Digital depression screening in HIV primary care in South Africa: mood in retroviral + application monitoring [MIR + IAM].

BACKGROUND: Integrating mental health care into HIV services is critical to addressing the high unmet treatment needs for people living with HIV and comorbid major depressive disorder. Introducing routine mental health screening at the primary health care level is a much needed diagonal approach to enhancing HIV care. In low-resource settings with a shortage of mental health care providers, eMental Health may provide a novel opportunity to attenuate this treatment gap and strengthen the health system. OBJECTIVE: To conduct formative health systems research on the implementation of routine depression screening using a digital tool - Mood in Retroviral Positive Individuals Application Monitoring (MIR  +  IAM) - in an HIV primary care setting in South Africa. METHODS: A Theory of Change (ToC) approach was utilised through individual and group session interviews to design an intervention that is embedded in the local context. Ten experts and local stakeholders were selected from the UK and South Africa. Data were analysed thematically using Atlas.ti to identify interventions, assumptions, barriers and facilitators of implementation. FINDINGS: The participants considered digital depression screening in HIV care services relevant for the improvement of mental health in this population. The six main themes identified from the ToC process were: (1) user experience including acceptability by patients, issues of patient privacy and digital literacy, and the need for a patient-centred tool; (2) benefits of the digital tool for data collection and health promotion; (3) availability of treatment after diagnosis; (4) human and physical resource capacity of primary health care; (5) training for lay health care workers; and (6) demonstration of the intervention's usefulness to generate interest from decision-makers. CONCLUSION: Digital depression screening coupled with routine mental health data collection and analysis in HIV care is an applicable service that could improve the mental and physical health outcomes of this population. Careful consideration of the local health system capacity, including both workers and patients, is required. Future research to refine this intervention should focus on service users, government stakeholders and funders.

The temporal expression of estrogen receptor alpha-36 and runx2 in human bone marrow derived stromal cells during osteogenesis.

During bone maintenance in vivo, estrogen signals through estrogen receptor (ER)-α. The objectives of this study were to investigate the temporal expression of ERα36 and ascertain its functional relevance during osteogenesis in human bone marrow derived stromal cells (BMSC). This was assessed in relation to runt-related transcription factor-2 (runx2), a main modulatory protein involved in bone formation. ERα36 and runx2 subcellular localisation was assessed using immunocytochemistry, and their mRNA expression levels by real time PCR throughout the process of osteogenesis. The osteogenically induced BMSCs demonstrated a rise in ERα36 mRNA during proliferation followed by a decline in expression at day 10, which represents a change in dynamics within the culture between the proliferative stage and the differentiative stage. The mRNA expression profile of runx2 mirrored that of ERα36 and showed a degree subcellular co-localisation with ERα36. This study suggests that ERα36 is involved in the process of osteogenesis in BMSCs, which has implications in estrogen deficient environments.

Identification of new cases of early-onset colorectal cancer with an MLH1 epimutation in an ethnically diverse South African cohort.

Lynch syndrome, characterized by young-onset microsatellite unstable colorectal, endometrial and other cancers, is caused by germline mutations of the mismatch repair genes, most commonly MLH1, MSH2 and MSH6. Constitutional MLH1 epimutations, which manifest as soma-wide methylation and transcriptional silencing of a single allele, have been identified in a subset of patients with a Lynch syndrome phenotype in the absence of a mismatch repair mutation. This study aimed to determine if MLH1 epimutations predispose to the development of young-onset colorectal cancer in an ethnically diverse population of South African subjects. A total of 122 index cases with a diagnosis of colorectal cancer below 50 years of age, who had tested negative for a definitive pathogenic mutation of the key mismatch repair genes, were screened for constitutional MLH1 methylation in their leukocyte DNA. Monoallelic MLH1 epimutations were identified in two sporadic cases (1.6%): a male of black African descent and an Asian Indian female. Few alleles were affected by methylation in the female, indicating mosaicism. These cases provide further evidence of the aetiological role for MLH1 epimutations in cancer development and the requirement for sensitive molecular screening techniques to identify mosaic epimutations. Furthermore, while this mechanism is rare, it affects patients of multiple ethnic origins.

The effect of force, timing, and location on bone-to-implant contact of miniscrew implants.

