Recent advancements and applications of ophthalmic gene therapy strategies: A breakthrough in ocular therapeutics.

Over the past twenty years, ocular gene therapy has primarily focused on addressing diseases linked to various genetic factors. The eye is an ideal candidate for gene therapy due to its unique characteristics, such as easy accessibility and the ability to target both corneal and retinal conditions, including retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), age-related macular degeneration (AMD), and Stargardt disease. Currently, literature documents 33 clinical trials in this field, with the most promising results emerging from trials focused on LCA. These successes have catalyzed further research into other ocular conditions such as glaucoma, AMD, RP, and choroideremia. The effectiveness of gene therapy relies on the efficient delivery of genetic material to specific cells, ensuring sustained and optimal gene expression over time. Viral vectors have been widely used for this purpose, although concerns about potential risks such as immune reactions and genetic mutations have led to the development of non-viral vector systems. Preliminary laboratory research and clinical investigations have shown a connection between vector dosage and the intensity of immune response and inflammation in the eye. The method of administration significantly influences these reactions, with subretinal delivery resulting in a milder humoral response compared to the intravitreal route. This review discusses various ophthalmic diseases, including both corneal and retinal conditions, and their underlying mechanisms, highlighting recent advances and applications in ocular gene therapies.

Expanding the Role of Chiral Drugs and Chiral Nanomaterials as a Potential Therapeutic Tool.

Chirality, the property of molecules having mirror-image forms, plays a crucial role in pharmaceutical and biomedical research. This review highlights its growing importance, emphasizing how chiral drugs and nanomaterials impact drug effectiveness, safety, and diagnostics. Chiral molecules serve as precise diagnostic tools, aiding in accurate disease detection through unique biomolecule interactions. The article extensively covers chiral drug applications in treating cardiovascular diseases, CNS disorders, local anesthesia, anti-inflammatories, antimicrobials, and anticancer drugs. Additionally, it explores the emerging field of chiral nanomaterials, highlighting their suitability for biomedical applications in diagnostics and therapeutics, enhancing medical treatments.

Health information management systems and practices in conflict-affected settings: the case of northwest Syria.

BACKGROUND: In conflict settings, as it is the case in Syria, it is crucial to enhance health information management to facilitate an effective and sustainable approach to strengthening health systems in such contexts. In this study, we aim to provide a baseline understanding of the present state of health information management in Northwest Syria (NWS) to better plan for strengthening the health information system of the area that is transitioning to an early-recovery stage. METHODS: A combination of questionnaires and subsequent interviews was used for data collection. Purposive sampling was used to select twenty-one respondents directly involved in managing and directing different domains of health information in the NWS who worked with local NGOs, INGOs, UN-agencies, or part of the Health Working Group. A scoring system for each public health domain was constructed based on the number and quality of the available datasets for these domains, which were established by Checci and others. RESULTS & CONCLUSIONS: Reliable and aggregate health information in the NWS is limited, despite some improvements made over the past decade. The conflict restricted and challenged efforts to establish a concentrated and harmonized HIS in the NWS, which led to a lack of leadership, poor coordination, and duplication of key activities. Although the UN established the EWARN and HeRAMS as common data collection systems in the NWS, they are directed toward advocacy and managed by external experts with little participation or access from local stakeholders to these datasets. RECOMMENDATIONS: There is a need for participatory approaches and the empowerment of local actors and local NGOs, cooperation between local and international stakeholders to increase access to data, and a central domain for planning, organization, and harmonizing the process. To enhance the humanitarian health response in Syria and other crisis areas, it is imperative to invest in data collection and utilisation, mHealth and eHealth technologies, capacity building, and robust technical and autonomous leadership.

A New Insight Into The Huisgen Reaction: Heterogeneous Copper Catalyzed Azide-Alkyne Cycloaddition for the Synthesis of 1,4-Disubstituted Triazole (From 2018-2023).

