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Despite their role as innate sentinels, macrophages can serve as cellular reservoirs of chikungunya virus (CHIKV), a highly-pathogenic arthropod-borne alphavirus that has caused large outbreaks among human populations. Here, with the use of viral chimeras and evolutionary selection analysis, we define CHIKV glycoproteins E1 and E2 as critical for virion production in THP-1 derived human macrophages. Through proteomic analysis and functional validation, we further identify signal peptidase complex subunit 3 (SPCS3) and eukaryotic translation initiation factor 3 subunit K (eIF3k) as E1-binding host proteins with anti-CHIKV activities. We find that E1 residue V220, which has undergone positive selection, is indispensable for CHIKV production in macrophages, as its mutation attenuates E1 interaction with the host restriction factors SPCS3 and eIF3k. Finally, we show that the antiviral activity of eIF3k is translation-independent, and that CHIKV infection promotes eIF3k translocation from the nucleus to the cytoplasm, where it associates with SPCS3. These functions of CHIKV glycoproteins late in the viral life cycle provide a new example of an intracellular evolutionary arms race with host restriction factors, as well as potential targets for therapeutic intervention.

The fundamental trade-off between current and future reproduction has long been considered to result in a tendency for species that can grow large to begin reproduction at a larger size. Due to the prolonged time required to reach maturity, estimates of tree maturation size remain very rare and we lack a global view on the generality and the shape of this trade-off. Using seed production from five continents, we estimate tree maturation sizes for 486 tree species spanning tropical to boreal climates. Results show that a species' maturation size increases with maximum size, but in a non-proportional way: the largest species begin reproduction at smaller sizes than would be expected if maturation were simply proportional to maximum size. Furthermore, the decrease in relative maturation size is steepest in cold climates. These findings on maturation size drivers are key to accurately represent forests' responses to disturbance and climate change.

While studying transgene expression after systemic administration of lentiviral vectors, we found that splenic B cells are robustly transduced, regardless of the types of pseudotyped envelope proteins. However, the administration of two different pseudotypes resulted in transduction of two distinct B cell populations, suggesting that each pseudotype uses unique and specific receptors for its attachment and entry into splenic B cells. Single-cell RNA sequencing analysis of the transduced cells demonstrated that different pseudotypes transduce distinct B cell subpopulations characterized by specific B cell receptor (BCR) genotypes. Functional analysis of the BCRs of the transduced cells demonstrated that BCRs specific to the pseudotyping envelope proteins mediate viral entry, enabling the vectors to selectively transduce the B cell populations that are capable of producing antibodies specific to their envelope proteins. Lentiviral vector entry via the BCR activated the transduced B cells and induced proliferation and differentiation into mature effectors, such as memory B and plasma cells. BCR-mediated viral entry into clonally specific B cell subpopulations raises new concepts for understanding the biodistribution of transgene expression after systemic administration of lentiviral vectors and offers new opportunities for BCR-targeted gene delivery by pseudotyped lentiviral vectors.

The host interferon pathway upregulates intrinsic restriction factors in response to viral infection. Many of them block a diverse range of viruses, suggesting that their antiviral functions might have been shaped by multiple viral families during evolution. Host-virus conflicts have led to the rapid adaptation of host and viral proteins at their interaction hotspots. Hence, we can use evolutionary genetic analyses to elucidate antiviral mechanisms and domain functions of restriction factors. Zinc finger antiviral protein (ZAP) is a restriction factor against RNA viruses such as alphaviruses, in addition to other RNA, retro-, and DNA viruses, yet its precise antiviral mechanism is not fully characterized. Previously, an analysis of 13 primate ZAP orthologs identified three positively selected residues in the poly(ADP-ribose) polymerase-like domain. However, selective pressure from ancient alphaviruses and others likely drove ZAP adaptation in a wider representation of mammals. We performed positive selection analyses in 261 mammalian ZAP using more robust methods with complementary strengths and identified seven positively selected sites in all domains of the protein. We generated ZAP inducible cell lines in which the positively selected residues of ZAP are mutated and tested their effects on alphavirus replication and known ZAP activities. Interestingly, the mutant in the second WWE domain of ZAP (N658A) is dramatically better than wild-type ZAP at blocking replication of Sindbis virus and other ZAP-sensitive alphaviruses due to enhanced viral translation inhibition. The N658A mutant is adjacent to the previously reported poly(ADP-ribose) (PAR) binding pocket, but surprisingly has reduced binding to PAR. In summary, the second WWE domain is critical for engineering a more potent ZAP and fluctuations in PAR binding modulate ZAP antiviral activity. Our study has the potential to unravel the role of ADP-ribosylation in the host innate immune defense and viral evolutionary strategies that antagonize this post-translational modification.

ObjectiveTransgender and gender diverse (TGD) people experience higher levels of stigma, discrimination, and interpersonal violence due to their gender identity and/or expression, particularly TGD people with a migration background. This study aimed to conduct and evaluate group psychotherapy for TGD migrants to provide opportunities for exploring and developing interpersonal skills and relationships.MethodThe group therapy included five individuals who identified as TGD and originated from the Middle East. The TGD group therapy consisted of 12 weekly sessions of 90 minutes each and was facilitated by a psychiatrist. All sessions were conducted online and in Turkish. The sessions were guided by the group process and discussions.ResultsAfter completing 12 group therapy sessions, members of the group reported benefiting from observing and emulating others who shared their problem constellation. Through the interpersonal skills that they built up throughout the sessions, they became more open to share their feelings experiencing fewer social barriers, and reduced anxiety.ConclusionThis observational study indicates the significance of offering group-based psychotherapy to enhance affirmation and social connection within gender minority groups and emphasizes the need to empirically evaluate the effectiveness of group psychotherapy with TGD individuals, with special attention to the unique needs of TGD migrants.

Tan Thanh Nguyen,1 Lac Duy Le,1 Thanh Tri Vu,2 Anh Thai Nguyen,1 Duc Binh Doan,1 Duyen Thi Pham,1 Tung Thanh Pham,1 Chuc Ngoc Vu,3 Minh Hoang Nguyen Vo4 1Cardiac Intensive Department, Thu Duc City Hospital, Ho Chi Minh City, Vietnam; 2Board of Directors, Thu Duc City Hospital, Ho Chi Minh City, Vietnam; 3Emergency Department, Thu Duc City Hospital, Ho Chi Minh City, Vietnam; 4Office of Science Management and International Affairs, Thu Duc City Hospital, Ho Chi Minh City, VietnamCorrespondence: Minh Hoang Nguyen Vo, Office of Science Management and International Affairs, Thu Duc City Hospital, No. 29 Phu Chau Street, Tam Phu ward, Thu Duc, Ho Chi Minh City, 700000, Vietnam, Tel +84 389135014, Email minhhoangytcc87@gmail.comIntroduction: Tricyclic antidepressants (TCAs) were once commonly used to treat major depressive disorder (MDD), but are now considered second-line options after SSRIs and SNRIs. Additionally, TCAs are used to treat other conditions such as chronic pain and enuresis in children. Due to their numerous side effects and potential for drug interactions, cases of poisoning and death from TCA overdose, particularly amitriptyline, are on the rise. Therefore, this article revisits the overview and describes the clinical progression regarding blood gases, ECG, and electrolytes of the patient, as well as the use of 4.2% sodium bicarbonate and 2% lidocaine to treat cases of amitriptyline overdose poisoning.Case Presentation: A 49-year-old female patient was admitted to the hospital due to cardiac and respiratory arrest. The patient had a past medical history of untreated cervical cancer and sleep disorders. Prior to admission, the patient had taken about 20 tablets of amitriptyline 25mg and was in a drowsy state with gasping breaths. During transportation to the hospital, the patient experienced cardiac arrest once and was successfully resuscitated, with a total arrest and resuscitation time of approximately 10 minutes.Results: The use of 4.2% Sodium Bicarbonate and 2% Lidocaine, the patient was not used plasma exchange in this case, proved effective in this case. Continuous monitoring of blood gas levels, ECG, and electrolytes was maintained. The patient was able to walk independently and was discharged after 12 days of treatment.Conclusion: The key factor was the healthcare staff’s quick recognition and timely management of TCA poisoning, in this case, amitriptyline.Keywords: tricyclic antidepressants, amitriptyline, cardiac arrhythmia

