Background:
The Multidimensional Scale of Perceived Social Support (MSPSS) is a short and reliable instrument that assesses perceived social support from the social network of an individual. A ...previous study in Pakistan among postpartum women has demonstrated a unidimensional factor structure in contrast to the original three-factor structure. The emergence of a one-factor structure for postpartum women in Pakistan may be due to traditional postpartum practices unique to the women of the subcontinent. Building upon the previous evidence, this study aims to explore the psychometric properties of MSPSS among pregnant women in their third trimester in rural Pakistan.
Methods:
A cross-sectional survey was conducted from October 2014 to February 2016, in rural Pakistan. A sample of 1,154 pregnant women (aged ≥ 18 years) in their third trimester who were registered with the local Lady Health Worker Program and were living in the north of the Punjab Province was included in this study. They were assessed using Urdu translated scales of Patient Health Questionnaire, MSPSS, Maternal Social Support Index, and Perceived Stress Scale. Principal Axis Factoring was used to assess the construct validity of the MSPSS.
Results:
The MSPSS scale showed an excellent internal consistency, yielding a Cronbach's α-value of 0.933. The MSPSS scale exhibited an excellent construct validity, and confirmatory factor analysis retained three factors (family, friends, and significant others) for both the depressed and non-depressed samples. Internal reliability and construct validity were also established.
Conclusion:
The psychometric findings suggest that the tridimensional structure of MSPSS is a valid and reliable measure of perceived social support among the Pakistani population with and without perinatal depression. The perceived social support is an important predictor of maternal mental well-being and psychopathologies, and the MSPSS can serve as a useful tool in mental health research in Pakistan.
Bacterial proteins with MCE domains were first described as being important for Mammalian Cell Entry. More recent evidence suggests they are components of lipid ABC transporters. In Escherichia coli, ...the single-domain protein MlaD is known to be part of an inner membrane transporter that is important for maintenance of outer membrane lipid asymmetry. Here we describe two multi MCE domain-containing proteins in Escherichia coli, PqiB and YebT, the latter of which is an orthologue of MAM-7 that was previously reported to be an outer membrane protein. We show that all three MCE domain-containing proteins localise to the inner membrane. Bioinformatic analyses revealed that MCE domains are widely distributed across bacterial phyla but multi MCE domain-containing proteins evolved in Proteobacteria from single-domain proteins. Mutants defective in mlaD, pqiAB and yebST were shown to have distinct but partially overlapping phenotypes, but the primary functions of PqiB and YebT differ from MlaD. Complementing our previous findings that all three proteins bind phospholipids, results presented here indicate that multi-domain proteins evolved in Proteobacteria for specific functions in maintaining cell envelope homeostasis.
Abstract
Background
The lack of trained mental health professionals is a key barrier to scale-up of evidence-based psychological interventions in low and middle-income countries. We have developed an ...app that allows a peer with no prior experience of health-care delivery to deliver the cognitive therapy-based intervention for perinatal depression, the Thinking Healthy Programme (THP). This trial aims to assess the effectiveness and cost-effectiveness of this Technology-assisted peer-delivered THP versus standard face-to-face Thinking Healthy Programme delivered by trained health workers.
Methods
We will employ a non-inferiority stratified cluster randomized controlled trial design comparing the two formats of intervention delivery. A total of 980 women in the second or third trimester of pregnancy with a diagnosis of Major Depressive Episode, evaluated with the Structured Clinical Interview for DSM-V Disorders (SCID), will be recruited into the trial. The unit of randomization will be 70 village clusters randomly allocated in a 1:1 ratio to the intervention and control arms.
The primary outcome is defined as remission from major depressive episode at 3 months postnatal measured with the SCID. Data will also be collected on symptoms of anxiety, disability, quality of life, service use and costs, and infant-related outcomes such as exclusive breastfeeding and immunization rates. Data will be collected on the primary outcome and selected secondary outcomes (depression and anxiety scores, exclusive breastfeeding) at 6 months postnatal to evaluate if the improvements are sustained in the longer-term. We are especially interested in sustained improvement (recovery) from major depressive episode.
