Design and Evaluation of Peer Supervision for Community Mental Health Workers: A Task-Shifting Strategy in Low-Resource Settings.

The use of Lay Mental Health Workers (LMHWs) to tackle the treatment gap in low-resource settings is well established, and although they often receive training, the potential of proper supervision to improve outcomes remains untapped. Indeed, given the strain on expert resources, peer-supervision models based on supervisors' seniority of work experience have significant potential especially in relation to community knowledge and embedding of LMHWs. This study summarizes the evaluation of a pilot program for peer supervision on the basis of Social Cognitive Theories of Self-Efficacy for LMHWs in Kerala, India. Two experienced LMHWs worked as supervisors for a total of 12 LMHWs over the course of a year. These participants were subsequently interviewed to analyze their experiences in order to evaluate the potential of peer supervision and distil relevant information to improve future training of LMHWs. The findings include improved performance and emotional support for the participants.

Vulnerabilities Prompting Use of Technology and Screen by Mothers of Autistic Children in India: Lived Experiences and Comparison to Scientific Literature.

Technology and screen media has its place in every home, yet the influences of the same are less known. This research aims to explore the vulnerabilities that prompt the mothers to use screen media for their children, prior to a diagnosis of autism for their child. It also aims to explore literature the influence of screen media on speech and language development in children. This study combined semi-structured interviews with 16 mothers of autistic children in Southern India and a scoping literature review that resulted in 24 articles. The literature refers to a positive influence when co-viewing with the child, and it predominantly highlights improvements in speech and not in language. The interviews revealed that screens were used as a means of support, a language and learning development tool, or as a calming technique. Thus, the study shows that the mothers resorted to screen use for their children more out of helplessness, and not as an informed choice. Mothers of autistic children clearly express their vulnerabilities and indicate feelings of being lost without advice, with regard to use of screen-time. This suggests a need for more research into how they can be supported.

Perceived coercion in persons with mental disorder in India: A cross-sectional study.

BACKGROUND: Little is known about how patients in India perceive coercion in psychiatric care. AIMS: To assess perceived coercion in persons with mental disorder admitted involuntarily and correlate with sociodemographic factors and illness variables. MATERIALS AND METHODS: We administered the short MacArthur Admission Experience Interview Questionnaire to all consecutive involuntary psychiatric patients admitted in 2014 in Mysore, India. Multivariate linear regression was used. RESULTS: Three hundred and one patients participated. "Perceived coercion" subscale scores increased with female gender, nuclear family status, Muslim and Christian religion, lower income, and depressive disorder. It decreased with former coercion, forensic history, and longer illness duration. Drug use increased total scores; the extended family item decreased them. "Negative pressure" increased with male gender, extended family, lower income, forensic history, and longer illness duration. CONCLUSIONS: The study shows perceived coercion is a reality in India. Levels of perceived coercion and the populations affected are similar to high-income countries.

Staff and caregiver attitude to coercion in India.

OBJECTIVES: The objective of this study was to assess attitudes of Indian psychiatrists and caregivers toward coercion. MATERIALS AND: Methods: The study was conducted at the Department of Psychiatry, Krishna Rajendra Hospital, Mysore, India. Staff Attitude to Coercion Scale (SACS), a 15-item questionnaire, was administered to self-selected psychiatrists across India and caregivers from Mysore to measure attitudes on coercion. Data were analyzed using descriptive statistics and investigating differences in subgroups by means of Chi-square test, Student's t-test, and analysis of variance. Reliability of the SACS was tested in this Indian sample. RESULTS: A total of 210 psychiatrists and 210 caregivers participated in the study. Both groups agreed that coercion was related to scarce resources, security concerns, and harm reduction. Both groups agreed that coercion is necessary, but not as treatment. Older caregivers and male experienced psychiatrists considered coercion related to scarce resources to violate patient integrity. All participants considered coercion necessary for protection in dangerous situations. Professionals and caregivers significantly disagreed on most items. The reliability of the SACS was reasonable to good among the psychiatrists group, but not in the caregiver group (alpha 0.58 vs. 0.07). CONCLUSION: Caregivers and psychiatrists felt that the lack of resources is one of the reasons for coercion. Furthermore, they felt that the need on early identification of aggressive behavior, interventions to reduce aggressiveness, empowering patients, improving hospital resources, staff training in verbal de-escalation techniques is essential. There is an urgent need in the standardized operating procedure in the use of coercive measure in Indian mental health setting.

