Integrating depression care within NCD provision in Bangladesh and Pakistan : a qualitative study

Background Co-morbidity of depression with other non-communicable diseases (NCDs) worsens clinical outcomes for both conditions. Low- and middle-income countries need to strengthen mechanisms for detection and management of co-morbid depression within NCDs. The Behavioural Activation for Comorbid Depression in Non-communicable Disease (BEACON) study explored the acceptability and feasibility of integrating a brief depression intervention (behavioural activation, BA) into NCD services in healthcare facilities in Bangladesh and Pakistan. Methods Face-to-face qualitative interviews were conducted with 43 patients and 18 health workers attending or working in NCD centres in four healthcare facilities in Bangladesh and Pakistan, and with three policy makers in each country. The interviews addressed four research questions (1) how NCD care is delivered, (2) how NCD patients experience distress, (3) how depression care is integrated within NCD provision, and (4) the challenges and opportunities for integrating a brief depression intervention into usual NCD care. The data were analysed using framework analysis, organised by capability, opportunity and motivation factors, cross-synthesised across countries and participant groups. Results Patients and health workers described NCD centres as crowded and time pressured, with waiting times as long as five hours, and consultation times as short as five minutes; resulting in some patient frustration. They did not perceive direct links between their distress and their NCD conditions, instead describing worries about family and finance including affordability of NCD services. Health worker and policy maker accounts suggested these NCD centres lacked preparedness for treating depression in the absence of specific guidelines, standard screening tools, recording systems or training. Barriers and drivers to integrating a brief depression intervention reflected capability, opportunity and motivation factors for all participant groups. While generally valuing the purpose, significant challenges included the busy hospital environment, skill deficits and different conceptions of depression. Conclusions Given current resource constraints and priorities, integrating a brief psychological intervention at these NCD centres appears premature. An opportune first step calls for responding to patients’ expressed concerns on service gaps in provisioning steady and affordable NCD care. Acknowledging differences of conceptions of depression and strengthening psychologically informed NCD care will in turn be required before the introduction of a specific psychological intervention such as BA

Adiponectin negatively regulates pigmentation, Wnt/β-catenin and HGF/c-Met signalling within human scalp hair follicles ex vivo

NoAdiponectin reportedly stimulates proliferation and elongation of human scalp hair follicles (HFs) ex vivo. In the current study, we investigated how adiponectin oligomers produced by perifollicular dermal white adipose tissue (dWAT), a potent source of adiponectin isoforms, influence human HF proliferation and pigmentation. To do so, we treated microdissected, organ-cultured HFs in the presence or absence of dWAT with a recombinant human adiponectin oligomer mix, or inhibited dWAT-derived adiponectin using a neutralizing antibody. Multiplex qPCR (Fluidigm) revealed that adiponectin oligomers downregulated pigmentation genes KITLG, PMEL and TYRP1 and Wnt genes AXIN2, LEF1 and WNT10B. In situ hybridization showed that adiponectin downregulated AXIN2 and LEF1, and up-regulated DKK1 within the dermal papilla (DP), a highly unusual transcriptional profile for a putative hair growth-promoting agent. Adiponectin oligomers also downregulated protein expression of the HGF receptor c-Met within the matrix and DP. However, adiponectin did not alter hair matrix keratinocyte proliferation within 48 h ex vivo, irrespective of the presence/absence of dWAT; HF pigmentation (Masson-Fontana histochemistry, tyrosinase activity) was also unchanged. In contrast, neutralizing adiponectin isoforms within HF + dWAT increased proliferation, melanin content and tyrosinase activity but resulted in fewer melanocytes and melanocytic dendrites, as assessed by gp100 immunostaining. These seemingly contradictory effects suggest that adiponectin exerts complex effects upon human HF biology, likely in parallel with the pro-pigmentation effects of dWAT- and DP-derived HGF. Our data suggest that dWAT-derived ratios of adiponectin isoforms and the cleaved, globular version of adiponectin may in fact determine how adiponectin impacts upon follicular pigmentation and growth.Biotechnology and Biological Science Research Council (BBSRC) iCASE Studentship (awardees: R.P., J.P., recipient: C.N.), co-funded by Unilever, Colworth, UK; NIHR Manchester Biomedical Research Centre, Inflammatory Hair Diseases Programme (Lead: R.P.), University of Miami start-up funds (R.P.), and Frost Endowed Scholarship to R.P. (Dept. of Dermatology)