Elizabeth Elizabeth,1,2,&ast; Enny Rohmawaty,3,&ast; Muhammad Hasan Bashari3 1Postgraduate Program of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, West Java, Indonesia; 2Department of Pharmacology, Faculty of Medicine, Universitas Kristen Maranatha, West Java, Indonesia; 3Division of Pharmacology and Therapy, Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, West Java, Indonesia&ast;These authors contributed equally to this workCorrespondence: Enny Rohmawaty, Division of Pharmacology and Therapy, Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang, KM.21, Hegarmanah, Kec. Jatinangor, Kabupaten Sumedang, West Java, 45363, Indonesia, Email e.rohmawaty@unpad.ac.idBackground: Asthma is a chronic respiratory disease that is characterized by inflammation, bronchial hyperreactivity, and airway remodeling. The long-term use of corticosteroids at high doses causes various side effects. Traditional herbal medicine has been suggested as an alternative therapy that is safe and effective in dealing with asthma. Natural plants such as turmeric and mangosteen are known to treat asthma and reduce inflammation.Objective: The purpose of this study was to investigate the effects of turmeric and mangosteen pericarp ethanol extracts on the eosinophil counts, TNF-α and TGF-β 1 gene expression, and inflammatory cell counts in the histopathology of an asthmatic rat model.Methods: The preliminary study used 30 rats, which were divided into a normal group, negative control group (OVA-sensitized), turmeric normal group, mangosteen group, and positive control group. Blood samples were collected after the sensitization period to determine eosinophil counts. TNF-α and TGF-β 1 gene expression, and histopathology were observed in the rat’s lungs. The follow-up study used 30 rats divided into a normal group, negative control group (OVA-sensitized), combination of turmeric and mangosteen group (54m/200gr rats, 36mg/200gr rats, and 36mg/200gr rats), and positive control group. The examination procedures were the same as in the preliminary study.Results: The administration of single ethanol extracts of turmeric and mangosteen significantly decreased eosinophils and improved the histopathological features of the lungs (inflammatory cell counts, bronchial inflammatory score, and bronchial smooth muscle thickness) (p< 0.05). The combination of turmeric and mangosteen extracts at all doses significantly decreased eosinophils and improved the histopathological features of the lungs (inflammatory cell counts, bronchial inflammatory score, and bronchial smooth muscle thickness) (p< 0.05). Both the single and combined administration of turmeric and mangosteen ethanol extracts did not cause significant changes in TNF-alpha and TGF-beta (p> 0.05).Conclusion: Turmeric ethanol extract and mangosteen pericarp ethanol extract have a reductional effect on the parameters of asthma based on the eosinophil counts, the inflammatory cell counts and score, and bronchial smooth muscle thickness. Keywords: bronchial smooth muscle thickness, eosinophils, mangosteen, inflammatory cells, turmeric

Joo Sung Shim,1 Youhyun Kim,1 Taeho Yuh,1 Jii Bum Lee,2 Hye Ryun Kim,2 Min Hee Hong,2 Byoung Chul Cho,2 Sun Min Lim2 1Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; 2Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of KoreaCorrespondence: Sun Min Lim, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea, Tel +82-2-2228-1946 ; +82-10-2520-3969, Email Limlove2008@yuhs.acPurpose: Small-cell lung cancer (SCLC) accounts for approximately 10– 15% of all lung cancers and is characterized by a high recurrence rate, early metastasis, and poor prognosis. Before the FDA approved lurbinectedin for SCLC that progressed on or after platinum-based chemotherapy in 2020, topotecan was the sole second-line option associated with hematological toxicities and modest efficacy. Lurbinectedin received conditional approval in Korea in September 2022 for metastatic SCLC progression, with the same indications. Real-world data on its efficacy remains scarce owing to its recent implementation.Patients and Methods: Patients with metastatic SCLC who progressed on or after first-line therapy (n = 51) at Yonsei Cancer Center, Seoul, received lurbinectedin at 3.2 mg/m². Efficacy data, including tumor response, progression, survival, and demographics, were recorded.Results: A total of fifty-one patients received lurbinectedin between April 2023 and March 2024, with thirty-four patients being eligible for the assessment. At diagnosis, approximately one-third of the patients were female, 3% had a poor performance status with an Eastern Cooperative Oncology Group Performance Score (ECOG PS ≥ 2), and the median age was 68. Most patients (80%) had extensive disease. Overall objective response rate (ORR) and disease control rate (DCR) were 20% and 47%, respectively. The median progression-free survival (PFS) was 2.8 months, and the median overall survival (OS) was 3.3 months. Never smokers showed prolonged OS compared with current/former smokers (Smokers; 3.0 vs 7.3 months). Common adverse effects were nausea (53%), loss of appetite (24%), general weakness (18%), anemia (29%), neutropenia (12%), dizziness (6%), alopecia (6%), thrombocytopenia (3%), and pneumonia (3%). Overall, 24% of the patients experienced grade ≥ 3 adverse events (AEs), with the most common being anemia (9%) and neutropenia (9%).Conclusion: Real-world data suggest that lurbinectedin is a viable option for patients with SCLC who have progressed on or after platinum-based chemotherapy.Keywords: SCLC, lurbinectedin, real-world evidence, second line

Chung Hyun Nahm,1 Moon Hee Lee,2 Noriyoshi Fujii,3 Tatsuyoshi Fujii,4 Jong Weon Choi1 1Department of Laboratory Medicine, College of Medicine, Inha University, Incheon, Republic of Korea; 2Department of Internal Medicine, College of Medicine, Inha University, Incheon, Republic of Korea; 3Department of Dermatology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan; 4Department of Internal Medicine, Teikyo University Chiba Medical Center, Chiba, JapanCorrespondence: Jong Weon Choi, Department of Laboratory Medicine, College of Medicine, Inha University, Inhang-ro 27, Jung-gu, Incheon, Republic of Korea, Tel +82-32-890-2503, Fax +82-32-890-2529, Email jwchoi@inha.ac.krBackground: Nitric oxide (NO) is a bioactive signaling molecule that mediates various physiological and biological processes. Type 2 diabetes mellitus (T2DM) can be categorized into several subgroups according to fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) levels. Few studies have closely examined the effect of NO and lipocalin-2 on albuminuria and insulin resistance in T2DM subgroups. This study investigated the role of NO, lipocalin-2, and proinflammatory cytokines on the development of proteinuria and insulin resistance in patients with T2DM subgroups.Methods: A total of 256 subjects, including 191 patients with T2DM and 65 non-diabetic healthy individuals, were evaluated. NO metabolites (NOx), lipocalin-2, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels were measured. Patients with T2DM were classified into three subgroups: patients with FPG-defined diabetes (PG-DM), those with HbA1c-defined diabetes (HA-DM), and those who met the criteria for both FPG and HbA1c (PG/HA-DM). The albumin-to-creatinine ratio (ACR) and the homeostasis model assessment of β-cell function (HOMA-B) and insulin resistance (HOMA-IR) were calculated.Results: NOx, lipocalin-2, and TNF-α levels were significantly higher in patients with T2DM than in healthy individuals. Patients with PG/HA-DM had significantly higher NOx levels than those with PG-DM or HA-DM. Of the patients with high NOx levels, patients with lipocalin-2 elevation exhibited higher ACR and HOMA-IR than those without lipocalin-2 elevation. NOx was positively correlated with lipocalin-2, ACR, HOMA-IR, and TNF-α but not with HOMA-B and IL-6. The upper quartile of NOx levels led to a 1.2-fold increase in the risk of albuminuria (odds ratio: 1.215; 95% CI: 1.012– 2.418; p < 0.001).Conclusion: NO plays a crucial role in proteinuria and insulin resistance by collaborating with lipocalin-2 and TNF-α, showing significantly higher levels in patients with PG/HA-DM than in those with PG-DM or HA-DM.Keywords: nitric oxide, lipocalin-2, proteinuria, insulin resistance, diabetes subgroups

Rr Tutik Sri Hariyati,1,2 Hanny Handiyani,1,2 Andi Amalia Wildani,1,2 Tuti Afriani,1 Tuti Nuraini,1 Muhammad Hanif Amiruddin3 1Faculty of Nursing, Universitas Indonesia, Depok, West Java, Indonesia; 2The University of Indonesia Hospital, Depok, West Java, Indonesia; 3Taipei Medical University, Taipei, TaiwanCorrespondence: Rr Tutik Sri Hariyati, Email tutik@ui.ac.id; rrtutik@yahoo.comPurpose: The digitalization of healthcare is developing quickly. Every care provider needs to be up-to-date on this technology. The purpose of this research was to identify the digital literacy of nursing staff and nurse managers.Methods: A cross-sectional study assessed nurses’ digital literacy, specifically with regard to nursing informatics competencies in hospitals, primary healthcare, and clinics. The study sample included 100 nurses and 83 nurse managers. Researchers applied a modified questionnaire on nurses’ informatics competencies from TIGER Nursing Informatics, with a validity range of 0.497– 0.897 and a reliability value of 0.975.Results: Participants showed an acceptable level of computer literacy, although their scores were below 80%. Their scores were unrelated to workplace, duration and type of technology used, or gender. Nursing informatics competencies correlated significantly with age and work experience (p = 0.001). Age correlated negatively with technical computer skills but positively with competence in the implementation of healthcare. There was a positive link with a nurse’s position and education level, indicating that nurses with more education acquire higher levels of informatics competencies than those with less education. Additionally, those in higher positions tended to possess more advanced digital competence.Conclusion: Nurse managers play a significant role in training nursing staff members to enhance their informatics competencies. This study’s findings underscore the need to raise staff members’ informatics competencies by providing additional training.Keywords: digital literacy, nursing informatics competencies, education, nurse, nurse manager, technology

Bo-Chieh Chang,1 Meng-Hsuan Kuo,1 Chi-Hui Lee,1 Ya-Lan Chu,1 Kuang-Peng Chen,2 Chun-Liong Tung,2 Ya-Hui Yang,3 Chuan-Sheng Hung,4 Jui-Hsiu Tsai,2,5 Hung-Yi Chuang6 1Department of Pharmacy, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan; 2Department of Psychiatry, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan; 3Department of Long-Term Care and Health Management, Cheng Shiu University, Kaohsiung, Taiwan; 4Department of Computer Science and Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan; 5School of Medicine, Tzu Chi University, Hualien, Taiwan; 6Department of Environmental and Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanCorrespondence: Jui-Hsiu Tsai, Department of Psychiatry, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 2, Min-Sheng Road, Dalin Town, Chiayi, 622, Taiwan, Email faanvangogh@gmail.comIntroduction: Poor adherence to antipsychotics in patients with schizophrenia is a leading cause of relapse and functional deterioration. Long-acting injectable paliperidone may reduce relapse risks, health-care utilisation, and health-care costs in these patients.Methods: In this 24-month mirror-image study, we compared health-care utilization and costs before and after the initiation of paliperidone palmitate 3-monthly (PP3M) treatment in patients with schizophrenia spectrum disorders. Before the initiation of PP3M, the patients received paliperidone 1-monthly (PP1M) treatment. The primary study outcomes were changes in health-care utilisation and costs over the study period.Results: This study included 34 patients with schizophrenia spectrum disorders. During the 12-months period after the initiation of PP3M treatment, the mean duration of hospitalisation decreased from 57.7 to 28.5 days (p = 0.03). Moreover, significant reductions were noted in emergency room visits (PP1M vs PP3M: 0.3 vs 0.0, respectively; p = 0.05) and health-care costs (PP1M vs PP3M: 107,328.8 vs 57,848.6, respectively; p = 0.03).Conclusion: PP3M may significantly reduce hospitalisation duration, emergency room visits, and health-care costs in patients with schizophrenia.Keywords: schizophrenia, long-acting injectable antipsychotics, paliperidone palmitate, health-care cost, health-care utilisation