This study was conducted to evaluate the effect of timing and force of loading, as well as implant location, on bone-to-implant contact (BIC) of loaded and control miniscrew implants (MSI). Using seven skeletally mature male beagle dogs, 1-2 years of age, followed over a 110 day period, a randomized split-mouth design compared immediate versus delayed loading, 50 versus 25 g loading, and 25 g loads in the maxilla versus the mandible. Mobility was evaluated using a 0-3 point scale before the MSIs were prepared for histological analysis. Histomorphometric analyses were performed under light microscopy using Metamorph software on undecalcified sections. The percentage BIC was measured at three levels (coronal, middle, and apical) of the MSI. BIC was compared statistically using pairwise Wilcoxon signed-rank tests. Mobility was detected in three of the 56 (5.4 per cent) MSIs. The mobile implants were all unloaded controls and showed no BIC. All remaining stable MSIs showed some BIC. However, variation in BIC was large, ranging from 2.2 to 100 per cent. There were no significant (P > 0.05) differences in BIC associated with timing of force application, amount of force applied, or implant location. There was a tendency for less BIC at the coronal level, but the differences between levels were not statistically significant. Within the limits of this study, it is concluded that the timing and amount of force at loading and location of implant placement do not affect BIC. Moreover, it appears that only limited amounts of osseointegration are necessary to ensure implant stability.

Tositumomab and iodine I 131 tositumomab for recurrent indolent and transformed B-cell non-Hodgkin's lymphoma.

PURPOSE: An open-label phase II study was conducted at two centers to establish the efficacy and safety of tositumomab and iodine I 131 tositumomab at first or second recurrence of indolent or transformed indolent B-cell lymphoma. PATIENTS AND METHODS: A single dosimetric dose was followed at 7 to 14 days by the patient-specific administered radioactivity required to deliver a total body dose of 0.75 Gy (reduced to 0.65 Gy for patients with platelets counts of 100 to 149 x 10(9)/L). Forty of 41 patients received both infusions. RESULTS: Thirty-one of 41 patients (76%) responded, with 20 patients (49%) achieving either a complete (CR) or unconfirmed complete remission [CR(u)] and 11 patients (27%) achieving a partial remission. Response rates were similar in both indolent (76%) and transformed disease (71%). The overall median duration of remission was 1.3 years. The median duration of remission has not yet been reached for those patients who achieved a CR or CR(u). Eleven patients continue in CR or CR(u) between 2.6+ and 5.2+ years after therapy. Therapy was well tolerated; hematologic toxicity was the principal adverse event. Grade 3 or 4 anemia, neutropenia, and thrombocytopenia were observed in 5%, 45%, and 32% of patients, respectively. Secondary myelodysplasia has occurred in one patient. Four patients developed human antimouse antibodies after therapy. Five of 38 assessable patients have developed an elevated thyroid-stimulating hormone; treatment with thyroxine has been initiated in one patient. CONCLUSION: High overall and CR rates were observed after a single dose of tositumomab and iodine I 131 tositumomab in this patient group. Toxicity was modest and easily managed.

A comparison of shear bond strengths of three visible light-cured orthodontic adhesives.

The purpose of this study was to evaluate the shear bond strength and the site of bond failure for 2 visible light-cured composites (Transbond XT and Enlight) and a resin-modified glass ionomer cement (RMGIC; Fuji Ortho LC). Seventy-five extracted human premolars were collected and randomly divided into 3 test groups. Brackets were bonded to the teeth in each test group with the respective adhesive according to the manufacturers' instructions. Each specimen was debonded using an Instron Universal Testing Machine at a crosshead speed of 0.1 mm/min. The mode of bond failure was observed by using light microscopy. The results of this study demonstrated that the light-cured composites had a higher shear bond strength than the RMGIC. The adhesive-remnant scores were similar for the composites with the mean values at about 2, which indicates that more than half of the adhesive remained on the tooth. The RMGIC had a mean score of 3, which was significantly different from the composites and indicated that all of the adhesive remained on the tooth with a distinct impression of the bracket.

Clinical auscultation skills in pediatric residents.

OBJECTIVE: The aim of this study is to determine the level of clinical auscultation skills in pediatric residents at Duke University Medical Center. METHODS: Forty-seven residents from pediatrics and joint medicine/pediatrics training programs at Duke University Medical Center were enrolled in this study. They were asked to examine the cardiovascular patient simulator, Harvey, and report their findings. Five common conditions seen in the pediatric population were presented: ventricular septal defect, atrial septal defect, pulmonary valve stenosis, combined aortic valve stenosis and insufficiency, and innocent systolic ejection murmur. The responses were scored by the number of features and diagnoses accurately reported. Five pediatric cardiologists and cardiologists in training were also asked to participate in a manner similar to the trainees. RESULTS: The mean score of features identified for the resident group was 11.4 +/- 2.6 of a possible 19. The diagnostic accuracy was 33%. There was no significant difference between residents by year of training or by type of residency program, although there was a trend toward improved performance with more training. The difference in performance between the pediatric cardiology group and the residents group was striking. The condition that was most frequently misdiagnosed was the innocent systolic ejection murmur. CONCLUSIONS: The clinical auscultation skills of pediatric residents in this study were suboptimal. There was a trend toward improvement as training progressed, although not statistically significant. These skills are likely to improve further with increased exposure to patients with cardiovascular disease especially in the ambulatory care setting.

