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Eng Hui Gan,1 Wen Wei Woo,1 Kheong Fang Seng,1 Pall Singh,2 Ming Yueh Lee,3 Vui Yin Kong,4 Say Peng Khoo,4 Mun Wai Lee,5 Liau Kok Liang6 1International Specialist Eye Centre, Kuala Lumpur, Selangor, Malaysia; 2Tun Hussein Onn National Eye Hospital, Petaling Jaya, Selangor, Malaysia; 3Parkcity Medical Centre, Kuala Lumpur, Selangor, Malaysia; 4Synergy Specialist Eye Centre, Kota Kinabalu, Sabah, Malaysia; 5LEC Eye Centre, Ipoh, Perak, Malaysia; 6Mahkota Medical Centre, Melaka, MalaysiaCorrespondence: Eng Hui Gan, International Specialist Eye Centre (ISEC) Kuala Lumpur, Level 8 Centrepoint South MidValley City, Kuala Lumpur, 59200, Malaysia, Tel +603 2284 8989, Fax +603 2284 4330, Email ganenghui@yahoo.com.myBackground: Ocular surface disease (OSD) severity varies among glaucoma patients and is exacerbated by intraocular pressure (IOP)-lowering medications.Purpose: To determine OSD prevalence and dry eye severity among glaucoma patients at nine private clinics in Malaysia.Methods: This multicentre, cross-sectional observational study recruited glaucoma patients undergoing routine eye examinations, with IOP ≤ 21mmHg receiving anti-glaucoma eye drops. OSD was assessed through National Eye Institute (NEI) scoring, tear film break-up time (TBUT), hyperaemia grading, Schirmer’s tests and questionnaires on symptom evaluation, OSD index and quality of life (QoL).Results: Our cohort (n = 406, mostly male, ethnically Chinese, mean 63.5 ± 11.5 years, mean IOP 15.34 ± 2.95mmHg) frequently used prostaglandin analogues or PGA/beta-blockers and had cornea total NEI scores of 3.64 ± 2.76, mostly with minimal (51.2%) or mild (40.4%) epitheliopathy. Mean TBUT was 6.59 ± 3.08s (25.0%) in patients with severe lipid deficiency dry eye (DE). Bulbar conjunctiva hyperemia (70.4%) and palpebral conjunctiva hyperemia (68.0%) were mild. Schirmer’s test showed that most had tear deficiency (70.2%) with severe DE (38.9%). Questionnaires reported ocular symptoms in few patients, but 69.2% had DE symptoms (13.1% moderate/severe). While QoL was good, several patients had QoL and OSD index scores suggesting some adaptation to ocular symptoms and discomfort, with most patients being unconcerned (43– 60%) by the occurrence of eye drop side effects (75.4%).Conclusion: Normal-mild DE or OSD can be asymptomatic, and the symptoms are unlikely to bother most patients. However, as OSD severity varies in patients with glaucoma, it should be evaluated using questionnaires and clinical tests to ensure that subjectively asymptomatic individuals are not missed.Keywords: glaucoma, ocular surface disease, prevalence, questionnaires, clinical tests

Abstract Geographic distribution, as well as evolutionary and biogeographic processes and patterns of marine invertebrate benthic species are strongly shaped by dispersal ability during the life cycle. Remote oceanic islands lie at the brink of complex biotic and abiotic interactions which have significantly influenced the biodiversity patterns we see today. The interaction between geological environmental change and taxon-specific dispersal modes can influence species evolutionary patterns, eventually delimiting species-specific biogeographic regions. In this study, we compare the population genetic patterns of the marine bivalve Cardita calyculata in the northeast Atlantic, discussing the role of Macaronesian islands during past climatic cycles. The genetic structure and diversity patterns were outlined based on SSR-GBAS loci of 165 individuals and on the mitochondrial COI marker of 22 individuals from the Canary Islands, Madeira, Azores and the Mediterranean. The highly structured genetic pattern found among regions and within archipelagos suggests the central role of oceanic islands in promoting the divergence of the species in both the NE Atlantic and the Mediterranean. The high degree of divergence in the COI dataset (> 7%) suggests the existence of potential cryptic speciation that needs to be further explored with a more comprehensive sampling. Such patterns are only congruent with a scenario where C. calyculata populations were maintained during glacial/interglacial cycles, supporting the role of the studied archipelagos as drivers of diversity for marine biota. We stress the importance of developing studies for species with various life history and dispersal modes. In such a way, a more profound understanding of the biogeographic and evolutionary significance of oceanic islands can catalyse directed conservation efforts, especially in the context of the ongoing climate crisis.

Sujata P Sarda,1 Guillaume Germain,2 Malena Mahendran,3 Jacob Klimek,3 Wendy Y Cheng,3 Roger Luo,1 Mei Sheng Duh3 1Apellis Pharmaceuticals, Waltham, MA, USA; 2Groupe d’analyse, Ltée, Montreal, Québec, Canada; 3Analysis Group, Inc, Boston, MA, USACorrespondence: Guillaume Germain, Vice President, Analysis Group, Inc, 1190 avenue des Canadiens-de-Montréal, Suite 1500, Montréal, QC, H3B 0G7, Canada, Tel +1-514-394-4446, Email guillaume.germain@analysisgroup.comPurpose: This study assessed the clinical and economic burden of geographic atrophy (GA) using real-world data from elderly patients with Medicare Advantage plans in the United States.Patients and Methods: A retrospective cohort design of patients with GA only, GA + visual impairment (GA + VI), GA + blindness (GA + B), and patients without GA were identified using administrative healthcare claims data from Optum Clinformatics Data Mart. Inverse probability of treatment weighting controlled for confounding when comparing patients with GA only vs without GA, GA + VI vs GA only, and GA + B vs GA only. Endpoints included all-cause and ophthalmic condition-related healthcare resource utilization (HRU), injurious falls, and healthcare costs. HRU and injurious falls were assessed per-person-per-year and per 100 person-years, respectively. Cohorts were compared using rate ratios, 95% confidence intervals (CIs), and p-values from weighted Poisson regression models. Healthcare costs were evaluated per-person-per-year using mean cost differences, 95% CIs, and p-values from weighted linear regression.Results: The study included 18,119 patients with GA only, 2,285 with GA + VI, 1,716 with GA + B, and 72,476 patients without GA. Higher rates of all-cause hospitalizations (RR [95% CI]: 1.08 [1.03, 1.12]), outpatient visits (1.08 [1.05, 1.10]), other visits (1.14 [1.08, 1.21]), and falls with head injuries (1.24 [1.05, 1.45]) were observed in patients with GA vs without GA (P< 0.05). GA was associated with higher annual all-cause total healthcare costs, spending an average of &dollar;1,171 more after adjustment (P< 0.05). Progression to GA + VI and GA + B was associated with a more pronounced burden.Conclusion: The clinical and economic burden of GA is substantial and escalates as the disease advances. These findings suggest early intervention aimed at slowing GA progression may help to mitigate the healthcare burden associated with advancement of GA to visual impairment and blindness.Keywords: geographic atrophy, economic burden, claims data, retrospective, visual impairment, blindness

Pati Aji Achdiat,1 Dini Atiyah,1 Fitri Yulianti,1 Endang Sutedja,1 Srie Prihianti Gondokaryono,1 Hermin Aminah Usman,2 Retno Hesty Maharani1 1Department of Dermatology and Venereology, Faculty of Medicine, Universitas Padjadjaran – Dr. Hasan Sadikin General Hospital, Bandung, Indonesia; 2Department of Pathology Anatomy, Faculty of Medicine, Universitas Padjadjaran - Dr. Hasan Sadikin General Hospital, Bandung, IndonesiaCorrespondence: Pati Aji Achdiat, Department of Dermatology and Venereology, Faculty of Medicine, Universitas Padjadjaran – Dr. Hasan Sadikin General Hospital, Jl. Pasteur No. 38, Bandung, West Java, 40161, Indonesia, Tel/Fax +62222032426 Ext. 3449, Email pati.aji.achdiat@unpad.ac.idIntroduction: Anogenital warts (AGW) are sexually transmitted infections (STIs) caused by the human papillomavirus (HPV), particularly types 6 and 11. The highest incidence of AGW occurs in the age group of 15– 24 years. However, as life expectancy increases, there is a significant rise in the geriatric population worldwide. This demographic shift is directly proportional to the increasing number of STIs cases within the geriatric group.Cases: A case of AGW was reported in a 75-year-old man who had a history of erectile dysfunction medication use and recent sexual contact. During the physical examination, a hyperpigmented plaque with a verrucous surface was observed at the base of the penis. The results of the histopathological examination were consistent with the characteristics of AGW. In addition, HPV genotyping, through polymerase chain reaction (PCR) showed the presence of HPV type 6.Discussion: The aging process leads to a decline in immune function among geriatric individuals, which causes susceptibility to infections, including STIs. Moreover, the geriatric population has a different level of susceptibility to STIs compared to younger individuals. Factors such as physiological changes, decreased sexual function, low awareness of STIs, and having multiple sexual partners further increase the risk of STIs in this age group.Conclusion: Sexual intercourse is an important component of the human life. However, the natural decline in sexual function due to the aging process often occurs with advancing age. As a result, many geriatrics seek various solutions in order to maintain sexual function and activity in old age. Since STIs can occur at any age, early detection and education are essential, particularly for the geriatric population.Keywords: anogenital warts, geriatric, HPV, immunosenescence, sexually transmitted disease

