Browse publications by year: 2023

  1. Aggarwal D, Yang J, Salam MA, Sengupta S, Al-Amin MY, Mustafa S, et al.
    Front Immunol, 2023;14:1203073.
    PMID: 37671162 DOI: 10.3389/fimmu.2023.1203073
    Cancer is one of the deadliest diseases, causing million of deaths each year globally. Conventional anti-cancer therapies are non-targeted and have systemic toxicities limiting their versatile applications in many cancers. So, there is an unmet need for more specific therapeutic options that will be effective as well as free from toxicities. Antibody-drug conjugates (ADCs) are suitable alternatives with the right potential and improved therapeutic index for cancer therapy. The ADCs are highly precise new class of biopharmaceutical products that covalently linked a monoclonal antibody (mAb) (binds explicitly to a tumor-associated surface antigen) with a customized cytotoxic drug (kills cancer cells) and tied via a chemical linker (releases the drug). Due to its precise design, it brings about the target cell killing sparing the normal counterpart and free from the toxicities of conventional chemotherapy. It has never been so easy to develop potential ADCs for successful therapeutic usage. With relentless efforts, it took almost a century for scientists to advance the formula and design ADCs for its current clinical applications. Until now, several ADCs have passed successfully through preclinical and clinical trials and because of proven efficacy, a few are approved by the FDA to treat various cancer types. Even though ADCs posed some shortcomings like adverse effects and resistance at various stages of development, with continuous efforts most of these limitations are addressed and overcome to improve their efficacy. In this review, the basics of ADCs, physical and chemical properties, the evolution of design, limitations, and future potentials are discussed.
    MeSH terms: Antibodies, Monoclonal; Biological Products*; Humans; Neoplasms*; Immunoconjugates*; Drug-Related Side Effects and Adverse Reactions*
  2. Azhar AA, Jamil K, Abd Rasid AF
    Cureus, 2023 Aug;15(8):e42986.
    PMID: 37671211 DOI: 10.7759/cureus.42986
    Septic arthritis of the shoulder in pediatric patients should be diagnosed and treated urgently to prevent complications of the disease. However, early detection can be a challenge due to mild symptoms with ambiguous laboratory and radiological findings. We report a case of an eight-month-old girl who presented to us initially with pseudo paresis of her right shoulder without any signs suggestive of infection. After a negative ultrasound, she was discharged with analgesia upon improvement of range of motion. Three weeks later, she presented with recurrent shoulder pain associated with fever, swelling, elevated CRP, and osteomyelitis changes of the humeral head on a plain radiograph. We proceeded with a minimally invasive arthrotomy washout and commenced on IV antibiotics. At one month follow-up, she regained her full range of motion and recovered fully. No recurrence of septic arthritis until six-month follow-up. This write-up discusses the diagnostic challenge of pediatric shoulder septic arthritis and the surgical technique of minimally invasive arthrotomy washout in a pediatric patient.
  3. Mahmoudi Azar L, Öncel MM, Karaman E, Soysal LF, Fatima A, Choi SB, et al.
    Comput Struct Biotechnol J, 2023;21:4096-4109.
    PMID: 37671240 DOI: 10.1016/j.csbj.2023.07.022
    Computational methods coupled with experimental validation play a critical role in the identification of novel inhibitory peptides that interact with viral antigenic determinants. The interaction between the receptor binding domain (RBD) of SARS-CoV-2 spike protein and the helical peptide of human angiotensin-converting enzyme-2 (ACE2) is a necessity for the initiation of viral infection. Herein, natural orthologs of human ACE2 helical peptide were evaluated for competitive inhibitory binding to the viral RBD by use of a computational approach, which was experimentally validated. A total of 624 natural ACE2 orthologous 32-amino acid long peptides were identified through a similarity search. Molecular docking was used to virtually screen and rank the peptides based on binding affinity metrics, benchmarked against human ACE2 peptide docked to the RBD. Molecular dynamics (MD) simulations were done for the human reference and the Nipponia nippon peptide as it exhibited the highest binding affinity (Gibbs free energy; -14 kcal/mol) predicted from the docking results. The MD simulation confirmed the stability of the assessed peptide in the complex (-12.3 kcal/mol). The top three docked-peptides (from Chitinophaga sancti, Nipponia nippon, and Mus musculus) and the human reference were experimentally validated by use of surface plasmon resonance technology. The human reference exhibited the weakest binding affinity (Kd of 318-441 pM) among the peptides tested, in agreement with the docking prediction, while the peptide from Nipponia nippon was the best, with 267-538-fold higher affinity than the reference. The validated peptides merit further investigation. This work showcases that the approach herein can aid in the identification of inhibitory biosimilar peptides for other viruses.
  4. Gupta SM, Behera A, Jain NK, Tripathi A, Rishipathak D, Singh S, et al.
    RSC Adv, 2023 Sep 04;13(38):26344-26356.
    PMID: 37671344 DOI: 10.1039/d3ra03224h
    Leading pathological markers of Alzheimer's disease (AD) include Acetylcholinesterase (AChE), Butyrylcholinesterase (BuChE), Amyloid beta (Aβ) and reactive oxygen species (ROS). Indole derivatives were identified and optimized to improve the potency against AChE, BuChE, Aβ and ROS. The lead molecule IND-30 was found to be selective for AChE (selectivity ratio: 22.92) in comparison to BuChE and showed maximum inhibition potential for human AChE (IC50: 4.16 ± 0.063 μM). IND-30 was found to be safe on the SH-SY5Y cell line until the dose of 30 mM. Further, molecule IND-30 was evaluated for its ability to inhibit AChE-induced Aβ aggregation at 0.5, 10 and 20 μM doses. Approximately, 50% of AChE-induced Aβ aggregation was inhibited by IND-30. Thus, IND-30 was found to be multitargeting for AD.
  5. Kishi K, Jarutach J, Ooi YK, Wong NL, Che Mood M, Kandhavello G, et al.
    Cardiol Young, 2023 Aug;33(8):1359-1366.
    PMID: 35950412 DOI: 10.1017/S104795112200244X
    INTRODUCTION: Current guidelines discourage shunt closure in patients with pulmonary vascular resistance index >8 Wood units x m2. The study examined the long-term outcome of patients over 15 years old, with pulmonary vascular resistance index >8 Wood units x m2 and patent ductus arteriosus.

