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BACKGROUND: Highly reactive oxygen species (ROS) could lead to serious damage in living cells and are associated with many diseases like cancers. Metal cluster with strong fluorescence has great potential in biosensing and many thiolate ligands-protected clusters have been applied in ROS sensing. RESULTS: In this work, we synthesized levonorgestrel protected Au10 cluster with specific sensing ability for highly ROS via crystal transformation from Au8 cluster, demonstrating the significance of inner core structure on detecting performance. The detection limit of Au10 cluster for ClO- could reach as low as 0.1 µM. This fluorescent probe not only achieving detection of exogenous ClO- in living cells and zebrafish, but also successful imaging of endogenous ClO- in HeLa and HepG2 cells. SIGNIFICANCE: In comparison to previously reported cluster-based sensors for ROS, this work proposes a different reaction mechanism of metal nanoclusters for ROS detection (breakage of gold-alkynyl bond and oxidation of alkynyl group). This provides new directions for designing specific ROS probes and broadens the applications of metal clusters in disease diagnostics.
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Corantes Fluorescentes , Ouro , Ácido Hipocloroso , Levanogestrel , Peixe-Zebra , Humanos , Ouro/química , Células HeLa , Ácido Hipocloroso/análise , Animais , Células Hep G2 , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Levanogestrel/química , Imagem Óptica , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/análise , Nanopartículas Metálicas/químicaRESUMO
Lately, carbazole-based self-assembled monolayers (SAMs) are widely employed as effective hole-selective layers (HSLs) in inverted perovskite solar cells (PSCs). Nevertheless, these SAMs tend to aggregate in solvents due to their amphiphilic nature, hindering the formation of a monolayer on the ITO substrate and impeding effective passivation of deep defects in the perovskites. In this study, a series of new SAMs including DPA-B-PY, CBZ-B-PY, POZ-B-PY, POZ-PY, POZ-T-PY, and POZ-BT-PY are synthesized, which are employed as interfacial repairers and coated atop CNph SAM to form a robust CNph SAM@pseudo-planar monolayer as HSL in efficient inverted PSCs. The CNph SAM@pseudo-planar monolayer strategy enables a well-aligned interface with perovskites, synergistically promoting perovskite crystal growth, improving charge extraction/transport, and minimizing nonradiative interfacial recombination loss. As a result, the POZ-BT-PY-modified PSC realizes an impressively enhanced solar efficiency of up to 24.45% together with a fill factor of 82.63%. Furthermore, a wide bandgap PSC achieving over 19% efficiency. Upon treatment with the CNph SAM@pseudo-planar monolayer, also demonstrates a non-fullerene organic photovoltaics (OPVs) based on the PM6:BTP-eC9 blend, which achieves an efficiency of 17.07%. Importantly, these modified PSCs and OPVs all show remarkably improved stability under various testing conditions compared to their control counterparts.
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Eukaryotic ribosomal proteins contain extended regions essential for translation coordination. Dedicated chaperones stabilize the associated ribosomal proteins. We identified Bcp1 as the chaperone of uL14 in Saccharomyces cerevisiae. Rkm1, the lysine methyltransferase of uL14, forms a ternary complex with Bcp1 and uL14 to protect uL14. Rkm1 is transported with uL14 by importins to the nucleus, and Bcp1 disassembles Rkm1 and importin from uL14 simultaneously in a RanGTP-independent manner. Molecular docking, guided by crosslinking mass spectrometry and validated by a low-resolution cryo-EM map, reveals the correlation between Bcp1, Rkm1, and uL14, demonstrating the protection model. In addition, the ternary complex also serves as a surveillance point, whereas incorrect uL14 is retained on Rkm1 and prevented from loading to the pre-60S ribosomal subunits. This study reveals the molecular mechanism of how uL14 is protected and quality checked by serial steps to ensure its safe delivery from the cytoplasm until its incorporation into the 60S ribosomal subunit.
