Comparison of Sonographic Findings with Diagnostic Mammography.

BACKGROUND: Breast cancer is the leading female cancer worldwide with a high mortality rate. Early detection of the suspicious lesion is crucial for better prognosis. Higher breast density decreases the sensitivity of mammogram. Ultrasound can differentiate between cystic and solid masses and further characterize these as benign or possibly malignant. Our objective was to compare the findings of sonography with diagnostic mammography. METHODS: This was a cross sectional study including 125 females who underwent diagnostic mammogram in a tertiary care center. The mammograms were evaluated and the patients were scanned by ultrasound and categorized as per ACR- BIRADS category. The findings of diagnostic mammography were compared with that of ultrasonography using SPSS version 25. RESULTS: The heterogeneously dense breast in diagnostic mammography corresponded to the heterogenous- fibroglandular breast in ultrasonography. In majority, ultrasound increased the BIRADS category for the lesion than designated by the diagnostic mammography. It was particularly useful for category 0 and 3 lesions which were indeterminate and required further imaging. CONCLUSIONS: Ultrasound was useful in evaluation of dense breasts with ACR-BIRADS 0 and 3 in diagnostic mammogram. For category 3 and 4 in diagnostic mammogram, ultrasound showed category 1 or 2 lesions which aided to alleviate patient anxiety and avoid unnecessary biopsies. With emerging technological advances in ultrasound, it can used as a powerful tool for breast lesion detection and patient management.

An Online Pediatric Palliative Care Education and Mentoring (Project ECHO) in Nepal: A Program Implementation Case Study and Assessment of Changes in Healthcare Providers' Knowledge, Confidence, and Attitudes.

OBJECTIVES: The goal of this implementation study was to describe the implementation and evaluation of the impact of an online pediatric palliative care training program in Nepal, using the Project ECHO model. METHODS: The study used mixed methods, including a program case study describing the online learning program and before-and-after surveys of program participants, assessing learning through changes in knowledge, comfort, and attitudes. An end-of-program survey was used to evaluate participants' overall experiences with the learning program and use of the learning resources. RESULTS: A literature review, stakeholder surveys, and expert input informed the design of the intervention. The course used the Project ECHO model of online education, with modifications based on the leadership team's previous ECHO experiences and local stakeholder input. The intervention occurred over 9 months, with 22 online teaching sessions. Each session consisted of a didactic lecture, case presentation, and interactive discussion with expert clinical teachers. Fifty-five clinicians in Nepal participated, including physicians (47%), nurses (44%), and psychotherapists (5%). Clinicians reported improvements in knowledge, skills, and attitudes after program participation. Program acceptability scores were high, with 93% of participants reporting that the course provided effective learning. CONCLUSIONS: Project ECHO can be successfully implemented to deliver continuing professional development in Nepal. Delivering palliative care education online using the Project ECHO model, leads to improved knowledge, skills, and attitudes for clinicians. Project ECHO suggests an innovative solution which can provide training and support to clinicians in settings where educational opportunities in palliative care are limited.

Co-constructing collaboration: An evidence-based approach to advance and evaluate equitable global public health research partnerships.

Equitable global health partnerships are essential to promote innovative research and strengthen research capacity to address critical public health challenges, but how to optimally evaluate such collaborations is unclear. This was a sequential, multi-method study that utilized an electronic survey informed by the literature followed by semi-structured interviews to comprehensively evaluate the experience of participating in a global research-capacity building collaboration between Nepal and U.S. clinicians and investigators. De-identified quantitative survey were analyzed to calculate descriptive and summary statistics, along with crosstabs of each variable by group. Groups were defined based on country-of-origin and Chi Square statistics calculated to assess for statistically significant differences (p<0.05) between groups. Interviews were analyzed using a descriptive qualitative approach to develop an overall thematic map. 22 survey responses (52.4% response rate) were analyzed; 13 (59.1%) from Nepal, 9 (40.9%) from the U.S. Eight participants (4 Nepal; 4 U.S.) were interviewed. Over the course of the project, all participants reported gaining experience and confidence with research. The majority of participants "strongly agreed" there was a shared understanding of goals, priorities and strategies (Nepal, 58.3%, n = 7; U.S., 88.9%, n = 8;) and that power was shared equally (Nepal, 58.3%, n = 7; U.S., 55.6%, n = 5). The over-arching theme that emerged from the interviews was the importance of 'establishing community' which participants discussed within the broader context of COVID-19. Overall, team members reported strong bi-directional benefit and a greater emphasis on perceived benefits versus challenges. Our survey tool and interview guide, designed to holistically evaluate the impact of a global partnership across various levels of the Social Ecological Model, with particular attention to power dynamics and equity, can be adapted and used by others engaged in similar research capacity collaborations.