    MATERIALS AND METHODS: This was a multi-institutional, retrospective study involving all consecutive patients (>15 years old) with patent ductus arteriosus and severe pulmonary hypertension. Patients who had patent ductus arteriosus closure were divided into the Good (no death or hospital admissions due to worsening pulmonary hypertension) and the Poor Outcome groups and these groups were compared.

    RESULTS: Thirty-seven patients [male: 9 (24.3%); mean age: 30.49 ± 9.56 years; median follow-up: 3 (IQR: 1.5,10) years] were included from four centers. Twenty-two patients who underwent patent ductus arteriosus closure, 15 (71.4%) had good outcomes while 7 (28.6%) had poor outcomes. Pulmonary vascular resistance index and pulmonary to systemic resistance ratio (Rp:Rs) were lower in the Good Outcome Group (14.35 ± 1.66 Wood units x m2 vs. 20.07 ± 2.44; p = 0.033 and 0.44 ± 0.16 vs. 1.08 ± 1.21; p = 0.042). Haemoglobin concentrations (<14.3 g/dL) were associated with good long-term outcomes in the Closed Group.

    CONCLUSIONS: Patients with patent ductus arteriosus with severe pulmonary hypertension have a dismal outcome with or without closure. High haemoglobin levels at the time of occlusion predict a worse outcome for patients with patent ductus arteriosus and pulmonary hypertension.