QuillBot is one of the online programs that can be utilized to enhance students’ writing skills. By integrating the paraphrasing tool QuillBot into the writing instruction, this study aimed to examine the effectiveness of QuillBot paraphraser on the students’ paraphrasing ability. Additionally, this study sought to find out the students' opinions on paraphrasing and on the use of QuillBot in paraphrasing. Adopting a mixed method with explanatory design, this study employed quasi-experimental research with a one group pretest posttest design. There were 44 fourth-semester students taking the Academic Writing course in the English study program at the University of Mataram participating in this study. The students’ paraphrasing ability was tested before and after the treatment with both manual paraphrasing instruction and QuillBot paraphrasing tool. While, the students’ opinions towards paraphrasing instruction integrating the QuillBot paraphrasing tool was discovered through questionnaire. Further, the collected data were analyzed quantitatively and qualitatively to answer the predetermined research objectives. The results of t-test showed that there was a significant difference between the students’ paraphrasing ability before and after the treatment with significance value 0.000 lower than 0.05. In addition, most students responded positively to the integration of QuillBot in paraphrasing instruction, as it not only improved their literacy skills but also their motivation in learning paraphrasing in which the use of QuillBot paraphraser is simple, easy, instant and time-saving. This study highlights and confirms the potential of AI tools like QuillBot to enhance language instruction. Other reseachers might compare the efficacy of QuillBot paraphraser to other automatic paraphraser in writing instruction and use both questionnaire and interview to obtain more detailed information about the students’ attitudes or opinions.

Muhammad Haroon Stanikzai,1 Mohammad Nasim Zafar,2 Khalid Akbari,3 Ahmad Haroon Baray,1 Hadia Sayam1 1Department of Public Health, Faculty of Medicine, Kandahar University, Kandahar, Afghanistan; 2Department of Para-Clinic, Faculty of Medicine, Kandahar University, Kandahar, Afghanistan; 3Department of Internal Medicine, Faculty of Medicine, Paktia University, Gardez, Paktia, AfghanistanCorrespondence: Muhammad Haroon Stanikzai, Department of Public Health, Faculty of Medicine, Kandahar University, District &num; 10, 3801, Kandahar, Afghanistan, Tel +93704775578, Email haroonstanikzai1@gmail.comBackground: Although depression is a frequently occurring mental disorder in patients with hypertension, little is known about the symptoms of depression among Afghan hypertensive patients.Objective: This study aimed to analyze the prevalence and predictors of depression symptoms among Afghan hypertensive patients.Methods: This was a secondary analysis of a multi-center cross-sectional study conducted between August and December 2022 across three major provinces in Afghanistan. Socio-demographic and clinical characteristics of the eligible participants were used in the analysis. A score of ≥ 5 on the PHQ-9 (Patient Health Questionnaire) was considered the cut-off point for labeling hypertensive patients as screening positive for depressive symptoms. We performed binary logistic regression to determine the predictors of depression symptoms among hypertensive patients.Results: Out of 853 hypertensive patients, 51.8% (95% CI: 48.4– 55.2%) had depressive symptoms. Binary logistic regression revealed that low monthly household income [AOR=1.42, 95% CI (1.01– 1.97), low education level [2.41 (1.57– 3.71)], physical inactivity [1.81 (1.22– 2.71)], poor blood pressure control [2.41 (1.57– 3.71)], and the presence of medical comorbidity [1.59 (1.15– 2.19)] were the predictors of depression symptoms.Conclusion: This study showed a high prevalence of depressive symptoms among Afghan hypertensive patients. Moreover, we found that low monthly household income, physical inactivity, low education level, poor blood pressure control, and the presence of medical comorbidity were the predictors of depression symptoms. Our findings suggest that hypertensive patients should be screened for mental health symptoms, and those most at risk for depression should seek supportive counseling.Keywords: hypertension, depression, determinants, Afghanistan

Widad Aghnia Shalannandia,1 Yoan Chou,2 Muhammad Hasan Bashari,1,3 Astrid Feinisa Khairani1,3 1Graduate School of Master Program in Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Sumedang, Jatinangor, West Java, Indonesia; 2Graduate School of Master Program in Anti Aging and Aesthetic Medicine, Faculty of Medicine, Universitas Padjadjaran, Sumedang, Jatinangor, West Java, Indonesia; 3Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Sumedang, Jatinangor, West Java, IndonesiaCorrespondence: Astrid Feinisa Khairani, Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Jalan Raya Bandung – Sumedang Km 21, Jatinangor, Sumedang, West Java, 45363, Indonesia, Tel +62-22-7795594, Email astrid.khairani@unpad.ac.idAbstract: Intermediate filaments are one of the three components of the cytoskeletons, along with actin and microtubules. The intermediate filaments consist of extensive variations of structurally related proteins with specific expression patterns in cell types. The expression pattern alteration of intermediate filaments is frequently correlated with cancer progression, specifically with the epithelial-to-mesenchymal transition process closely related to increasing cellular migration and invasion. This review will discuss the involvement of cytoplasmic intermediate filaments, specifically vimentin, nestin, and cytokeratin (CK5/CK6, CK7, CK8/CK18, CK17, CK19, CK20, CSK1), in breast cancer progression and as prognostic or diagnostic biomarkers. The potential for drug development targeting intermediate filaments in cancer will be reviewed. Keywords: breast malignancy, cytokeratin, EMT, intermediate filament, keratin, nestin, vimentin

Dwi Agustian,1 Insi Farisa Desy Arya,1 Qorinah Estiningtyas Sakilah Adnani,1 Guswan Wiwaha,1 Muhammad Hasan Bashari,2 Windi Nurdiawan,3 Ria Bandiara,4 Wijana Hasansulama,5 Afiat Berbudi,2 Gaga Irawan Nugraha,2 Wiryawan Permadi,3 Ruswana Anwar,3 Irvan Afriandi,1 Arief Kartasasmita,6 Yudi Mulyana Hidayat,3 Tri Hanggono Achmad,2 John Norcini7 1Department of Public Health, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia; 2Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia; 3Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia; 4Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia; 5Department of Otolaryngology, Head and Neck Surgery, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia; 6Department of Ophthalmology, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia; 7Department of Psychiatry, SUNY Upstate Medical University, Philadelphia, PA, USACorrespondence: Dwi Agustian, Department of Public Health, Faculty of Medicine, Universitas Padjadjaran, Jl. Prof. Eyckman No. 38, Bandung, West Java, 40161, Indonesia, Email dwi.agustian@unpad.ac.idAbstract: Although the field of medicine has made significant progress in recent decades, low and middle-income countries continue to face significant difficulties in addressing the unprecedented obstacles to improving health. Medical schools should play a critical role in driving health services reform and take on a new leadership role in strengthening the health system. This paper discusses a conceptual framework and outlines the Academic Health Systems (AHS) agenda in Indonesia. A comprehensive analysis was conducted on the existing literature and frameworks regarding AHS, applying the system thinking method, which engages stakeholders actively. The findings and interpretations from interviews, focus groups, and collaborative workshops were consolidated and a set of proposed frameworks, fundamental principles, and a route for enhancing the health system in Indonesia were put forward. Our recommendations include transformative learning, community engagement, and translational research as pillar principles of AHS program. These recommendations have the potential to be modified and implemented in other low- and middle-income countries.Keywords: academic health system, medical education, Indonesia, health system reform, health services transformation

Quan-fang Liu,1 Cui-na Shi,1 Jian-hua Tong,1 Kun-peng Li,1 Jian-jun Yang,2 Mu-huo Ji,1 Qing-ren Liu3 1Department of Anesthesiology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 3Department of Anesthesiology, Xishan People’s Hospital of Wuxi City, Wuxi, People’s Republic of ChinaCorrespondence: Qing-ren Liu, Department of Anesthesiology, Xishan People’s Hospital of Wuxi City, Wuxi, People’s Republic of China, Email liuqr5250@163.com Mu-huo Ji, Department of Anesthesiology, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, People’s Republic of China, Email jimuhuo2009@sina.comBackground: The utilization of adjuvants such as dexamethasone and dexmedetomidine in combination with local anesthetics has proven effective in extending analgesia duration. We aimed to investigate the potential efficacy of combining dexmedetomidine and dexamethasone in rhomboid intercostal and sub-serratus (RISS) block for prolonging postoperative analgesia in patients undergoing video-assisted thoracoscopic surgery (VATS).Methods: We did this randomized, double-blind, controlled trial in two tertiary-care hospitals. A total of eighty-eight patients undergoing VATS under general anesthesia were enrolled in this study. They were randomly assigned into four groups: ropivacaine (R) group, ropivacaine + dexmedetomidine (RM) group, ropivacaine + dexamethasone (RS) group, or ropivacaine + dexmedetomidine + dexamethasone (RSM) group. The primary outcome measure was the duration of analgesia. Secondary outcomes included Numeric Rating Scale (NRS) scores, cumulative oxycodone consumption, and adverse effects.Results: The RSM group exhibited a significantly prolonged duration of analgesia at 1073.5 min (932.0– 1283.3) compared to the R group with a duration of 154.5 min (80.5– 199.3) and the RS group with a duration of 282.0 min (195.3– 350.0, P < 0 0.001). The cumulative oxycodone consumption during the 0– 12 hours and 0– 24-hours period was significantly reduced in the RSM group compared to the R group (P < 0.05). There was also a lower incidence of nausea at 48 hours postoperatively in the RSM group compared to the RM group. However, there were no significant differences between the four groups regarding NRS pain scores.Conclusion: The combination of ropivacaine, dexmedetomidine, and dexamethasone in RISS block significantly prolongs the duration of postoperative analgesia following VATS.Keywords: nerve block, pain, postoperative, anesthesia, video-assisted thoracoscopic surgery