Outcome of Epidermal Growth Factor Receptor Mutated and Non Mutated Adenocarcinoma Lung to Standard Therapy.

BACKGROUND: Asian patients with adenocarcinoma of lung have higher incidence of epidermal growth factor receptor mutations which predict increased response and survival in patients to oral tyrosine kinase inhibitors. This study was conducted to study the frequency of epidermal growth factor receptor mutation in patients in Nepal and compare the outcome in epidermal growth factor receptor mutated versus non-mutated patients receiving standard therapy. METHODS: This is an observational study conducted among newly diagnosed patients with stage IV adenocarcinoma of lung in Bir Hospital from April 2017 to June 2018. Demographic and clinical data collection along with epidermal growth factor receptor mutation testing was done. Patients with epidermal growth factor receptor mutations received Gefitinib while non-mutated patients received systemic chemotherapy. Response evaluation, progression free survival at 1 year, objective response rate and quality of life were compared. Follow up period was for 1 year. RESULTS: Eighty three (33%, n=253) patients were diagnosed with adenocarcinoma of the lung with mean age at diagnosis being 59.4 years. epidermal growth factor receptor mutations were found in 29% patients. Complete response was achieved in 9.1% vs 3.0 % (p=0.46), objective response rate was 27.3% versus 15.2% (p=0.23), progression free survival at 1 year was 39% vs 27%, (p = 0.29) and mean score of global health status was 68.1 versus 61.6 in epidermal growth factor receptor mutated versus non-mutated (p = 0.036). CONCLUSIONS: The frequency of epidermal growth factor receptor mutation in patients with adenocarcinoma of the lung was lower than in Eastern Asian studies, but higher than in western populations. epidermal growth factor receptor mutated patients had improved survival, better treatment response and quality of life in comparison with non-mutated.

Real-time single-molecule observation of chaperone-assisted protein folding.

The ability of heat shock protein 70 (Hsp70) molecular chaperones to remodel the conformation of their clients is central to their biological function; however, questions remain regarding the precise molecular mechanisms by which Hsp70 machinery interacts with the client and how this contributes toward efficient protein folding. Here, we used total internal reflection fluorescence (TIRF) microscopy and single-molecule fluorescence resonance energy transfer (smFRET) to temporally observe the conformational changes that occur to individual firefly luciferase proteins as they are folded by the bacterial Hsp70 system. We observed multiple cycles of chaperone binding and release to an individual client during refolding and determined that high rates of chaperone cycling improves refolding yield. Furthermore, we demonstrate that DnaJ remodels misfolded proteins via a conformational selection mechanism, whereas DnaK resolves misfolded states via mechanical unfolding. This study illustrates that the temporal observation of chaperone-assisted folding enables the elucidation of key mechanistic details inaccessible using other approaches.

The role of auxiliary domains in modulating CHD4 activity suggests mechanistic commonality between enzyme families.