The Huisgen cycloaddition, often referred to as 1,3-Dipolar cycloaddition, is a well-established method for synthesizing 1,4-disubstituted triazoles. Originally conducted under thermal conditions [3+2] cycloaddition reactions were limited by temperature, prolonged reaction time, and regioselectivity. The introduction of copper catalyzed azide-alkyne cycloaddition (CuAAC) revitalized interest, giving rise to the concept of "click chemistry". The CuAAC has emerged as a prominent method for producing 1,2,3-triazole with excellent yields and exceptional regioselectivity even in unfavorable conditions. Copper catalysts conventionally facilitate azide-alkyne cycloadditions, but challenges include instability and recycling issues. In recent years, there has been a growing demand for heterogeneous and porous catalysts in various chemical reactions. Chemists have been more interested in heterogenous catalysts as a result of the difficulties in separating homogenous catalysts from reaction products. These catalysts are favored for their abundant active sites, extensive surface area, easy separation from reaction mixtures, and the ability to be reused. Heterogeneous catalysts have garnered significant attention due to their broad industrial utility, characterized by cost-effectiveness, stability, resistance to thermal degradation, and ease of removal compared to their homogeneous counterparts. The present review covers recent advancements from year 2018 to 2023 in the field of click reactions for obtaining 1,2,3-triazoles through Cu catalyzed 1,3-dipolar azide-alkyne cycloaddition and the properties of the catalyst, reaction conditions such as solvent, temperature, reaction time, and the impact of different heterogeneous copper catalysts on product yield.

Recent updates on structural insights of MAO-B inhibitors: a review on target-based approach.

Parkinson's disease is a neurodegenerative disorder characterized by slow movement, tremors, and stiffness caused due to loss of dopaminergic neurons caused in the brain's substantia nigra. The concentration of dopamine is decreased in the brain. Parkinson's disease may be happened because of various genetic and environmental factors. Parkinson's disease is related to the irregular expression of the monoamine oxidase (MAO) enzyme, precisely type B, which causes the oxidative deamination of biogenic amines such as dopamine. MAO-B inhibitors, available currently in the market, carry various adverse effects such as dizziness, nausea, vomiting, lightheadedness, fainting, etc. So, there is an urgent need to develop new MAO-B inhibitors with minimum side effects. In this review, we have included recently studied compounds (2018 onwards). Agrawal et al. reported MAO-B inhibitors with IC50 0.0051 µM and showed good binding affinity. Enriquez et al. reported a compound with IC50 144 nM and bind with some critical amino acid residue Tyr60, Ile198, and Ile199. This article also describes the structure-activity relationship of the compounds and clinical trial studies of related derivatives. These compounds may be used as lead compounds to develop potent compounds as MAO-B inhibitors.

An insight on medicinal attributes of 1,2,3- and 1,2,4-triazole derivatives as alpha-amylase and alpha-glucosidase inhibitors.

Diabetes Mellitus (DM) is the globe's common leading disease which is caused by high consumption of glucose. DM compiles groups of metabolic disorders which are characterized by inadequate secretion of insulin from pancreas, resulting in hyperglycemia condition. Many enzymes play a vital role in the metabolism of carbohydrate known as α-amylase and α-glucosidase which is calcium metalloenzyme that leads to breakdown of complex polysaccharides into glucose. To tackle this problem, search for newer antidiabetic drugs is the utmost need for the treatment and/or management of increasing diabetic burden. The inhibition of α-amylase and α-glucosidase is one of the effective therapeutic approaches for the development of antidiabetic therapeutics. The exhaustive literature survey has shown the importance of medicinally privileged triazole specifically 1,2,3-triazol and 1,2,4-triazoles scaffold tethered, fused and/or clubbed with other heterocyclic rings structures as promising agents for designing and development of novel antidiabetic therapeutics. Molecular hybrids namely pyridazine-triazole, pyrazoline-triazole, benzothiazole-triazole, benzimidazole-triazole, curcumin-triazole, (bis)coumarin-triazole, acridine-9-carboxamide linked triazole, quinazolinone-triazole, xanthone-triazole, thiazolo-triazole, thiosemicarbazide-triazole, and indole clubbed-triazole are few examples which have shown promising antidiabetic activity by inhibiting α-amylase and/or α-glucosidase. The present review summarizes the structure-activity relationship (SAR), enzyme inhibitory activity including IC50 values, percentage inhibition, kinetic studies, molecular docking studies, and patents filed of the both scaffolds as alpha-amylase and alpha-glucosidase inhibitors, which may be used for further development of potent inhibitors against both enzymes.