Danielle Modeste,1 Christopher Stewart,2 Hajani Premanandhan,2 Mahmoud Husseiny Awad,1 Gwyn Samuel Williams1 1Ophthalmology, Singleton Hospital, Swansea Bay University Health Board, Swansea, Wales, UK; 2Swansea Bay University, Medical School, Swansea, Wales, UKCorrespondence: Danielle Modeste, Ophthalmology Department, Singleton Hospital Sketty Ln, Sketty, Swansea, UK, SA2 8QA, Email danielle.modeste@wales.nhs.ukPurpose: To evaluate the efficiency and safety of Faricimab on treatment-naive neovascular age related macular degeneration (nAMD) in a real world UK clinic.Patients and Methods: This single centre, retrospective note review was conducted on treatment-naive patients with nAMD. The data collected included demographics, best corrected visual acuity (BCVA), central macular thickness (CMT), total retinal fluid (TRF), the presence of intraretinal fluid (IRF) and subretinal fluid (SRF).Results: A total of 66 eyes from 62 patients were analysed. The average age was 77 years (range 36– 91) and 54% of patients were female. After the first dose of faricimab, the average BCVA improved by 0.05 LogMAR (+2.5 letters), the average CMT decreased by 65.9μm and 41% of patients were found to be inactive. The follow-up intervals after the third loading dose were divided into 2 subsets of 4 and 8 week extensions. The 4 week extension subset saw a smaller improvement in BCVA (+3 letters) than the 8 week extension (+6 letters) while both had an average decrease in CMT by 86.6 μm. The total retinal fluid decreased by 45% and 70.7%, leaving only 30% and 12.2% residual intraretinal fluid (IRF) and 30% and 24.4% residual subretinal fluid (SRF), respectively. Over a ten-month period, the average number of injections received was 6.6, including 3 initial loading doses. There was only one reported case of an adverse event out of 66 eyes (1/66, 1.5%).Conclusion: Three loading doses of Faricimab appear efficacious and safe for the treatment of nAMD.Plain language Summary: What is already known on this topic:Faricimab is recombinant humanised bispecific IgG monoclonal antibody which binds and neutralises both VEGF-A and angiopoietin-2 (VEGFA and ANG2).Clinical trials have reported faricimab dosing intervals of up to Q16W.What this study adds:To offer a glimpse into real-world effectiveness and safety of faricimab beyond the constraints of a randomised controlled study in treatment naïve nAMD patients.Presents results derived from implementing a “Treat and Extend” algorithm with faricimab in nAMD management, showcasing its beneficial impact on the strategic planning and execution of patient care.How this research may affect research, practice or policy:Faricimab should be seen as a viable therapy in treatment-naive patients with nAMD.Employing a shortened loading regimen of three doses presents no discernible detriment to treatment efficacy when compared to the established four-dose schedule.Keywords: treatment-naïve, nAMD, Faricimab, dosing interval

Yu-Chi Wang,1,&ast; Meng-Ting Cai,1,&ast; Ming-Hong Chen,2,3 Fu-I Tung,4,5 Mei-Hsiu Chen,6,7 Tse-Ying Liu1 1Department of Biomedical Engineering, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan; 2Division of Neurosurgery, Department of Surgery, Far Eastern Memorial Hospital, New Taipei City, 220216, Taiwan; 3Department of Electrical Engineering, Yuan Ze University, Taoyuan City, 320315, Taiwan; 4Department of Orthopaedics, Yang-Ming Branch, Taipei City Hospital, Taipei, 111024, Taiwan; 5Department of Health and Welfare, College of City Management, University of Taipei, Taipei, 111036, Taiwan; 6Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, 220216, Taiwan; 7Department of Biomedical Engineering, Ming Chuang University, Taoyuan, 333, Taiwan&ast;These authors contributed equally to this workCorrespondence: Tse-Ying Liu; Mei-Hsiu Chen, Email tyliu5@nycu.edu.tw; michelle8989@gmail.comPurpose: Osteoporosis, characterized by reduced bone mass and structural deterioration, poses a significant healthcare challenge. Traditional treatments, while effective in reducing fracture risks, are often limited by side effects. This study introduces a novel nanocomplex, europium (Eu) ions-doped superparamagnetic iron oxide (SPIO) nanocrystals encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanospheres, abbreviated as SPIO:Eu@PLGA nanospheres, as a potential therapeutic agent for osteoporosis by modulating macrophage polarization, enhancing osteoblast differentiation and inhibiting osteoclastogenesis.Methods: SPIO and SPIO:Eu nanocrystals were synthesized through pyrolysis and encapsulated in PLGA using an emulsification method. To evaluate the impact of SPIO:Eu@PLGA nanospheres on macrophage reprogramming and reactive oxygen species (ROS) production, flow cytometry analysis was conducted. Furthermore, an ovariectomized (OVX) rat model was employed to assess the therapeutic efficacy of SPIO:Eu@PLGA nanospheres in preventing the deterioration of osteoporosis.Results: In vitro, SPIO:Eu@PLGA nanospheres significantly attenuated M1 macrophage activation induced by lipopolysaccharides, promoting a shift towards the M2 phenotype. This action is linked to the modulation of ROS and the NF-κB pathway. Unlike free Eu ions, which do not achieve similar results when not incorporated into the SPIO nanocrystals. SPIO:Eu@PLGA nanospheres enhanced osteoblast differentiation and matrix mineralization while inhibiting RANKL-induced osteoclastogenesis. In vivo studies demonstrated that SPIO:Eu@PLGA nanospheres effectively targeted trabecular bone surfaces in OVX rats under magnetic guidance, preserving their structure and repairing trabecular bone loss by modulating macrophage polarization, thus restoring bone remodeling homeostasis. The study underscores the critical role of Eu doping in boosting the anti-osteoporotic effects of SPIO:Eu@PLGA nanospheres, evident at both cellular and tissue levels in vitro and in vivo.Conclusion: The inclusion of Eu into SPIO matrix suggests a novel approach for developing more effective osteoporosis treatments, particularly for conditions induced by OVX. This research provides essential insights into SPIO:Eu@PLGA nanospheres as an innovative osteoporosis treatment, addressing the limitations of conventional therapies through targeted delivery and macrophage polarization modulation.Keywords: osteoporosis, macrophage polarization, osteoblast, osteoclast, nanocrystals, poly(lactic-co-glycolic acid)

Fariha Kamal,1 Elaha Somaya Ghafary,2 Mohammad Hassan Hamrah,3 Ghulam Sarwar Khalid,4 Mohammad Hussain Hamrah,5 Zaheruddin Hasam,6 Neghat Ghafoory7 1Department of Oral Medicine, Kabul University of Medical Sciences, Kabul, Afghanistan; 2Department of Periodontics, Kabul University of Medical Sciences, Kabul, Afghanistan; 3Department of Public Health and Health Systems, Nagoya University Graduate School of Medicine, Nagoya, Japan; 4Department of Pharmacology, Alberoni University, Kapisa, Afghanistan; 5Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan; 6Department of Dentistry, Jawzjan Public Hospital, Sheberghan, Afghanistan; 7Oral and MaxillofacialSurgery Department, Stomatology Teaching Hospital Kabul University of Medical Sciences, Kabul, AfghanistanCorrespondence: Elaha Somaya Ghafary, Department of Periodontics, Kabul University of Medical Sciences, Kabul, Afghanistan, Email elaha.somayaghafary@gmail.comBackground: Oral cancer (OC) is a major global health issue, with tobacco use being one of the most significant preventable risk factors. Despite its strong association with OC, public awareness about the harmful effects of tobacco remains limited. This study aims to evaluate the awareness and knowledge of tobacco use related to oral cancer among patients referred to the Stomatology Teaching Hospital.Methods: A cross-sectional survey was conducted at the Stomatology Teaching Hospital of Kabul University of Medical Sciences (KUMS) between January 1 and July 30, 2023. Using a convenience sampling method, the study included 435 patients aged 15 to 76 years. Logistic regression analysis was employed to determine factors associated with tobacco use, and the data were analyzed using SPSS version 26.0.Results: Participants were divided into two groups: tobacco users and non-tobacco users. Most of them were young (18 to 30 years old) with a significant difference in oral cancer knowledge between the two groups (p < 0.001). Cigarettes were the most common tobacco type among users (62.1%), which was also statistically significant (p < 0.001). Tobacco users were 3.04 times more likely to have knowledge about oral cancer (OR: 3.04, p < 0.001, 95% CI: 1.93– 4.80), indicating a significant association.Conclusion: The study reveals a general lack of awareness about oral cancer in our study population, particularly regarding specific risk factors. To improve awareness, it is essential for both public awareness campaigns and dentists to play a more active role in educating the public about oral cancer.Keywords: awareness, cigarette smoking, tobacco, oral cancer