Semei Christopher Mukama,1 Jane Senyondo Nakawesi,1 Dedrix Stephenson Bindeeba,1 Simon Ezajobo,1 Andrew Mugisa,1 Catherine Senyimba,1 Eve Namitala,1 Robert Onzima DDM Anguyo,2 Simon Peter Katongole,3 Barbara Mukasa1 1Mildmay Uganda, Kampala, Uganda; 2Department of International Public Health, Liverpool School of Tropical Medicine (LSTM), Kampala, Uganda; 3Department of Public Health, Gudie University Project, Kampala, UgandaCorrespondence: Simon Peter Katongole, Email spkatongole@gmail.comBackground: This study evaluated the effectiveness and responsiveness of differentiated Human Immunodeficiency Virus (HIV)/Acquired Immuno-Deficiency Syndrome (AIDS) service delivery models (DSDMs) implemented to enhance antiretroviral therapy (ART) access and outcomes for patients while addressing Tuberculosis (TB)-HIV integration, focusing on four of the five DSDMs currently implemented in Uganda.Methodology: A descriptive cross-sectional survey was conducted in eight districts of central Uganda using Lot Quality Assurance Sampling approach from 7th to 23rd March 2023. We randomly sampled 2668 patients who have been on ART for at least 1 year in a Facility-Based Individual Management (FBIM) model or in a non-FBIM DSDM for at least one year. Data were collected through patient interviews and review of records in ART and DSDM registers as well as ART cards. We analyzed the data in proportions, comparing the selected ART outcome and responsiveness indicators between Community Client Led ART Distribution (CCLAD), Community Drugs Distribution Point (CDDP) and Fast-Track Drug Refill (FTDR) DSDMs with the standard care (FBIM) model. The ART outcome variables include patients retained in the 1st line of the ART regimen, patients in World Health Organization clinical stage 1 during the last facility visit, patients who had no CD4 request during the past 12 months, viral load suppression, ART adherence, and patients who reported that they did not experience HIV/AIDS-related symptoms in the past 6 months. The variables on TB care include screening for TB using the intensified case finding form and patients tested positive for TB. Responsiveness variables include the perceived; travel time for ART refill, travel distance for ART refill, convenience and flexibility during ART refill, cost of travel for ART refill, fear of being seen at ART refill point, waiting time before service, adequacy of service time, crowding and risk of infections, social support, ability to address ART treatment challenges, HIV status disclosure and barriers to access. Non-overlap in 95% confidence interval in indicator proportion between non-FBIM DSDM and FBIM means a statistically significant difference in proportion, or otherwise non-significant.Results: Higher proportions of ART patients in the CCLAD and CDDP DSDMs adhered to ART, had suppressed viral load, and a lower TB prevalence than those in FBIM model. Additionally, more CCLAD and CDDP clients reported shorter travel time and distance to access ART than their counterparts in the FBIM model. Compared to FBIM model, higher proportions of those in CCLAD and CDDP also reported flexibility in ART refill scheduling, reduced transport costs, fewer privacy concerns, less HIV/AIDS-related stigma, shorter waiting times, more efficient services, decreased congestion at ART pickup sites, enhanced peer support, improved problem-solving assistance, and increased HIV status disclosure. The FTDR model outperformed FBIM in proportions with fewer requests for CD4 testing, viral load suppression, as well as proportions of clients who reported; shorter travel time, lower transportation cost, decreased privacy concerns, shorter waiting time, and efficient service provision. Compared to both CDDP and FTDR, the FBIM had a higher proportion of clients remain on the first-line ART regimen.Conclusion: Community-based DSDMs show responsiveness to clients’ needs without compromising the effectiveness of ART care for patients. Although FTDR also demonstrates high effectiveness and responsiveness for clients on ART, there is potential for further improvement. Planners and implementers of ART programs should consider both demand- and supply-side innovations to sustain the continuation of DSDMs.Keywords: HIV/AIDS, TB-HIV, DSDM, LQAS

Sophie J Bakri,1 Winfried MK Amoaku,2 Danielle Altman,3 Stéphane Quéré,4 Jaclyn Quilantan,5 Julia Carpenter-Conlin,5 Sujata P Sarda,5 Daniel L Jones,5 Jared S Nielsen6, † 1Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA; 2Faculty of Medicine & Health Sciences, University of Nottingham, Queens Medical Centre, Nottingham, England, UK; 3Modus Outcomes, a THREAD Company, Cary, NC, USA; 4Modus Outcomes, a THREAD Company, Lyon, France; 5Apellis Pharmaceuticals, Inc, Waltham, MA, USA; 6Wolfe Eye Clinic PC, West Des Moines, IA, USA†Dr Jared S Nielsen passed away on June 14, 2024Correspondence: Sophie J Bakri, Department of Ophthalmology, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA, Tel +1 507-284-3614, Email bakri.sophie@mayo.eduPurpose: Geographic atrophy (GA) impacts both patients and caregivers, yet little is understood about their respective burdens. The MOSAIC study aimed to identify the clinical, emotional, and financial burden among patients with GA and caregivers.Methods: A total of 28 patients with GA and 17 caregivers from the United States (US), the United Kingdom, and Australia participated in individualized qualitative interviews followed by a cross-sectional quantitative survey of 102 patients and 102 caregivers in the US. Interview transcripts were analyzed to develop conceptual models, which were then used to guide the design of quantitative surveys. Data were described at the item level and score level when appropriate (National Eye Institute Visual Function Questionnaire [NEI VFQ]-39 and Zarit Burden Interview [ZBI]). For the patient/caregiver dyad sample, the association between the NEI VFQ-39 scores and ZBI score was explored through correlation coefficients and scatterplots.Results: GA had a substantial impact on patients’ vision-related quality of life, activities of daily living, and instrumental activities of daily living. There was considerable overlap between perspectives and key concerns identified by patients and caregivers. Eighty-three percent of caregivers reported having to drive patients to appointments due to limited patient mobility, for example, and 41% reported a change in their employment status after becoming a caregiver, with 50% of them unable to work due to caregiving. The burden of patients and caregivers had a correlation ranging from − 0.63 to − 0.21 between NEI VFQ-39 subscale and composite scores and ZBI score.Conclusion: This study confirms the paucity of support for both patients with GA and caregivers. Both groups require expanded access to financial, social, and mental health resources.Plain Language Summary: What is this summary about?People with geographic atrophy, also called GA, can lose their eyesight and have a hard time driving, reading, and recognizing faces. This can worsen their quality of life. Often, people with GA need someone to care for them. The MOSAIC study was done to find out how GA affects health, happiness, and finances of people with GA and their caregivers.What were the results?One hundred and two people with GA and 102 caregivers in the United States were interviewed. The average age of people with GA was 68 years and of caregivers was 46 years. The findings showed that most people with GA did not drive because of their poor eyesight and instead counted on their caregivers to drive them to doctor appointments and other places. They also had a reading and doing things around their home because of their worsened eyesight.Both people with GA and caregivers said they felt stressed. They both worried about spending money on things they need to make living with GA easier. They also felt stressed about their finances because they could not work as much. People with GA worried most about losing their independence and caregivers worried most about the future of their loved one with GA.What do the results mean?This study showed that GA has a serious effect on people’s health and quality of life while also having a major impact on their caregivers.Keywords: age-related macular degeneration, functional vision, geographic atrophy, health-related quality of life, caregiver burden, disease burden

Naomi Davey,1 Eimear Connolly,1 Paul Mc Elwaine,1,2 Sean P Kennelly1,2 1Department of Age Related Healthcare, Tallaght University Hospital, Dublin, Ireland; 2Department of Medical Gerontology, School of Medicine, Trinity College Dublin, Dublin, IrelandCorrespondence: Naomi Davey, Department of Age-Related Healthcare, Tallaght University Hospital, Dublin, Ireland, Email Naomi.davey@tuh.ieAbstract: This review article assesses the effectiveness and limitations of strategies to reduce falls among hospitalized older adults with frailty and dementia. It explores the efficacy of existing fall prevention strategies for a cohort that is acutely susceptible to falls and fall-related consequences. A systematic literature search was conducted across MEDLINE, Embase, CINAHL, and PsycINFO, employing Medical Subject Headings (MeSH) to identify studies on fall prevention strategies in hospitalized older adults with both dementia and frailty published from 2013 to 2023. The initial 643 records were distilled to eight articles, with Structured Interdisciplinary Bedside Rounds (SIBR) emerging as a notable intervention. SIBR demonstrated a reduction in falls by fostering improved interdisciplinary communication and care planning. However, a decline in family engagement during consecutive sessions suggests a need for strategies to sustain familial involvement. The findings advocate for patient-centered interventions that address the cognitive and functional challenges faced by this cohort of older adults. This review advocates for comprehensive and inclusive research in hospital environments to improve fall prevention strategies for frail older adults with dementia.Keywords: fall prevention, frailty, dementia, hospitalized older adults, interdisciplinary collaboration, patient-centered interventions

The primary causes of low sesame production are a lack of high-yielding varieties, an inability to adjust to environmental challenges, and a poor response to enhanced crop management. The potential for improving sesame has been investigated using a variety of breeding approaches, including mutation and recombination breeding; however, these methods have only produced a minor increase in productivity. Recombination and mutant breeding have recently been proposed as novel, cutting-edge approaches to overcome the limitations of conventional breeding practices. This study was conducted to assess the recurrent mutagenesis efficacy of sesame crosses, followed by the isolation and evaluation of superior breeding lines that could be released as varieties in the future. In the F4M4 generation, the populations were grown in a randomized block design (RBD), and the efficacy of recurrent mutagenesis was assessed in terms of variability parameters such as the mean, standard deviation, and coefficient of variation. During the F5M5 generation, the materials were grown in three separate trials in Compact Family Block Design to evaluate the between-family and within-family variations, followed by the isolation of improved breeding lines based on per se performance. The improved breeding lines were further advanced to the F6M6 generation for evaluation in three separate trials in an RBD. In the F6M6 generation, ANOVA, correlation, regression, path coefficient, and Mahalanobis’s D 2 analysis were computed, followed by the construction of selection indices to select superior lines. The results showed the importance of three or four EMS treatment cycles for sesame improvement in the F4M4 generation. Twenty of the top lines based on per se performance (with a selection intensity of 27%) from each category in the F5M5 generation were carried forward to the F6M6 generation. In the F6M6 generation, the top six breeding lines (with a selection intensity of 30%) from each category, for a total of 18 breeding lines, were chosen based on these index scores. These high-yielding micromutant lines could be subsequently released as varieties through multiplication trials with standard checks. After a thorough evaluation, these lines have the potential to replace the current varieties and increase production, productivity, and adoption of sesame in India.