    MeSH terms: Adolescent; Adult; Hemoglobins; Humans; Male; Retrospective Studies; Treatment Outcome; Young Adult
  6. Jorfi S, Ansa-Addo EA, Mariniello K, Warde P, Bin Senian AA, Stratton D, et al.
    J Gen Virol, 2023 Sep;104(9).
    PMID: 37665326 DOI: 10.1099/jgv.0.001884
    Like most non-enveloped viruses, CVB1 mainly uses cell lysis to spread. Details of a nonlytic virus transmission remain unclear. Extracellular Vesicles (EVs) transfer biomolecules between cells. We show that CVB1 entry into HeLa cells results in apoptosis and release of CVB1-induced 'medium-sized' EVs (CVB1i-mEVs). These mEVs (100-300 nm) harbour CVB1 as shown by immunoblotting with anti-CVB1-antibody; viral capsids were detected by transmission electron microscopy and RT-PCR revealed CVB1 RNA. The percentage of mEVs released from CVB1-infected HeLa cells harbouring virus was estimated from TEM at 34 %. Inhibition of CVB1i-mEV production, with calpeptin or siRNA knockdown of CAPNS1 in HeLa cells limited spread of CVB1 suggesting these vesicles disseminate CVB1 virions to new host cells by a nonlytic EV-to-cell mechanism. This was confirmed by detecting CVB1 virions inside HeLa cells after co-culture with CVB1i-mEVs; EV release may also prevent apoptosis of infected cells whilst spreading apoptosis to secondary sites of infection.
    MeSH terms: Extracellular Vesicles*; HeLa Cells; Humans; Cell Death; Apoptosis*; RNA, Small Interfering
  7. Zhou Z, Zhao J, de Cruz CR, Xu H, Wang L, Xu Q
    Fish Physiol Biochem, 2023 Oct;49(5):951-965.
    PMID: 37665506 DOI: 10.1007/s10695-023-01234-0
    The study investigated the alleviated effects of Alpha-ketoglutaric acid (AKG) on the intestinal health of mirror carp (Cyprinus carpio Songpu) caused by soy antigenic protein. The diets were formulated from fishmeal (CON), 50% soybean meal (SBM), the mixture of glycinin and β-conglycinin (11 + 7S) and adding 1% AKG in the 11 + 7S (AKG). Carp (~ 4 g) in triplicate (30 fish per tank) was fed to apparent satiation thrice a day for six weeks. Compared with CON, SBM treatment resulted in significantly poor growth performance (P  0.05). Gene expression of tumor necrosis factor (TNF-α) and interleukin-1 β (IL-1β) in proximal intestines (PI) and distal intestines (DI) were increased (P 
    MeSH terms: Animals; Animal Feed/analysis; Diet/veterinary; Intestines; Ketoglutaric Acids; Tumor Necrosis Factor-alpha/metabolism; Transforming Growth Factor beta; Dietary Supplements; Caspase 3/metabolism; Caspase 9; AMP-Activated Protein Kinases
  8. Zhang JB, Dai C, Wang Z, You X, Duan Y, Lai X, et al.
    Water Res, 2023 Oct 01;244:120555.
    PMID: 37666149 DOI: 10.1016/j.watres.2023.120555
    Herein, biochar was prepared using rice straw, and it served as the peroxymonosulfate (PMS) activator to degrade naphthalene (NAP). The results showed that pyrolysis temperature has played an important role in regulating biochar structure and properties. The biochar prepared at 900°C (BC900) had the best activation capacity and could remove NAP in a wide range of initial pH (5-11). In the system of BC900/PMS, multi-reactive species were produced, in which 1O2 and electron transfer mainly contributed to NAP degradation. In addition, the interference of complex groundwater components on the NAP removal rate must get attention. Cl- had a significant promotional effect but risked the formation of chlorinated disinfection by-products. HCO3-, CO32-, and humic acid (HA) had an inhibitory effect; surfactants had compatibility problems with the BC900/PMS system, which could lead to unproductive consumption of PMS. Significantly, the BC900/PMS system showed satisfactory remediation performance in spiked natural groundwater and soil, and it could solve the problem of persistent groundwater contamination caused by NAP desorption from the soil. Besides, the degradation pathway of NAP was proposed, and the BC900/PMS system could degrade NAP into low or nontoxic products. These suggest that the BC900/PMS system has promising applications in in-situ groundwater remediation.