Fu-Xing-Zi Li,1 Feng Xu,1 Chang-Chun Li,1 Li-Min Lei,1 Su-Kang Shan,1 Ming-Hui Zheng,1 Xiao Lin,2 Bei Guo,1 Ke-Xin Tang,1 Jia-Yue Duan,1 Yun-Yun Wu,1 Ye-Chi Cao,1 Jun-Jie Liu,3 Ling-Qing Yuan1 1Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 2Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 3Department of Periodontal Division, Hunan Xiangya Stomatological Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of ChinaCorrespondence: Ling-Qing Yuan, Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China, Email allenylq@csu.edu.cnPurpose: Anecdotal reports have praised the benefits of cold exposure, exemplified by activities like winter swimming and cold water immersion. Cold exposure has garnered acclaim for its potential to confer benefits and potentially alleviate diabetes. We posited that systemic cold temperature (CT, 4– 8°C) likely influences the organism’s blood components through ambient temperature, prompting our investigation into the effects of chronic cold exposure on type 2 diabetic (T2DM) mice and our initial exploration of how cold exposure mitigates the incidence of T2DM.Methods: The effects of CT (4– 8°C) or room temperature (RT, 22– 25°C) on T2DM mice were investigated. Mice blood and organ specimens were collected for fully automated biochemical testing, ELISA, HE staining, immunohistochemistry, and immunofluorescence. Glucose uptake was assessed using flow cytometry with 2-NBDG. Changes in potential signaling pathways such as protein kinase B (AKT), phosphorylated AKT (p-AKT), insulin receptor substrates 1 (IRS1), and phosphorylated IRS1 (p-IRS1) were evaluated by Western blot.Results: CT or CT mice plasma-derived extracellular vesicles (CT-EVs) remarkably reduced blood glucose levels and improved insulin sensitivity in T2DM mice. This treatment enhanced glucose metabolism, systemic insulin sensitivity, and insulin secretion function while promoting glycogen accumulation in the liver and muscle. Additionally, CT-EVs treatment protected against the streptozocin (STZ)-induced destruction of islets in T2DM mice by inhibiting β-cell apoptosis. CT-EVs also shielded islets from destruction and increased the expression of p-IRS1 and p-AKT in adipocytes and hepatocytes. In vitro experiments further confirmed its pro-insulin sensitivity effect.Conclusion: Our data indicate that cold exposure may have a potentially beneficial effect on the development of T2DM, mainly through the anti-diabetic effect of plasma-derived EVs released during cold stimulation. This phenomenon could significantly contribute to understanding the lower prevalence of diabetes in colder regions.Keywords: cold exposure, plasma-derived extracellular vesicles, type 2 diabetes, insulin sensitivity, β‑cell destruction

Kenneth Kenyon,1 Eugene B McLaurin,2 Steven M Silverstein,3 John C Meyer,4 Erik Anderson,5 Ravi H Patel,6 Paul J Gomes,7 Erin Reilly,8 Srilatha Vantipalli,8 Matthew W Cheung,8 Michael H Goldstein8 1Andover Eye Associates, Andover, MA, USA; 2Total Eye Care, P.A., Memphis, TN, USA; 3Silverstein Eye Centers, Kansas City, MO, USA; 4The Eye Care Institute, Louisville, KY, USA; 5Vision Institute, Colorado Springs, CO, USA; 6Eye Associates of Texas, Round Rock, TX, USA; 7Ora, Inc., Andover, MA, USA; 8Ocular Therapeutix, Inc., Bedford, MA, USACorrespondence: Matthew W Cheung, Ocular Therapeutix, Inc., 15 Crosby Drive, Bedford, MA, 01730, USA, Tel +1 516-287-7678, Email mcheung@ocutx.comPurpose: To evaluate the efficacy and safety of a dexamethasone intracanalicular insert (DEX) for treatment of allergic conjunctivitis (AC).Patients and Methods: In this multicenter, randomized, double-masked, placebo-controlled phase 3 study, adults (≥ 18 years) with AC were randomized 1:1 to DEX or placebo insert (PBO) placed bilaterally. Subjects underwent repetitive conjunctival allergen challenges (CAC) across 30 days and were assessed for changes in AC signs and symptoms. The primary endpoint was ocular itching score at 3, 5, and 7 minutes post-CAC at Day 8 (7 days post-insertion). This trial is registered on ClinicalTrials.gov (NCT04050865).Results: Ninety-six subjects were randomized (n=48 DEX, n=48 PBO). Compared to PBO, there were statistically significant treatment differences favoring DEX for the primary endpoint of mean ocular itching score at Day 8 (− 0.86, − 0.98, − 0.96 at 3, 5, and 7 minutes post-CAC respectively; P< 0.0001 for all). Treatment differences favored DEX for all 24 time points across 6 visits and were statistically significant (P< 0.05) except for the first post-insertion (Day 7, 3 minutes). For the 18 time points at which conjunctival redness was assessed, DEX had lower scores than PBO (P< 0.05 for all). The most common ocular adverse events (AEs) in DEX subjects were eye discharge and irritation. No serious AEs, elevated intraocular pressure, dacryocanaliculitis, or use of rescue medications were reported.Conclusion: Results of this study support the potential use of dexamethasone insert as a physician-administered, preservative-free treatment for AC, with significant improvements in ocular itching and conjunctival redness compared with placebo. The dexamethasone insert was generally safe with a favorable safety profile.Keywords: allergy, conjunctivitis, dexamethasone, insert, intracanalicular

Abstract Background Cryopreservation is a crucial procedure for safeguarding cells or other biological constructs, showcasing considerable potential for applications in tissue engineering and regenerative medicine. Aims This study aimed to evaluate the effectiveness of different cryopreservation conditions on human cells viability. Methods A set of cryopreserved data from Department of Tissue Engineering and Regenerative Medicine (DTERM) cell bank were analyse for cells attachment after 24 h being revived. The revived cells were analysed based on different cryopreservation conditions which includes cell types (skin keratinocytes and fibroblasts, respiratory epithelial, bone marrow mesenchymal stem cell (MSC); cryo mediums (FBS + 10% DMSO; commercial medium); storage durations (0 to > 24 months) and locations (tank 1–2; box 1–5), and revival methods (direct; indirect methods). Human dermal fibroblasts (HDF) were then cultured, cryopreserved in different cryo mediums (HPL + 10% DMSO; FBS + 10% DMSO; Cryostor) and stored for 1 and 3 months. The HDFs were revived using either direct or indirect method and cell number, viability and protein expression analysis were compared. Results In the analysis cell cryopreserved data; fibroblast cells; FBS + 10% DMSO cryo medium; storage duration of 0–6 months; direct cell revival; storage in vapor phase of cryo tank; had the highest number of vials with optimal cell attachment after 24 h revived. HDFs cryopreserved in FBS + 10% DMSO for 1 and 3 months with both revival methods, showed optimal live cell numbers and viability above 80%, higher than other cryo medium groups. Morphologically, the fibroblasts were able to retain their phenotype with positive expression of Ki67 and Col-1. HDFs cryopreserved in FBS + 10% DMSO at 3 months showed significantly higher expression of Ki67 (97.3% ± 4.62) with the indirect revival method, while Col-1 expression (100%) was significantly higher at both 1 and 3 months compared to other groups. Conclusion In conclusion, fibroblasts were able to retain their characteristics after various cryopreservation conditions with a slight decrease in viability that may be due to the thermal-cycling effect. However, further investigation on the longer cryopreservation periods should be conducted for other types of cells and cryo mediums to achieve optimal cryopreservation outcomes.

Type 2 diabetes mellitus (type 2 DM) is a disease including on metabolic disorder that characterized by an increase in glucose levels above normal. This glucose increase is caused by reduced insulin function which can be in the form of abnormalities in insulin secretion, impaired insulin action in peripheral tissues, or both. Metformin is one of the recommended therapies for type 2 DM. AMPK is the main pathway of metformin's mechanism. AMPKa2 encoded by PRKAA2 gene is an AMPK subunit that plays an important role in AMPK activation. OCT3 encoded by SLC22A3 plays a role in the metformin transport mechanism. OCT3 is needed in the metformin pharmacokinetic like absorption and elimination, this process determines metformin bioavailability, clearance, and its pharmacological effects. Mutations in PRKAA2 and SLC22A3 cause variations in the pharmacodynamic effects and pharmacokinetic of metformin in individuals directly. These changes will ultimately affect the effectiveness of metformin in type 2 DM patients.