Differentiated thyroid cancer: lobectomy and radioiodine, a treatment suitable for all cases?

When treating differentiated carcinoma of the thyroid, lobectomy is the minimum surgical requirement, but there is a strong case for ablation of the whole gland. Controversy centres on the management of the contralateral lobe, which may be ablated by total thyroidectomy, by near total thyroidectomy and ablation of thyroid fragments by 131I, or by 131I alone. Operative morbidity is increased after total thyroidectomy compared with lobectomy. However, radioactive 131I ablation of the contralateral lobe is associated with a longer period of hospitalization than if radioactive 131I is given to ablate residual fragments of thyroid tissue after total thyroidectomy. The use of lobectomy may lead to a higher incidence of patients requiring more than one administration of 131I. The evidence available indicates that radioactive 131I ablation of the contralateral lobe is a safe procedure unless tumour deposits within this lobe are large enough to be visualized on an ultrasound scan, when total thyroidectomy becomes mandatory. Clinical trials are necessary to test this hypothesis.

Does salivary gland scintigraphy predict response to pilocarpine in patients with post-radiotherapy xerostomia?

This study was undertaken to determine whether standard salivary gland scintigraphy may be used for the objective assessment of salivary gland sialogogues, in particular oral pilocarpine, in the treatment of post-radiotherapy xerostomia. Nine patients, with xerostomia following radiotherapy to the head and neck region underwent salivary gland scintigraphy with technetium-99m pertechnetate (40 MBq) both before and following 1 month of oral pilocarpine (5 mg tds). For each scan, the percentage uptake in the first 14 min, the peak uptake, time to peak uptake and the percentage of activity excreted following lemon juice stimulation were calculated. The results were correlated with the subjective response as assessed by questionnaire and visual analogue scale. We found no correlation between subjective response and any of the four scan parameters analysed. We could not identify any parameter that predicted those patients who would respond to pilocarpine. In addition, only one parameter, the percentage of activity excreted following stimulation, correlated with previous dose of radiotherapy to the gland. In conclusion, in this study salivary gland scintigraphy did not appear to correlate with or predict response to oral pilocarpine. However, future studies might consider performing salivary gland scintigraphy prior to radiotherapy as well as at differing time points following the commencement of pilocarpine.

An American Board of Orthodontics case report.

This case report describes an adult patient with a bilateral Class II malocclusion and an extremely deep overbite. The patient was treated without extraction to the standards of the American Board of Orthodontics. [This case was presented to the American Board of Orthodontics in partial fulfillment of the requirements for the certification process conducted by the Board.]

An American Board of Orthodontics case report.

A case report is presented of a skeletal Class III malocclusion with an underdeveloped maxilla, severe arch-length deficiency, and steep mandibular plane angle. [This case was presented to the American Board of Orthodontics in partial fulfillment of the requirements for the certification process conducted by the Board.

Induction of micronuclei in cultured human bronchial epithelial cells by direct-acting carcinogens.

The sensitivity of human bronchial epithelial cells to induction of micronuclei was determined in cultures derived from seven different donors. Two direct-acting carcinogens, dl-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene and N-methyl-N'-nitro-N-nitrosoguanidine were used to induce micronuclei. Both agents increased the incidence of micronuclei in a concentration-dependent fashion in cells from most donors, event at concentrations that did not produce appreciable cytotoxicity; there were considerable variations in the responses of different donors. Cytokinesis was blocked with cytochalasin B so that micronuclei were counted only in binucleate cells, thereby decreasing the total number of cells that needed to be examined and also eliminating variations due to possible differences in cell growth rates. The results demonstrate the potential usefulness of the micronucleus assay as a sensitive measure of genetic damage in human epithelial cells from the lung.

Response of primary human lung carcinomas to autocrine growth factors produced by a lung carcinoma cell line.