Identifying novel strategies for treating human hair loss disorders: Cyclosporine A suppresses the Wnt inhibitor, SFRP1, in the dermal papilla of human scalp hair follicles

10.1371/journal.pbio.2003705PLoS Biology165e200370

Differential expression and functionality of ATP-binding cassette transporters in the human hair follicle

BACKGROUND ATP-binding cassette (ABC) transporters are involved in the active transport of an extremely diverse range of substrates across biological membranes. These transporters are commonly implicated in the development of multidrug resistance and are also involved in numerous physiological and homeostatic processes, including lipid transport, cell migration and differentiation. OBJECTIVES To close the knowledge gap in the expression of ABC transporters in the human hair follicle (HF). METHODS Quantitative polymerase chain reaction (qPCR) of ABC genes and immunofluorescence microscopy analysis of cryosections of human HFs. RESULTS By qPCR analysis, numerous members of the ABC transporter superfamily, such as ABCB1, ABCG2 and ABCA12, were found to be transcribed in full-length human scalp HFs. Immunofluorescence microscopy demonstrated that the intrafollicular protein expression of different xenobiotic ABC transporters (ABCB1, ABCC1, ABCC4, ABCG2) varies greatly, with ABCG2 expression restricted primarily to the epithelial stem cell region of the outer root sheath (bulge), whereas expression of ABCB1, ABCC1 and ABCC4 was more widespread. Lipid transporters ABCA1, ABCA12 and ABCA4 were almost uniformly expressed throughout the HF epithelium. Functional ABCB1/G2 activity was demonstrated by exclusion of the substrate dye, Hoechst 33342. In the bulge, this was reversed by ABCB1 and ABCG2 inhibition. CONCLUSIONS These data encourage further investigation of ABC transporters as potentially important regulators of HF epithelial biology. Clinically, pharmacological modulation of the activity of selected intrafollicular ABC transporters may permit novel therapeutic interventions, such as protecting HF stem cells from chemotherapy-induced damage, counteracting cholesterol-associated hypertrichosis, and manipulating the intrafollicular prostaglandin balance in androgenetic alopecia

CsA treatment down-regulates SFRP1 in the DP of human HFs ex vivo.

<p>(<b>A</b>) Microarray analysis of CsA-treated (6 hours) human HFs (<i>n</i> = 3 male patient samples). (<b>B–E</b>) Characterisation of <i>SFRP1</i> mRNA (in situ hybridisation; <b>B–D</b>) and protein (immunofluorescence; <b>E</b>) expression in the human HF bulb. (<b>F</b>) Schematic of SFRP1 in the human HF bulb. (<b>G–J</b>) SFRP1 protein analysis after CsA treatment (48 hours) in the human HF bulb (<i>n</i> = 10 HFs Control, 11 HFs CsA; from 2 male patient samples). <b>(K–N)</b> In situ hybridisation of <i>SFRP1</i> mRNA with CsA treatment (48 hours). (<b>O</b>) qRT-PCR analysis of <i>SFRP1</i> after CsA treatment (48 hours) (<i>n</i> = 3 male patient samples). (H and J) Two-tailed unpaired <i>t</i> test, (I) Mann-Whitney test, and (O) one-sample <i>t</i> test. Data are expressed as mean ± SEM. Scale bars = 50 μm. Underlying data can be found in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2003705#pbio.2003705.s016" target="_blank">S1 Data</a>. <i>ANP32E</i>, acidic nuclear phosphoprotein 32 family member E; <i>APOBEC3A</i>, apolipoprotein B mRNA editing enzyme catalytic subunit 3A; <i>BDP1</i>, B double prime 1, subunit of RNA polymerase III transcription initiation factor IIIB; <i>CCND2</i>, cyclin D2; CsA, Cyclosporine A; <i>CLCN5</i>, chloride voltage-gated channel 5; <i>CXCL8</i>, C-X-C motif chemokine ligand 8; <i>DAB2</i>, DAB2, clathrin adaptor protein; DP, dermal papilla; <i>EEA1</i>, early endosome antigen 1; <i>FDCSP</i>, follicular dendritic cell secreted protein; <i>FLG2</i>, filaggrin family member 2; HF, hair follicle; HM, hair matrix; <i>KISS1R</i>, KISS1 receptor; <i>MALAT1</i>, metastasis associated lung adenocarcinoma transcript 1; <i>NLRP2</i>, NLR family pyrin domain containing 2; Pre-Cx, pre-cortex; qRT-PCR, quantitative real-time PCR; <i>PPIB</i>, peptidylprolyl isomerase B; <i>PTX3</i>, pentraxin 3; <i>RTCA</i>, RNA 3′-terminal phosphate cyclase; SFRP1, secreted frizzled related protein 1; <i>SLFN11</i>, schlafen family member 11; <i>SPP1</i>, secreted phosphoprotein 1; <i>TET2</i>, tet methylcytosine dioxygenase 2.</p