Frederik PB Kristensen,1 Sia K Nicolaisen,1 Jens S Nielsen,2,3 Diana H Christensen,1,4 Kurt Højlund,2,3 Henning Beck-Nielsen,2 Jørgen Rungby,5 Søren G Friborg,6 Ivan Brandslund,7,8 Jens S Christiansen4 ,† Peter Vestergaard,9,10 Niels Jessen,11– 13 Michael H Olsen,14,15 Mette K Andersen,16 Torben Hansen,16 Charlotte Brøns,5 Allan Vaag,5,17 Reimar W Thomsen,1 Henrik T Sørensen1 1Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark; 2Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark; 3Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 4Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark; 5Steno Diabetes Center Copenhagen, Herlev, Denmark; 6Department of Endocrinology, Odense University Hospital, Odense, Denmark; 7Department of Biochemistry, Lillebaelt Hospital, Vejle, Denmark; 8Regional Health Research, University of Southern Denmark, Odense, Denmark; 9Department of Clinical Medicine and Endocrinology, Aalborg University Hospital, Aalborg, Denmark; 10Steno Diabetes Center North Denmark, Aalborg, Denmark; 11Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark; 12Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark; 13Department of Biomedicine, Aarhus University, Aarhus, Denmark; 14Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; 15Department of Internal Medicine and Steno Diabetes Center Zealand, Holbæk Hospital, Holbæk, Denmark; 16Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, København, Denmark; 17Lund University Diabetes Centre, Lund University, Malmö, Sweden†Dr Jens S Christiansen passed away on 16 December 2015Correspondence: Frederik PB Kristensen, Department of Clinical Epidemiology, Aarhus University, Olof Palmes Alle 43-45, Aarhus N, 8200, Denmark, Tel +45 87 16 82 37, Email fpk@clin.au.dkPurpose: This paper provides an overview of the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort and biobank, including baseline characteristics of participants enrolled up to 2023, and post-enrollment rates of cardiovascular disease outcomes and mortality.Methods: Since 2010, the DD2 project has enrolled individuals with type 2 diabetes mellitus (T2DM) recently diagnosed by general practitioners and by hospital-based clinicians across Denmark. Data from questionnaires, clinical examinations, and biological samples are collected at enrollment. Additional baseline and longitudinal follow-up data are accessed via linkage to health registries.Results: Between 2010 and 2023, the DD2 project enrolled 11,369 participants (41.3% women, median age 61.4 years). Median T2DM duration at enrollment was 1.3 years, and median BMI was 31.6 kg/m2 for women and 30.5 kg/m2 for men. 18.3% were smokers, 5.7% consumed more than 14/21 units of alcohol weekly (women/men), and 17.9% reported leisure-time physical inactivity. Original midwife records dating back > 80 years revealed that 20.2% of cohort participants had birth weights < 3000 g. Based on complete hospital contact history 10 years before enrollment, 20.7% of cohort participants had macrovascular complications, 17.0% had microvascular complications, and 21.7% had kidney disease based on eGFR or urine albumin-creatinine measurements. At enrollment, statins were used by 68.2%, antihypertensive drugs by 69.9%, and glucose-lowering drugs by 86.5% of individuals. Median HbA1c was 48 mmol/mol and median LDL cholesterol 2.2 mmol/L. Genome-wide genotyping and biomarker data have been analyzed for over 9000 individuals. During the current follow-up time from the enrollment date (median 7.9 years), incident cardiovascular disease rate has been 13.8 per 1000 person-years and the mortality rate has been 17.6 per 1000 person-years.Conclusion: The DD2 cohort, with its detailed information and long-term follow up, can improve our understanding of the progression and prevention of complications among individuals with newly diagnosed T2DM.Keywords: cohort profile, type 2 diabetes mellitus, patient characteristics, Denmark

Sarah A Alobaid,1 Mohammed Basem Beyari,1 Reem Bin Idris,1 Mohammed H Alhumud,1 Lamia A Alkuwaiz,2 Faisal Alsaif,3 Mansour Aljabry,4 Bandar Aljafen,5 Mona Soliman6 1College of Medicine, King Saud University, Riyadh, Saudi Arabia; 2Division of Orthopaedic Surgery, McGill University Health Centre, Montréal, Quebec, Canada; 3Fellowship and Residency Training Program, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia; 4Pathology Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 5Medicine Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 6Medical Education & Physiology, Vice Dean of Academic Affairs, College of Medicine, King Saud University, Riyadh, Saudi ArabiaCorrespondence: Mona Soliman, Medical Education and Physiology, College of Medicine, King Saud University, College of Medicine, King Saud University, Riyadh, Saudi Arabia, Tel +966505468581, Email msoliman1@ksu.edu.saBackground: The Big Sibling Program is an innovative peer student mentoring method that was designed and implemented by the students’ council in 2021 to complement the faculty mentoring program of first-year medical students in the College of Medicine, King Saud University, Saudi Arabia. The aim of the study was to evaluate the medical students’ perception of the peer students “Big Sibling” mentoring program and to assess the effectiveness of the program in terms of changes in the behavior and academic performance of the students.Methods: This is a retrospective study that was conducted in 2021. A registration form that includes demographic data, personal information, and academic performance (GPA and extracurricular achievements) was sent to all second- and third-year medical students to select the Big Siblings. A total of 49 mentors “Big Siblings” were accepted (30 males, 19 females) and matched randomly with the little siblings from first-year medical students. A written consent was obtained from the participants. The survey was structured on a 5-point Likert scale, and composed of four sections of closed-ended questions, that includes: the demographic data, the students’ (little sibling) evaluation of the mentorship sessions, the little sibling perception of the Big Sibling Program and its effectiveness of the Big Sibling Program in terms of behavioral or quality effects.Results: Out of 297 first-year medical students, 284 (95.62%) responded. The majority significantly agreed that the Big Sibling was readily available and they personally benefitted from the relationship (94.36%, p< 0.001; 90.14%, p< 0.001). They significantly disagreed that the relationship requires too much time (72.54%, p< 0.001) or that they do not need a mentor (78.87%, p< 0.001). Most significantly agreed that mentoring is a good idea (94.37%, p< 0.001), the program helped reduce their stress (84.51%, p< 0.001), helped them adjust to college (89.44%, p< 0.001), and advance academically (78.52%, p< 0.001). The program also encouraged their involvement in extracurricular activities (58.10%, p< 0.0001), research (43.31%, p< 0.001), and social engagement with peers (71.48%, p< 0.001). Moreover, the majority thought the program significantly improved their self-confidence (73.94%, p< 0.001), self-awareness (84.51%), accountability (54.51%), leadership (54.93%), resilience (71.13%), punctuality (69.01%, p< 0.001), time management (75.70%), stress coping (77.82%), problem-solving (76.76%), and teamwork (75.35%).Conclusion: Peer students’ big Siblings program has succeeded in reducing first-year medical students stress levels, improving their self-confidence, self-awareness, accountability and responsibility, leadership, resilience, punctuality and engaging them in research and extracurricular activities.Keywords: Medical students, big sibling program, mentoring, peer mentoring, mentoring program

Ryan S D’Souza,1 Yeng F Her,1 Nasir Hussain,2 Jay Karri,3 Michael E Schatman,4 Aaron K Calodney,5 Christopher Lam,6 Thomas Buchheit,7 Brennan J Boettcher,8 George C Chang Chien,9 Scott G Pritzlaff,10 Christopher Centeno,11 Shane A Shapiro,12 Johana Klasova,1 Jay S Grider,13 Ryan Hubbard,14 Eliana Ege,15 Shelby Johnson,8 Max H Epstein,16 Eva Kubrova,8 Mohamed Ehab Ramadan,17 Alexandra Michelle Moreira,18 Swarnima Vardhan,19 Yashar Eshraghi,20 Saba Javed,21 Newaj M Abdullah,22 Paul J Christo,17 Sudhir Diwan,23 Leslie C Hassett,24 Dawood Sayed,6 Timothy R Deer25 1Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA; 2Department of Anesthesiology, The Ohio State Wexner Medical Center, Columbus, OH, USA; 3Departments of Orthopedic Surgery and Anesthesiology, University of Maryland School of Medicine, Baltimore, MD, USA; 4Department of Anesthesiology, Perioperative Care, & Pain Medicine, NYU Grossman School of Medicine, New York, NY, USA; 5Precision Spine Care, Tyler, TX, USA; 6Department of Anesthesiology and Pain Medicine, The University of Kansas Medical Center, Kansas City, KS, USA; 7Department of Anesthesiology, Duke University, Durham, NC, USA; 8Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USA; 9Department of Regenerative Medicine, GCC Institute, Torrance, CA, USA; 10Department of Anesthesiology and Pain Medicine, University of California, Davis, Sacramento, CA, USA; 11Centeno-Schultz Clinic, Broomfield, CO, USA; 12Department of Orthopedic Surgery, Mayo Clinic, Jacksonville, FL, USA; 13Department of Anesthesiology, University of Kentucky College of Medicine, Lexington, KY, USA; 14Department of Sports Medicine, Anderson Orthopedic Clinic, Arlington, VA, USA; 15Department of Physical Medicine & Rehabilitation, Baylor College of Medicine, Houston, TX, USA; 16Department of Physical Medicine & Rehabilitation, Harvard Medical School, Boston, MA, USA; 17Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Hospital, Baltimore, MD, USA; 18Department of Physical Medicine & Rehabilitation, University of Miami/Jackson Memorial Hospital, Miami, FL, USA; 19Department of Internal Medicine, Yale New Haven Health – Bridgeport Hospital, Bridgeport, CT, USA; 20Department of Anesthesiology & Critical Care Medicine, Ochsner Health System, New Orleans, LA, USA; 21Department of Pain Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA; 22Department of Anesthesiology, University of Utah, Salt Lake City, UT, USA; 23Department of Pain Medicine, Advanced Spine on Park Avenue, New York City, NY, USA; 24Mayo Clinic Libraries, Mayo Clinic, Rochester, MN, USA; 25Department of Anesthesiology and Pain Medicine, West Virginia University School of Medicine, Charleston, WV, USACorrespondence: Ryan S D’Souza, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA, Tel +1-(507)-284-9696, Fax +1-(507)-266-7732, Email dsouza.ryan@mayo.eduPurpose: Injectable biologics have not only been described and developed to treat dermal wounds, cardiovascular disease, and cancer, but have also been reported to treat chronic pain conditions. Despite emerging evidence supporting regenerative medicine therapy for pain, many aspects remain controversial.Methods: The American Society of Pain and Neuroscience (ASPN) identified the educational need for an evidence-based guideline on regenerative medicine therapy for chronic pain. The executive board nominated experts spanning multiple specialties including anesthesiology, physical medicine and rehabilitation, and sports medicine based on expertise, publications, research, and clinical practice. A steering committee selected preliminary questions, which were reviewed and refined. Evidence was appraised using the United States Preventive Services Task Force (USPSTF) criteria for evidence level and degree of recommendation. Using a modified Delphi approach, consensus points were distributed to all collaborators and each collaborator voted on each point. If collaborators provided a decision of “disagree” or “abstain”, they were invited to provide a rationale in a non-blinded fashion to the committee chair, who incorporated the respective comments and distributed revised versions to the committee until consensus was achieved.Results: Sixteen questions were selected for guideline development. Questions that were addressed included type of injectable biologics and mechanism, evidence in treating chronic pain indications (eg, tendinopathy, muscular pathology, osteoarthritis, intervertebral disc disease, neuropathic pain), role in surgical augmentation, dosing, comparative efficacy between injectable biologics, peri-procedural practices to optimize therapeutic response and quality of injectate, federal regulations, and complications with mitigating strategies.Conclusion: In well-selected individuals with certain chronic pain indications, use of injectable biologics may provide superior analgesia, functionality, and/or quality of life compared to conventional medical management or placebo. Future high-quality randomized clinical trials are warranted with implementation of minimum reporting standards, standardization of preparation protocols, investigation of dose–response associations, and comparative analysis between different injectable biologics.Keywords: regenerative medicine, injectable biologics, platelet-rich plasma, mesenchymal stem cell, bone marrow aspirate concentrate, pain medicine