Discussion
This trial will evaluate the effectiveness and cost-effectiveness of a technology-assisted peer-delivered cognitive behavioral therapy-based intervention in rural Pakistan. If shown to be effective, the novel delivery format could play a role in reducing the treatment gap for perinatal depression and other common mental disorders in LMIC.
Trial registration
The trial was registered at Clinicaltrials.gov (NCT05353491) on 29 April 2022.
Objective:
To determine the prevalence and association of prenatal depression with socioeconomic, demographic and personal factors among pregnant women living in Kallar Syedan, Rawalpindi, Pakistan.
...Methods:
Five hundred women in the second and third trimester of pregnancy, living in Kallar Syedan, a rural area of district Rawalpindi Pakistan, were included in the study. Depression was assessed using “Patient health questionnaire” (PHQ9) in Urdu, with a cut-off score of 10. Multi-dimensional scale of perceived social support (MSPSS) was used to assess perceived social support. Life Events and Difficulties Schedule (LEDS) were used to measure stressful life events in past 1 year. Tool to assess intimate partner violence (IPV) was based on WHO Multi Country Study on “Women's Health and Domestic Violence against Women.”
Results:
Prevalence of prenatal depression was found to be 27%. Number of pregnancies was significantly associated with prenatal depression (
p
< 0.01). Women living in a joint family and those who perceived themselves as moderately satisfied or not satisfied with their life in the next 4 years were found to be depressed (
p
< 0.01, OR 6.9, CI 1.77–26.73). Depressive symptomatology in women who experienced more than five stressful life events in last 1 year was three times higher (
p
< 0.001, OR 3.2, CI 1.68–5.98) than in women with 1–2 stressful events. Women who were supported by their significant others or their family members had 0.9 times (
p
< 0.01, OR 0.9, CI 0.85–0.96) less chance of getting depressed. Pregnant women who were psychologically abused by their partners were 1.5 times more depressed (
p
< 0.05 CI 1.12–2.51). Odds of having depression was also high in women who had less mean score of MSSI (
p
< 0.05, OR 1.1, CI 1.01–1.09). Women who had suitable accommodation had 0.5 times less chance of having depression than others (
p
< 0.05, OR 0.5, CI 0.27–0.92).
Conclusion:
Over a quarter of the women in the study population reported prenatal depression, which were predicted predominantly by psychosocial variables.
The Thinking Healthy Programme (THP), which is endorsed by WHO, is an evidence-based intervention for perinatal depression. We adapted THP for delivery by volunteer peers (laywomen from the ...community) to address the human resource needs in bridging the treatment gap, and we aimed to assess its effectiveness and cost-effectiveness in Rawalpindi, Pakistan.
In this cluster randomised controlled trial, we randomly assigned 40 village clusters (1:1) to provide either THP peer-delivered (THPP) and enhanced usual care (EUC; intervention group) or EUC only (control group) to the participants within clusters. These villages were randomly selected from eligible villages by an independent researcher. The participants were pregnant women aged 18 years or older who had scored at least 10 on the Patient Health Questionnaire-9 (PHQ-9), who we recruited from households within communities in Rawalpindi, Pakistan. The research teams who were responsible for recruiting trial participants were masked to treatment allocations. Participants attended follow-up visits at 3 and 6 months after childbirth. The primary outcomes were the severity of depressive symptoms (assessed by PHQ-9 score) and the prevalence of remission (defined as a PHQ-9 score of less than 5) in participants with available data 6 months after childbirth, which was assessed by researchers who were masked to treatment allocations. We analysed outcomes by intention to treat, adjusting for covariates that were defined a priori or that showed imbalance at baseline. The trial was registered with ClinicalTrials.gov, number NCT02111915.