Strengthening health systems and peacebuilding through women's leadership: a qualitative study.

BACKGROUND: Active and protracted conflict settings demonstrate the need to prioritise the peace through health agenda. This can be achieved by reorienting attention toward gender diverse leadership and more effective governance within health systems. This approach may enable women to have a greater voice in the decision-making of health and social interventions, thereby enabling the community led and context specific knowledge required to address the root causes of persistent inequalities and inequities in systems and societies. METHODS: We conducted a qualitative study, which included semi-structured interviews with 25 key informants, two focus group discussions and one workshop with humanitarian workers in local and international non-governmental organisations (NGOs), United Nations (UN) agencies, health practitioners, and academics, from Sub-Saharan Africa, Middle East and North Africa (MENA), and Latin America. Findings were then applied to the peacebuilding pyramid designed by John Paul Lederach which provides a practical framework for mediation and conflict resolution in several conflict-affected settings. The purpose of the framework was to propose an adapted conceptualisation of leadership to include women's leadership in the health system and be more applicable in protracted conflict settings. RESULTS: Five interrelated themes emerged. First, perceptions of terms such as gender equality, equity, mainstreaming, and leadership varied across participants and contexts. Second, armed conflict is both a barrier and an enabler for advancing women's leadership in health systems. Third, health systems themselves are critical in advancing the nexus between women's leadership, health systems and peacebuilding. Fourth, across all contexts we found strong evidence of an instrumental relationship between women's leadership in health systems in conflict-affected settings and peacebuilding. Lastly, the role of donors emerged as a critical obstacle to advance women's leadership. CONCLUSION: Continuing to empower women against social, cultural, and institutional barriers is crucial, as the emerging correlation between women's leadership, health systems, and peacebuilding is essential for long-term stability, the right to health, and health system responsiveness.

Health aid displacement during a decade of conflict (2011-19) in Syria: an exploratory analysis.

BACKGROUND: Syria has been in continuous conflict since 2011, resulting in more than 874,000 deaths and 13.7 million internally displaced people (IDPs) and refugees. The health and humanitarian sectors have been severely affected by the protracted, complex conflict and have relied heavily on donor aid in the last decade. This study examines the extent and implications of health aid displacement in Syria during acute humanitarian health crises from 2011 to 2019. METHODS: We conducted a trend analysis on data related to humanitarian and health aid for Syria between 2011 and 2019 from the OECD's Creditor Reporting System. We linked the data obtained for health aid displacement to four key dimensions of the Syrian conflict. The data were compared with other fragile states. We conducted a workshop in Turkey and key informants with experts, policy makers and aid practitioners involved in the humanitarian and health response in Syria between August and October 2021 to corroborate the quantitative data obtained by analysing aid repository data. RESULTS: The findings suggest that there was health aid displacement in Syria during key periods of crisis by a few key donors, such as the EU, Germany, Norway and Canada supporting responses to certain humanitarian crises. However, considering that the value of humanitarian aid is 50 times that of health aid, this displacement cannot be considered as critical. Also, there was insufficient evidence of health displacement across all donors. The results also showed that the value of health aid as a proportion of aggregate health and humanitarian aid is only 2% in Syria, compared to 22% for the combined average of fragile states, which further indicates the predominance of humanitarian aid over health aid in the Syrian crisis context. CONCLUSION: This study highlights that in very complex conflict-affected contexts such as Syria, it is difficult to suggest the use of health aid displacement as an effective tool for aid-effectiveness for donors as it does not reflect domestic needs and priorities. Yet there seems to be evidence of slight displacement for individual donors. However, we can suggest that donors vastly prefer to focus their investment in the humanitarian sector rather than the health sector in conflict-affected areas. There is an urgent need to increase donors' focus on Syria's health development aid and adopt the humanitarian-development-peace nexus to improve aid effectiveness that aligns with the increasing health needs of local communities, including IDPs, in this protracted conflict.

Novel VEGFR-2 Kinase Inhibitors as Anticancer Agents: A Review Focusing on SAR and Molecular Docking Studies (2016-2021).