Comparing the perception of community members towards leprosy and tuberculosis stigmatization.

BACKGROUND: Health professionals at all levels gradually recognise the impact of stigma on case detection and treatment of various health conditions such as leprosy and tuberculosis. These diseases are identified as chronic diseases which are prone to stigmatisation. PURPOSE: To assess the perception of community members towards stigma related to leprosy and tuberculosis, in order to verify and compare the existence of stigma towards these two diseases in the community, and to provide baseline data for the evaluation of future de-stigmatising interventions. METHODS: This study was done in four sub-districts of Chaiyaphum province. Community members were interviewed using the EMIC stigma scale. Frequency was used to identify the percentage of community members who perceived stigma. A T-test was applied to compare the mean EMIC scores of community members between leprosy and tuberculosis. A P-value of < 0.05 was considered indicative of a statistically significant difference or association. RESULTS: It was found that community members perceived that people affected by leprosy or tuberculosis were stigmatised by the community. However, community members perceived more stigma towards leprosy than towards tuberculosis, particularly in terms of shame, embarrassment, and problems in getting married. The difference was highly significant (P = 0.001, paired t-test). CONCLUSION: The community's perceived stigma against people affected by either leprosy or tuberculosis may affect many aspects of their lives. The authors recommend use of strategically targeted de-stigmatising interventions that take local attitudes and perceptions into consideration.

How to reduce stigma in leprosy--a systematic literature review.

BACKGROUND: Interventions to reduce leprosy-related stigma reduce the manifestations of stigma that cause so much suffering to individuals and their families. PURPOSE: This systematic review aims to identify interventions that have been used to reduce such stigma and to summarise what is known about their efficacy. METHOD: Electronic searches were undertaken using PubMed (Medline), CINAHL and PsycInfo databases. The internet was searched using Google Scholar for papers not published in these databases. All relevant papers written in Thai or English were included. RESULTS: After reading 55 papers, three duplications and parallel literatures were removed, 18 were removed on abstract screening and nine after reading the full papers; eventually, 25 were included in this review. Interventions with some evidence of effectiveness in terms of stigma reduction comprise the integration of leprosy programmes into general health care; Information Education and Communication (IEC) programmes; and socio-economic rehabilitation. CONCLUSION: More evaluations are needed of the effect of the integration of leprosy programmes into general health services. The design and implementation of IEC interventions need to be preceded by careful study of the target area and population and should be undertaken in combination with other activities.

NMR studies of the major coat protein of bacteriophage M13. Structural information of gVIIIp in dodecylphosphocholine micelles.

The membrane-bound form of the major coat protein (gVIIIp) of bacteriophage M13 has been studied using nuclear magnetic resonance spectroscopy. As membrane mimetics, we used dodecylphosphocholine (DodPCho) detergent micelles to solubilize the protein. We were able to nearly completely assign all resonances of the protein solubilized in DodPCho micelles by using both homonuclear and heteronuclear multidimensional experiments. Based on the patterns of the nuclear Overhauser enhancements and the chemical shifts of the resonances, we deduced the secondary structure of the protein. Additional structural information was obtained from amide proton exchange data and J-coupling constants. The protein consists of two alpha-helices which are connected by a hinge region around residue 21. From spin-label experiments, the location of the protein relative to the DodPCho micelles was determined. One, hydrophobic, helix spans the micelle, and another, amphipathic, helix, is located beneath the surface of the micelle. Comparison of the data of gVIIIp in DodPCho micelles with those of gVIIIp in sodium dodecyl sulfate (SDS) micelles [Van de Ven, F. J. M., van Os, J. W. M., Aelen, J. M. A., Wymenga, S. S., Remerowski, M. L., Konings, R. N. H. & Hilbers, C. W. (1993) Biochemistry 32, 8322-8328; Papavoine, C. H. M., Konings, R. N. H., Hilbers, C. W. & Van de Ven, F. J. M. (1994) Biochemistry 33, 12,990-12,997] reveals that the structures of the protein in the two detergent micelles are very similar. They differ only in the arrangement of the detergent molecules around the protein. For gVIIIp in SDS micelles, we found a micellar structure which is distorted near the C-terminus of the protein; whereas for DodPCho micelles, both distorted and regular elliptical micelles occur. This distortion is probably due to the interaction of the positively charged lysine side chains with the negatively charged head group of the detergent molecules.

Secondary structure of the single-stranded DNA binding protein encoded by filamentous phage Pf3 as determined by NMR.