CHD4 is an essential, widely conserved ATP-dependent translocase that is also a broad tumour dependency. In common with other SF2-family chromatin remodelling enzymes, it alters chromatin accessibility by repositioning histone octamers. Besides the helicase and adjacent tandem chromodomains and PHD domains, CHD4 features 1000 residues of N- and C-terminal sequence with unknown structure and function. We demonstrate that these regions regulate CHD4 activity through different mechanisms. An N-terminal intrinsically disordered region (IDR) promotes remodelling integrity in a manner that depends on the composition but not sequence of the IDR. The C-terminal region harbours an auto-inhibitory region that contacts the helicase domain. Auto-inhibition is relieved by a previously unrecognized C-terminal SANT-SLIDE domain split by ~150 residues of disordered sequence, most likely by binding of this domain to substrate DNA. Our data shed light on CHD4 regulation and reveal strong mechanistic commonality between CHD family members, as well as with ISWI-family remodellers.

Building a 'Virtual Library': continuing a global collaboration to strengthen research capacity within Nepal and other low- and middle-income countries.

To fill the gap in health research capacity-building efforts, we created the 'Virtual Library' (VL) - a web-based repository of context-relevant resources for health researchers in low- and middle-income countries (LMICs). This paper describes the participatory process used to systematically develop the VL, and describes how our interprofessional team - representing both an LMIC (Nepal) and a high-income country (HIC) (USA, US) - engaged in shared meaning-making. A team of researchers and clinicians representing a range of subdisciplines from Nepal and the US created a replicable search strategy and standardized Resource Screening Guide (RSG) to systematically assess resources to be included within the VL. Descriptive methods were used to summarize findings from the RSG and lessons learned from the collaborative process. Collectively, 14 team members reviewed 564 potential resources (mean = 40, SD = 22.7). Mean RSG score was 7.02/10 (SD = 2). More than 76% of resources met each of the four quality criteria (relevant; reputable, accessible; understandable). Within the published VL, 298 resources were included, organized by 15 topics and 45 sub-topics. Of these, 223 resources were evaluated by the RSG; 75 were identified by team member expertise. The collaborative process involved regular meetings, iterative document revisions, and peer review. Resource quality was better than expected, perhaps because best practices/principles related to health research are universally relevant, regardless of context. While the RSG was essential to systematize our search and ensure reproducibility, team member expertise was valuable. Pairing team members during peer-review led to bi-directional knowledge sharing and was particularly successful. This work reflects a highly collaborative global partnership and offers a model for future health research capacity-building efforts. We invite engagement with the Virtual Library as one supportive pillar of infrastructure to develop individual and institutional research capacity.

A Global Collaboration to Develop and Pilot Test a Mobile Application to Improve Cancer Pain Management in Nepal.

Introduction: Quality palliative care, which prioritizes comfort and symptom control, can reduce global suffering from non-communicable diseases, such as cancer. To address this need, the Nepalese Association of Palliative Care (NAPCare) created pain management guidelines (PMG) to support healthcare providers in assessing and treating serious pain. The NAPCare PMG are grounded in World Health Organization best practices but adapted for the cultural and resource context of Nepal. Wider adoption of the NAPCare PMG has been limited due to distribution of the guidelines as paper booklets. Methods: Building on a long-standing partnership between clinicians and researchers in the US and Nepal, the NAPCare PMG mobile application ("app") was collaboratively designed. Healthcare providers in Nepal were recruited to pilot test the app using patient case studies. Then, participants completed a Qualtrics survey to evaluate the app which included the System Usability Scale (SUS) and selected items from the Mobile App Rating Scale (MARS). Descriptive and summary statistics were calculated and compared across institutions and roles. Regression analyses to explore relationships (α = 0.05) between selected demographic variables and SUS and MARS scores were also conducted. Results: Ninety eight healthcare providers (n = 98) pilot tested the NAPCare PMG app. Overall, across institutions and roles, the app received an SUS score of 76.0 (a score > 68 is considered above average) and a MARS score of 4.10 (on a scale of 1 = poor, 5 = excellent). 89.8% (n = 88) "agreed" or "strongly agreed" that the app will help them better manage cancer pain. Age, years of experience, and training in palliative care were significant in predicting SUS scores (p-values, 0.0124, 0.0371, and 0.0189, respectively); institution was significant in predicting MARS scores (p = 0.0030). Conclusion: The NAPCare PMG mobile app was well-received, and participants rated it highly on both the SUS and MARS. Regression analyses suggest end-user variables important to consider in designing and evaluating mobile apps in lower resourced settings. Our app design and pilot testing process illustrate the benefits of cross global collaborations to build research capacity and generate knowledge within the local context.