Between April 15 and July 30, 2014, we randomly selected 40 of 46 eligible village clusters for assessment, as per sample size calculations. Between Oct 15, 2014, and Feb 25, 2016, we identified and screened 971 women from 20 village clusters that had been randomly assigned to the THPP and EUC group and 939 women from 20 village clusters that had been randomly assigned to the EUC only group. In the intervention group, 79 women were ineligible for inclusion, 11 women refused screening, 597 women screened negative on the PHQ-9, and one woman did not consent to participate. In the control group, 75 women were ineligible for inclusion, 14 women refused screening, 562 women screened negative on the PHQ-9, and one woman did not consent to participate. We enrolled 283 (29%) women in the intervention group and 287 (31%) women in the control group. At 6 months after childbirth, 227 (80%) women in the THPP and EUC group and 226 (79%) women in the EUC only group were assessed for the primary outcome. The severity of depression (assessed by PHQ-9 scores; standardised mean difference -0·13, 95% CI -0·31 to 0·06; p=0·07) and prevalence of remission (49% in the intervention group vs 45% in the control group; prevalence ratio 1·12, 95% CI 0·95 to 1·29; p=0·14) did not significantly differ between the groups 6 months after childbirth. There was no evidence of significant differences in serious adverse events between the groups.
THPP had no effect on symptom severity or remission from perinatal depression at 6 months after childbirth, but we found that it was beneficial on some other metrics of severity and disability and that it was cost-effective. THPP could be a step towards use of an unused human resource to address the treatment gap in perinatal depression.
National Institute of Mental Health (USA).
Vγ9/Vδ2 T-cells are activated by pyrophosphate-containing small molecules known as phosphoantigens (PAgs). The presence of the pyrophosphate group in these PAgs has limited their drug-like properties ...because of its instability and polar nature. In this work, we report a novel and short Grubbs olefin metathesis-mediated synthesis of methylene and difluoromethylene monophosphonate derivatives of the PAg (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBP) as well as their aryloxy diester phosphonamidate prodrugs, termed ProPAgens. These prodrugs showed excellent stability in human serum (t 1/2 > 12 h) and potent activation of Vγ9/Vδ2 T-cells (EC50 ranging from 5 fM to 73 nM), which translated into sub-nanomolar γδ T-cell-mediated eradication of bladder cancer cells in vitro. Additionally, a combination of in silico and in vitro enzymatic assays demonstrated the metabolism of these phosphonamidates to release the unmasked PAg monophosphonate species. Collectively, this work establishes HMBP monophosphonate ProPAgens as ideal candidates for further investigation as novel cancer immunotherapeutic agents.
The phosphoantigen ( E )-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) is an established activator of Vγ9/Vδ2 T cells and stimulates downstream effector functions including cytotoxicity and ...cytokine production. In order to improve its drug-like properties, we herein report the design, synthesis, serum stability, in vitro metabolism, and biological evaluation of a new class of symmetrical phosphonodiamidate prodrugs of methylene and difluoromethylene monophosphonate derivatives of HMBPP. These prodrugs, termed phosphonodiamidate ProPAgens, were synthesized in good yields, exhibited excellent serum stability (>7 h), and their in vitro metabolism was shown to be initiated by carboxypeptidase Y. These phosphonodiamidate ProPAgens triggered potent activation of Vγ9/Vδ2 T cells, which translated into efficient Vγ9/Vδ2 T cell-mediated eradication of bladder cancer cells in vitro . Together, these findings showcase the potential of these phosphonodiamidate ProPAgens as Vγ9/Vδ2 T cell modulators that could be further developed as novel cancer immunotherapeutic agents.
Aryloxy triester phosphoramidate prodrugs of the monophosphate derivatives of isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) were synthesized as lipophilic derivatives that ...can improve cell uptake. Despite the structural similarity of IPP and DMAPP, it was noted that their phosphoramidate prodrugs exhibited distinct stability profiles in aqueous environments, which we show is due to the position of the allyl bond in the backbones of the IPP and DMAPP monophosphates. As the IPP monophosphate aryloxy triester phosphoramidates showed favorable stability, they were subsequently investigated for their ability to activate Vγ9/Vδ2 T cells and they showed promising activation of this subset of T cells. Together, these findings represent the first report of IPP and DMAPP monophosphate prodrugs and the ability of IPP aryloxy triester phosphoramidate prodrugs to activate Vγ9/Vδ2 T cells highlighting their potential as possible immunotherapeutics.