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Proteínas Ribossômicas , Subunidades Ribossômicas Maiores de Eucariotos , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Subunidades Ribossômicas Maiores de Eucariotos/metabolismo , Subunidades Ribossômicas Maiores de Eucariotos/genética , Proteínas Ribossômicas/metabolismo , Proteínas Ribossômicas/genética , Chaperonas Moleculares/metabolismo , Chaperonas Moleculares/genética , Ligação Proteica , Simulação de Acoplamento Molecular , Microscopia Crioeletrônica , Núcleo Celular/metabolismo , Núcleo Celular/genéticaRESUMO
Cervical cancer (CC) remains a major cause of cancer-related mortality among women globally. Long noncoding RNAs (lncRNAs) play crucial regulatory roles in various cancers, including CC. This study investigates the function of a novel lncRNA, USP30 antisense RNA 1 (USP30-AS1), in CC tumorigenesis. We analyzed USP30-AS1 expression using RT-qPCR and conducted in vitro loss-of-function assays, as well as in vivo assays, to evaluate the effects of USP30-AS1 silencing on CC cell growth and migration. Additional mechanistic experiments, including RNA pull-down, RNA immunoprecipitation (RIP), and co-immunoprecipitation (Co-IP) assays, were performed to elucidate the regulatory mechanisms influenced by USP30-AS1. We discovered that USP30-AS1 is overexpressed in CC tissues and cells. Silencing USP30-AS1 significantly reduced cell proliferation, migration, invasion, and tumor growth. Moreover, USP30-AS1 was found to modulate the expression of ubiquitin-specific peptidase 30 (USP30) by sponging microRNA-2467-3p (miR-2467-3p) and recruiting the FUS RNA binding protein (FUS), thereby stabilizing ß-catenin and activating the Wnt/ß-catenin signaling pathway. These findings suggest that USP30-AS1 enhances CC cell growth and migration through the miR-2467-3p/FUS/USP30 axis, highlighting its potential as a biomarker for CC.
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Proliferação de Células , RNA Longo não Codificante , Neoplasias do Colo do Útero , Via de Sinalização Wnt , beta Catenina , Animais , Feminino , Humanos , Camundongos , beta Catenina/metabolismo , beta Catenina/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Exossomos/metabolismo , Exossomos/genética , Regulação Neoplásica da Expressão Gênica/genética , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Via de Sinalização Wnt/genéticaRESUMO
There is an unmet need for safe and efficacious oral therapies for COVID-19 with low potential for drug-drug interactions. Obeldesivir is an orally administered nucleoside prodrug that has shown antiviral potency in nonclinical studies against SARS-CoV-2 and its circulating variants. Obeldesivir is metabolized to the active nucleoside triphosphate (GS-443902), which acts as an inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase, thereby inhibiting viral RNA synthesis. Here, we report the safety, tolerability, and pharmacokinetics from a first-in-human, randomized, placebo-controlled, phase I study following oral administration of obeldesivir and a phase I, open-label absorption, distribution, metabolism, and excretion study following oral administration of [14C]-obeldesivir. Overall, obeldesivir was safe and well tolerated at single and multiple doses between 100 and 1,600 mg, with low potential for QT prolongation as assessed by QT-concentration analysis. The exposures to GS-441524 increased dose proportionally in the 100-900-mg dose range. GS-441524 accumulated by 35% after twice-daily and 12% after once-daily dosing for 5 days. Dose-proportional increases in the intracellular concentration of GS-443902 were also observed in peripheral blood mononuclar cells. Plasma exposure of GS-441524 was not significantly altered by food intake. Following oral administration of [14C]-obeldesivir (500 mg; 100 µCi), the mean cumulative [14C]-dose recovery was 90.7% with 58.5% in urine and 32.2% in feces. GS-441524 was the predominant plasma component (90% of 14C-area under the concentration-time curve) and was primarily eliminated via renal excretion. Collectively, data from these studies support selection of the obeldesivir 350 mg twice-daily dosing regimen for further evaluation in phase III studies for COVID-19.