    MeSH terms: Naphthalenes; Oryza*; Soil; Groundwater*
  9. Shahab M, Aiman S, Alshammari A, Alasmari AF, Alharbi M, Khan A, et al.
    Int J Biol Macromol, 2023 Dec 31;253(Pt 2):126678.
    PMID: 37666399 DOI: 10.1016/j.ijbiomac.2023.126678
    Jamestown Canyon virus (JCV) is a deadly viral infection transmitted by various mosquito species. This mosquito-borne virus belongs to Bunyaviridae family, posing a high public health threat in the in tropical regions of the United States causing encephalitis in humans. Common symptoms of JCV include fever, headache, stiff neck, photophobia, nausea, vomiting, and seizures. Despite the availability of resources, there is currently no vaccine or drug available to combat JCV. The purpose of this study was to develop an epitope-based vaccine using immunoinformatics approaches. The vaccine aimed to be secure, efficient, bio-compatible, and capable of stimulating both innate and adaptive immune responses. In this study, the protein sequence of JCV was obtained from the NCBI database. Various bioinformatics methods, including toxicity evaluation, antigenicity testing, conservancy analysis, and allergenicity assessment were utilized to identify the most promising epitopes. Suitable linkers and adjuvant sequences were used in the design of vaccine construct. 50s ribosomal protein sequence was used as an adjuvant at the N-terminus of the construct. A total of 5 CTL, 5 HTL, and 5 linear B cell epitopes were selected based on non-allergenicity, immunological potential, and antigenicity scores to design a highly immunogenic multi-peptide vaccine construct. Strong interactions between the proposed vaccine and human immune receptors, i.e., TLR-2 and TLR-4, were revealed in a docking study using ClusPro software, suggesting their possible relevance in the immunological response to the vaccine. Immunological and physicochemical properties assessment ensured that the proposed vaccine demonstrated high immunogenicity, solubility and thermostability. Molecular dynamics simulations confirmed the strong binding affinities, as well as dynamic and structural stability of the proposed vaccine. Immune simulation suggest that the vaccine has the potential to effectively stimulate cellular and humoral immune responses to combat JCV infection. Experimental and clinical assays are required to validate the results of this study.
    MeSH terms: Animals; Encephalitis Virus, California*; Humans; Epitopes, T-Lymphocyte/chemistry; Epitopes, B-Lymphocyte; Computational Biology/methods; Vaccines, Subunit; Molecular Dynamics Simulation; Immunity, Humoral; Molecular Docking Simulation
  10. Tabu I, Goh EL, Appelbe D, Parsons N, Lekamwasam S, Lee JK, et al.
    Bone Jt Open, 2023 Sep 05;4(9):676-681.
    PMID: 37666496 DOI: 10.1302/2633-1462.49.BJO-2023-0075.R1
    AIMS: The aim of this study was to describe the current pathways of care for patients with a fracture of the hip in five low- and middle-income countries (LMIC) in South Asia (Nepal and Sri Lanka) and Southeast Asia (Malaysia, Thailand, and the Philippines).