Background: The fusarium verticillioides produces the mycotoxin fumonisin b1 (Fb1), commonly infects corn and other agricultural commodities. The Fb1 showed hepatotoxicity, cytotoxicity, and carcinogenicity in animals. Aim of the study: There are limited literature available on cytotoxicity exerted by Fb1. Hence, the present investigation aimed to evaluate the cytotoxic effects of Fb1 and its mechanism in the neuroblastoma (SH-SY5Y) cell line and its amelioration by apocynin. Methods: We investigated the molecular mechanism of Fb1-induced cytotoxicity in SH-SY5Y cells and investigated the effect of Fb1 oxidative stress markers, and apoptosis. Results: The results explained that the Fb1 showed dose-dependent cytotoxicity in SH-SY5Y cells with the IC50 value 150 µM. Fb1 elevated reactive oxygen species and depolarized mitochondrial membrane potential, vacuolation and apoptotic changes were observed in SH-SY5Y cells. The protein expression of CAT and GPx were downregulated with Fb1 treatment, and apoptotic markers caspase-3 and caspase-8 were upregulated. When the apocynin was pretreated, followed by Fb1 exposure for 24 h, all the changes were normalized with the treatment. Hence, these results suggest that ROS is the primary upstream signal leading to increased Fb1-mediated cytotoxicity in SH-SY5Y cells. Conclusion: Apocynin reversed the Fb1-induced oxidative stress and apoptosis by its antioxidant potency in SH-SY5Y cell lines.

Introdução: O Linfoma de Burkitt é uma neoplasia hematológica altamente agressiva derivada de células B, marcada pela translocação do gene MYC no cromossomo 8. Suas formas incluem a endêmica, a esporádica e a associada à imunossupressão, como em pacientes com HIV. O linfoma de Burkitt tem uma prevalência 10 vezes maior em indivíduos HIV positivos do que na população geral, sendo uma condição definidora de AIDS. A patogênese envolve imunossupressão crônica, permitindo proliferação descontrolada das células B e reativação do EBV, que frequentemente é latente em pacientes com HIV. A apresentação clínica pode variar, incluindo linfadenopatia generalizada, febre, perda de peso e envolvimento extranodal. O diagnóstico requer avaliação clínica, radiológica e confirmação histopatológica através de biópsia e imunohistoquímica. O tratamento envolve quimioterapia intensiva, além da gestão eficaz do HIV para melhorar a resposta imunológica e reduzir complicações infecciosas. Relato do caso: Paciente masculino, 28 anos, sem comorbidades, apresentou nódulo de 1 cm em região infraclavicular direita, que, em 7 meses, evoluiu progressivamente para uma massa palpável, com cerca de 20 cm, sem sinais flogísticos, pétrea, imóvel e indolor. Paciente nega febre, sudorese noturna ou emagrecimento durante o período. Tomografia computadorizada (TC) de Tórax e Pescoço evidenciou conglomerado linfonodal infraclavicular à direita (13 × 7 cm) de aspecto suspeito para doença linfoproliferativa. Realizada biópsia percutânea da massa, cujo histopatológico identificou uma neoplasia maligna com imunorreatividade para os marcadores CD20, BCL6, CD10, cMYC e Ki-67 (> 95%) na imunohistoquímica, compatível com Linfoma não-Hodgkin de células B, tipo Burkitt. Concomitantemente, realizou investigação para HIV, com Teste de Antígenos e Anticorpos reagente para HIV-1 e HIV-2, e Imunoblot rápido reagente para HIV-1. Realizada a investigação de TB pelo LF-LAM com resultado não reagente, análise liquórica sem alterações, dosagem de Carga Viral em 161 mil cópias e Contagem de CD4 em 295 céls/mm3, sendo iniciada a Terapia Antirretroviral com Lamivudina, Tenofovir e Dolutegravir. A Biópsia de Medula Óssea não evidenciou infiltração por Linfoma. Iniciado quimioterapia com o protocolo CODOX/IVAC, que cursou com redução considerável da massa com cerca de 1 semana de tratamento, levando a significativa melhora clínica. Conclusão: Este caso discute uma doença rara, que representa 1-2% dos linfomas não-Hodgkin em adultos, e enfatiza a necessidade de uma abordagem integrada no manejo do Linfoma de Burkitt associado ao HIV. A detecção precoce e o tratamento quimioterápico são essenciais devido à natureza agressiva do linfoma. Deve-se destacar ainda a associação de anticorpos monoclonais, que aumenta as taxas de remissão, mas ainda tem acesso limitado no Sistema Único de Saúde. A ausência de infiltração medular e a resposta positiva ao tratamento destacam a eficácia do protocolo para linfomas de alta agressividade e a importância do controle eficaz da AIDS para melhorar a sobrevida. O manejo adequado da infecção por HIV, incluindo monitoramento da carga viral e contagem de CD4, juntamente com quimioterapia intensiva, é crucial para melhorar os desfechos clínicos e otimizar estratégias para pacientes com doenças malignas associadas ao HIV.

Objetivos: Analisar os casos diagnosticados de linfoma não-Hodgkin na população de 0 a 19 anos, de 2019 a 2024. Material e método: Foi realizado o levantamento de dados de ano do diagnóstico no território brasileiro, durante o período de 2019 a 2024, disponíveis nos seguintes sistemas: Sistema de Informação Ambulatorial (SIA), através do Boletim de Produção Ambulatorial Individualizado (BPA-I) e da Autorização de Procedimento de Alta Complexidade; Sistema de Informação Hospitalar (SIH); Sistema de Informações de Câncer (SISCAN). Resultados: Entre 2019 a 2025, foram diagnosticados no Brasil 1.869 casos de Linfoma Não-Hodgkin (LNH), sendo o número de casos de LNH Difuso (1.754) significantemente superior ao LNH Folicular (115). O Sudeste foi a região com maior quantidade de casos de LNH difuso (604) e de Linfoma Folicular (45). Em comparação, a região Norte possui a menor quantidade de casos do tipo difuso (170) e apresenta 16 casos diagnosticados do tipo folicular. Além disso, podemos observar que no mesmo período descrito acima o Sul foi a região que apresentava menos casos de Linfoma Folicular (15) e sobre casos de LNH Difuso seriam 332. Já a região Centro-Oeste obteve o menor índice de casos de LNH Difuso (169) e, sobre os casos de Linfoma Folicular, foram diagnosticados 21. Por último, a região Nordeste teve um número baixo de casos de Linfoma Folicular (18), porém apresentou o segundo maior índice de casos de LNH difuso (479). Discussão: Os dados de 2019 a 2024 revelam que, no tocante ao perfil sociodemográfico, o Linfoma Não-Hodgkin difuso (LNH) é consideravelmente mais prevalente do que o linfoma folicular no Brasil. As disparidades regionais na incidência, que se correlacionam com a prevalência de LNH em todas as regiões, sugerem interferência devido a fatores como as condições socioeconômicas e as diferenças nas infraestruturas médicas, sublinhando a importância das estratégias de saúde pública para melhorar o acesso ao diagnóstico e ao tratamento nas zonas sub atendidas. Assim, vale ressaltar que o maior registro de número de casos corresponde a região sudeste, o que pode ser explicado por uma maior densidade populacional e melhor acesso aos serviços de saúde. Por outro lado, nas regiões centro-oeste e norte, há uma quantidade consideravelmente menor de casos de LNH difuso e folicular, provavelmente, devido às barreiras no acesso ao diagnóstico e tratamento, bem como potenciais subnotificações. Conclusão: Diante dos dados apresentados, observa-se que as internações por Linfoma Não-Hodgkin (LNH) na faixa etária de 0 a 19 anos no Brasil, entre 2019 a 2024, superam as ocorrências de linfoma folicular. Ademais, os dados evidenciam disparidades regionais que refletem a influência de fatores socioeconômicos e estruturais na incidência e no registro dos casos de LNH. As discrepâncias na disponibilidade e qualidade dos serviços de saúde destacam a necessidade urgente de estratégias de saúde pública que visem melhorar o acesso ao diagnóstico precoce e ao tratamento adequado. Portanto, este estudo sublinha a importância de intervenções estratégicas e planejadas no sistema de saúde brasileiro, com o objetivo de não apenas promover a detecção precoce e o tratamento eficaz, mas também de reduzir as desigualdades regionais.

A leucemia linfocítica crônica (LLC) caracteriza-se pela alta frequência de alterações genéticas, que se correlacionam com o prognóstico da doença. O cariótipo com bandas G permite a investigação simultânea de alterações citogenéticas em todos os cromossomos. Entretanto, o linfócito apresenta baixa taxa de divisão celular em cultura, e por isto o cariótipo pode não ser informativo. A hibridização in situ fluorescente (FISH), por dispensar a necessidade de células metafásicas, apresenta maior sensibilidade na detecção de alterações citogenéticas na LLC. Este estudo tem como objetivo investigar a frequência de alterações citogenéticas detectadas por FISH realizadas entre abril/2017 a abril/2024 no laboratório de Citogenética do Instituto Hermes Pardini. Foi utilizado um painel de sondas para pesquisa de oito alterações citogenéticas em núcleos interfásicos: as deleções de MYB (6q23.3), ATM (11q22.3), 13q14.3 e TP53 (17p13), trissomia de cromossomo 12, rearranjo em IGH (14q32) e as fusões IGH::CCND1 e IGH::BCL2. Neste período foram analisados 155 pacientes (96 do sexo masculino), com média de idade de 70 ± 10 anos. Foi detectada pelo menos uma alteração citogenética em 107 casos (69%), com 1 a 5 alterações por caso. A alteração citogenética mais frequente foi a deleção em 13q14.3 (71 casos/66,4%), seguida pela trissomia de cromossomo 12 (26 casos/24,3%), deleção TP53 (15 casos/14,0%), deleção de ATM (13 casos/12,1%), fusão IGH::CCND1 (8 casos/7,5%), deleção de MYB (5 casos/4,7%) e fusão IGH::BCL2 (2 casos/1,9%). Dentre os 107 casos com alteração citogenética, em 33 (30,8%) foram detectadas entre duas a cinco alterações, destacando-se por maior frequência a dupla alteração trissomia 12 com deleção 13q14.3. A frequência das alterações citogenéticas detectadas é semelhante ao observado em outros estudos. Foram detectadas alterações citogenéticas importantes para o prognóstico da LLC, como a deleção de TP53, cujo prognóstico é desfavorável e relevante para terapia.

