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Junie B Billones,1,2 Maria Constancia O Carrillo,1 Voltaire G Organo,1 Stephani Joy Y Macalino,1 Jamie Bernadette A Sy,1 Inno A Emnacen,1 Nina Abigail B Clavio,1 Gisela P Concepcion31Office of the Vice President for Academic Affairs – Emerging Interdisciplinary Research Program: “Computer-aided Discovery of Compounds for the treatment of Tuberculosis in the Philippines,” Department of Physical Sciences and Mathematics, College of Arts and Sciences, 2Institute of Pharmaceutical Sciences, National Institutes of Health, University of the Philippines Manila, Manila, 3Marine Science Institute, University of the Philippines Diliman, Diliman, Quezon City, PhilippinesAbstract: Mycobacterium tuberculosis (Mtb) the main causative agent of tuberculosis, is the main reason why this disease continues to be a global public health threat. It is therefore imperative to find a novel antitubercular drug target that is unique to the structural machinery or is essential to the growth and survival of the bacterium. One such target is the enzyme L,D-transpeptidase 2, also known as LdtMt2, a protein primarily responsible for the catalysis of 3→3 cross-linkages that make up the mycolyl–arabinogalactan–peptidoglycan complex of Mtb. In this study, structure-based pharmacophore screening, molecular docking, and in silico toxicity evaluations were employed in screening compounds from a database of synthetic compounds. Out of the 4.5 million database compounds, 18 structures were identified as high-scoring, high-binding hits with very satisfactory absorption, distribution, metabolism, excretion, and toxicity properties. Two out of the 18 compounds were further subjected to in vitro bioactivity assays, with one exhibiting a good inhibitory activity against the Mtb H37Ra strain.Keywords: antituberculosis drug discovery, virtual screening, docking

Steven E Meredith,1 Brantley P Jarvis,2 Bethany R Raiff,3 Alana M Rojewski,2 Allison Kurti,2 Rachel N Cassidy,2 Philip Erb,2 Jolene R Sy,4 Jesse Dallery2 1Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2Department of Psychology, University of Florida, Gainesville, FL, USA; 3Department of Psychology, Rowan University, Glassboro, NJ, USA; 4Saint Louis University School of Social Work, St Louis, MO, USA Abstract: Behavior plays an important role in health promotion. Exercise, smoking cessation, medication adherence, and other healthy behavior can help prevent, or even treat, some diseases. Consequently, interventions that promote healthy behavior have become increasingly common in health care settings. Many of these interventions award incentives contingent upon preventive health-related behavior. Incentive-based interventions vary considerably along several dimensions, including who is targeted in the intervention, which behavior is targeted, and what type of incentive is used. More research on the quantitative and qualitative features of many of these variables is still needed to inform treatment. However, extensive literature on basic and applied behavior analytic research is currently available to help guide the study and practice of incentive-based treatment in health care. In this integrated review, we discuss how behavior analytic research and theory can help treatment providers design and implement incentive-based interventions that promote healthy behavior. Keywords: incentives, contingency management, conditional cash transfer, pay-for-performance, wellness

Background: Retinoblastoma is the most common intraocular cancer in childhood in the Philippines. Most data though on demographics, clinical profile, treatment options, and outcomes in the country are from the National Capital Region., Objectives: This study aimed to describe the demographics, clinical profile, treatment done, and outcomes of retinoblastoma patients seen in a public tertiary referral center in Davao from 2011-2020 to make available literature more representative of the status of retinoblastoma in the Philippines., Methods: An analytical cross-sectional study was conducted using the records of retinoblastoma patients seen in a tertiary government hospital located in Davao Region from January 2011 to December 2020., Results: There were 157 patients included in the analysis. Seventy-three (46%) were female with 44% coming from the Davao Region. One hundred seven (69%) patients had unilateral disease. Median age at initial consultation for patients with unilateral disease was significantly older than those with bilateral disease (p<0.003). Tumors were extraocular in 82 (40%) eyes. In the intraocular group, 36% of the eyes belonged to International Classification of Retinoblastoma (ICRB) Groups D and E. Enucleation was the most commonly performed treatment. Survival rate was 28%.This is the first report to provide epidemiologic and clinical data on retinoblastoma in the literature, including survival data, from Mindanao. Advanced stages and extraocular cases of retinoblastoma remain high. Delay of consultation contributed to the prognosis and clinical outcome of the disease., Conclusion: Advanced stages and extraocular cases of retinoblastoma remain significantly high in the country, even in Mindanao., Competing Interests: All authors declared no conflicts of interest., (© 2024 Acta Medica Philippina.)