Immunotherapeutic potential: Aryloxy triester phosphoramidates of the monophosphate derivatives of DMAPP and IPP were designed and synthesized. Despite their structural similarity, the aryloxy triester phosphoramidates of the IPP monophosphate derivative were more stable in aqueous environments than those of DMAPP, and they induced specific activation of Vγ9/Vδ2 T cells.
The phosphoantigen (
E
)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) is an established activator of V9/Vδ2 T cells and stimulates downstream effector functions including cytotoxicity and ...cytokine production. In order to improve its drug-like properties, we herein report the design, synthesis, serum stability,
in vitro
metabolism, and biological evaluation of a new class of symmetrical phosphonodiamidate prodrugs of methylene and difluoromethylene monophosphonate derivatives of HMBPP. These prodrugs, termed phosphonodiamidate ProPAgens, were synthesized in good yields, exhibited excellent serum stability (>7 h), and their
in vitro
metabolism was shown to be initiated by carboxypeptidase Y. These phosphonodiamidate ProPAgens triggered potent activation of V9/Vδ2 T cells, which translated into efficient V9/V2 T cell-mediated eradication of bladder cancer cells
in vitro
. Together, these findings showcase the potential of these phosphonodiamidate ProPAgens as V9/Vδ2 T cell modulators that could be further developed as novel cancer immunotherapeutic agents.
Phosphonodiamidate prodrugs of the monophosphonate derivatives of HMBPP, a natural phosphoantigen, exhibit potent activation of V9V2 T cells resulting in the lysis of bladder cancer cells
in vitro
.
•We found consistent benefits of the Thinking Healthy Programme adapted for delivery by Peers (THPP) on maternal outcomes.•THPP resulted in 35% higher odds of remission at 6 months post-childbirth ...compared to enhanced usual care only.•We found beneficial intervention effects across a number of secondary outcomes, and in repeated measures analyses.•We have demonstrated feasibility and acceptability of this peer-delivered intervention, and external validity of our results.
The Thinking Healthy Programme (THP) is recommended to treat perinatal depression in resource-limited settings, but scale-up is hampered by a paucity of community health workers. THP was adapted for peer-delivery (THPP) and evaluated in two randomized controlled trials in India and Pakistan. Our aim was to estimate the effectiveness of THPP on maternal outcomes across these two settings, and evaluate effect-modification by country and other pre-defined covariates.
Participants were pregnant women aged≥18 years with depression (Patient Health Questionnaire (PHQ-9) score≥10), randomized to THPP plus enhanced usual care (EUC) or EUC-only. Primary outcomes were symptom severity and remission (PHQ-9 score<5) 6 months post-childbirth. Secondary outcomes included further measures of depression, disability and social support at 3 and 6 months post-childbirth.
Among 850 women (280 India; 570 Pakistan), 704 (83%) attended 6-month follow-up. Participants in the intervention arm had lower symptom severity (PHQ-9 score adjusted mean difference -0.78 (95% confidence interval -1.47,-0.09)) and higher odds of remission (adjusted odds ratio 1.35 (1.02,1.78)) versus EUC-only. There was a greater intervention effect on remission among women with short chronicity of depression, and those primiparous. There were beneficial intervention effects across multiple secondary outcomes.
The trials were not powered to assess effect-modifications. 10–20% of participants were missing outcome data.
This pooled analysis demonstrates the effectiveness, acceptability and feasibility of THPP, which can be scaled-up within a stepped-care approach by engaging with the existing health care systems and the communities to address the treatment gap for perinatal depression in resource-limited settings.
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