ABCs and LRP transport proteins are involved in several metabolic processes, among which the transport of lipids and xenobiotics can be highlighted. Thus, the overexpression of some of these proteins, such as ABC-G2 and the LRP protein, are associated with the phenotype of resistance to multiple drugs, one of the main causes of relapses and relapses in patients with acute myeloid leukemia. Mesenchymal stem cells (MSC) are multipotent cells present in the bone marrow and are part of the hematopoietic niche. Phenotypic changes in MSCs are related to AML progression. The oxysterols, 7-KC and Triol, are derived from the auto-oxidation of the cholesterol molecule; and have functions in cell signaling, survival and death. Therefore, the objective of this work was to evaluate the action of oxysterols, in subtoxic concentrations, of 7-KC (30 μM, 50 μM and 70 μM) and Triol (20 μM, 30 μM and 40 μM) on the ABCs and LRP transport proteins of MSCs derived from bone marrow from patients with AML (MSC-D), being used as a comparator MSC of bone marrow from healthy individuals (MSC-S). Using the indirect immunofluorescence technique, it was observed that the amount of ABC-A1 protein was higher in MSC-S strains and that treatment with 30 μM of 7-KC increased ABC-A1 only in MSC-S strains. On the other hand, treatment with Triol decreased the concentration of ABC-A1 in MSC-S strains, and this decrease in ABC-A1 was associated with a decrease in the amount of the LXR-β receptor. Furthermore, treatment with 70 μM of 7-KC decreased LRP protein expression in MSC-S strains, while in MSC-D strains there was no difference. Treatment with Triol showed no significant effect on LRP protein expression in MSC-S, only in MSC-D strains, where there was an increase in the concentration of 20 μM, followed by a decrease in the concentrations of 30 μM and 40 μM of Triol. Both 7-KC and Triol treatment increased the concentration of SMO protein in the cytoplasm and its translocation to the nucleus in MSC-S cell lines. This effect was not observed in MSC-D strains. Treatment with Triol increased the concentration of ABC-D4 protein in the cytoplasm. Furthermore, the presence of ABC-D4 protein was observed in the nucleus of MSC-S and MSC-D strains. Our results demonstrated that in the MSCs lineages the effect of 7-KC and Triol is mainly metabolic, in which an increase in the oxidized glutathione content, alteration in the processes of mitochondrial dynamics with induction of genes related to the fission and fusion process in both 7-KC and Triol-treated MSC lines. Increased expression of the BCL2 gene and cytoplasmic survivin was also observed in MSCs treated with 7-KC. In conclusion, it is possible to observe differences in the expression of ABC transporters and LRP between CTM-S and CTM-D strains. Furthermore, at the same concentrations of 7-KC and Triol used, the observed effect was different between MSC-S and MSC-D, which demonstrates that there are different mechanisms between mesenchymal stem cell lines. In summary, our results are characteristic of the metabolic action of the oxysterols 7-KC and Triol on MSCs.

Objetivo: Descrever as principais reações transfusionais imediatas e tardias ocorridas em hospitais atendidos pelo Grupo GSH no país. Material e métodos: O levantamento dos dados, foi realizado pelas informações obtidas do sistema informatizado do Grupo GSH e da avaliação do livro de registro de notificações de reações transfusionais imediatas e tardias com o parecer do responsável médico, ocorridas no período de janeiro a dezembro de 2023, os dados são referentes à atendimentos de cerca de 240 hospitais e clínicas. Para a caracterização das reações transfusionais foram avaliadas quanto ao tipo de reação transfusional que podem ser classificadas como imediatas (aguda) ocorridas durante ou em até 24h da transfusão. E reações do tipo tardia que ocorrem após 24h até cerca de 3 semanas, após a transfusão. Resultado: Dos casos analisados, constatou-se que, das 390.000 bolsas transfundidas, 2.812 apresentaram sinais ou sintomas relacionados a reações transfusionais, afetando o total de 1.039 receptores. Isso representa um percentual de 0,72% de reações transfusionais. Das reações identificadas, suas causas foram classificadas das seguintes formas: 0,04% de distúrbios metabólicos (1 caso), 0,07% de dor aguda relacionada à transfusão (2 casos), 0,18% de reação hemolítica tardia (5 casos), 0,25% de outras reações tardias (7 casos), 0,3% de reação hipotensiva relacionada à transfusão (8 casos), 0,4% de reação hemolítica aguda imunológica (11 casos), 0,82% de lesão pulmonar aguda relacionada à transfusão (23 casos), 1,03% de dispneia associada à transfusão (29 casos), 1,21% de aloimunização/aparecimento de anticorpos irregular (34 casos), 4,1% de outras reações imediatas (116 casos), 5,7% de sobrecarga circulatória associada à transfusão (159 casos), 28,3% de reação febril não hemolítica (797casos) e 57,6% de reação alérgica (1620). Discussão: Durante os meses avaliados pode-se observar uma maior incidência das reações imediatas com 98,36%, com predominância dos tipos alérgica com 57,6% e febril não hemolítica com 28,3%. Quanto as reações tardias, totalizou 1,64%, sendo descritos três tipos de reações tardias no período, todas com baixa expressividade, sendo a aloimunização com 1,21%, outras reações tardias 0,25% e hemolítica tardia 0,18%. Como limitação do presente estudo, pode haver subnotificação de reações transfusionais, devido a não correlação de sinais apresentados por receptores, principalmente tardios, que possam ser associados à transfusão prévia. Conclusão: Os resultados obtidos com este estudo corroboram com os dados já descritos na literatura. Sabe-se que as reações podem ocorrer em decorrência de algum incidente do ciclo do sangue, ou do resultado inerente do processo. Portanto, a hemovigilância é a principal forma de garantir a segurança transfusional dos receptores com o registro e notificação dos eventos adversos, evitando-se a incidência de subnotificações. Sendo assim, é importante que as reações sejam identificadas corretamente e as condutas tomadas sejam adequadas, prevenindo-as através de equipes bem treinadas, processos bem definidos e qualidade dos hemocomponentes, a fim de manter a taxa de reações transfusionais conforme literatura.

Objetivo: Analisar a incidência de aloimunização em pacientes internados nos hospitais das agências transfusionais do país atendidas pela Grupo GSH. Material e métodos: Estudo retrospectivo realizado através do levantamento de dados obtidos do sistema informatizado no período de janeiro de 2021 a dezembro de 2023, os quais foram agrupados e tratados em planilha do programa Microsoft Excel. Os dados coletados incluíam sexo, idade e resultados de anticorpos eritrocitários detectados. Resultados: No período do estudo, foram registrados 62 casos de reações transfusionais classificadas como aloimunização, envolvendo a identificação de 86 anticorpos, dentre os quais pode-se observar a ocorrência da identificação em 23 casos (26,7%) do anticorpo anti-E e 14 casos (16,8%) identificados anti-Kell, seguidos de anti-Jka com 11 casos (12,8%), anti-c e anti-D com 7 casos cada ( 8,1%), anti-C 6 casos (7%), anti-M 5 casos (5,8%) e os demais anticorpos identificados que apresentaram baixa expressividade, que somados representam 13 casos (15,1%), sendo identificados: anti-Ch, anti-Dia, anti-Fya, anti-Jkb, anti-Lea, anti-Lua, anti-s, anticorpo frio. Quanto ao sexo dos receptores, 33 casos (53,2%) eram de receptores do sexo feminino e 29 casos do sexo masculino (46,8%). Quanto a idade, na distribuição por faixa etária observou-se 21 pacientes entre 61-75 anos (34%), 20 pacientes entre 46-60 anos (32,2%), 15 pacientes acima dos 75 anos (24,2%), 3 pacientes entre 16-30 anos (5%), 2 pacientes entre 0-15 anos (3,2%) e 1 paciente entre 31-45 anos (1,4%). Discussão: Ao analisar os dados, observou-se que a maior prevalência dos anticorpos identificados com 26,7% foi de anticorpos anti-E, 16,8% anti-K e 12,8% anti-Jka, os demais anticorpos identificados apresentaram baixa incidência variando de 1 e 7 casos, ficando entre 1,1% e 8,1%. A relação com o sexo dos receptores que aloimunizaram, após serem submetidos às transfusões tem-se a prevalência no sexo feminino (53,2%). As idades dos receptores variaram de 5 anos a 99 anos, com maior incidência na faixa etária de 61 a 75 anos, resultados estes que são correlacionadas as condições clínicas e laboratoriais dos receptores, que consequentemente acarretaram um maior número de transfusões com exposição maior a diferentes doadores. Conclusão: A Organização Mundial de Saúde (OMS) recomenda que o fornecimento de sangue seguro e adequado seja parte da política e infraestrutura de saúde de todos os países. Atualmente a transfusão de sangue é um recurso que salva vidas e melhora a saúde de quem se beneficia em diversas circunstâncias, porém pode resultar no desenvolvimento de aloanticorpos. Essa aloimunização predispõe o paciente ao risco de reações transfusionais hemolíticas tardias. Os anticorpos mais encontrados na aloimunização são dirigidos contra antígenos dos sistemas Rh e Kell, por serem estes considerados os mais imunogênicos. A identificação dos fenótipos eritrocitários dos grupos sanguíneos em pacientes e doadores de sangue, possibilita a classificação da frequência dos genes mais imunogênicos de cada sistema, sendo essencial para diminuir o risco de aloimunização, havendo a possiblidade do sangue compatível tornar a transfusão mais segura.