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INTRODUCTION: Solid pseudopapillary neoplasms (SPNs) of the pancreas are rare neoplasms, accounting for only 1 %-2 % of all pancreatic tumors, and predominantly affect female patients. CASE PRESENTATION: The present case report details a patient presenting to the emergency department with abdominal pain for 3 days who ultimately received a diagnosis of SPNs in the pancreatic body and tail. A contrast-enhanced computed tomography (CT) scan revealed a sizable mass arising from the pancreas, featuring an enhancing cystic component with involvement of the liver and spleen. The patient underwent subsequent exploratory laparotomy, a distal pancreatectomy, splenectomy, and partial hepatectomy. SPN diagnosis was confirmed by histopathology and immunohistochemistry with negative resection margins. CLINICAL DISCUSSION: Approximately 70 % of SPN cases are asymptomatic and are incidentally discovered. Despite advances in diagnostic modalities, preoperative diagnosis of SPNs remains a clinical challenge. Surgical management with negative resection margins remains the primary treatment approach. The recurrence rate after surgical resection has been reported to be 3 %-9 %. The prognosis for SPNs limited to the pancreas is generally favorable, with a cure rate exceeding 95 % after complete surgical resection. CONCLUSION: An SPN of the pancreas is a rare tumor observed in young female patients. Although it is classified as a malignant tumor, SPN has low malignant potential. Aggressive surgical resection, however, has proven effective in curing SPN for the majority of patients.
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OBJECTIVES: To estimate whether the association of transfusion and acute kidney injury (AKI) has a threshold of oxygen delivery below which transfusion is beneficial but above which it is harmful. DESIGN: Retrospective study SETTING: Cardiovascular operating room and intensive care unit PARTICIPANTS: Patients undergoing cardiac surgery with continuous oxygen delivery monitoring during cardiopulmonary bypass INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: Logistic regression was used to estimate the associations between oxygen delivery (mean, cumulative deficit, and bands of oxygen delivery), transfusion, and their interaction and AKI. A subgroup analysis of transfused and nontransfused patients with exact matching on cumulative oxygen deficit and time on bypass with adjustment for propensity to receive a transfusion using logistic regression. Nine hundred ninety-one of 4,203 patients developed AKI within 7 days. After adjustment for confounders, lower mean oxygen delivery (odds ratio [OR], 0.968; 95% confidence interval [CI], 0.949-0.988; p = 0.002) and transfusions (OR, 1.442; 95% CI, 1.077, 1.932; p = 0.014) were associated with increased odds of AKI by 7 days. As oxygen delivery decreased, the risk of AKI increased, with the slope of the OR steeper at <160 mL/m2/min. In the subgroup analysis, matched transfused patients were more likely than matched nontransfused patients to develop AKI (45% [n = 145] v 31% [n = 101]; p < 0.001). However, after propensity score adjustment, the difference was nonsignificant (OR, 1.181; 95% CI, 0.796-1.752; p = 0.406). CONCLUSIONS: We found a nonlinear relationship between oxygen delivery and AKI. We found no level of oxygen delivery at which transfusion was associated with a decreased risk of AKI.
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BACKGROUND: Violence against children (VAC) has garnered attention as a priority issue, in part, due to the Violence Against Children and Youth Surveys (VACS). Although children are disproportionately represented among forcibly displaced people, VACS are a novelty in humanitarian settings. OBJECTIVE: This paper presents the approach to the first-ever VACS conducted exclusively in a humanitarian setting (HVACS) in Uganda, in addition to providing an overview of the results of this novel survey, along with their implications. PARTICIPANTS AND SETTING: Participants included 1338 females and 927 males aged 13-24 years living in refugee settlements in Uganda. METHODS: This was a cross-sectional representative household survey conducted in all 13 refugee settlements in Uganda between March and April 2022. A three-stage sampling process was used to identify participants. Descriptive analysis was conducted, involving the application of sample weights to obtain estimates that are representative of the study population. RESULTS: VAC in refugee settings is pervasive, with females being more likely than males to experience sexual violence and males being more likely than females to experience physical violence. VAC perpetrators were mostly people who were known to child survivors. Whereas knowledge of where to seek help for violence was relatively high (more so for males compared to females), the levels of disclosure and help-seeking were very low for both groups. CONCLUSION: Robust surveys that have traditionally excluded humanitarian settings can be conducted in these contexts. Data emanating from such surveys are critical for developing relevant guidance on interventions to appropriately address major public health issues, such as VAC.