Nuclear magnetic resonance spectroscopy was employed to study the single-stranded DNA binding protein encoded by the filamentous Pseudomonas bacteriophage Pf3. The protein is 78 amino acids long and occurs in solution predominantly as a homodimer with a molecular mass of 18 kDa. Sequence-specific 1H and 15N resonance assignments have been obtained using homo- and heteronuclear two- and three-dimensional experiments. The secondary structure of the protein monomer was determined from a qualitative interpretation of nuclear Overhauser enhancement spectra and amide exchange data. It consists of a five-stranded antiparallel beta-sheet and three beta-hairpins. Problems caused by the protein's tendency to aggregate at concentrations needed for NMR spectroscopy were largely overcome by designing a mutant (Phe36-->His) which exhibits significantly improved solubility characteristics over the wild-type protein. It is shown that this mutation only locally affects the structure of the protein; the chemical shifts of the wild-type and mutant species differ only for a few residues near the site of the mutation, and the secondary structures of the proteins are identical. The secondary structure of the Pf3 single-stranded DNA binding protein is compared to that of the Ff gene V protein, the only single-stranded DNA binding protein for which the complete three-dimensional structure is known to date [Folkers, P. J. M., Nilges, M., Folmer, R. H. A., Konings, R. N. H. & Hilbers, C. W. (1994) J. Mol. Biol. 236, 229-246; Skinner, M. M., Zhang, H., Leschnitzer, D. H., Guan, Y., Bellamy, H., Sweet, R. M., Gray, C. W., Konings, R. N. H., Wang, A. H.-J. & Terwilliger, T. C. (1994) Proc. Natl Acad. Sci. USA 91, 2071-2075]. It is found that the secondary structures of the two proteins are very similar which supports the hypothesis that a five-stranded antiparallel beta-sheet with protruding beta-hairpins is a common motif in a certain class of single-stranded DNA binding proteins. In addition, the sequence and folding predicted earlier for the DNA binding wing in the single-stranded DNA binding protein of phage Pf3 [de Jong, E. A. M., van Duynhoven, J. P. M., Harmsen, B. J. M., Tesser, G. I., Konings, R. N. H. & Hilbers, C. W. (1989) J. Mol. Biol. 206, 133-156] is borne out by the present study. It closely resembles that in the single-stranded DNA binding protein of phage Ff, which may indicate that such a wing is a recurrent motif as well.

L-DNAs as potential antimessenger oligonucleotides: a reassessment.

Unnatural L-2'-deoxyribonucleosides L-T, L-dC, L-dA and L-dG were prepared from L-arabinose and assembled, by solution or solid phase synthesis, to give L-oligonucleotides (L-DNAs), which contain all four natural bases. The affinity of these modified oligomers for complementary D-ribo- and D-deoxyribo-oligomers was studied with NMR, UV and CD spectroscopies and mobility shift assay on native PAGE. All experimental results indicate that L-DNAs do not, in general, recognize single-stranded, natural DNA and RNA. Hence, contrary to previous suggestions, it is not possible to envisage their use as wide scope antimessenger agents in the selective control of gene expression.

Assignment of 1H, 15N, and backbone 13C resonances in detergent-solubilized M13 coat protein via multinuclear multidimensional NMR: a model for the coat protein monomer.

The major coat protein (gVIIIp) of bacteriophage M13 complexed with SDS detergent micelles was used as a model system to study the lipid-bound conformation of the protein. Conditions were found that allowed the recording of good quality of NMR spectra. By making extensive use of three-dimensional heteronuclear (13C, 15N) NMR, we obtained a complete set of resonance assignments for 1HN, 1H alpha, 1H beta, 13C alpha, CO, and 15N and partially assigned the rest of the 1H spectrum. Analysis of NOE and chemical shift data reveals that gVIIIp is composed of two alpha-helical domains, one ranging from Pro-6 to Glu20 and the other ranging from Tyr-24 all the way to the C-terminus Ser-50. In contrast to the results reported by Henry and Sykes [Henry, G.D., & Sykes, B.D. (1992) Biochemistry 31, 5285-5297], at a high SDS to protein ratio the protein appears to be monomeric.

Effects of base sequence on the loop folding in DNA hairpins.