Introduction: The EBMT recommends an ATG (Thymoglobulin) dose of 4.5‒6.0 mg/kg for an unrelated (URD) hematopoietic cell transplant (HCT). The PTCy-based Baltimore protocol for haploidentical (Haplo) HCT included MMF 45 mg/kg starting at D+5, however MMF 30 mg/kg starting at D0 has also been reported. In our institution, the first 6 Haplo received 45 mg/kg MMF, with a 50% incidence of CMV disease, prompting us to reduce MMF to 30 mg/kg. Objective: To compare 6.0 mg/kg ATG-based URD versus PTCy-based with MMF 30 mg/kg Haplo HCT. Methods: This single-center study was conducted in a public hospital in Rio de Janeiro, Brazil. We included all patients who underwent Haplo or URD HCT for acute leukemia or myelodysplasia between 2016 and 2024. URD received 6 mg/kg ATG with a Calcineurin Inhibitor (CNI) and an antimetabolite. Haplo received PTCy combined with a CNI and approximately, due to rounding, MMF 30 mg/kg. All follow-up times were longer than 30 days. Survival and cumulative incidence curves were carried out with Kaplan-Meier and Gray methods and compared with logrank and Gray tests. Propensity Score (PS) weighted-Cox models were performed to control for relevant variables. The study was approved by the Ethics Committee and registered at ClinicalTrials (NCT02759822). Results: With a median follow-up of 13- and 28-months, 74 Haplo and 83 URD were included, respectively. Except for conditioning intensity (reduced-intensity conditioning in 30% of Haplo and 6% of URD) and graft (peripheral blood in 51% of Haplo and 35% of URD), all other variables were relatively well-balanced. In the URD group, 82% were HLA 8/8 matched, while 18% were 7/8 matched. 2-y OS, for Haplo and URD, respectively, were 51% and 70% (p = 0.10); 2-y RFS 51% and 64% (p = 0.23); GRFS 22% and 47% (p = 0.01); 2-y relapse 17% and 18% (p = 0.62); 2-y NRM 32% and 17% (p = 0.08); 2-y cGVHD 39% and 35% (p = 0.52), 2-y moderate/severe cGVHD 22% and 15% (p = 0.49); 6-month II‒IV aGVHD 50% and 49% (p = 0.72); and 6-month III‒IV aGVHD 15% and 23% (p = 0.51). In the PS-weighted model, only GRFS was different: HR = 1.70 for Haplo vs. URD, p = 0.01. In other PS-weighted models, nor OS, HR = 1.50, p = 0.17; PFS, HR = 1.40, p = 0.24; relapse, HR = 1.00, p = 0.97; II‒IV aGVHD, HR = 1.10, p = 0.63; III‒IV aGVHD, HR = 1.30, p = 0.56; cGVHD, HR = 1.40, p = 0.24; nor moderate and severe cGVHD, HR = 1.70, p = 0.23 were statistically different, although, numerically, most outcomes favored the URD group. Discussion: Our results suggest it might not be safe to systematically offer Haplo transplants for patients with suitable URD. PS-weighted GRFS was statistically improved with URD, compared with Haplo. Overall, our Haplo results were comparable with those already reported, although, in most comparisons of Haplo versus URD, ATG was not given to all URD patients. Importantly, GVHD control was not hampered by MMF reduction from 45 mg/kg to 30 mg/kg in the Haplo arm, even in a highly miscegenated country like Brazil. Time to transplant is usually shorter in Haplo, and therefore we cannot rule out survival bias favoring the URD group. Although not randomized, it was a relatively large sample that included patients with only hematologic malignancies.

Objetivo: Avaliar a frequência de consulta odontológica antes do transplante de células tronco hematopoiéticas (TCTH) no Instituto Nacional de Câncer. Materiais e métodos: Trata-se de um estudo observacional, descritivo, transversal, retrospectivo, com base em dados secundários provenientes dos prontuários da instituição. Foram incluídos pacientes submetidos ao TCTH na instituição, no período de janeiro de 2020 a dezembro de 2023. As variáveis de interesse foram referentes às características epidemiológicas, diagnóstico e tratamento oncológicos e consulta odontológica na Instituição antes do TCTH. Os dados foram submetidos à análise descritiva no programa estatístico SPSS. Este estudo foi aprovado pelo Comitê de Ética em Pesquisa responsável (CAAE 79133224.0.0000.5274; parecer 6.834.603). Resultados: Entre 2020 e 2023 foram realizados 276 TCTH na Instituição. Destes, 129 foram alogênicos e 147 autólogos, tendo 2023 (29,5%) e 2021 (32,7%) como os anos de maior número de transplantes, respectivamente. Dentre os pacientes submetidos ao transplante alogênico, a maioria era do sexo masculino (52,7%), com 40 anos e diagnosticados com Leucemia Mielóide Aguda (31,7%). Os transplantes alogênicos aparentados foram maioria (43,4%). No transplante autólogo, houve predominância de mulheres (59,9%), com 50 anos e diagnosticadas com Mieloma Múltiplo (42,2%). Para ambos os tipos de transplante, o sangue periférico foi a fonte de células mais utilizado, representando 64,3% nos alogênicos e 99,3% nos autólogos. A realização de consulta odontológica antes do TCTH, na Seção de Odontologia do hospital, ocorreu em 86,6% considerando ambos os transplantes, 77,5% nos transplantes alogênicos e 94,6% nos autólogos. Discussão: O tratamento citotóxico realizado antes do TCTH resulta em neutropenia e trombocitopenia transitórias, tornando o paciente suscetível a complicações como hemorragia e infecção, inclusive na cavidade oral, que podem ter consequências fatais. O preparo odontológico tem por objetivo a eliminação de focos infecciosos dentários crônicos ou agudos com a intenção de prevenir complicações durante e/ou após o tratamento que podem ocorrer devido a aplasia apresentada por esses pacientes. O encaminhamento dos pacientes para o cirurgião-dentista deve fazer parte do check list dos centros transplantadores. A avaliação em um serviço odontológico especializado que faz parte da equipe multiprofissional permite um atendimento realizado por profissionais com expertise na área permitindo um alinhamento do plano de tratamento com a equipe médica. Um estudo realizado em Edimburgo refere que 94,7% dos pacientes transplantados realizaram consulta odontológica prévia, o que se assemelha à taxa de encaminhamento observada para os transplantes autólogos neste estudo e é superior à constatada nos transplantes alogênicos. Vale ressaltar que os pacientes que não foram avaliados pelos cirurgiões-dentistas da Instituição podem ter sido avaliados nos hospitais de origem. Conclusão: A frequência de avaliação odontológica antes do TCTH no Instituto Nacional de Câncer foi alta para ambos os tipos de transplante, apesar de menor no transplante alogênico. Desta forma, ratifica-se a necessidade de educação continuada da equipe multiprofissional para reforçar o fluxo de encaminhamento, assim como, da importância de cirurgiões-dentistas especializados na Instituição para realizar o atendimento destes pacientes.

Objetivo: Descrever a perspectiva dos profissionais acerca do grupo de familiares destinado aos acompanhantes de pacientes da oncologia pediátrica. Método: Relato de experiência de profissionais da equipe assistencial sobre o grupo de acolhimento aos familiares da unidade de oncologia pediátrica em hospital de referência do sul do Brasil. A atividade é realizada semanalmente e coordenada por duas enfermeiras assistenciais, juntamente com a psicóloga da unidade. Resultados: Os encontros semanais são caracterizados por um espaço de acolhimento, em que ocorre a valorização do cuidador através de um momento de convivência social. É utilizado como um espaço de troca de experiência entre familiares a respeito da doença do seu filho, proporcionando o desenvolvimento de uma rede de apoio, assim como o fortalecimento de vínculos com a equipe assistencial. Por ser um espaço seguro e de educação em saúde, os profissionais ali presentes acabam desmistificando algumas temáticas, como também somando informações pertinentes sobre rotinas da unidade, cuidados a serem seguidos durante o tratamento. Além disso, são trabalhadas demandas psicológicas dos acompanhantes, as quais surgem durante o processo de tratamento da doença. Desta forma, novos questionamentos emergem, e as temáticas são adaptadas para serem abordadas de acordo com as necessidades expostas pelos familiares, trazendo uma devolutiva de novos assuntos em próximos grupos. Conclusão: Por meio deste momento semanal foi possível observar o fortalecimento do vínculo com a equipe assistencial. As famílias relatam sentir-se mais inseridas nos contextos do cuidado, gerando autonomia no que tange os conhecimentos acerca de temáticas que submergem durante o período da internação hospitalar. Além disso, proporciona um melhor entendimento do tratamento e seus impactos na vida cotidiana da família, promovendo um momento de protagonismo e de valorização do acompanhante.