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BACKGROUND: The COVID-19 pandemic disrupted global economic and healthcare systems. People living with HIV (PLWH) represent a marginalized and stigmatized population who may have been particularly impacted. The purpose of this analysis was to describe the impact of the COVID-19 pandemic on PLWH in the United States. SETTING: United States. METHODS: We analyzed surveys of behavioral and clinical characteristics of PLWH residing in 5 states that participated in the Medical Monitoring Project between 2020 and 2022. We described the impact of COVID-19 illness, testing, and diagnoses; receipt of medical care; social service access; employment; and preventive measures by project site and demographic characteristics. RESULTS: Unweighted data from 1715 PLWH were analyzed. A high proportion of PLWH had medical care disrupted by the pandemic; 31% of PLWH missed medical appointments, 26% missed routine laboratory test results, and 7% missed antiretroviral therapy doses. In total, 30% of PLWH reported losing wages and 19% reported difficulty in accessing social services. Overall, 88% reported receiving at least 1 dose of COVID-19 vaccine, but vaccine uptake was low among younger, Black, and Hispanic or Latina/o/x PLWH. CONCLUSIONS: This descriptive analysis reinforces previous findings that show that COVID-19 negatively impacted PLWH and their ability to obtain medical care. Additional efforts will be critical to ameliorating the longer-term impacts of COVID-19 on the health of PLWH and supporting PLWH through future pandemics and healthcare system disruptions.
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COVID-19 , Infecções por HIV , Humanos , COVID-19/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/complicações , Masculino , Feminino , Estados Unidos/epidemiologia , Adulto , Pessoa de Meia-Idade , SARS-CoV-2 , Acessibilidade aos Serviços de Saúde , Adulto Jovem , AdolescenteRESUMO
Australia's approach to its biosecurity and borders has always been two-pronged - quarantine first, vaccination second. This article asks what this combination looked like in practice by exploring two neglected smallpox vaccination campaigns directed towards Indigenous peoples in the early twentieth century. We argue these were important campaigns because they were the first two pre-emptive, rather than reactionary, vaccination programs directed towards First Nations people. Second, both episodes occurred in Australia's northern coastline, where the porous maritime geography and proximity to Southeast Asia posed a point of vulnerability for Australian health officials. While smallpox was never endemic, (though epidemic), in Australia, it was endemic at various times and places across Southeast Asia. This shifting spectre of smallpox along the northern coastline was made even more acute for state and federal health officials because of the existing polyethnic relationships, communities, and economies. By vaccinating Indigenous peoples in this smallpox geography, they were envisioned and embedded into a 'hygienic' border for the protection of white Australia, entwining the two-prongs as one approach. In this article, we place public health into a recent scholarship that has 'turned the map upside down' to re-spatialise Australia's history and geography to the north and its global connections, while demonstrating how particular coastlines and their connections were drawn into a national imaginary through a health lens.