Najib Isse Dirie,1 Maryan Abdullahi Sh Nur,2 Abdirahman Khalif Mohamud,3 Bashiru Garba,4,5 Hassan Abdullahi Dahie,6 Mohamed Hussein Adam,4 Jamal Hassan Mohamoud4 1Department of Urology, Dr Sumait Hospital, Faculty of Medicine, and Health Sciences, SIMAD University, Mogadishu, Somalia; 2Department of Obstetrics and Gynecology, Dr Sumait Hospital, Faculty of Medicine and Health Sciences, SIMAD University, Mogadishu, Somalia; 3Faculty of Medicine, and Health Science, SIMAD University, Mogadishu, Somalia; 4Department of Public Health, Faculty of Medicine and Health Sciences, SIMAD University, Mogadishu, Somalia; 5Department of Veterinary Public Health and Preventive Medicine, Faculty of Veterinary Medicine, Usmanu Danfodiyo University, Sokoto, SK, Nigeria; 6Nursing and Midwifery Department, Faculty of Medicine and Health Sciences, SIMAD University, Mogadishu, 2526, SomaliaCorrespondence: Maryan Abdullahi Sh Nur, Email dr.maryan.abdullahi@gmail.comBackground: Pregnant women exhibit COVID-19 vaccine hesitancy due to concerns regarding potential risks to their babies, doubts about vaccine efficacy, and limited access to information. Therefore, this study aims to estimate COVID-19 vaccine uptake and factors associated with pregnant women in Mogadishu, Somalia.Methods: A cross-sectional study was conducted on pregnant women using a questionnaire covering socio-demographic information, pregnancy-related characteristics, perceptions about the COVID-19 vaccine, and vaccination status. Univariable and multivariable logistic regression analyses were utilized to identify factors associated with the outcome variable.Results: Among the 400 pregnant women who participated in this study, 26.8% had received a COVID-19 vaccine dose, with only 14.9% receiving it during pregnancy. Reasons for not receiving the vaccine included a lack of information about the vaccine (47.4%), concerns about its adverse effects on personal health (33.8%), misconceptions regarding impacts on fertility or menstrual cycles (14.3%), belief in the vaccine’s inefficacy (3.4%), and fears about adverse effects on their fetus. In multivariable logistic regression, pregnant women with a history of chronic diseases (AOR=3.27, 95% CI=1.992– 6.145), those who perceived themselves at risk of contracting COVID-19 (AOR=3.81, 95% CI=2.11– 5.10), those who believed that the vaccine was accessible to them (AOR=4.34, 95% CI=2.915– 6.165), and those who discussed the COVID-19 vaccine with their healthcare provider (AOR=3.91, 95% CI=2.123– 7.878) were more likely to receive the COVID-19 vaccine compared to their counterparts.Conclusion: Pregnant women in Mogadishu, Somalia, face challenges with sub-optimal covid-19 vaccine uptake. Implementations should improve awareness of COVID-19 risks and facilitate discussions between healthcare providers and pregnant women. In addition, efforts to provide reliable information about the vaccine, alleviate concerns about its adverse effects, and dispel misconceptions about fertility, menstrual cycles, efficacy, and foetal impact are crucial.Keywords: COVID-19 vaccine uptake, willingness, hesitancy and acceptance, factors associated, pregnant women, Mogadishu, Somalia

Abdullahi Abdirahman Omar,1 Jamal Hassan Mohamoud,2 Mohamed Hussein Adam,2 Bashiru Garba,2 Mariam Abdi Hassan,1 Ibrahim Abdullahi Mohamed,1 Zakaria Mohamed Adam1 1Dr.Sumait Hospitals, Faculty of Medicine and Health Sciences, SIMAD University, Mogadishu, Somalia; 2Department Public Health, Faculty of Medicine and Health Sciences of SIMAD University, Mogadishu, SomaliaCorrespondence: Abdullahi Abdirahman Omar, Tel +252615444315, Email dr.abdullahi.yare@simad.edu.soBackground: The COVID-19 pandemic’s first wave and subsequent lockdowns disrupted global healthcare systems, significantly impacting essential services including tuberculosis (TB) care. Non-adherence to anti-TB drugs is a critical concern, leading to treatment failure, drug resistance, and increased morbidity and mortality. This study assessed the rate and determinants of non-adherence to TB treatment among patients at TB centers during the first wave of the pandemic.Material and Methods: A cross-sectional study was conducted from June 15 to July 30, 2020, involving 255 TB patients at three centers in Mogadishu. Data were gathered using the Morisky Medication Adherence Scale-8 (MMAS-8) through structured interviews and analyzed using descriptive statistics and binary logistic regression.Results: The study found a 34.5% non-adherence rate during the pandemic. Key reasons for non-adherence included forgetting to take medication (33%), feeling well (29%), experiencing side effects (18%), and fear of contracting COVID-19 (16%). Significant factors associated with non-adherence were age groups 25– 34 years (OR = 2.96, p = 0.024) and 35– 44 years (OR = 4.55, p = 0.005), unemployment (OR = 2.57, p = 0.037), smoking (OR = 3.49, p = 0.029), tobacco use (OR = 4.15, p = 0.034), proximity to a health facility (OR = 0.44, p = 0.033), perception of healthcare providers as very friendly (OR = 0.24, p = 0.031) or friendly (OR = 0.45, p = 0.023), being in the continuous treatment phase (OR = 3.2, p < 0.001), and experiencing adverse treatment effects (OR = 2.42, p = 0.003).Conclusion: Non-adherence to anti-tuberculosis treatment was notably high in Mogadishu during the first wave of the pandemic, necessitating targeted interventions to improve adherence.Keywords: non-adherence, anti-tuberculosis drugs, COVID-19, Tuberculosis

Gusgus Ghraha Ramdhanie,1,&ast; Altia Nurrohmah,2,&ast; Adelse Prima Mulya,3,&ast; Henny Suzana Mediani,1,&ast; Nina Sumarni,3,&ast; Aep Maulid Mulyana,4,&ast; Mega Hasanul Huda5,&ast; 1Department of Pediatric Nursing, Faculty of Nursing, Universitas Padjadjaran, Bandung, West Java, 40132, Indonesia; 2Undergraduate Nursing Program, Faculty of Nursing, Universitas Padjadjaran, Bandung, West Java, 40132, Indonesia; 3Department of Community Health Nursing, Faculty of Nursing, Universitas Padjadjaran, Bandung, West Java, 40132, Indonesia; 4Internship Nursing Program, Faculty of Nursing, Universitas Padjadjaran, Bandung, West Java, 40132, Indonesia; 5Department of Pediatric Nursing, Faculty of Nursing Science, Universitas Indonesia, Depok, West Java, 16424, Indonesia&ast;These authors contributed equally to this workCorrespondence: Gusgus Ghraha Ramdhanie, Department of Pediatric Nursing, Faculty of Nursing, Universitas Padjadjaran, Bandung, West Java, 40132, Indonesia, Tel +62 813-2397-3679, Email gusgus.ghraha.ramdhanie@unpad.ac.idBackground: Invasive procedures in children can lead to painful and uncooperative procedures. It is essential to determine the appropriate method to create a comfortable environment for children during invasive procedures. However, audiovisuals are one of the distraction techniques used in pain management.Purpose: This study aims to identify and categorize related audiovisual distraction techniques in reducing pain due to invasive procedures among children.Methods: This study uses a systematic scoping review. A literature review was conducted using PubMed, EBSCO, Science Direct, Scopus and grey literature through Google Scholar. The study was eligible for inclusion if it included articles published from 2012 to 2022, full-text and open accessed articles, and in Indonesian and English language. Studies were excluded if they were review studies and the adult population. The keywords in English were ”Children” OR ‘Child’ OR ”Kids” OR ‘Youth’ OR ‘Adolescents’ OR ‘Teenager’ OR ‘Teens’ OR ‘Young People’ OR ‘Pediatric’ OR ‘Paediatric’ OR ‘Childhood’ AND ”Audiovisual” OR ‘Movie’ OR ‘Video’ OR ‘Animation’ AND ”Pain” AND ”Invasive procedures” and keyword in Indonesia were ”Anak” OR ‘Remaja’ OR ‘Bayi’ OR ‘Balita’ AND ”Audiovisual” OR ‘Film’ OR ”Video” OR ‘Animasi’ OR “Nyeri” AND ‘Prosedur invasif’.Results: We found 15 articles showing audiovisual distraction techniques in managing pain among children undergoing invasive procedures. Three types of audiovisual interventions were used, including virtual reality (VR), video music, and animated cartoons. In addition, types of invasive procedures that benefited from the analyzed interventions were infusion, surgery, injection, blood draw, dressing change, circumcision, endoscopy, and phlebotomy.Conclusion: Our findings highlight that virtual reality, video music, and animated cartoons have clinical implications in helping to distract from pain in children undergoing invasive procedures. Our study indicates that the potential of audiovisual intervention can be used as an intervention strategy in the pediatric nursing area.Keywords: audiovisual, child, invasive procedures, pain