Cancer growth, annexation, and metastatic spread are all aided by the formation of new blood vessels (angiogenesis). The commencement of the VEGF pathway leads to signal transduction that enhances endothelial cell survival, relocation, and divergence from pre-existing vasculature. The ability of solid malignancies to bloom and spread depends critically on their ability to establish their independent blood circulation (tumor angiogenesis). VEGFR is a major receptor tyrosine kinase that regulates angiogenesis, cell growth, and metastasis, diminishing apoptosis, cytoskeletal function, and other biological processes VEGFR has proven to be a remarkable focus for a variety of anticancer medicines in clinical studies. This Review explores the development of anti-VEGF-based antiangiogenic therapies having different scaffolds. This review had focused on SAR and docking studies of previously reported molecules.

Current progress in the targeted therapy of breast cancer: Structure-activity correlation and docking studies (2015-2021).

Despite cancer research and therapy, breast cancer remains a complicated health crisis in women and represents a top biomedical research priority. Nowadays, breast cancer is an extremely heterogeneous disease and is known as the leading cause of death among women worldwide. The incidence and mortality rates of breast cancer have been increasing gradually for the past decades. Nowadays, common treatments for breast cancer are chemotherapy, endocrine therapy, immunotherapy, radiotherapy, and surgery. The most common targets in breast cancer treatment are human epidermal growth factor receptor 2 (HER2) and estrogen receptors. The literature suggests that several targets/pathways are also involved in the development of breast cancer, that is, poly(ADP-ribose) polymerase (PARP), bromodomain-containing protein 4 (BRD4), cyclin-dependent kinase 4/6 (CDK4/6), epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR), polo-like kinase 1 (PLK1), phosphoinositide 3-kinases/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR), histone deacetylase (HDAC), nuclear factor kappa B (NF-κB), PD-L1, and aromatase inhibitors. Meanwhile, the study of breast cancer is a hot topic in the current scenario of basic/clinical research. This review article provides information on different targets associated with breast cancer and summarizes the progress of current research on synthesized inhibitors as anti-breast cancer agents from 2015 to 2021. The review aims to provide structure-activity relationship and docking studies for designing novel compounds for breast cancer therapy.

Biotic elicitor-induced changes in growth, antioxidative defense, and metabolites in an improved prickleless Solanum viarum.

Solanum viarum serves as a raw material for the steroidal drug industry due to its alkaloid and glycoalkaloid content. Elicitation is well-known for measuring the increase in the yield of bioactive compounds in in vitro cultures. The current study was performed for the accumulation of metabolites viz. solasodine, solanidine, and α-solanine in S. viarum culture using microbial-based elicitors added in 1%, 3%, 5%, and 7% on 25th and 35th day of culture period and harvested on 45th and 50th days of culture cycle. The treatment of 3% Trichoderma reesei and Bacillus tequilensis culture filtrate (CF) significantly increased biomass, alkaloids/glycoalkaloid content, and yield in S. viarum. T. reesei was found to be the best treatment for enhanced growth (GI = 11.65) and glycoalkaloid yield (2.54 mg DW plant-1) after the 50th day of the culture cycle when added on the 25th day. The abundance of gene transcripts involved in the biosynthesis of alkaloids/glycoalkaloids, revealed by quantitative real-time PCR expression analysis correlates with the accumulation of their respective metabolites in elicited plants. Biochemical analysis shows that elicited plants inhibited oxidative damage caused by reactive oxygen species by activating enzymes (superoxide dismutase and ascorbate peroxidase) as well as non-enzymatic antioxidant mechanisms (alkaloids, total phenols, total flavonoids, carotenoids, and proline). The findings of this study clearly demonstrate that the application of T. reesei and B. tequilensis CF at a specific dose and time significantly improve biomass as well as upregulates the metabolite biosynthetic pathway in an important medicinal plant- S. viarum. KEY POINTS: • Biotic elicitors stimulated the alkaloids/glycoalkaloid content in S. viarum plant cultures. • T. reesei was found to be most efficient for enhancing the growth and alkaloids content. • Elicited plants activate ROS based-defense mechanism to overcome oxidative damage.

Health research in the Syrian conflict: opportunities for equitable and multidisciplinary collaboration.