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Varíola , Humanos , Austrália , Vacinação , Povos Indígenas , GeografiaRESUMO
Cisplatin resistance remains a persistent challenge in cervical cancer (CC) treatment. Molecular biomarkers have garnered attention for their association with cisplatin resistance in various diseases. Long non-coding RNAs (lncRNAs) exert significant influence on CC development. This study explores the role of LOC644656 in regulating cisplatin resistance in CC. Parental and cisplatin-resistant CC cells underwent cisplatin treatment. Functional assays assessed cell proliferation and apoptosis under different conditions. RNA pull-down with mass spectrometry, along with literature review, elucidated the interaction between LOC644656, ZNF143, and E6-AP. Mechanistic assays analyzed the relationship between different factors. RT-qPCR and western blot quantified RNA and protein levels, respectively. In vivo models validated E6-AP's function. Results revealed LOC644656 overexpression in cisplatin-resistant CC cells, exacerbating cell growth. LOC644656 recruited ZNF143 to activate E6-AP transcription, promoting cisplatin resistance in CC. In conclusion, LOC644656 positively modulates E6-AP expression via ZNF143-mediated transcriptional activation, contributing to cisplatin resistance in CC.
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Cisplatino , Resistencia a Medicamentos Antineoplásicos , MicroRNAs , Transativadores , Ubiquitina-Proteína Ligases , Neoplasias do Colo do Útero , Feminino , Humanos , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/uso terapêutico , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , RNA , Transativadores/metabolismo , Ativação Transcricional , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
OBJECTIVE: Psoas muscle size is a reliable marker of sarcopenia and frailty that correlates with adverse outcomes after cardiac surgery. However, its use in mitral and minimally invasive cardiac surgery is lacking. We sought to determine whether frailty, as measured by psoas muscle index, increases surgical risk for minimally invasive mitral valve surgery. METHODS: Patients undergoing isolated minimally invasive mitral surgery via right minithoracotomy were identified. Patients who underwent maze, tricuspid intervention, and those who were emergent were excluded. Total psoas muscle area was calculated using the average cross-sectional area at the L3 vertebra on computed tomography scan and indexed to body surface area. Sarcopenia was defined as <25th gender-specific percentile. Patients were stratified by sarcopenia status and outcomes compared. RESULTS: Of 287 total patients, 192 patients met inclusion criteria. Sarcopenic patients were 6 years older (66 vs 60 years, P = 0.01), had lower preoperative albumin levels (4.0 vs 4.3 g/dL, P < 0.001), and had higher Society of Thoracic Surgeons risk of morbidity/mortality (13.1% vs 9.0%, P = 0.003). Operative major morbidity or mortality was 6.4% versus 5.5% (P = 0.824), while the 1-year mortality rate was 2.1% versus 0% (P = 0.08). After risk adjustment, psoas index did not predict operative morbidity or mortality. However, sarcopenia was associated with higher odds of readmission (odds ratio = 0.74, P = 0.02). CONCLUSIONS: Contrary to other cardiac operations, for patients undergoing isolated minimally invasive mitral valve surgery, sarcopenia was not associated with increased perioperative risk except for higher readmission rates. Minimally invasive surgical approaches should be strongly considered as the approach of choice in frail patients.
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Procedimentos Cirúrgicos Cardíacos , Fragilidade , Sarcopenia , Humanos , Fragilidade/complicações , Fragilidade/epidemiologia , Valva Mitral/cirurgia , Fatores de Risco , Estudos Retrospectivos , Sarcopenia/complicações , Sarcopenia/epidemiologia , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Resultado do TratamentoRESUMO
The chapter on the thiol-related hydrogen bond (H-bond) and its excited-state intramolecular proton-transfer (ESIPT) reaction was recently opened where compound 4'-diethylamino-3-mercaptoflavone (3NTF) undergoes ESIPT in both cyclohexane solution and solid, giving a 710 nm tautomer emission with an anomalously large Stokes shift of 12,230 cm-1. Considering the thiol H-bond to be unconventional compared to the conventional Pauling-type -OH or -NH H-bond, it is thus essential and timely to probe its fundamental difference between their ESIPT. However, thiol-associated ESIPT tends to be nonemissive due to the dominant nπ* character of the tautomeric lowest excited state. Herein, based on the 3-mercaptoflavone scaffold and π-elongation concept, a new series of 4'-substituted-7-diethylamino-3-mercaptoflavones, NTFs, was designed and synthesized with varied H-bond strength and 690-720 nm tautomeric emission upon ultraviolet (UV) excitation in cyclohexane. The order of their H-bonding strength was experimentally determined to be N-NTF < O-NTF < H-NTF < F-NTF, while the rate of -SH ESIPT measured by fluorescence upconversion was F-NTF (398 fs)-1 < H-NTF (232 fs)-1 < O-NTF (123 fs)-1 < N-NTF (101 fs)-1 in toluene. Unexpectedly, the strongest H-bonded F-NTF gives the slowest ESIPT, which does not conform to the traditional ESIPT model. The results are rationalized by the trend of carbonyl oxygen basicity rather than -SH acidity. Namely, the thiol acidity relevant to the H-bond strength plays a minor role in the driving force of ESIPT. Instead, the proton-accepting strength governs ESIPT. That is to say, the noncanonical thiol H-bonding system undergoes an unconventional type of ESIPT.