    METHODS: The World Health Organization Service Availability and Readiness Assessment tool was used to collect data on the care of hip fractures in Malaysia, Thailand, the Philippines, Sri Lanka, and Nepal. Respondents were asked to provide details about the current pathway of care for patients with hip fracture, including pre-hospital transport, time to admission, time to surgery, and time to weightbearing, along with healthcare professionals involved at different stages of care, information on discharge, and patient follow-up.

    RESULTS: Responses were received from 98 representative hospitals across the five countries. Most hospitals were publicly funded. There was consistency in clinical pathways of care within country, but considerable variation between countries. Patients mostly travel to hospital via ambulance (both publicly- and privately-funded) or private transport, with only half arriving at hospital within 12 hours of their injury. Access to surgery was variable and time to surgery ranged between one day and more than five days. The majority of hospitals mobilized patients on the first or second day after surgery, but there was notable variation in postoperative weightbearing protocols. Senior medical input was variable and specialist orthogeriatric expertise was unavailable in most hospitals.

    CONCLUSION: This study provides the first step in mapping care pathways for patients with hip fracture in LMIC in South Asia. The previous lack of data in these countries hampers efforts to identify quality standards (key performance indicators) that are relevant to each different healthcare system.

  11. Ing SK, Ng Han Sim B, Lee YH, Ling TY
    BMJ Case Rep, 2023 Sep 04;16(9).
    PMID: 37666566 DOI: 10.1136/bcr-2023-256408
    Rabies, a fatal viral zoonotic disease, has become a public health concern in Sarawak, Malaysia. Despite pre-exposure and post-exposure prophylaxis being available, there has been limited progress in developing treatments for rabies, emphasising the pressing need for productive solutions. We present a laboratory-confirmed human rabies case in which the patient survived without neurological sequelae after receiving intrathecal rabies immunoglobulin.
    MeSH terms: Humans; Immunoglobulins/therapeutic use; Immunologic Factors; Disease Progression; Post-Exposure Prophylaxis*
  12. AlDahoul N, Momo MA, Chong KL, Ahmed AN, Huang YF, Sherif M, et al.
    Sci Rep, 2023 Sep 04;13(1):14574.
    PMID: 37666880 DOI: 10.1038/s41598-023-41735-9
    Due to excessive streamflow (SF), Peninsular Malaysia has historically experienced floods and droughts. Forecasting streamflow to mitigate municipal and environmental damage is therefore crucial. Streamflow prediction has been extensively demonstrated in the literature to estimate the continuous values of streamflow level. Prediction of continuous values of streamflow is not necessary in several applications and at the same time it is very challenging task because of uncertainty. A streamflow category prediction is more advantageous for addressing the uncertainty in numerical point forecasting, considering that its predictions are linked to a propensity to belong to the pre-defined classes. Here, we formulate streamflow prediction as a time series classification with discrete ranges of values, each representing a class to classify streamflow into five or ten, respectively, using machine learning approaches in various rivers in Malaysia. The findings reveal that several models, specifically LSTM, outperform others in predicting the following n-time steps of streamflow because LSTM is able to learn the mapping between streamflow time series of 2 or 3 days ahead more than support vector machine (SVM) and gradient boosting (GB). LSTM produces higher F1 score in various rivers (by 5% in Johor, 2% in Kelantan and Melaka and Selangor, 4% in Perlis) in 2 days ahead scenario. Furthermore, the ensemble stacking of the SVM and GB achieves high performance in terms of F1 score and quadratic weighted kappa. Ensemble stacking gives 3% higher F1 score in Perak river compared to SVM and gradient boosting.
  13. Zheng LQ, Kosai NR, Ani MFC, Maaya M
    Obes Surg, 2023 Oct;33(10):3141-3146.
    PMID: 37667104 DOI: 10.1007/s11695-023-06777-y
    PURPOSE: Laparoscopic intraperitoneal instillation of local anaesthetic in bariatric surgery proven to reduce postoperative pain. Limited data are available regarding the use of instillation ropivacaine and its impact on the recovery of respiratory effort. This study aims to evaluate the efficacy of laparoscopic intraperitoneal instillation of ropivacaine in reducing acute postoperative pain and enhancing the recovery of respiratory effort in laparoscopic sleeve gastrectomy.