Objectives: Sexual objectification is related to negative outcomes for young adult women, but whether sexual objectification operates similarly for women in mid-life or older adulthood is less clear. Our aim was to assess self-objectification and sexually objectifying experiences for women in two different age groups, 18-27 and 48-90 and, further, test the relationship between objectification and psychological functioning. Based on objectification theory, we hypothesized that young adults would report higher self-objectification and sexually objectifying experiences compared to women in the older group. We further expected that these age differences would be related to body esteem and psychological functioning., Methods: We surveyed 218 women regarding their sexually objectifying experiences and self-objectification, as well as body esteem, global self-esteem, and mood/anxiety, all outcomes theoretically expected to be related to sexual objectification and self-objectification., Results: Sexually objectifying experiences and self-objectification were correlated with lower body esteem, lower global self-esteem, and higher mood/anxiety symptoms. Further, older women reported lower objectification and better psychological functioning. Tests of serial mediation showed that the relationship between age and two outcomes (self-esteem and mood/anxiety symptoms) was mediated by self-objectification and body esteem, while the model using experiences of sexually objectifying experiences was not supported., Conclusion: Older women differed from younger women in the impact of self-objectification. We discuss these outcomes referencing age patterns and objectification theory.

Central nervous system (CNS) tumours were one of the first cancer types to adopt and integrate molecular profiling into routine clinical diagnosis in 2016. The vast majority of these biomarkers, used to discriminate between tumour types, also offered prognostic information. With the advent of The Cancer Genome Atlas (TCGA) and other large genomic datasets, further prognostic sub-stratification was possible within tumour types, leading to increased precision in CNS tumour grading. This review outlines the evolution of the molecular landscape of adult CNS tumours, through the prism of World Health Organization (WHO) Classifications. We begin our journey in the pre-molecular era, where high-grade gliomas were divided into 'primary' and 'secondary' glioblastomas. Molecular alterations explaining these clinicopathological observations were the first branching points of glioma diagnostics, with the discovery of IDH1/2 mutations and 1p/19q codeletion. Subsequently, the rigorous characterisation of paediatric gliomas led to the unearthing of histone H3 alterations as a key event in gliomagenesis, which also had implications for young adult patients. Simultaneously, studies investigating prognostic biomarkers within tumour types were undertaken. Certain genomic phenotypes were found to portend unfavourable outcomes, for example, MYCN amplification in spinal ependymoma. The arrival of methylation profiling, having revolutionised the diagnosis of CNS tumours, now promises to bring increased prognostic accuracy, as has been shown in meningiomas. While MGMT promoter hypermethylation has remained a reliable biomarker of response to cytotoxic chemotherapy, targeted therapy in CNS tumours has unfortunately not had the success of other cancers. Therefore, predictive biomarkers have lagged behind the identification of prognostic biomarkers in CNS tumours. Emerging research from new clinical trials is cause for guarded optimism and may shift our conceptualisation of predictive biomarker testing in CNS tumours., (Copyright © 2023. Published by Elsevier B.V.)

Objectives: 3D-printing is a rapidly developing technology with applications in orthopaedics including pre-operative planning, intraoperative guides, design of patient specific instruments and prosthetics, and education. Existing literature demonstrates that in the surgical treatment of a wide range of orthopaedic pathology, using 3D printing shows favourable outcomes. Despite this evidence 3D printing is not routinely used in orthopaedic practice. We aim to evaluate the advantages of 3D printing in orthopaedic surgery to demonstrate its widespread applications throughout the field., Methods: We performed a comprehensive systematic review and meta-analysis. AMED, EMBASE, EMCARE, HMIC, PsycINFO, PubMed, BNI, CINAHL and Medline databases were searched using Healthcare Databases Advanced Search (HDAS) platform. The search was conducted to include papers published before 8th November 2020. Clinical trials, journal articles, Randomised Control Trials and Case Series were included across any area of orthopaedic surgery. The primary outcomes measured were operation time, blood loss, fluoroscopy time, bone fusion time and length of hospital stay., Results: A total of 65 studies met the inclusion criteria and were reviewed, and 15 were suitable for the meta-analysis, producing a data set of 609 patients. The use of 3D printing in any of its recognised applications across orthopaedic surgery showed an overall reduction in operative time (SMD = -1.30; 95%CI: -1.73, -0.87), reduction in intraoperative blood loss (SMD = -1.58; 95%CI: -2.16, -1.00) and reduction in intraoperative fluoroscopy time (SMD = -1.86; 95%CI: -2.60, -1.12). There was no significant difference in length of hospital stay or in bone fusion time post-operatively., Conclusion: The use of 3D printing in orthopaedics leads to an improvement in primary outcome measures showing reduced operative time, intraoperative blood loss and number of times fluoroscopy is used. With its wide-reaching applications and as the technology improves, 3D printing could become a valuable addition to an orthopaedic surgeon's toolbox., Competing Interests: None, (2024 © BY THE ARCHIVES OF BONE AND JOINT SURGERY.)

