid droplet. When the temperature was subsequently lowered, islands became supersaturated with Ge, which crystallized on the island edges.

Barriers to the treatment of childhood tuberculous infection and tuberculosis disease: a qualitative study.

SETTING: In 2012, Peru's National TB Program (NTP) reported approximately 2400 incident cases of tuberculosis (TB) disease in children aged <15 years. Peru's TB burden is concentrated in the Lima metropolitan area, particularly in poor districts such as El Agustino and La Victoria, where this study was conducted. OBJECTIVE: To identify barriers to the treatment of childhood tuberculous infection and TB disease in Lima from the perspective of front-line providers and patients' families. DESIGN: We conducted 10 semi-structured focus groups with 53 purposefully sampled primary care providers, community health workers, and parents/guardians of pediatric TB patients. We also completed nine in-depth interviews with National TB Program administrators and pulmonologists specializing in TB. Two authors performed inductive thematic analysis and identified emerging themes. RESULTS: Four main treatment barriers emerged from the data: 1) dosing errors, 2) time- and labor-intensive preparation and administration of medications, 3) provider concern that isoniazid preventive therapy (IPT) generates isoniazid resistance, and 4) poor adherence to IPT. CONCLUSION: Our findings highlight the urgent need for child-friendly formulations, provider and parent/guardian education about IPT, and strategies to promote adherence to IPT, including support and supervision by health workers and/or regimens with fewer doses.

Cartilage MRI T2∗ relaxation time and perfusion changes of the knee in a 5/6 nephrectomy rat model of chronic kidney disease.

OBJECTIVE: Chronic kidney disease (CKD) is characterized by metabolic disturbances in calcium and phosphorus homeostasis as kidney function declines. Alterations in blood perfusion in bone resulting from arteriosclerosis of bone vessels may relate to the progression of CKD. Herein, change in dynamic contrast enhanced (DCE) MRI parameters (A: amplitude, kel: elimination constant, and kep: permeability rate constant) and MRI T2∗ relaxation time of the knee cartilage were measured in a rodent nephrectomy model in order to (1) examine the relationship of peripheral blood perfusion to CKD and (2) demonstrate the feasibility of using DCE-MRI parameters and MRI T2∗ as imaging biomarkers to monitor disease progression. DESIGN: Two groups of male Sprague-Dawley rats received either (1) no intervention or (2) 5/6 nephrectomy. RESULTS: We found that the CKD group (compared with the control group) had lower A and kel values and similar kep value in the lateral and medial articular cartilages beginning at 12 weeks (P < 0.05); statistically significantly higher T2∗ values in the lateral and medial articular cartilages beginning at 18 weeks (P < 0.05); statistically significantly decreased inner luminal diameter of the popliteal artery, and altered structure of the lateral and medial articular cartilages (P < 0.05). CONCLUSION: Perfusion deficiency and CKD may be related. DCE parameters and MRI T2∗ could serve as imaging biomarkers of cartilage degeneration in CKD progression.

PARTIAL OCULOCUTANEOUS ALBINISM AND IMMUNODEFICIENCY SYNDROMES: TEN YEARS EXPERIENCE FROM A SINGLE CENTER IN TURKEY.

BACKGROUND AND AIM: Partial oculocutaneous albinism and immunodeficiency (OCA-ID) diseases are autosomal recessive syndromes characterized by partial hypopigmentation and recurrent infections. Moreover, some OCA-ID syndromes confer susceptibility to develop a life-threatening hyperinflammatory condition called hemophagocytic lymphohistiocytosis (HLH). We investigated the genetic, clinical and immunological characteristics of 20 OCA patients. MATERIAL AND METHODS: Herein, we present the clinical and immunological characteristics of 20 OCA patients who referred to the Department of Pediatric Immunology, Erciyes University Medical Faculty in Kayseri, Turkey between 2004 and 2014. RESULTS: Of the 20 OCA patients, 7 fulfilled diagnostic criteria for HLH, 9 showed defective functions of CD8 T cells and natural killer cells, and 8 received a definitive molecular diagnosis. Among the patients, we also report a patient diagnosed with two different genetic defects, in TYR and JAK3 genes, causing, respectively, OCA and ID. CONCLUSION: Our results illustrate the variability of clinical presentations and disease severity in OCA-ID patients, with consequent challenges in diagnosing and treating these patients.