Inhibiting SFRP1 activity with WAY-316606 enhances human hair growth, increases K85 protein expression, and inhibits spontaneous catagen ex vivo.

<p><b>(A)</b> Hair shaft elongation of human HFs ex vivo with WAY-316606 treatment (<i>n</i> = 31 HFs Control, 30 HFs WAY-316606; from 3 male patient samples). (<b>B</b>) K85 protein quantification using immunofluorescence after 48 hours of treatment with WAY-316606 (<i>n</i> = 16 HFs control, 14 HFs WAY-316606; from 3 male patient samples). (<b>C</b>) Macroscopic quantification of hair cycle stage on day 6 with WAY-316606 treatment. (<b>D–H</b>) Validation of HF cycle stage with Ki-67/TUNEL analysis (<i>n</i> = 21 HFs control, 20 HFs WAY-316606; from 3 male patient samples) and Masson's-Fontana (<i>n</i> = 17 HFs control, 20 HFs WAY-316606; from 3 male patient samples). <b>(I)</b> Working hypothesis. Data are expressed as mean ± SEM. (A, B, E, G, and H) Two-tailed unpaired <i>t</i> test and (F) Mann-Whitney test. Scale bars, A = 1 mm; B, D, and H = 50 μm. Underlying data can be found in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2003705#pbio.2003705.s016" target="_blank">S1 Data</a>. AL, Auber’s line; Axin2, axis inhibition protein 2; CsA, Cyclosporine A; DC, differentiating cell; DP, dermal papilla; DPC, dermal papilla cell; HF, hair follicle; K85, Keratin 85; LEF1, lymphoid enhancer binding factor 1; SFRP1, secreted frizzled related protein 1; TAC, transient amplifying cell; WAY, WAY-316606.</p

Task Sharing or Task Dumping: Counsellors Experiences of Delivering a Psychosocial Intervention for Mental Health Problems in South Africa

Given task-sharing mental health counselling to non-specialist providers is a recognised strategy to increase service capacity, ensuring that their training, supervision, and support needs are met is necessary to facilitate the sustainable delivery of a high-quality service. Using in-depth interviews, we qualitatively explored the experiences of 18 facility-based counsellors (FBCs) tasked with delivering a counselling intervention within chronic disease services offered within primary care facilities participating in the project MIND cluster randomised controlled trial. Findings show that project MIND training with a strong emphasis on role playing and skills rehearsal improved FBCs’ confidence and competence, complemented by highly structured supervision and debriefing provided by a registered counsellor, were key strategies for supporting the implementation of task-shared mental health counselling. FBCs perceived many benefits to providing mental health counselling in primary healthcare but systemic interventions are needed for sustained implementation