BackgroundMicro- and nanoplastics (MNPs) are emerging pollutants of concern with ubiquitous presence in global ecosystems. MNPs pose potential implications for human health; however, the health impacts of MNP exposures are not yet understood. Recent evidence suggests that MNPs can cross the placental barrier, underlying the urgent need to understand their impact on reproductive health and development. ObjectiveThe Actionable eUropean ROadmap for early-life health Risk Assessment of micro- and nanoplastics (AURORA) project will investigate MNP exposures and their biological and health effects during pregnancy and early life, which are critical periods due to heightened vulnerability to environmental stressors. The AURORA project will enhance exposure assessment capabilities for measuring MNPs, MNP-associated chemicals, and plastic additives in human tissues, including placenta and blood. MethodsIn this interdisciplinary project, we will advance methods for in-depth characterization and scalable chemical analytical strategies, enabling high-resolution and large-scale toxicological, exposure assessment, and epidemiological studies. The AURORA project performs observational studies to investigate determinants and health impacts of MNPs by including 800 mother-child pairs from 2 existing birth cohorts and 110 women of reproductive age from a newly established cohort. This will be complemented by toxicological studies using a tiered-testing approach and epidemiological investigations to evaluate associations between maternal and prenatal MNP exposures and health perturbations, such as placental function, immune-inflammatory responses, oxidative stress, accelerated aging, endocrine disruption, and child growth and development. The ultimate goal of the AURORA project is to create an MNP risk assessment framework and identify the remaining knowledge gaps and priorities needed to comprehensively assess the impact of MNPs on early-life health. ResultsIn the first 3 years of this 5-year project (2021-2026), progress was made toward all objectives. This includes completion of recruitment and data collection for new and existing cohorts, development of analytical methodological protocols, and initiation of the toxicological tiered assessments. As of September 2024, data analysis is ongoing and results are expected to be published starting in 2025. ConclusionsAs plastic pollution increases globally, it is imperative to understand the impact of MNPs on human health, particularly during vulnerable developmental stages such as early life. The contributions of the AURORA project will inform future risk assessment. International Registered Report Identifier (IRRID)DERR1-10.2196/63176

Background & Aims: Senescence has been reported to have differential functions in cholangiocytes and hepatic stellate cells (HSCs) during human and murine cholestatic disease, being detrimental in biliary cells and anti-fibrotic in HSCs. Cholestatic liver disease is associated with loss of intestinal barrier function and changes in the microbiome, the mechanistic cause of which is undetermined. Methods: Intestinal samples were analysed from controls and patients with primary sclerosing cholangitis, as well as wild-type (WT) and p16-3MR transgenic mice. Cholestatic liver disease was induced by bile duct ligation (BDL) and DDC diet feeding. Fexaramine was used as an intestinal-restricted FXR agonist and antibiotics were given to eliminate the intestinal microbiome. Senescent cells were eliminated in p16-3MR mice with ganciclovir and in WT mice with the senolytic drug ABT-263. In vitro studies were done in intestinal CaCo-2 cells and organoids were generated from intestinal crypts isolated from mice. Results: Herein, we show increased senescence in intestinal epithelial cells (IECs) in patients with primary sclerosing cholangitis and in mice after BDL and DDC diet feeding. Intestinal senescence was increased in response to reduced exposure to bile acids and increased presence of lipopolysaccharide in vitro and in vivo during cholestatic liver disease. Senescence of IECs was associated with lower proliferation but increased intestinal stem cell activation, as supported by increased organoid growth from intestinal stem cells. Elimination of senescent cells with genetic and pharmacological approaches exacerbated liver injury and fibrosis during cholestatic liver disease, which was associated with increased IEC apoptosis and permeability. Conclusions: Senescence occurs in IECs during cholestatic disease and the elimination of senescent cells has a detrimental impact on the gut-liver axis. Our results point to cell-specific rather than systemic targeting of senescence as a therapeutic approach to treat cholestatic liver disease. Impact and implications:: Cholestatic liver disease associates with the dysregulation of intestinal barrier function, while the mechanisms mediating the disruption of the gut-liver axis remain largely undefined. Here, we demonstrate that senescence, a cellular response to stress, is activated in intestinal cells during cholestatic liver disease in humans and mice. Mechanistically, we demonstrate that the reduction of bile acids and the increased presence of bacterial products mediate the activation of intestinal senescence during cholestatic liver disease. Importantly, the elimination of these senescent cells promotes further damage to the intestine that aggravates liver disease, with increased tissue damage and fibrosis. Our results provide evidence that therapeutic strategies to treat cholestatic liver disease by eliminating senescent cells may have unwanted effects in the intestine and support the need to develop cell/organ-specific approaches.

Weeds are the major menace to agriculture, which greatly impact crop growth and development, resulting in economic yield loss or crop failures. Therefore, it is indispensable to take up appropriate weed management practices to prevent the effects of weeds on crops. Chemical herbicides have immense potential for effective control of weeds, but, in the long run, the persistent nature of herbicides adversely affects the soil microbes and also that terrestrial and aquatic ecosystems. Bioherbicides are products derived from plant extracts, allelochemicals or microbes and their secondary metabolites with weed-suppressing abilities. Most microbial bioherbicides are based on fungi and its active ingredients, which successfully control weeds with different mode of actions. Moreover, the toxins or secondary metabolites the fungi produce also possess herbicidal properties. So, exploring the fungal pathogens and their toxins for managing weeds seems to be a feasible and eco-friendly way for the management of weeds. There is a wider scope for utilizing fungi and their secondary metabolites as mycoherbicides, which have the potential to replace hazardous chemical herbicides in the near future. This review article mainly emphasizes the scope of mycoherbicides and explores the fungal secondary metabolites for eco-friendly weed control.

Frizam Dwindamuldan Sutisna, Srie Prihianti Gondokaryono, Reiva Farah Dwiyana, Raden Mohamad Rendy Ariezal Effendi, Nisrina Tache, Rafithia Anandita Department of Dermatology and Venereology, Faculty of Medicine, Universitas Padjadjaran, Hasan Sadikin Hospital, Bandung, IndonesiaCorrespondence: Srie Prihianti Gondokaryono, Department of Dermatology and Venereology, Faculty of Medicine, Universitas Padjadjaran - Hasan Sadikin Hospital, Jl. Pasteur 38, Bandung, West Java, 40161, Indonesia, Tel +62 817114116, Email prihianti@gmail.comAbstract: Congenital triangular alopecia (CTA) is a rare entity of non-cicatricial alopecia characterized by triangular or oval-shaped alopecia patches on the frontotemporal region of the scalp. Few therapeutic options exist, and there is currently no effective treatment except for hair transplantation. We report the case of an adolescent boy with CTA who was treated with 5% topical minoxidil solution. During therapy, the patient showed improvement in the form of the appearance of terminal hairs, which started to show after two months of treatment. After eight months of treatment, the affected area was fully covered with dense terminal hairs. The patient did not report any adverse reactions/side effects.Keywords: Congenital triangular alopecia, minoxidil, trichoscopy

Vipul Vilas Wagh,1 Tanvi Kottat,1 Suchita Agrawal,2 Shruti Purohit,2 Tejaswini Arun Pachpor,3,4 Leelavati Narlikar,5 Vasudeo Paralikar,2 Satyajeet Pramod Khare1 1Symbiosis School of Biological Sciences, Symbiosis International (Deemed University), Pune, MH, India; 2Psychiatry Unit, KEM Hospital Research Centre, Pune, MH, India; 3Department of Biosciences and Technology, School of Science and Environment Studies, Dr. Vishwanath Karad MIT World Peace University, Pune, MH, India; 4Department of Biotechnology, MES Abasaheb Garware College, Pune, MH, India; 5Department of Data Science, Indian Institute of Science Education and Research, Pune, MH, IndiaCorrespondence: Vasudeo Paralikar; Satyajeet Pramod Khare, Email paralikarv2010@gmail.com; satyajeetkhare@gmail.comIntroduction: Stigma contributes to a significant part of the burden of schizophrenia (SCZ), therefore reducing false positives from the diagnosis would be liberating for the individuals with SCZ and desirable for the clinicians. The stigmatization associated with schizophrenia advocates the need for high-precision diagnosis. In this study, we present an ensemble learning-based approach for high-precision diagnosis of SCZ using peripheral blood gene expression profiles.Methodology: The machine learning (ML) models, support vector machines (SVM), and prediction analysis for microarrays (PAM) were developed using differentially expressed genes (DEGs) as features. The SCZ samples were classified based on a voting ensemble classifier of SVM and PAM. Further, microarray-based learning was used to classify RNA sequencing (RNA-Seq) samples from our case-control study (Pune-SCZ) to assess cross-platform compatibility.Results: Ensemble learning using ML models resulted in a significantly higher precision of 80.41% (SD: 0.04) when compared to the individual models (SVM-radial: 71.69%, SD: 0.04 and PAM 77.20%, SD: 0.02). The RNA sequencing samples from our case-control study (Pune-SCZ) resulted in a moderate precision (59.92%, SD: 0.05). The feature genes used for model building were enriched for biological processes such as response to stress, regulation of the immune system, and metabolism of organic nitrogen compounds. The network analysis identified RBX1, CUL4B, DDB1, PRPF19, and COPS4 as hub genes.Conclusion: In summary, this study developed robust models for higher diagnostic precision in psychiatric disorders. Future efforts will be directed towards multi-omic integration and developing “explainable” diagnostic models. Keywords: Schizophrenia, peripheral blood, gene expression, machine learning, ensemble learning