There is considerable global momentum from Syrian researchers, policy makers and diaspora to address health, security and development challenges posed by almost a decade of armed conflict and complex geopolitics that has resulted in different areas of political control. However, research funders have been so far reluctant to invest in large-scale research programmes in severely conflict-affected areas such as northern Syria. This paper presents examples of collaborations and programmes that could change this through equitable partnerships between academic and operational humanitarian organizations involving local Syrian researchers-a tremendous way forward to capitalize and accelerate this global momentum. Several academic and humanitarian organizations have initiated collaborations to build new networks and partnerships for better research and policy engagement in Syria. The networks conducted two consecutive annual conferences in 2019 and 2020. Key messages from these conference include: (1) equitable partnerships between organizations and individual researchers must form the basis of conducting better research; (2) ensuring the inclusion of local Syrian researchers is crucial in the development of any viable partnership; (3) capacity strengthening in health research is urgently needed in Syria's current phase of active conflict to inform, develop and implement strengthened and sustainable health systems in the post-conflict phase.

Exploring the role of gender and women in the political economy of health in armed conflict: a narrative review.

BACKGROUND: The ripple effects of protracted armed conflicts include: significant gender-specific barriers to accessing essential services such as health, education, water and sanitation and broader macroeconomic challenges such as increased poverty rates, higher debt burdens, and deteriorating employment prospects. These factors influence the wider social and political determinants of health for women and a gendered analysis of the political economy of health in conflict may support strengthening health systems during conflict. This will in turn lead to equality and equity across not only health, but broader sectors and systems, that contribute to sustainable peace building. METHODS: The methodology employed is a multidisciplinary narrative review of the published and grey literature on women and gender in the political economy of health in conflict. RESULTS: The existing literature that contributes to the emerging area on the political economy of health in conflict has overlooked gender and specifically the role of women as a critical component. Gender analysis is incorporated into existing post-conflict health systems research, but this does not extend to countries actively affected by armed conflict and humanitarian crises. The analysis also tends to ignore the socially constructed patriarchal systems, power relations and gender norms that often lead to vastly different health system needs, experiences and health outcomes. CONCLUSIONS: Detailed case studies on the gendered political economy of health in countries impacted by complex protracted conflict will support efforts to improve health equity and understanding of gender relations that support health systems strengthening.

Genome-wide identification, phylogeny, and expression analysis of the bHLH gene family in tobacco (Nicotiana tabacum).

The basic helix-loop-helix (bHLH) is the second-largest TF family in plants that play important roles in plant growth, development, and stress responses. In this study, a total of 100 bHLHs were identified using Hidden Markov Model profiles in the Nicotiana tabacum genome, clustered into 15 major groups (I-XV) based on their conserved domains and phylogenetic relationships. Group VIII genes were found to be the most abundant, with 27 NtbHLH members. The expansion of NtbHLHs in the genome was due to segmental and tandem duplication. The purifying selection was found to have an important role in the evolution of NtHLHs. Subsequent qRT-PCR validation of five selected genes from transcriptome data revealed that NtbHLH3.1, NtbHLH3.2, NtbHLH24, NtbHLH50, and NtbHLH59.2 have higher expressions at 12 and 24 h in comparison to 0 h (control) of chilling stress. The validated results demonstrated that NtbHLH3.2 and NtbHLH24 genes have 3 and fivefold higher expression at 12 h and 2 and threefold higher expression at 24 h than control plant, shows high sensitivity towards chilling stress. Moreover, the co-expression of positively correlated genes of NtbHLH3.2 and NtbHLH24 confirmed their functional significance in chilling stress response. Therefore, suggesting the importance of NtbHLH3.2 and NtbHLH24 genes in exerting control over the chilling stress responses in tobacco. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-01042-x.

The combination of histone deacetylase inhibitors and radiotherapy: a promising novel approach for cancer treatment.

HDAC inhibitors (HDACi) play an essential role in various cellular processes, such as differentiation and transcriptional regulation of key genes and cytostatic factors, cell cycle arrest and apoptosis that facilitates the targeting of epigenome of eukaryotic cells. In the majority of cancers, only a handful of patients receive optimal benefit from chemotherapeutics. Additionally, there is emerging interest in the use of HDACi to modulate the effects of ionizing radiations. The use of HDACi with radiotherapy, with the goal of reaching dissimilar, often distinct pathways or multiple biological targets, with the expectation of synergistic effects, reduced toxicity and diminished intrinsic and acquired resistance, conveys an approach of increasing interest. In this review, the clinical potential of HDACi in combination with radiotherapy is described as an efficient synergy for cancer treatment will be overviewed.