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Exciplex-forming systems that display thermally activated delayed fluorescence are widely used for fabricating organic light-emitting diodes. However, their further development can be hindered through a lack of structural and thermodynamic characterization. Here we report the generation of inclusion complexes between a cage-like, macrocyclic, electron-accepting host (A) and various N-methyl-indolocarbazole-based electron-donating guests (D), which exhibit exciplex-like thermally activated delayed fluorescence via a through-space electron-transfer process. The D/A cocrystals are fully resolved by X-ray analyses, and UV-visible titration data show their formation to be an endothermic and entropy-driven process. Moreover, their emission can be fine-tuned through the molecular orbitals of the donor. Organic light-emitting diodes were fabricated using one of the D/A systems, and the maximum external quantum efficiency measured was 15.2%. An external quantum efficiency of 10.3% was maintained under a luminance of 1,000 cd m-2. The results show the potential of adopting inclusion complexation to better understand the relationships between the structure, formation thermodynamics and properties of exciplexes.
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BACKGROUND: Drug resistance may be acquired in people starting HIV pre-exposure prophylaxis (PrEP) during undiagnosed infection. Population-based estimates of PrEP-related resistance are lacking. METHODS: We used New York City surveillance and partner services data to measure the effect of PrEP use (tenofovir disoproxil fumarate/tenofivir alafenamide fumarate with emtricitabine) history on baseline prevalence of M184I/V mutations in people diagnosed with HIV, 2015-2022. PrEP use was categorized as "Recent" defined as PrEP stopped ≤ 90 days before diagnosis, "Past" as PrEP stopped >90 days before diagnosis, and "No known use". Resistance associated mutations were determined using the Stanford Algorithm. We used log binomial regression to generate adjusted relative risk (aRR) of M184I/V by PrEP use history in people with and without acute HIV infection (AHI). RESULTS: Of 4,246 newly diagnosed people with a genotype ≤30 days of diagnosis, 560 (13%) had AHI, 136 (3%) reported recent, and 124 (35%) past PrEP use; 98 (2%) harbored M184I/V. In people with AHI, recent PrEP use was associated with 6 times greater risk of M184I/V than no known use (aRR: 5.86; 95% confidence interval [CI]: 2.49-13.77). In people without AHI, risk of M184I/V in recent users was 7 times (aRR:7.26; 95% CI: 3.98-13.24), and in past users, 4 times that of people with no known use (aRR: 4.46; 95% CI: 2.15-9.24). CONCLUSIONS: PrEP use was strongly associated with baseline M184I/V in NYC, regardless of AHI. Ordering a nucleic acid test when indicated after assessment of exposure, antiretroviral history and AHI symptoms can decrease PrEP initiation in people with undetected infection.