Malarmugila Manimaran,1,&ast; Yin Yin Teo,2 James Chen Yong Kah,3 Adilet Beishenaliev,1 Yean Leng Loke,2 Yiing Yee Foo,1 Shiow-Fern Ng,4 Chin Fei Chee,5 Sek Peng Chin,6 Farid Nazer Faruqu,1 Chia-Yu Chang,7 Misni Misran,2 Lip Yong Chung,6 Bey Fen Leo,8,&ast; Shih-Hwa Chiou,9,10 Chia-Ching Chang,7,11– 13 Sun Tee Tay,14 Lik Voon Kiew1,7 1Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia; 2Department of Chemistry, Faculty of Science, Universiti Malaya, Kuala Lumpur, Malaysia; 3Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, Singapore, Singapore; 4Centre for Drug Delivery Technology and Vaccine, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia; 5Nanotechnology Catalysis Research Centre, Universiti Malaya, Kuala Lumpur, Malaysia; 6Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universiti Malaya, Kuala Lumpur, Malaysia; 7Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, Republic of China; 8Department of Molecular Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia; 9Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China; 10Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan, Republic of China; 11Department of Electrophysics, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, Republic of China; 12Center for Intelligent Drug Systems and Smart Bio-devices, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, Republic of China; 13Institute of Physics, Academia Sinica, Nankang, Taipei, Taiwan, Republic of China; 14Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia&ast;These authors contributed equally to this workCorrespondence: Chia-Ching Chang; Lik Voon Kiew, Email ccchang01@nycu.edu.tw; lvkiew@um.edu.myIntroduction: Over 75% of clinical microbiological infections are caused by bacterial biofilms that grow on wounds or implantable medical devices. This work describes the development of a new poly(diallyldimethylammonium chloride) (PDADMAC)/alginate-coated gold nanorod (GNR/Alg/PDADMAC) that effectively disintegrates the biofilms of Staphylococcus aureus (S. aureus), a prominent pathogen responsible for hospital-acquired infections.Methods: GNR was synthesised via seed-mediated growth method, and the resulting nanoparticles were coated first with Alg and then PDADMAC. FTIR, zeta potential, transmission electron microscopy, and UV–Vis spectrophotometry analysis were performed to characterise the nanoparticles. The efficacy and speed of the non-coated GNR and GNR/Alg/PDADMAC in disintegrating S. aureus-preformed biofilms, as well as their in vitro biocompatibility (L929 murine fibroblast) were then studied.Results: The synthesised GNR/Alg/PDADMAC (mean length: 55.71 ± 1.15 nm, mean width: 23.70 ± 1.13 nm, aspect ratio: 2.35) was biocompatible and potent in eradicating preformed biofilms of methicillin-resistant (MRSA) and methicillin-susceptible S. aureus (MSSA) when compared to triclosan, an antiseptic used for disinfecting S. aureus colonisation on abiotic surfaces in the hospital. The minimum biofilm eradication concentrations of GNR/Alg/PDADMAC (MBEC50 for MRSA biofilm = 0.029 nM; MBEC50 for MSSA biofilm = 0.032 nM) were significantly lower than those of triclosan (MBEC50 for MRSA biofilm = 10,784 nM; MBEC50 for MRSA biofilm 5967 nM). Moreover, GNR/Alg/PDADMAC was effective in eradicating 50% of MRSA and MSSA biofilms within 17 min when used at a low concentration (0.15 nM), similar to triclosan at a much higher concentration (50 μM). Disintegration of MRSA and MSSA biofilms was confirmed by field emission scanning electron microscopy and confocal laser scanning microscopy.Conclusion: These findings support the potential application of GNR/Alg/PDADMAC as an alternative agent to conventional antiseptics and antibiotics for the eradication of medically important MRSA and MSSA biofilms.Keywords: biofilm, gold nanorod, S. aureus, PDADMAC, MRSA, MSSA

Zelalem Tilahun Mekonen,1 Teferi Gedif Fenta,1 Simon Peter Nadeem,2 Denny J Cho3 1Department of Pharmaceutics and Social Pharmacy, School of Pharmacy, Addis Ababa University, Addis Ababa, Ethiopia; 2Center for Supply Chain Improvement, University of Derby, Derby, UK; 3Logistics Department, Kyrgyz State Technical University, Bishkek, KyrgyzstanCorrespondence: Zelalem Tilahun Mekonen, Tel +251923 10 95 39, Email zelalem.tilahun@aau.edu.et; zelatilahun@gmail.comBackground: The COVID-19 pandemic led to the most substantial health crisis in the 21st Century. This pandemic interrupted the supply of essential commodities for human beings. Among the essential commodities for human survival, disruption of the supply of essential health commodities has become a global concern.Objective: The study aimed to systematically analyze published articles on the challenges, impacts, and prospects of the global health commodities’ supply chain in the era of the COVID-19 pandemic.Methods: A standard searching strategy was conducted in seven research databases to retrieve pertinent articles. Finally, 459 articles were retrieved for further screening, and only 13 articles were selected for final synthesis.Results: Almost 38.5% of the studies targeted the supply chain of health commodities used to treat HIV, TB, and malaria. Lockdown policies, travel restrictions, lack of transportation, low manufacturing capacity, and rising costs were the significant challenges indicated for the supply interruption of essential health commodities and COVID-19 vaccines. Findings indicated that the supply interruption of essential health commodities leads to a devastating impact on global health.Conclusion: Global medicine shortages due to the pandemic crisis can have a devastatingly harmful impact on patient outcomes and might result in a devastatingly long-lasting effect on the health of the world community. Supply-related challenges of the COVID-19 vaccine affect countries’ ambitions for achieving herd immunity quickly. Monitoring the pandemic’s effect on the health commodities’ supply system and designing a short-term and long-term resilient health supply chain system that can cope with current and future health catastrophes is pivotal.Keywords: global supply chain, health commodities, health product, pharmaceuticals, challenges, opportunities, prospects, COVID-19, COVID-19 vaccine

Traidit Thianthanyakij,1,2,&ast; Yinghui Zhou,1,&ast; Mengyi Wu,3,&ast; Yuting Zhang,4 Jui-Ming Lin,1 Yan Huang,4 Yuou Sha,1 Jiayi Wang,1 Sirapath Peter Kong,2 Jinran Lin,1 Qingmei Liu,1 Wenyu Wu1,5,6 1Department of Dermatology, Huashan Hospital, Fudan University, Shanghai Institute of Dermatology, Shanghai, 200040, People’s Republic of China; 2Faculty of Medicine, Thammasat University (Rangsit Campus), Pathumthani, 12120, Thailand; 3Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China; 4State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200433, People’s Republic of China; 5Department of Dermatology, Jing’an District Central Hospital, Shanghai, 200040, People’s Republic of China; 6Academy for Engineering and Technology, Fudan University, Shanghai, 200433, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingmei Liu; Wenyu Wu, Email liuqing.mei@163.com; wenyu_wu@fudan.edu.cnBackground: Existing research links oxidative stress and inflammation to hair loss. Salvianolic acid B (SAB) is known for its anti-oxidative, anti-inflammatory, and other beneficial pharmacological properties.Objective: To assess the efficacy of SAB in modulating hair growth.Methods: In vivo experiments were conducted using C57BL/6 mice to evaluate the effects of SAB on hair and skin parameters. The study involved ex vivo analysis of human hair follicles (HFs) for hair shaft length and hair growth cycle assessment. In vitro, human dermal papilla cells (hDPCs) were cultured with SAB, and their proliferation, protection against H2O2-induced oxidative damage, and gene/protein expression alterations were examined using various analytical techniques, including Real-Time Cell Analysis (RTCA), DCFH-DA Assay, RNA-seq, and KEGG pathway analysis.Results: SAB treatment in mice significantly improved hair growth and vascularization by day 21. In human HFs, SAB extended hair shaft length and delayed the transition to the catagen phase. SAB-treated hDPCs showed a notable decrease in the expression of oxidation-antioxidation-related genes and proteins, including reduced phosphorylation levels of ERK and p38.Conclusion: The study indicates that SAB promotes hDPC proliferation and offers protection against oxidative stress, highlighting its potential as a therapeutic agent for enhancing hair growth and treating hair loss.Keywords: salvianolic acid B, hair growth, hair cycle, hair follicle, dermal papilla cells

Introduction: Multiple Myeloma (MM) represents a malignant proliferation of plasma cells derived from a single clone. Imaging of the skeleton beyond symptomatic areas is useful for myeloma staging and subsequent follow-up for treatment response and disease relapse. Despite research comparing the Dixon sequence to conventional sequences in a variety of musculoskeletal disorders, there is a lack of studies regarding the Dixon sequence’s application in MM. Aim: To compare the contrast of MM focal lesions in all four T2-weighted Dixon and Conventional T1-weighted spin-echo and Short Tau Inversion Recovery (STIR) images. Materials and Methods: This cross-sectional study was conducted in the Department of Radiology at Kovai Medical Centre and Hospitals (KMCH), Coimbatore, Tamil Nadu, India. All newly diagnosed and known cases of MM, either biopsy-proven or strongly suspected based on other diagnostic testing conforming to International Myeloma Working Group (IMWG) criteria from December 2020 to July 2022, were included in the study. A total of 43 patients with 142 focal MM lesions were included. Contrast between focal MM lesions and surrounding bone marrow was calculated on T1-weighted spin-echo, STIR, and T2-weighted Dixon (all four) images. Statistical analysis was done using repeated measures of Analysis of Variance (ANOVA) with Bonferroni correction to control the type I error on multiple comparisons to find the significant difference between multivariate analyses. A probability value of 0.05 was considered a significant level for all statistical tools. Results: The study population consisted of 21 men and 22 women with a mean age of 65.3±8.6 years {Mean±Standard Deviation (SD)}. Contrast values in all four T2 Dixon images, STIR, and T1-weighted images were as follows: T2 Dixon Fat-only (FO) images (0.86.±0.09) (SD); range: (0.46-0.99), T2-weighted Dixon Water-only (WO) images (0.54±0.14) (SD); range: (0.14-0.82), T2 Dixon In-phase (IP) images (0.20±0.13) (SD); range: (0.02-0.41), T2-weighted Dixon Out-phase (OP) images (0.53±0.19) (SD); range: (0.12-0.87), STIR images (0.47±0.12) (SD); range: (0.12-0.73), and T1 images (0.23±0.12) (SD); range: (0.01-0.55). The mean contrast was highest on T2 Dixon fat-only images (p

Introduction Breast reconstruction has become integral part of breast cancer treatment. Deep inferior epigastric perforator (DIEP)-based flap is considered the gold standard in autologous breast reconstruction.