COVID-19 response in northwest Syria: innovation and community engagement in a complex conflict.

Despite lacking capacity and resources, the health system in the northwest Syria is using innovative approaches for the containment of COVID-19. Lessons drawn from previous outbreaks in the region, such as the polio outbreak in 2013 and the annual seasonal influenza, have enabled the Early Warning and Response Network, a surveillance system to develop mechanisms of predicting risk and strengthening surveillance for the new pandemic. Social media tools such as WhatsApp are effectively collecting health information and communicating health messaging about COVID-19. Community engagement has also been scaled up, mobilizing local resources and encouraging thousands of volunteers to join the 'Volunteers against Corona' campaign. Bottom-up local governance technical entities, such as Idleb Health Directorate and the White Helmets, have played key leadership role in the response. These efforts need to be scaled up to prevent the transmission of COVID-19 in a region chronically affected by a complex armed conflict.

Chemical Weapons and public health: assessing impact and responses.

BACKGROUND: The recent use of Chemical Weapons (CWs) in armed conflicts and terror attacks highlights the importance of understanding their full impact in order to inform an effective response. This article argues that while the consequences of CWs on individual health have dominated our understanding of the impact of these weapons, far less attention has been directed to their impact on public health. METHODS: A review of the literature on the health impact of CWs was conducted, and two case studies of their use in urban settings were explored - Halabja in northern Iraq in 1988 and throughout Syria's ongoing conflict. RESULTS: The importance of considering the long-term health consequences of CW use and their impact on healthcare and health systems was demonstrated. CONCLUSIONS: This article highlights the importance of supporting future research on the topic and proposes a framework for assessing the public health impact of CW use.

A narrative review of health research capacity strengthening in low and middle-income countries: lessons for conflict-affected areas.

Conducting health research in conflict-affected areas and other complex environments is difficult, yet vital. However, the capacity to undertake such research is often limited and with little translation into practice, particularly in poorer countries. There is therefore a need to strengthen health research capacity in conflict-affected countries and regions.In this narrative review, we draw together evidence from low and middle-income countries to highlight challenges to research capacity strengthening in conflict, as well as examples of good practice. We find that authorship trends in health research indicate global imbalances in research capacity, with implications for the type and priorities of research produced, equity within epistemic communities and the development of sustainable research capacity in low and middle-income countries. Yet, there is little evidence on what constitutes effective health research capacity strengthening in conflict-affected areas. There is more evidence on health research capacity strengthening in general, from which several key enablers emerge: adequate and sustained financing; effective stewardship and equitable research partnerships; mentorship of researchers of all levels; and effective linkages of research to policy and practice.Strengthening health research capacity in conflict-affected areas needs to occur at multiple levels to ensure sustainability and equity. Capacity strengthening interventions need to take into consideration the dynamics of conflict, power dynamics within research collaborations, the potential impact of technology, and the wider political environment in which they take place.

A conceptual framework for capacity strengthening of health research in conflict: the case of the Middle East and North Africa region.

BACKGROUND: In conflict settings, research capacities have often been de-prioritized as resources are diverted to emergency needs, such as addressing elevated morbidity, mortality and health system challenges directly and/or indirectly associated to war. This has had an adverse long-term impact in such protracted conflicts such as those found in the Middle East and North Africa region (MENA), where research knowledge and skills have often been compromised. In this paper, we propose a conceptual framework for health research capacity strengthening that adapts existing models and frameworks in low- and middle-income countries and uses our knowledge of the MENA context to contextualise them for conflict settings. METHODS: The framework was synthesized using "best fit" framework synthesis methodology. Relevant literature, available in English and Arabic, was collected through PubMed, Google Scholar and Google using the keywords: capacity building; capacity strengthening; health research; framework and conflict. Grey literature was also assessed. RESULTS: The framework is composed of eight principal themes: "structural levels", "the influence of the external environment", "funding, community needs and policy environment", "assessing existing capacity and needs", "infrastructure and communication", "training, leadership and partnership", "adaptability and sustainability", and "monitoring and evaluation"; with each theme being supported by examples from the MENA region. Our proposed framework takes into consideration safety, infrastructure, communication and adaptability as key factors that affect research capacity strengthening in conflict. As it is the case more generally, funding, permissible political environments and sustainability are major determinants of success for capacity strengthening for health research programmes, though these are significantly more challenging in conflict settings. Nonetheless, health research capacity strengthening should remain a priority. CONCLUSION: The model presented is the first framework that focuses on strengthening health research capacity in conflict with a focus on the MENA region. It should be viewed as a non-prescriptive reference tool for health researchers and practitioners, from various disciplines, involved in research capacity strengthening to evaluate, use, adapt and improve. It can be further extended to include representative indicators and can be later evaluated by assessing its efficacy for interventions in conflict settings.