    MATERIALS AND METHODS: This double-blinded RCT enrolled 110 patients who underwent laparoscopic sleeve gastrectomy at Hospital Canselor Tuanku Muhriz UKM from November 2020 to May 2021. Any patients with previous abdominal surgery, chronic kidney disease, or liver disease were excluded. The patients were randomised into two groups: (i) the IPLA group which received ropivacaine intraperitoneal instillation at the dissected left crus and (ii) the placebo group (sterile water instillation). Perioperative analgesia was standardised. The first 24-h postoperative pain was assessed using a VAS. The respiratory effort was assessed using incentive spirometry simultaneously.

    RESULTS: Total of 110 patients were recruited. The VAS score was lower with an enhanced recovery of respiratory effort in the local anaesthetic group compared to the placebo group (P < 0.05) within the first 24 h postoperatively. In addition, the placebo group required additional postoperative analgesia (P < 0.05). No side effects were reported with the use of intraperitoneal instillation of ropivacaine.

    CONCLUSION: The use of intraperitoneal instillation of ropivacaine in laparoscopic sleeve gastrectomy is recommended as it is safe, effectively reduces acute postoperative pain, and enhances the recovery of respiratory effort postoperatively.

    MeSH terms: Anesthetics, Local; Gastrectomy/adverse effects; Humans; Pain, Postoperative/drug therapy; Pain, Postoperative/prevention & control; Laparoscopy*
  14. Yong PYA, Yip AJW, Islam F, Hong HJ, Teh YE, Tham CL, et al.
    BMC Complement Med Ther, 2023 Sep 04;23(1):307.
    PMID: 37667314 DOI: 10.1186/s12906-023-04129-y
    BACKGROUND: Allergy is an inflammatory disorder affecting around 20% of the global population. The adverse effects of current conventional treatments give rise to the increased popularity of using natural food products as complementary and alternative medicine against allergic diseases. Stingless bee honey, commonly known as Kelulut honey (KH) in Malaysia, has been used locally as a traditional remedy to relieve cough and asthma. This study evaluated the anti-allergic potential of KH collected from four different botanical sources on phorbol ester 12-myristate-3-acetate and calcium ionophore-activated human mast cells.

    METHODS: The present study examined the inhibitory effects of all collected honey on the release of selected inflammatory mediators, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-4, IL-6, IL-8, histamine, and β-hexosaminidase in an activated HMC. Besides that, all honey's total phenolic content (TPC) was also examined, followed by using liquid chromatography with tandem mass spectrometry (LC-MS/MS) to identify the phytochemicals in the honey. Further examination of the identified phytochemicals on their potential interaction with selected signaling molecules in an activated mast cell was conducted using computational methods.

    RESULTS: The results indicated that there were significant inhibitory effects on all selected inflammatory mediators' release by KH sourced from bamboo (BH) and rubber tree (RH) at 0.5% and 1%, but not KH sourced from mango (AH) and noni (EH). BH and RH were found to have higher TPC values and were rich in their phytochemical profiles based on the LC-MS/MS results. Computational studies were employed to determine the possible molecular target of KH through molecular docking using HADDOCK and PRODIGY web servers.

    CONCLUSIONS: In short, the results indicated that KH possesses anti-allergic effects towards an activated HMC, possibly by targeting downstream MAPKs. However, their anti-allergic effects may vary according to their botanical sources. Nevertheless, the present study has provided insight into the potential application of stingless bee honey as a complementary and alternative medicine to treat various allergic diseases.

    MeSH terms: Animals; Bees; Chromatography, Liquid; Honey*; Humans; Hypersensitivity*; Mast Cells; Cell Degranulation; Tandem Mass Spectrometry; Molecular Docking Simulation
  15. Faustine I, Marteka D, Malik A, Supriyanto E, Syafhan NF
    BMC Res Notes, 2023 Sep 04;16(1):194.
    PMID: 37667339 DOI: 10.1186/s13104-023-06483-z
    OBJECTIVE: Genetic polymorphisms in ACE and ACE2 genes are involved in the RAS regulation of blood pressure and their activity may confer susceptibility to hypertension. In addition, they may play a role in SARS-CoV-2 pathogenesis and the severity of COVID-19. This study aims to determine the effect of genetic variations in the ACE (rs4331) and ACE2 (rs2074192) genes with hypertension comorbidity on the severity of COVID-19 in the Indonesian population.