Industrial tuna and artisanal fisheries targeting multiple species in the eastern Pacific Ocean (EPO) interact with the Critically Endangered East Pacific (EP) leatherback turtle Dermochelys coriacea. In 2021, a revised Inter-American Tropical Tuna Commission (IATTC) resolution on sea turtles aimed to reduce sea turtle bycatch in EPO industrial tuna fisheries and ensure their safe handling and release. A new ecological risk assessment approach—Ecological Assessment for the Sustainable Impacts of Fisheries (EASI-Fish)—was used to assess vulnerability status and to better understand the potential efficacy of 70 scenarios that compared simulated conservation and management measures (CMMs) for EPO industrial (purse-seine and longline) and artisanal (longline and gillnet) fisheries to the status quo in 2019. In 2019, a fishing mortality proxy (F̃2019) and the breeding stock biomass per recruit (BSR2019) exceeded precautionary biological reference points (F80% and BSR80%), classifying the stock as ‘most vulnerable’. Industrial and artisanal longline fisheries had the highest impacts because they had the highest areal overlap with the modelled EP leatherback distribution. Of the 70 CMM scenarios, 42 resulted in significant improvements in vulnerability status (i.e. to ‘least vulnerable’). The use of large circle hooks, finfish bait, and best handling and release practices each decreased vulnerability; however, the most effective scenarios involved using these 3 measures in concert. The benefits predicted from EASI-Fish for CMM scenarios assume full compliance and attaining the modelled levels of efficacy, our modelling provides stakeholders with evidence-based recommendations to address key threats to EP leatherback turtles to improve their conservation status by reducing fishing impacts.

Yessica Cusquisibán-Alcantara,1,&ast; Cesia Toledo-Garrido,1,&ast; Yaquelin E Calizaya-Milla,1 Sandra P Carranza-Cubas,2 Jacksaint Saintila2 1Research Group for Nutrition and Lifestyle, School of Human Nutrition, Universidad Peruana Unión, Lima, Perú; 2School of Medicine, Faculty of Health Sciences, Universidad Señor de Sipán, Chiclayo, Perú&ast;These authors contributed equally to this workCorrespondence: Yaquelin E Calizaya-Milla, Research Group for Nutrition and Lifestyle, School of Human Nutrition, Universidad Peruana Unión, Lima, Chosica, 15, Perú, Email yaquelincalizaya@upeu.edu.pe Jacksaint Saintila, School of Medicine, Faculty of Health Sciences, Universidad Señor de Sipán, Carretera a Pimentel, Chiclayo, Lambayeque, 14001, Perú, Email jacksaintsaintila@gmail.comBackground: Non-communicable diseases in adults and anemia in children represent a major global public health problem, with multiple causes including poor dietary quality. However, nutrition education interventions can empower individuals to make appropriate dietary changes.Objective: To evaluate the impact of a nutritional education intervention on nutrition knowledge (NK), healthy eating index (HEI), and biochemical profile in families in the community in Peru.Methods: A pre-experimental study was conducted in the community of Sinchicuy, located on the banks of the Amazon River, Iquitos, Peru. Nutrition education was provided over a 16-week period to a total of 61 heads of household (23 children under 5 years of age and 23 older adults). Fasting glucose and hemoglobin (Hb) concentration analyses were also carried out before and after the intervention.Results: After the intervention, a significant improvement in the NK score was observed, increasing by 90% (p < 0.001). Additionally, the average HEI scores experienced a significant increase, rising by approximately 11.4% (p < 0.001). In children under 5 years of age, the Hb level showed a significant increase of 5.1% (p = 0.017). However, no statistically significant difference in glucose concentration was observed in older adults after the intervention.Conclusion: The findings of this study indicated a positive impact on NK, HEI, and Hb in heads of households, older adults, and children under five in a rural community where there is limited access to basic services.Keywords: nutrition education, nutritional knowledge, hemoglobin, glucose, children, rural communities

Roshni Ramesh,&ast; Anoop Sasi,&ast; Shahana C Mohamed, Sonia P Joseph Department of Periodontology, Government Dental College, Thiruvananthapuram, Kerala, India&ast;These authors contributed equally to this workCorrespondence: Roshni Ramesh, Department of Periodontology, Government Dental College, Thiruvananthapuram, Kerala, India, Email roshniarun73@gmail.comPurpose: Compression necrosis refers to bone tissue damage that can occur when excessive pressure or force is applied to surrounding bone during implant placement. This pressure can compromise blood supply to the bone, leading to necrosis. Compression necrosis is a concern, because it can affect the stability and long-term success of dental implant.Patients and Methods: This case report highlights a case of early bone loss and implant failure possibly due to compression necrosis. Clinical data, photographs, radiographs, blood examination report and histology were presented to document the early failure of an implant placed in the mandibular left posterior region of a 33-year-old female patient.Results: Radiograph taken six weeks after implant placement showed severe angular defect. Therefore, the implant was surgically removed. Histological examination of the area showed bony trabeculae with an absence of osteoblastic riming, suggestive of necrotic bone.Conclusion: Using excessive torque values when placing implants in dense bones can increase the risk of implant failure due to bone over compression. Dental professionals must follow the manufacturer’s instructions and employ quality surgical techniques during implant placement into dense cortical bone to minimise risks.Keywords: bone loss, dental implants, implant failure, necrosis

Sanjay Kalra,1 Nitin Kapoor,2 Jeevan Joseph,3 Abhishek Arun,4 Supratik Bhattacharyya,5 Siba Prasad Dalai6 1Endocrinology Department, Bharti Hospital, Karnal, Haryana, India; 2Endocrinology Department, Christian Medical College, Vellore, Tamil Nadu, India; 3Endocrinology Department, Vimala Hospital, Ettumanoor, Kerala, India; 4Endocrinology Department, Vishudh Diabetes Clinic, Lucknow, Uttar Pradesh, India; 5Endocrinology Department, Apollo Sugar Clinic, Kolkata, West Bengal, India; 6Endocrinology Department, IMS & SUM Hospital, Bhubaneshwar, Odisha, IndiaCorrespondence: Sanjay Kalra, Bharti Hospital, BRIDE Kunjpura Road, Model Town, Near State Bank of India, Sector 12, Karnal, Haryana, 132001, India, Tel +91 98960 48555, Fax +91 124-407 8652, Email brideknl@gmail.comPurpose: The study aimed to evaluate the effect of Vidaslim®, meal replacement on weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), and other cardiometabolic parameters and to see the impact of timing of Vidaslim meal replacement on the level of weight loss achieved.Methods: In a prospective, observational study, male and female subjects with obesity based on inclusion and exclusion criteria were administered Vidaslim (60 g in 200 mL water) once daily as a meal replacement (lunch or dinner) for 16 weeks.Results: A total of 107 subjects (mean age 34.09± 8.26 years) were included in the study. There was a significant reduction in weight by 13.4 kg (p=0.0001), BMI by 5.5 kg/m2 (p=0.00001), WC by 3.7 inches (p=0.0001), and HC by 4.5 inches (p=0.0001) at the end of 16 weeks. Statistically significant reductions were noted in heart rate, fasting blood glucose, postprandial blood glucose, lipid profile (p=0.0001 for all), and systolic blood pressure (p=0.002) at 16 weeks. A significant change in hunger (p=0.0001), appetite (p=0.014), mood (p=0.021), sleep quality (p=0.0001), and general well-being (p=0.013) was observed at the end of 16 weeks. Replacing lunch or dinner with Vidaslim resulted in a significant reduction in weight (− 9.8 kg versus − 14.3 kg, respectively; p=0.0001 for both) compared to replacing breakfast (− 3 kg, p=0.205) with Vidaslim over 16 weeks. No subject reported any side effects post–Vidaslim intervention.Conclusion: The medical nutrition therapy, Vidaslim, was found to be an effective and safe meal (lunch or dinner)-replacement strategy and brought a significant reduction in weight, WC, and HC over 16 weeks in overweight and obese individuals.Keywords: food supplement, overweight, anthropometric, cardiometabolic, meal replacement, blood glucose

This article covers the conceptual transition of Power from the era of Hard to that of Sharp, namely. It presents the main theoretical aspects of Sharp Power, identifying the empirical process with Russia and China. However, this article takes the analytical process a step further by presenting Turkish Sharp and Soft Power and its methods in both domestic and foreign policy, which combined constitute Compelling Power. For various analysts, Turkey’s current route in the international system seems to have taken a peculiar turn since the state moves away from the Western world, trying to adopt a more independent stance in the international arena. The article argues that this turn concerns the Neo-Ottoman identity that R.T. Erdogan strives to give his nation. In order to achieve this, Ankara and its propaganda mechanisms developed the Turkish version of Soft and Sharp Power. Given this rationale, an evaluation is being conducted on numerous instances of Sharp and Soft power implementation by the Turkish government spanning from 2009 to 2021.

Purpose — This study examines the influence of managerial and environmental factors on the adoption of eco-innovation practices to improve business sustainability in small manufacturing firms. Method — The research employs a quantitative approach, gathering primary data from 110 owners and managers of small manufacturing firms in Bandung, Indonesia. Structural Equation Modeling (SEM) is utilized to analyze the relationships between managerial and environmental drivers, eco-innovation practices, and business sustainability. The data was analyzed using the Partial Least Squares (PLS) method via SmartPLS 3.0 software. Result — The study's findings demonstrate that both managerial drivers (such as eco-commitment, eco-efficiency, and eco-capability) and environmental drivers (including eco-consumer demand, eco-regulation, and eco-competition) have a significant positive impact on the adoption of eco-innovation practices. These eco-innovation practices, in turn, significantly contribute to enhancing business sustainability. This underscores the importance of integrating sustainable practices into business operations and proactively responding to environmental pressures to achieve long-term competitive advantage. Novelty — This research offers new insights by focusing on small manufacturing firms in an emerging market—a context that has been relatively underexplored in existing literature. Unlike previous studies that mainly target large enterprises or developed markets, this study highlights the critical role of eco-innovation in promoting sustainability within small firms in Indonesia. Moreover, it distinguishes the unique impacts of both managerial and environmental drivers, providing a more comprehensive understanding of the factors that motivate the adoption of eco-innovation practices in small enterprises.