Introduction: Frailty in dialysis patients is a modifiable disease state which can increase mortality if left untreated but remains underdiagnosed as frailty evaluations can be arduous or time consuming. We evaluate the agreement between a clinical frailty construct (Fried frailty phenotype, FFP) against and an electronic health record-based Veterans Affairs Frailty Index (VAFI) and their association with mortality., Methods: A retrospective cohort analysis of 764 participants from the ACTIVE/ADIPOSE study was performed. Frailty as measured by VAFI and FFP was obtained and Kappa statistic estimating concordance between the two scores were calculated. Differences in mortality risk were analyzed according to presence or absence of frailty., Findings: When assessing agreement between the VAFI and FFP, the kappa statistic was 0.09 (95% confidence interval [CI] 0.02-0.16) suggesting a low level of agreement. Frailty was independently associated with higher mortality risk (hazards ratio [HR] 1.40-1.42 in fully adjusted models depending upon frailty construct). Discordantly frail patients by construct had a higher risk of mortality though this was not statistically significant after adjustment. However, concordantly frail patients had much higher mortality risk compared to concordantly nonfrail (adjusted HR 2.08, 95% CI 1.44-3.01)., Discussion: Poor agreement between constructs is likely reflective of the multifactorial definition of frailty. While further longitudinal studies are needed to determine if the VAFI would be beneficial in the reassessment of frailty, it may be beneficial as a cue for further frailty testing (e.g., with FFP) with the combination of multiple frail constructs providing improved prognostic information., (© 2023 The Authors. Hemodialysis International published by Wiley Periodicals LLC on behalf of International Society for Hemodialysis.)

Objective: Studies that evaluate YouTube videos on hydrocephalus often exclude non-English-language videos, even though hydrocephalus is more prevalent in low- and middle-income countries where English may not be widely understood. This study had two aims: to analyze the engagement, content, and quality of YouTube videos on hydrocephalus in the Filipino language, and to determine whether the videos' content matched the information needs of caregivers of children with hydrocephalus in the Philippines., Methods: The authors conducted an online survey among caregivers of patients with hydrocephalus, recruited through the Facebook page of the Hydrocephalus Foundation of the Philippines Inc. Data on demographics, social media use, and language and content preferences were collected. In parallel, the authors systematically evaluated the engagement and content of three groups of YouTube videos on hydrocephalus: 1) most viewed Filipino-language videos, 2) most viewed English-language videos, and 3) same-age English-language videos, matched to the first group based on upload date. The quality of the Filipino-language videos was assessed using the DISCERN criteria., Results: Among 280 respondents, 91% watched videos on hydrocephalus online and 89% preferred videos in Filipino. Compared with same-age English videos, Filipino videos had greater engagement, indicated by a higher median number of likes (40 vs 8, p = 0.005) and comments (8.5 vs 1, p = 0.007). English and Filipino videos emphasized similar topics on hydrocephalus, but the latter were more likely to discuss treatment cost and to solicit donations. Caregivers were most interested in the long-term care of patients with hydrocephalus, discussed only in 10 of 72 videos (14%) overall. The mean DISCERN score for Filipino videos was 30.1 ± 7.7, indicating poor quality., Conclusions: There is a gap between the information needs of Filipino caregivers and the content of YouTube videos on hydrocephalus. Neurosurgeons can serve as creators, resource persons, or curators of content, ensuring that up-to-date, accurate, and credible health information on hydrocephalus is available to caregivers in their preferred language.

Chronic levels of inflammation lead to autoimmune diseases such as rheumatoid arthritis and atherosclerosis. A key molecular mediator responsible for the progression of these diseases is Chemokine C-C motif ligand 2 (CCL2), a homodimerized cytokine that dissociates into monomeric form and binds to the CCR2 receptor. CCL2, also known as monocyte chemoattractant protein-1 (MCP-1), attracts monocytes to migrate to areas of injury and mature into macrophages, leading to positive feedback inflammation with further release of proinflammatory molecules such as IL-1β and TNF-α. Sequestering CCL2 to prevent its binding to CCR2 may prevent this inflammatory activity. Prior work adapted an α-helical CCL2-binding peptide (WKNFQTI) from murine CCR2 through extracellular loop analysis. Here, higher-affinity peptide binders were computationally designed through homology modeling and energy calculations, yielding an 11-amino acid peptide with high binding affinity. In addition, Rosetta mutations improved binding affinity in silico with blockage of the CCL2 dimerization site. Future work in analyzing binding kinetics and in vivo inflammation abrogation will confirm the accuracy of computational modeling techniques in de novo rational design of CCL2 cytokine binders.