Medium conditioned for 48 to 72 h by A549-1 lung carcinoma cells was used to culture primary solid lung tumors on feeder layers of inactivated Swiss 3T3 cells. Of 22 cases placed into culture, primary cultures of carcinoma cells were obtained in 20. Subcultures were obtained in 18 cases, and cell lines were established in nine cases. The neoplastic origin of the cultured cells was demonstrated by several criteria: tumorigenicity in athymic mice; anchorage-independent growth; expression of altered lactate dehydrogenase isoenzyme profiles; and expression of the lung tumor marker pregnancy-specific glycoprotein 1. The epithelial nature of cultured carcinoma cells was demonstrated by expression of keratin. These characteristics were compared to normal epithelial cells established in culture from bronchial explants from the same donors as tumor tissue, or other donors. The growth-stimulating effect of conditioned medium toward primary or newly cultured tumor cells was quantitated by clonal assays in soft agar and in monolayer culture. Growth response in clonal assays of newly cultured carcinoma cells to the purified growth factors transforming growth factor alpha and insulin-like growth factor 1, two known components of medium conditioned by A549-1 cells, was also demonstrated.

Immunoscintigraphy with 99mTc labelled F(ab')2 fragments of an anti melanoma monoclonal antibody (225.28S) in patients with metastatic malignant melanoma.

Immunoscintigraphy was performed in 25 patients with malignant melanoma using a 99mTc labelled monoclonal antibody (225.28S). In four cases, imaging was repeated following treatment with recombinant gamma interferon. In 11 cases, tissue samples of metastatic lesions were investigated for the expression of melanoma associated antigens by immunohistochemical techniques. Overall, 59% of known lesions were detected by imaging. The highest rates of detection were in bone, liver and lymph nodes and the lowest in lung, stomach and bowel. Six lesions were detected which had not shown up on routine clinical and radiological examination. There was no evidence of enhanced or induced HMW-MAA expression following interferon treatment. This technique has been found to be useful in staging patients and has been free from side effects.

Phase II trial of epirubicin in gastric cancer.

Patients with advanced inoperable or recurrent adenocarcinoma of the stomach received an iv bolus of epirubicin (75 mg/m2) every 3 weeks. Partial responses were observed in four of 24 evaluable patients (17%). Treatment was generally well tolerated; a drop in left ventricular ejection fraction was observed in one patient who had received 450 mg/m2 of epirubicin.

In vivo distribution studies of radioactively labelled platinum complexes; cis-dichlorodiammine platinum(II), cis-trans-dichlorodihydroxy-bis-(isopropylamine) platinum(IV), cis-dichloro-bis-cyclopropylamine platinum(II), and cis-diammine 1,1-cyclobutanedicarboxylate platinum(II) in patients with malignant disease, using a gamma camera.

The in vivo distribution in man of the four platinum derivatives cis-dichlorodiammine platinum(II) (DDP), cis-trans-dichlorodihydroxy-bis-(isopropylamine) platinum (IV) (CHIP), cis-dichloro-bis-cyclopropylamine platinum(II) (CP), and cis-diammine 1, 1-cyclobutanedicarboxylate platinum(II) (CBDCA) has been observed. The availability of these compounds labelled with the radioactive isotope of platinum, platinum-191, has made serial in vivo imaging of their distribution possible. Injection of 17-35 MBq (5-28 mg) of the labelled compound IV was followed by imaging, using a gamma camera, with particular reference to the kidneys, liver, and tumour site. Hepatic and renal clearances were observed in all nine patients, but no unequivocal evidence of tumour uptake was found. The left kidney uptake was estimated at times up to 7 days after injection. Mathematical analysis of some of the uptake curves failed to show any significant difference between the clearance times observed. However, the two patients who received CBDCA did show a higher initial renal uptake, falling within the 1st day to levels comparable with those of the other compounds, and the three patients who received DDP showed consistently liver uptake.

An electromyographic study of the human lateral pterygoid muscles.

An electromyographic investigation of the lateral pterygoid muscles was undertaken to determine their activity relative to isolated and functional movements of the mandible. Daerally in the lateral and medial pterygoid muscles. Surface electrodes were placed bilaterally on the skin over the temporalis and masseter muscles. Our data strongly suggest that separate roles for the superior and inferior heads of the lateral pterygoid cannot be supported electromyographically. In addition, the lateral pterygoid is active in protrusive movements, including an incisor clench, and not active in retrusion or a molar clench. Both lateral pterygoid muscles initiate depression of the mandible and the contralateral muscle initiates a lateral transversion. The ipsilateral activity present is not sufficient to be an active stabilizer of the temporomandibular joint. In the chewing cycle, the lateral pterygoids are bilaterally active, both in alternation with and overlapping the elevating musculature. The sequence of the lateral pterygoid activity in the chewing cycle is led by the ipsilateral lateral pterygoid muscle.