Mechanism of transcription modulation by the transcription-repair coupling factor.

Elongation by RNA polymerase is dynamically modulated by accessory factors. The transcription-repair coupling factor (TRCF) recognizes paused/stalled RNAPs and either rescues transcription or initiates transcription termination. Precisely how TRCFs choose to execute either outcome remains unclear. With Escherichia coli as a model, we used single-molecule assays to study dynamic modulation of elongation by Mfd, the bacterial TRCF. We found that nucleotide-bound Mfd converts the elongation complex (EC) into a catalytically poised state, presenting the EC with an opportunity to restart transcription. After long-lived residence in this catalytically poised state, ATP hydrolysis by Mfd remodels the EC through an irreversible process leading to loss of the RNA transcript. Further, biophysical studies revealed that the motor domain of Mfd binds and partially melts DNA containing a template strand overhang. The results explain pathway choice determining the fate of the EC and provide a molecular mechanism for transcription modulation by TRCF.

Cancer Prevention Strategies for Nepal.

In Nepal, the commonest major malignancies and causes of cancer death are lung, cervix, stomach, breast, head and neck (lip, mouth, pharynx, larynx), gallbladder, ovary and liver. There are seven cancer-causative exposures which should be the focus of attention such as; tobacco smoking in 29% of men, and 6% of women, solid fuel burning in 69% of homes (multiple cancers), betel-nut chewing in 40 % of men and 3% of women (head and neck cancers), alcohol abuse (liver and other cancers), Human Papilloma Virus (cervical cancer), Helicobacter pylori (stomach cancer) and Hepatitis B virus (liver cancer). To better address these reducible exposures, we suggest greater targeted strategies in three areas: Public health messaging for tobacco, solid-fuel burning, betel-nut, and alcohol; national policies for Hepatitis B virus vaccination; and analytic epidemiological and interventional research for Human Papilloma Virus and helicobacter.

A survey of cancer care institutions in Nepal to inform design of a pain management mobile application.

BACKGROUND: One way to improve the delivery of oncology palliative care in low and middle-income countries (LMICs) is to leverage mobile technology to support healthcare providers in implementing pain management guidelines (PMG). However, PMG are often developed in higher-resourced settings and may not be appropriate for the resource and cultural context of LMICs. OBJECTIVES: This research represents a collaboration between the University of Virginia and the Nepalese Association of Palliative Care (NAPCare) to design a mobile health application ('app') to scale-up implementation of existing locally developed PMG. METHODS: We conducted a cross-sectional survey of clinicians within Nepal to inform design of the app. Questions focused on knowledge, beliefs, and confidence in managing cancer pain; barriers to cancer pain management; awareness and use of the NAPCare PMG; barriers to smart phone use and desired features of a mobile app. FINDINGS: Surveys were completed by 97 palliative care and/or oncology healthcare providers from four diverse cancer care institutions in Nepal. 49.5% (n = 48) had training in palliative care/cancer pain management and the majority (63.9%, n = 62) reported high confidence levels (scores of 8 or higher/10) in managing cancer pain. Highest ranked barriers to cancer pain management included those at the country/cultural level, such as nursing and medical school curricula lacking adequate content about palliative care and pain management, and patients who live in rural areas experiencing difficulty accessing healthcare services (overall mean = 6.36/10). Most nurses and physicians use an Android Smart Phone (82%, n = 74), had heard of the NAPCare PMG (96%, n = 88), and reported frequent use of apps to provide clinical care (mean = 6.38/10, n = 92). Key barriers to smart phone use differed by discipline, with nurses reporting greater concerns related to cost of data access (70%, n = 45) and being prohibited from using a mobile phone at work (61%; n = 39). CONCLUSIONS: Smart phone apps can help implement PMG and support healthcare providers in managing cancer pain in Nepal and similar settings. However, such tools must be designed to be culturally and contextually congruent and address perceived barriers to pain management and app use.