Abdullah Dalboh,1 Walid M Abd El Maksoud,1 Khaled S Abbas,1 Hassan A Alzahrani,1 Mohammed A Bawahab,1 Fahad S Al Amri,1 Marei H Alshandeer,1 Maha A Alghamdi,1 Meshal S Alahmari,2 Abdulaziz M Alqahtani,2 Mansour S Alqahtani,2 Aljohrah M Alqahtani,2 Leinah H Alshahrani2 1Surgery Department, College of Medicine, King Khalid University, Abha, Saudi Arabia; 2College of Medicine, King Khalid University, Abha, Saudi ArabiaCorrespondence: Walid M Abd El Maksoud, General Surgery Department, Faculty of Medicine, King Khalid University, P. O. 641, Abha, 61421, Saudi Arabia, Tel +966543128555, Email wabdulmksoud@kku.edu.saBackground: The relationship between laparoscopic sleeve gastrectomy (LSG) and gastroesophageal reflux disease (GERD) is intricate. Hiatal hernia repair or gastropexy can have an impact on postoperative GERD.Aim: To assess the effect of the repair of an accidentally discovered HH and/or gastropexy on the development of de novo postoperative GERD symptoms after LSG.Methods: This retrospective study included all obese patients who underwent LSG at our hospital from January 2018 to June 2022. The data retrieved from patients’ files comprised demographic and clinical data, including BMI, GERD symptoms, and comorbidities. Hiatal hernias, surgical technique, gastropexy, duration, and intraoperative complications were recorded. Postoperative data included early and late postoperative complications, weight loss, de novo GERD, and medication use.Results: The study included 253 patients, 89 males (35.2%) and 164 females (64.8%), with a mean age of 33.3± 10.04 years. De novo GERD was detected in 94 individuals (37.15%). HH was accidentally found and repaired in 29 patients (11.5%). Only 10.3% of LSG and HH repair patients had de novo GERD symptoms, compared to 40.6% of non-HH patients. 149 patients (58.9%) had gastropexy with LSG. Postoperative de novo GERD symptoms were comparable for LSG with gastropexy (40.5%) and LSG alone (40.9%).Conclusion: After one year, concurrent hiatal hernia repair and LSG seem to be safe and beneficial in lowering postoperative de novo GERD symptoms. The inclusion of gastropexy with LSG had no significant impact on postoperative de novo GERD. Both HH repair and gastropexy lengthened the operation but did not increase its complications.Keywords: Obesity, Laparoscopic sleeve gastrectomy, Gastroesophageal reflux disease, GERD, Hiatal hernia, Gastropexy

Hany Ahmed Helaly,&ast; Mohamed Hassan Said,&ast; Osama Ramadan Elnaggar,&ast; Mohamed Hassan Elkhawaga&ast; Ophthalmology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt&ast;These authors contributed equally to this workCorrespondence: Hany Ahmed Helaly, Ophthalmology Department, Faculty of Medicine, Alexandria University, 30 Roshdy Street, Roshdy, Alexandria, Egypt, Tel +201225466733, Email hany209209@yahoo.comPurpose: To compare the accuracy of modern intraocular lens (IOL) power calculation formulas with that of older formulas, such as SRK/T and Hoffer Q, in pediatric cataract surgery.Methods: This retrospective study included 100 eyes of 100 children who underwent routine cataract surgery with primary IOL implantation in a bag. This study used four IOLMaster 700 integrated formulas: SRK/T, Hoffer Q, Haigis, and Barrett Universal II (BUII). In addition, the following formulas were used: EVO 2.0, Hill RBF 3.0, Hoffer QST, Kane, and PEARL DGS, which are available online.Results: There was a statistically significant difference between SRK/T and most other formulas, except for Hoffer Q, Hoffer QST, and BUII (p < 0.05). SRK/T yielded the lowest median absolute error (MedAE) of 0.63 D. This was followed by the BUII (0.66 D), Hoffer Q, and Hoffer QST (0.68 D). SRK/T also yielded the highest percentage of cases within ± 0.50 D (43% of the cases). For patients aged 2 to 5 years, SRK/T formula yielded statistically significantly better results than all other included formulas (p < 0.05) with MedAE = 0.44 D, 58.33% and 87.50% of the cases were within ± 0.50 D and ± 1.0 D of intended refraction, respectively.Conclusion: The SRK/T formula showed the best IOL power calculation results in pediatric cataract surgery, followed by BUII, Hoffer Q, and Hoffer QST. In children aged 2– 5 years, the SRK/T formula outperformed all other formulas, followed by the BUII and Hoffer QST formulas. In children older than 5 years, there was no statistically significant difference between the different formulas (p > 0.05); Hoffer Q and SRK/T showed slightly better MedAE in this age group (5– 10 years).Keywords: pediatric biometry, IOL calculation, haigis, Barrett universal II, SRK/T, EVO 2.0, hill RBF 3.0, Kane, Hoffer QST

Alcohol use disorders (AUD) are commonly occurring, heritable and polygenic disorders with etiological origins in the brain and the environment. To outline the causes and consequences of alcohol-related milestones, including AUD, and their related psychiatric comorbidities, the Collaborative Study on the Genetics of Alcoholism (COGA) was launched in 1989 with a gene-brain-behavior framework. COGA is a family based, diverse (~25% self-identified African American, ~52% female) sample, including data on 17,878 individuals, ages 7-97 years, in 2246 families of which a proportion are densely affected for AUD. All participants responded to questionnaires (e.g., personality) and the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) which gathers information on psychiatric diagnoses, conditions and related behaviors (e.g., parental monitoring). In addition, 9871 individuals have brain function data from electroencephalogram (EEG) recordings while 12,009 individuals have been genotyped on genome-wide association study (GWAS) arrays. A series of functional genomics studies examine the specific cellular and molecular mechanisms underlying AUD. This overview provides the framework for the development of COGA as a scientific resource in the past three decades, with individual reviews providing in-depth descriptions of data on and discoveries from behavioral and clinical, brain function, genetic and functional genomics data. The value of COGA also resides in its data sharing policies, its efforts to communicate scientific findings to the broader community via a project website and its potential to nurture early career investigators and to generate independent research that has broadened the impact of gene-brain-behavior research into AUD.

We report the first result of a direct search for a cosmic axion background (CaB)-a relativistic background of axions that is not dark matter-performed with the axion haloscope, the Axion Dark Matter eXperiment (ADMX). Conventional haloscope analyses search for a signal with a narrow bandwidth, as predicted for dark matter, whereas the CaB will be broad. We introduce a novel analysis strategy, which searches for a CaB induced daily modulation in the power measured by the haloscope. Using this, we repurpose data collected to search for dark matter to set a limit on the axion photon coupling of a CaB originating from dark matter cascade decay via a mediator in the 800-995 MHz frequency range. We find that the present sensitivity is limited by fluctuations in the cavity readout as the instrument scans across dark matter masses. Nevertheless, we suggest that these challenges can be surmounted using superconducting qubits as single photon counters, and allow ADMX to operate as a telescope searching for axions emerging from the decay of dark matter. The daily modulation analysis technique we introduce can be deployed for various broadband rf signals, such as other forms of a CaB or even high-frequency gravitational waves.

A 57-year-old male patient, with a known case of bronchial asthma presented with acute dyspnea, cough with expectoration, fever, severe myalgia, and pedal edema. On physical examination, he had tachypnea, high temperature, bilateral polyphonic rhonchi, audible wheeze, and asymmetric sensory and motor neuropathy. Cutaneous examination revealed multiple palpable purpuric lesions with few hemorrhagic bullae and crusted erosions distributed symmetrically over bilateral limbs suggestive of cutaneous small vessel vasculitis. Investigations showed elevated total counts, eosinophilia, deranged electrolytes, and abnormal liver and renal function tests. Histopathology revealed eosinophilic predominant vasculitis. Testing for perinuclear anti-cytoplasmic antibody was positive. A diagnosis of eosinophilic granulomatosis with polyangiitis (Churg–Strauss disease) was thus confirmed. The patient succumbed in 2 weeks due to multi-organ failure. All the characteristic findings were found in our patient, but a fatal outcome in a very short period after diagnosis was an unusual presentation.

In current toxicological research, 2D cell cultures and animal models are well- accepted and commonly employed methods. However, these approaches have many drawbacks and are distant from the actual environment in human. To embrace this, great efforts have been made to provide alternative methods for non-animal skin models in toxicology studies with the need for more mechanistically informative methods. This review focuses on the current state of knowledge regarding the in vitro 3D skin model methods, with different functional states that correspond to the sustainability in the field of toxicology testing. We discuss existing toxicology testing methods using in vitro 3D skin models which provide a better understanding of the testing requirements that are needed. The challenges and future landscape in using the in vitro 3D skin models in toxicology testing are also discussed. We are confident that the in vitro 3D skin models application may become an important tool in toxicology in the context of risk assessment.