    RESULT: 186 patients were enrolled and assigned into the COVID-19 group (n = 95) and non-COVID-19 group (n = 91) in this cross-sectional study. GG genotype frequency was dominant in ACE gene, but there were no significant differences between the groups (p = 0.163). The two groups had a significant difference (p = 0.000) for the CC genotype frequency (0,37 vs. 0.01) in the ACE2 gene. The proportion of women with COVID-19 is higher (51%), but men with hypertension had more severe symptoms (44%). Men with hypertension comorbidity, GG (ACE), and TT (ACE2) genotypes tended to have moderate-to-severe symptoms (25%). Similarly, women with hypertension as well as GG and CT genotypes tended to have moderate-to-severe symptoms (21%). We conclude that hypertension and mutations in the ACE (rs4331) and ACE2 (rs2074192) genes affect the severity of COVID-19.

    MeSH terms: Cross-Sectional Studies; Female; Genotype; Humans; Male
  16. Gamalo LE, Ilham K, Jones-Engel L, Gill M, Sweet R, Aldrich B, et al.
    Am J Primatol, 2023 Sep 04.
    PMID: 37667504 DOI: 10.1002/ajp.23547
    In 2022, long-tailed macaques (Macaca fascicularis), a once ubiquitous primate species, was elevated to Endangered on the International Union for Conservation of Nature (IUCN) Red List of Threatened Species. In 2023, recognizing that the long-tailed macaque is threatened by multiple factors: (1) declining native habitats across Southeast Asia; (2) overutilization for scientific, commercial, and recreational purposes; (3) inadequate regulatory mechanisms; and (4) culling due to human-macaque conflicts, a petition for rulemaking was submitted to the United States Fish and Wildlife Service to add the species to the US Endangered Species Act, the nation's most effective law to protect at risk species. The long-tailed macaque remains unprotected across much of its geographical range despite the documented continual decline of the species and related sub-species and the recent IUCN reassessment. This commentary presents a review of the factors that have contributed to the dramatic decline of this keystone species and makes a case for raising the level of protection they receive.
  17. Paes-Leme B, Monteiro LDRN, Gholami K, Hoe SZ, Ferguson AV, Murphy D, et al.
    J Neuroendocrinol, 2023 Nov;35(11):e13334.
    PMID: 37667574 DOI: 10.1111/jne.13334
    In addition to being recognised for involvement in cardiovascular control and hydromineral balance, the renin-angiotensin system (RAS) has also been associated with the neuroendocrine control of energy balance. One of the main brain sites for angiotensin II (ANG II)/type 1 receptor (AT1 R) signalling is the subfornical organ (SFO), a circumventricular organ related to the control of autonomic functions, motivated behaviours and energy metabolism. Thus, we hypothesised that circulating ANG II may act on the SFO AT1 R receptors to integrate metabolic and hydromineral balance. We evaluated whether food deprivation can modulate systemic RAS activity and Agrt1a brain expression, and if ANG II/AT1 R signalling influences the hypothalamic expression of mRNAs encoding neuropeptides and food and water ingestion in fed and fasted Wistar rats. We found a significant increase in both ANG I and ANG II plasma levels after 24 and 48 h of fasting. Expression of Agrt1a mRNA in the SFO and paraventricular nucleus (PVN) also increased after food deprivation for 48 h. Treatment of fasted rats with low doses of losartan in drinking water attenuated the decrease in glycemia and meal-associated water intake without changing the expression in PVN or arcuate nucleus of mRNAs encoding selected neuropeptides related to energy homeostasis control. These findings point to a possible role of peripheral ANG II/SFO-AT1 R signalling in the control of refeeding-induced thirst. On the other hand, intracerebroventricular losartan treatment decreased food and water intake over dark time in fed but not in fasted rats.
    MeSH terms: Angiotensin II/pharmacology; Animals; Brain/metabolism; Male; Paraventricular Hypothalamic Nucleus/metabolism; Rats, Wistar; Losartan/pharmacology; Receptor, Angiotensin, Type 1/metabolism; Rats
  18. Sya'diyah H, Efendi F, Mahmudah, Saidah QI, Poddar S
    J Public Health Res, 2023 Jul;12(3):22799036231197172.
    PMID: 37667680 DOI: 10.1177/22799036231197172
    BACKGROUND: The elderly with dementia occur cognitive decline and they are considered normal by the family, and then causing the need for care from elderly. This is not following the ability of home care by the family as an informal caregiver for the elderly with dementia. The purpose of this study was to analyze the effect of caregiver demands on the ability of families to do home care for elderly dementia.