Assessment of Adult Women With Ovarian Masses and Treatment of Epithelial Ovarian Cancer: ASCO Resource-Stratified Guideline.

PURPOSE: To provide expert guidance to clinicians and policymakers in three resource-constrained settings on diagnosis and staging of adult women with ovarian masses and treatment of patients with epithelial ovarian (including fallopian tube and primary peritoneal) cancer. METHODS: A multidisciplinary, multinational ASCO Expert Panel reviewed existing guidelines, conducted a modified ADAPTE process, and conducted a formal consensus process with additional experts. RESULTS: Existing sets of guidelines from eight guideline developers were found and reviewed for resource-constrained settings; adapted recommendations from nine guidelines form the evidence base, informing two rounds of formal consensus; and all recommendations received ≥ 75% agreement. RECOMMENDATIONS: Evaluation of adult symptomatic women in all settings includes symptom assessment, family history, and ultrasound and cancer antigen 125 serum tumor marker levels where feasible. In limited and enhanced settings, additional imaging may be requested. Diagnosis, staging, and/or treatment involves surgery. Presurgical workup of every suspected ovarian cancer requires a metastatic workup. Only trained clinicians with logistical support should perform surgical staging; treatment requires histologic confirmation; surgical goal is staging disease and performing complete cytoreduction to no gross residual disease. In first-line therapy, platinum-based chemotherapy is recommended; in advanced stages, patients may receive neoadjuvant chemotherapy. After neoadjuvant chemotherapy, all patients should be evaluated for interval debulking surgery. Targeted therapy is not recommended in basic or limited settings. Specialized interventions are resource-dependent, for example, laparoscopy, fertility-sparing surgery, genetic testing, and targeted therapy. Multidisciplinary cancer care and palliative care should be offered.Additional information can be found at www.asco.org/resource-stratified-guidelines. It is ASCO's view that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines.

Cardiovascular Reactivity to Acute Mental Stress in Post Ovulatory Females.

BACKGROUND: Female hormones fluctuate with the phases of menstrual cycle. Estrogen, which has attributes in cardio-protection, is secreted less during luteal phase. In post-ovulatory phase, days 1-2 before menstruation has minimal female hormone influence due to less secretion. Mental stress subjected at this phase might enhance sympathetic activation which in long run may precipitate cardiovascular diseases. Hence, to explore the autonomic activity to mental stress during this phase of menstrual cycle the study was undertaken. METHODS: Thirty apparently healthy young postovulatory female medical students of B. P. Koirala Institute of Health Sciences, Nepal of age 19.93 (± 0.91) years with BMI of 20.70 kg/m2 (± 2.49) kg/m2 were recruited for the present study. Their short term heart rate variability (HRV) of 5 min was recorded during rest at sitting position. Then each subject was given a mental stress (nine questions selected from MENSA workout questionnaire) for 5 min. During the stress, HRV was recorded simultaneously. Data was statistically analyzed using Friedman test followed by multiple comparisons. The p<0.005 was considered statistically significant. RESULTS: Mental stress significantly decreased RMSSD (p= 0.001), NN50 (p= 0.001) and PNN50 (p=0.001) in time domain and HF nu (p=0.012) in frequency domain parameters of HRV. CONCLUSIONS: Young healthy post ovulatory females responded to acute mental stress by withdrawing cardiac parasympathetic activity.

Illness Representations of Hypertension among Nepali Patients at a Tertiary Care Hospital Clinic: An exploratory survey.