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BACKGROUND: Since 2013, the World Health Organization has recommended that reproductive coercion (RC) and intimate partner violence (IPV) be addressed within reproductive health services and, in 2018, the Lancet Commission on Sexual and Reproductive Health and Rights found that RC and IPV were significant contributors to unmet need for family planning (FP) and unintended pregnancy. In Kenya, the Ministry of Health (MOH) has made reduction of unintended pregnancy and gender-based violence a primary objective. Despite this need and guidance, no clinic-based intervention models outside of the U.S. (apart from the one described here) have demonstrated efficacy to improve FP use and reduce IPV or RC thereby reducing unintended pregnancy. ARCHES (Addressing Reproductive Coercion in Health Settings) is a brief, clinic-based intervention delivered by existing FP providers aiming to: (1) Increase women's ability to use FP without interference, (2) Provide a safe and supportive environment for IPV disclosure and referral to support services, and (3) Improve quality of FP counseling, including addressing RC and IPV. The objective of this study is to generate evidence on scaling integrated FP services (including FP, RC, and IPV) in public sector health facilities in Uasin Gishu county, Kenya via adaptation and implementation of ARCHES in partnership with the Kenya MOH. METHODS: A cluster-randomized controlled trial paired with concurrent implementation science assessments will test effectiveness of the ARCHES model, adapted for scale by the Kenya MOH, in reducing unintended pregnancy. Female FP clients aged 15-49 years at selected sites will complete baseline surveys (immediately prior to receiving care), immediately post-visit exit surveys, and 6-month follow-up surveys. Provider surveys will assess changes in gender-equitable attitudes and self-efficacy to address violence reported by their clients. Costs associated with scaling ARCHES will be tracked and utilized in combination with results of the effectiveness trial to assess costs and cost-effectiveness relative to the standard of care. DISCUSSION: This study will provide evidence of the effectiveness of a facility-based intervention to address RC and IPV within public sector FP services at scale, as adapted and implemented in Uasin Gishu county, Kenya. Trial registration Trial registered on 28 September 2023 with clinicaltrials.gov NCT06059196.
This study will document evidence of the effectiveness of the ARCHES intervention, a brief, clinic-based counselling intervention demonstrated to reduce intimate partner violence and reproductive coercion and promote women's reproductive health, as scaled in government health facilities in Kenya. ARCHES aims to (1) decrease unintended pregnancy, (2) increase family planning uptake and use/continuation, (3) decrease experiences of reproductive coercion and intimate partner violence of women and girls aged 1549 years seeking family planning services, and to (4) improve quality of care, (5) increase gender equitable attitudes, and (6) increase self-efficacy to provide comprehensive family planning counseling among providers trained in ARCHES.
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Coerção , Violência por Parceiro Íntimo , Gravidez , Feminino , Humanos , Quênia , Gravidez não Planejada , Instituições de Assistência Ambulatorial , Governo , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Self-assembled monolayers (SAMs) offer the advantage of facile interfacial modification, leading to significant improvements in device performance. In this study, we report the design and synthesis of a new series of carboxylic acid-functionalized porphyrin derivatives, namely AC-1, AC-3, and AC-5, and present, for the first time, a strategy to exploit the large π-moiety of porphyrins as a backbone for interfacing the indium tin oxide (ITO) electrode and perovskite active layer in an inverted perovskite solar cell (PSC) configuration. The electron-rich nature of porphyrins facilitates hole transfer and the formation of SAMs, resulting in a dense surface that minimizes defects. Comprehensive spectroscopic and dynamic studies demonstrate that the double-anchored AC-3 and AC-5 enhance SAMs on ITO, passivate the perovskite layer, and function as conduits to facilitate hole transfer, thus significantly boosting the performance of PSCs. The champion inverted PSC employing AC-5 SAM achieves an impressive solar efficiency of 23.19 % with a high fill factor of 84.05 %. This work presents a novel molecular engineering strategy for functionalizing SAMs to tune the energy levels, molecular dipoles, packing orientations to achieve stable and efficient solar performance. Importantly, our comprehensive investigation has unraveled the associated mechanisms, offering valuable insights for future advancements in PSCs.