Background: Serum globulin is a major component of total protein and can be elevated in inflammatory disease states. While inflammation is common in hemodialysis patients and associated with mortality and morbidity, the association between serum globulin and mortality has never been examined in hemodialysis patients., Methods: In a retrospective cohort of 104 164 incident hemodialysis patients treated by a large dialysis organization from 2007 to 2011, we explored the association between baseline serum globulin, albumin: globulin (A:G) ratio and serum protein levels and all-cause, cardiovascular and infection-related mortality with adjustments for demographic variables and laboratory markers of malnutrition and inflammation using Cox proportional hazards models., Results: Patients with a globulin concentration >3.8 g/dL had a higher all-cause and infection-related mortality risk {hazard ratio [HR] 1.11 [95% confidence interval (CI) 1.06-1.16] and HR 1.28 [95% CI 1.09-1.51], respectively} in the fully adjusted model when compared with the reference group of 3.0- <3.2 g/dL. In addition, patients with an A:G ratio <0.75 had a 45% higher all-cause mortality hazard [HR 1.45 (95% CI 1.38-1.52)] and patients with total serum protein <5.5 g/dL had a 34% higher risk of death [1.34 (95% CI 1.27-1.42)] when compared with the reference (A:G ratio 1.05- <1.15 and total serum protein 6.5- <7 g/dL)., Conclusions: Among incident hemodialysis patients, a higher globulin level was associated with a higher mortality risk independent of other markers of malnutrition and inflammation, including albumin. A lower A:G ratio and serum protein was also associated with a higher mortality hazard. The mechanisms that contribute to elevated serum globulin should be further explored., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

Chronic traumatic encephalopathy (CTE) is a neuropathological diagnosis defined by a unique pattern of hyperphosphorylated tau (p-tau) accumulation that begins in neocortical regions of the brain. It is associated with a range of neuropsychological symptoms, but a definitive diagnosis can only be made by postmortem brain examination. In 2018, we instituted CTE screening for all autopsy brains as part of our routine departmental protocol by performing p-tau immunohistochemistry on a restricted set of 3 neocortical blocks (frontal, temporal, and parietal). This strategy allowed us to identify 4 cases of low-stage CTE from 180 consecutive autopsies. Two of the 4 cases had a documented history of brain injury; for the remaining 2 cases, there was a long history of treatment-resistant tonic/clonic epilepsy suggesting that undocumented brain injuries may have occurred. Our experience indicates that 3-block CTE screening is useful in identifying CTE in routine practice. The results of this study further support the association between prior head injuries and CTE and demonstrate that, albeit uncommon, CTE does occur in the general population. Our findings suggest that p-tau screening should be routinely pursued in brain autopsy, particularly where there is a documented or likely history of traumatic brain injury., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Histone mutant gliomas (HMG) with histone H3 K27 and G34 mutations are recognized as biologically discrete entities with distinct anatomical locations, younger age at presentation (in comparison to the most common high-grade gliomas, IDH wildtype glioblastoma), and poor prognosis. There is a paucity of data regarding the management of adult HMG patients and no consensus on management. This study aims to identify current patterns of Australian and US neuro-oncology clinical practice for this entity., Methods: Following institutional approvals, patterns of care questionnaire designed to capture relevant clinical variables was circulated through the Cooperative Trials Group for Neuro-Oncology (COGNO) in Australia and the Caris Precision Oncology Alliance in the United States (US)., Results: Between 4/2021 and 10/2021, 43 responses were collected. 33% ( n = 14) of responders tested all patients for HMGs routinely; 40.92% ( n = 18) tested in select patients 26% ( n = 11) did not test for HMGs. The common indications for testing selected patients were midline anatomic location ( n = 18) and age ( n = 11) (<50 years). 23 used molecular sequencing, 22 used IHC at their centers. Nine participants stated knowledge of histone H3 mutations did not affect their management of these gliomas, 11 said it affected their management at the time of recurrence, 23 stated it affected the management of midline K27M patients, 11 participants stated it affected the management of K27M mutant gliomas in other locations, and 3 felt it affected the management of G34R/V mutant gliomas., Conclusion: Here we present a description of how the discovery of a new molecular subtype of primary glial tumors, histone mutated gliomas in adults, is being introduced into clinical practice., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)