High-resolution NMR and UV-melting experiments have been used to study the hairpin formation of partly self-complementary DNA fragments in an attempt to derive rules that describe the folding in these molecules. Earlier experiments on the hexadecanucleotide d(ATCCTA-TTTT-TAGGAT) had indicated that within the loop of four thymidines a wobble T-T pair is formed (Blommers et al., 1987). In the present paper it is shown that if the first and the last thymines of the intervening sequence are replaced by complementary bases, sometimes base pairs can be formed. Thus for the intervening sequences -CTTG- and -TTTA- with the pyrimidine in the 5'-position and the purine in the 3'-position, a base pair is formed leading to a loop consisting of two residues. For the intervening sequences -GTTC- and -ATTT- with the purine in the 5'-position and the pyrimidine in the 3'-position, this turns out not to be the case. It was found that it made no difference when the four-membered sequence was closed by a G-C base pair or an A-T base pair. Replacement of the two central thymidine residues by the more bulky adenine residues limits the hairpin to a four-membered loop scheme. Very surprisingly, it was found from 2D NOE experiments that the T-A base pair, formed in the loop consisting of the -TTTA- sequence, is a Hoogsteen pair. It is argued that the pairing of the bases in this scheme may facilitate the formation of a loop of two residues, since the distance of the C1' atoms in this base pair is 8.6 A instead of 10.4 A found in the canonical Watson-Crick base pair. Combination of the data obtained for the series of DNA fragments studied shows that the results can be explained by a simple, earlier proposed, loop folding principle which assumes that the folding of the four-membered loop is dictated by the stacking of the double-helical stem of the hairpin.

Newly-initiated DNA isolated from Physarum in early S phase consists of nascent-nascent duplexes.

We have studied the nature of newly initiated DNA released during DNA isolation at the beginning of S phase of Physarum polycephalum. The released DNA was separated from the bulk DNA by sedimentation through sucrose gradients. Gentle shearing strongly enhanced the release of newly initiated DNA. The additionally released material had a larger average molecular weight. Buoyant density analysis after labelling with bromodeoxyuridine (BrdU) revealed that the released DNA consisted of nascent-nascent duplexes for more than 90%. This indicates that the release of newly initiated DNA occurs by branch migration. We conclude that shearing enhances branch migration by destabilization of the double helix.

Organization of DNA replication in Physarum polycephalum. Attachment of origins of replicons and replication forks to the nuclear matrix.

We have investigated the attachment of the DNA to the nuclear matrix during the division cycle of the plasmodial slime mold Physarum polycephalum. The DNA of plasmodia was pulse labelled at different times during the S phase and the label distribution was studied by graded DNase digestion of the matrix-DNA complexes prepared from nuclei isolated by extraction with 2 M NaCl. Pulse labelled DNA was preferentially recovered from the matrix bound residual DNA at any time of the S phase. Label incorporated at the onset of the S phase remained preferentially associated with the matrix during the G2 phase and the subsequent S phase. The occurrence of the pulse label in the matrix associated DNA regions was transiently elevated at the onset of the subsequent S phase. Label incorporated at the end of the S phase was located at DNA regions which, in the G2 phase, were preferentially released from the matrix by DNase treatment. From the results and previously reported data on the distribution of attachment sites it can be concluded that origins of replicons or DNA sites very close to them are attached to the matrix during the entire nuclear cycle. The data further indicate that initiations of DNA replication occur at the same origins in successive S phases. Replicating DNA is bound to the matrix, in addition, by the replication fork or a region close to it. This binding is loosened after completion of the replication.

The origin of nascent single-stranded DNA extracted from mammalian cells.

In vitro cultured bovine liver cells were labelled with radioactive thymidine and dissolved in 0.5% sodium dodecyl sulphate. Centrifugation of the lysate through sucrose gradients in a zonal rotor revealed a slowly sedimenting fraction of preferentially pulse labelled DNA. The DNA of this zone was further analysed by chromatography on hydroxy-apatite, banding in CsCl density gradients, and sedimentation in neutral and alkaline sucrose gradients. It contained besides small amounts of fragmented bulk DNA, single-stranded nascent DNA and single-stranded pre-labelled DNA which could be separated from each other by using BrdU as a density label. The density labelling also revealed small amounts of nascent-nascent DNA duplexes. The slowly sedimenting fraction was practically absent from cell lysates which were prepared in 2 M NaCl - 50 microgram/ml pronase. The results suggest that nascent single-strands and nascent-nascent duplexes are released from the forks of replicating DNA by branch migration. Pre-labelled single strands may be released by the same branch migration. Pre-labelled single strands may be released by the same mechanism, but the in vivo structure from which they originate has yet to be elucidated.