Bladder Endometriosis: Management by Cystoscopic and Laparoscopic Approaches.

STUDY OBJECTIVE: Endometriosis of the urinary system accounts for less than 1% of all endometriosis, wherein bladder endometriosis is the most common. Bladder endometriosis is defined as endometriosis infiltrating the detrusor muscle and represents 85% of urinary tract endometriosis [1,2]. Segmental bladder resection/partial cystectomy is the bladder-preserving surgery and offers the complete removal of bladder endometriotic nodules [3,4]. Laparoscopic/robotic excision increases the chances of complete removal of nodules but may lead to inadvertent removal of excess bladder wall and increase the risk of complications, especially in cases of large lesions in close proximity to ureteric orifices. Thus, simultaneous laparoscopy and cystoscopy offers the most effective way of complete resection of bladder endometriotic nodules, relieving symptoms and minimizing intraoperative and postoperative complications and recurrence rates in patients [5-11]. This article with accompanying video describes the systematic approach and step-by-step surgical excision of a bladder endometriotic nodule in a patient with frozen pelvis. DESIGN: Step-by-step surgical excision of a bladder endometriotic nodule by simultaneous cystoscopy and laparoscopy. (Canadain Task Force classification: level III) SETTING: Jyoti Hospital and Minimum Invasive Surgery Center, Ahmedabad, India. PATIENT: A 41-year-old women, P2L2, presented with cyclical dysmenorrhea, dysuria, and chronic pelvic pain. Informed consent was obtained from the patient, and the local institutional board provided the approval. INTERVENTION: Simultaneous cystoscopy and laparoscopy. MEASUREMENTS AND MAIN RESULTS: A preoperative assessment was done with transvaginal ultrasonography with a partially full bladder that showed an intravesical 3-cm endometriotic nodule along with chocolate cysts of the ovary and adenomyosis of the uterus. A simultaneous cystoscopy by a urologist and laparoscopy by a gynecologist was performed. On cystoscopy the nodule was seen away from both the ureteric orifices. The nodule was marked cystoscopically with a monopolar needle and laparoscopically with bipolar scissors. Laparoscopy began with a full inspection of the abdomen, pelvis, and adhesions. Dissection started from the left round ligament, and both paravesical spaces were dissected gently, keeping the bladder partially full. Good uterine manipulation helped to delineate vaginal fornices during dissection. Dissection continued over the isthmus, and bladder was gently separated from the isthmus. The bladder was partially filled with methylene blue and intentionally cut opened to excise the demarcated bladder nodule with a monopolar hook, taking a disease-free margin of 5 mm [12]. Two stay sutures were taken at both the lateral angles of the bladder, and suture ends were brought outside the abdomen to facilitate closure of the bladder transversely. After mobilization of the bladder, both uterine vascular bundles were desiccated with bipolar and laparoscopic hysterectomy. Vaginal closure was done away from bladder stitches. The patient was discharged on day 3 with catheter and DJ stents. On day 21, 3-dimensional computed tomography cystogram showed adequate bladder volume. Catheter and DJ stents were removed, low-pressure cystoscopy showed a smooth stitch line with mucosa over it and no residual endometriosis. The patient was found to have no symptoms at the 2-year follow up. CONCLUSION: The video demonstrates the feasibility of simultaneous laparoscopic and cystoscopic approach for excision of a bladder endometriotic nodule. Marking the nodule by simultaneous cystoscopy and laparoscopy before excision helps in removing the disease completely and avoiding unnecessary normal bladder wall excision, thus reducing the risk of recurrence and resultant small bladder symptoms.