    DESIGN AND METHODS: An analytical observational study with a cross-sectional design. The sample size is 100 respondents with a cluster random sampling technique. Data were collected by questionnaire and analyzed using SEM-PLS.

    RESULTS: Caregiver demands have a direct effect on increasing the family's ability to do home care for elderly dementia with a p-value = 0.011 (p ≤ 0.05), t statistic value of 2.557 (≥1.96). Caregiver demands have four indicators, including care receiver impairment, caregiving activities, competency of caregivers, and caregiver/family relationship with elderly dementia. The condition of the elderly who experience various changes supports the increasing need for care to receive care and recovery as well as special attention from the family.

    CONCLUSION: The higher the need for care, the higher the family's ability to do home care. This research implies that the family has a duty in the health sector to provide care for the elderly at home/home care, which strengthens the need for care, this supports caregiver empowerment and increases the independence of the elderly with dementia.

  19. Wang X, Teh SH, Du XG, Wang XH
    Neuropsychiatr Dis Treat, 2023;19:1875-1886.
    PMID: 37667737 DOI: 10.2147/NDT.S424102
    OBJECTIVE: Cerebral palsy (CP) is a condition characterized by abnormal pronunciation, posture, and movement, particularly spastic CP, which involves Gross motor dysfunction due to increased muscle tone and stiffness. This monocentric clinical study aims to evaluate the effectiveness of acupuncture and tuina (AT) in improving gross motor function and alleviating associated symptoms in children diagnosed with spastic CP.

    METHODS: A total of 83 eligible patients received AT treatment, while 85 patients received conventional rehabilitation treatment. Both groups underwent a 12-week treatment period following the research protocol. Pre- and post-treatment assessments included the Modified Ashworth Muscle Tension Scale (MAS), Gross Motor Function Measure (GMFM-D and GMFM-E), 6-min walking distance measurement (6MWD), and Modified Children's Functional Independence Rating Scale (WeeFIM).

    RESULTS: After 12 weeks of treatment, when compared with baseline, the scores of MAS in both AT group and control group are decreased (p<0.01, p<0.01), the scores of GMFM-D, GMFME, 6MWD, WeeFIM in both group are increased (p<0.01 in all indicators). When compared with control group, AT group had significantly lower MAS scores compared to the control group (p<0.01), indicating reduced muscle tension. Moreover, AT group showed significantly higher scores in GMFM-D, GMFM-E, 6MWD, and WeeFIM compared to the control group (p<0.01 in all indicators), indicating improved gross motor function and functional independence. The study also revealed an inverse correlation between the children's age and treatment efficacy (r= -0.496, p<0.01 in AT group, r=-0.540, p<0.01 in control group), highlighting the importance of early intervention in the management of CP in children.

    CONCLUSION: These findings suggest that AT may effectively enhance gross motor function and alleviate associated symptoms in children diagnosed with spastic CP. Moreover, early initiation of treatment is crucial to maximize therapeutic efficacy in children with spastic CP.

    TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200059823. Registered on 12 May 2022.

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