BACKGROUND: The prevalence of stage 2 hypertension approaches one-third in adult Nepalis and despite inexpensive effective treatment, long-term compliance is poor. World-wide, a major impediment is the incongruity between hypertension and patients' symptom-based illness representations. The Common-Sense Model of Self-regulation was used to investigate Nepali illness representations through open-ended interviews of patients with hypertension. METHODS: In a tertiary hospital setting, 50 self-identified hypertensive patients were interviewed about their representations of health, hypertension, and hypertensive treatment. Responses were analyzed with a modified Interpretative Phenomenological Analysis. RESULTS: An Ayurvedic-influenced health model appeared in illness identity and coping responses. Hypertension was identified as a serious disease having observable, wide-ranging symptoms with chronic and intermittent timelines. Concerns included side-effects and barriers to treatment. CONCLUSIONS: Further confirmation and investigation of Nepali common-sense hypertension models in a sample size sufficient for factor analysis is warranted for effective adherence interventions.

Reorganizing Hospital Cancer Care In Nepal.

While mortality rates for major common cancers- of the lung, breast, stomach, ovary, and lymphomas-- have declined significantly in high-income countries over the last decade, comparable rates for these malignancies have not fallen in Nepal. The explanations for the high-income country mortality trends are multiple and certainly include incidence reductions, but better treatments are also contributory. How to bring to Nepal the global lessons in achieving better cancer care is uncertain. We need to create an environment of ideas and a powerful vision to meet the needs for better major cancer management for Nepalis. Broadly, the Nepalese challenges are in creating more accessible and affordable care of sufficiently high-quality to make a difference. Hospitals are the major places where these issues have to be considered. To address these challenges, we offer a vision and suggest here strategies of major organizational changes in: Innovative staffing models, emphasizing teamwork, with increases in responsibilities, activities and work force percentages of non-physician health professionals; Increased outpatient care and tele-health; 3.Creating and following evidence-based diagnostic pathway and treatment clinical practice guidelines and checklists; 4. Increased application of information technology tools, particularly electronic medical records; and 5. Service implementation research evaluating quality based on structure, process and outcomes of care. Developing such effective changes requires strong community linkages, local institutional-specific coalition initiatives and experimentation, and national and international collaborations and financial support to effect practical and data-based plans and budgets. Keywords: Guidelines; improving treatment; information technology tools; outpatient services; staffing models; tele-health.

KRAS Oncogene Mutations in Colorectal Cancer Patients in a Nepalese Tertiary Care Hospital.

BACKGROUND: Colorectal cancer is one of the most common cancers in the world and ranks among top ten cancer in Nepal. Limited data have been reported in the literature regarding the prevalence of Kristen Rat Sarcoma viral oncogene mutation in Nepalese patients with colorectal cancer. In a low income country such as Nepal where majority of cancer patient pay for treatment out-of-pocket, it is important to ascertain Kristen Rat Sarcoma viral oncogene mutation status before starting treatment with these agents. METHODS: We analysed 22 colorectal cancer specimens diagnosed histopathologically. Real Time Polymerase Chain Reaction was performed on extracted DNA using RoterGene from Qiagen. US Food and Drug Administration approved kit was used for detection of Kristen Rat Sarcoma viral oncogene mutation i.e. TheraScreen: K-RAS Mutation Kit: The K-RAS Kit detects seven Kristen Rat Sarcoma viral oncogene mutations in codons 12 and 13 of the Kristen Rat Sarcoma viral oncogene. RESULTS: Kristen Rat Sarcoma viral oncogene mutation was observed in 13 (59%) of the samples studied. All samples had point mutation on codons 12 while 5 samples (38%) also had a point mutation on codons 13. No association was found between the presence of Kristen Rat Sarcoma viral oncogene mutation and gender or age or sidedness of the cancer. CONCLUSIONS: Kristen Rat Sarcoma viral oncogene was commonly present in colorectal cancer specimens. Further efforts towards establishment of diagnostic test, generation of new database, development and scale up of laboratory services are needed throughout the nation.

Single-molecule fluorescence-based approach reveals novel mechanistic insights into human small heat shock protein chaperone function.

Small heat shock proteins (sHsps) are a family of ubiquitous intracellular molecular chaperones; some sHsp family members are upregulated under stress conditions and play a vital role in protein homeostasis (proteostasis). It is commonly accepted that these chaperones work by trapping misfolded proteins to prevent their aggregation; however, fundamental questions regarding the molecular mechanism by which sHsps interact with misfolded proteins remain unanswered. The dynamic and polydisperse nature of sHsp oligomers has made studying them challenging using traditional biochemical approaches. Therefore, we have utilized a single-molecule fluorescence-based approach to observe the chaperone action of human alphaB-crystallin (αBc, HSPB5). Using this approach we have, for the first time, determined the stoichiometries of complexes formed between αBc and a model client protein, chloride intracellular channel 1. By examining the dispersity and stoichiometries of these complexes over time, and in response to different concentrations of αBc, we have uncovered unique and important insights into a two-step mechanism by which αBc interacts with misfolded client proteins to prevent their aggregation.

An α-Cyanostilbene Derivative for the Enhanced Detection and Imaging of Amyloid Fibril Aggregates.

The aggregation of proteins into amyloid fibrils has been implicated in the pathogenesis of a variety of neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Benzothiazole dyes such as Thioflavin T (ThT) are well-characterized and widely used fluorescent probes for monitoring amyloid fibril formation. However, existing dyes lack sensitivity and specificity to oligomeric intermediates formed during fibril formation. In this work, we describe the use of an α-cyanostilbene derivative (called ASCP) with aggregation-induced emission properties as a fluorescent probe for the detection of amyloid fibrils. Similar to ThT, ASCP is fluorogenic in the presence of amyloid fibrils and, upon binding and excitation at 460 nm, produces a red-shifted emission with a large Stokes shift of 145 nm. ASCP has a higher binding affinity to fibrillar α-synuclein than ThT and likely shares the same binding sites to amyloid fibrils. Importantly, ASCP was found to also be fluorogenic in the presence of amorphous aggregates and can detect oligomeric species formed early during aggregation. Moreover, ASCP can be used to visualize fibrils via total internal reflection fluorescence microscopy and, due to its large Stokes shift, simultaneously monitor the fluorescence emission of other labelled proteins following excitation with the same laser used to excite ASCP. Consequently, ASCP possesses enhanced and unique spectral characteristics compared to ThT that make it a promising alternative for the in vitro study of amyloid fibrils and the mechanisms by which they form.

Distress Screening among Patients with Hematological Malignancies: A Descriptive Cross-sectional Study.

INTRODUCTION: Distress is a major concern during diagnosis and treatment of hematological malignancies. The Distress Thermometer is a commonly used screening tool to detect distress. The objectives of this study was to know the prevalence and identify distress score among patients with hematological malignancies in Nepal. METHODS: A descriptive cross sectional study was carried out at the Hematology Unit of Civil Service Hospital after obtaining an ethical approval from the Institutional Review Committee (reference number 931/076/077). A convenient sampling technique was used for this study. Statistical Package for the Social Sciences version 20.0 was used. All patients within one week of diagnosis and before the start of definitive treatment of hematological malignancies were included in the study. National Comprehensive Cancer Network Psychosocial Distress Screening Tool was used to measure the seriousness of distress. RESULTS: A total of 100 patients were enrolled in the study, among them 56 (56%) were male and 44 (44%) were female. The mean distress score in our study was found to be 5.68±1.75. Mean distress score among male and female patients were 5.84±1.65 and 5.48±1.86 respectively. Thirty three percentage (n=33) of patient had mild distress whereas, sixty six percentage (n=67) of patients experienced moderate to severe distress. CONCLUSIONS: There was a significant level of distress among the patients with hematological malignancies in Nepal. Therefore, distress screening should be done to all the patients when initial diagnosis is made.