Displaying all 12 publications

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  1. Hickey AC, Koster JA, Thalmann CM, Hardcastle K, Tio PH, Cardosa MJ, et al.
    Am J Trop Med Hyg, 2013 Dec;89(6):1043-57.
    PMID: 24062475 DOI: 10.4269/ajtmh.13-0145
    Dengue virus (DENV) is considered to be the most important arthropod-borne viral disease and causes more than 100 million human infections annually. To further characterize primary DENV infection in vivo, rhesus macaques were infected with DENV-1, DENV-2, DENV-3, or DENV-4 and clinical parameters, as well as specificity and longevity of serologic responses, were assessed. Overt clinical symptoms were not present after infection. However, abnormalities in blood biochemical parameters consistent with heart, kidney, and liver damage were observed, and changes in plasma fibrinogen, D-dimers, and protein C indicated systemic activation of the blood coagulation pathway. Significant homotypic and heterotypic serum immunoglobulins were present in all animals, and IgG persisted for at least 390 days. Serum neutralizing antibody responses were highly serotype specific by day 120. However, some heterotypic neutralizing activity was noted in infected animals. Identification of serotype-specific host responses may help elucidate mechanisms that mediate severe DENV disease after reinfection.
  2. Jacob A, Parolia A, Pau A, Davamani Amalraj F
    PMID: 26303848 DOI: 10.1186/s12906-015-0814-1
    To evaluate and compare the effects of ethanolic extracts of Malaysian propolis and Brazilian red propolis at different concentrations on the migration and proliferation of fibroblast cells.
  3. Santhosh K, Manzoor S, Sushanth A, Seralathan S, Rajasekar V, Jacob A
    J Contemp Dent Pract, 2020 Nov 01;21(11):1258-1261.
    PMID: 33850072
    AIM AND OBJECTIVE: To evaluate the possible genotoxic effect of X-rays on buccal mucosa while exposing to dental panoramic radiography using micronucleus test.

    MATERIALS AND METHODS: The study group comprised of 30 healthy subjects, 15 males and 15 females, aged between 24 years and 65 years. Samples were obtained from the exfoliated oral mucosa cells of buccal mucosa before and 12 days after exposing the patients to panoramic radiography.

    RESULTS: The study reported that there was no significant increase in the number of micronuclei cells present before and after panoramic radiography. Positive correlation existed between age with pre- and postexposure micronuclei.

    CONCLUSION: Diagnostic dental panoramic radiograph does not induce micronuclei in the target buccal epithelium cells. A positive correlation between age and micronuclei frequency was established.

    CLINICAL SIGNIFICANCE: Panoramic radiographs does not induce cytotoxicity but increase frequency may be vulnerable to genotoxic effects in buccal mucosal cells. Hence, dental radiographs should be prescribed only when necessary.

  4. Grismer LL, Wood PL, Mohamed M, Chan KO, Heinz HM, Sumarli AS, et al.
    Zootaxa, 2013;3746:463-72.
    PMID: 25113489 DOI: 10.11646/zootaxa.3746.3.5
    A new species of karst-adapted gekkonid lizard of the genus Cnemaspis Strauch is described from Gua Gunting and Gua Goyang in a karst region of Merapoh, Pahang, Peninsular Malaysia whose unique limestone formations are in immediate danger of being quarried. The new species differs from all other species of Cnemaspis based on its unique suite of morphological and color pattern characters. Its discovery underscores the unique biodiversity endemic to karst regions and adds to a growing list of karst-adapted reptiles from Peninsular Malaysia. We posit that new karst-adapted species endemic to limestone forests will continue to be discovered and these regions will harbor a significant percentage of Peninsular Malaysia's biodiversity and thusly should be conserved rather than quarried.
  5. Nations JA, Giarla TC, Morni MA, William Dee J, Swanson MT, Hiller AE, et al.
    Zookeys, 2022;1137:17-31.
    PMID: 36760481 DOI: 10.3897/zookeys.1137.94217
    Although Borneo has received more attention from biologists than most other islands in the Malay Archipelago, many questions regarding the systematic relationships of Bornean mammals remain. Using next-generation sequencing technology, we obtained mitochondrial DNA sequences from the holotype of Suncusater, the only known specimen of this shrew. Several shrews collected recently in Sarawak are closely aligned, both morphologically and mitochondrially, with the holotype of S.ater. Phylogenetic analyses of mitochondrial sequences indicate that the S.ater holotype and new Sarawak specimens do not belong to the genus Suncus, but instead are most closely related to Palawanosorexmuscorum. Until now Palawanosorex has been known only from the neighboring Philippine island of Palawan. Additional sequences from nuclear ultra-conserved elements from the new Sarawak specimens strongly support a sister relationship to P.muscorum. We therefore transfer ater to Palawanosorex. The new specimens demonstrate that P.ater is more widespread in northern Borneo than previously recorded. Continued sampling of Bornean mammal diversity and reexamination of type material are critical in understanding the evolutionary history of the biologically rich Malay Archipelago.
  6. Bala AA, Malami S, Muhammad YA, Kurfi B, Raji I, Salisu SM, et al.
    Toxicon X, 2022 Jun;14:100122.
    PMID: 35402895 DOI: 10.1016/j.toxcx.2022.100122
    Snakebite envenoming (SBE) is a neglected public health problem, especially in Asia, Latin America and Africa. There is inadequate knowledge of venom toxicokinetics especially from African snakes. To mimic a likely scenario of a snakebite envenoming, we used an enzyme-linked immunosorbent assay (ELISA) approach to study the toxicokinetic parameters in rabbits, following a single intramuscular (IM) administration of Northern Nigeria Naja nigricollis venom. We used a developed and validated non-compartmental approach in the R package PK to determine the toxicokinetic parameters of the venom and subsequently used pharmacometrics modelling to predict the movement of the toxin within biological systems. We found that N. nigricollis venom contained sixteen venom protein families following a mass spectrometric analysis of the whole venom. Most of these proteins belong to the three-finger toxins family (3FTx) and venom phospholipase A2 (PLA2) with molecular weight ranging from 3 to 16 kDa. Other venom protein families were in small proportions with higher molecular weights. The N. nigricollis venom was rapidly absorbed at 0.5 h, increased after 1 h and continued to decrease until the 16th hour (Tmax), where maximum concentration (Cmax) was observed. This was followed by a decrease in concentration at the 32nd hour. The venom of N. nigricollis was found to have high volume of distribution (1250 ± 245 mL) and low clearance (29.0 ± 2.5 mL/h) with an elimination half-life of 29 h. The area under the curve (AUC) showed that the venom remaining in the plasma over 32 h was 0.0392 ± 0.0025 mg h.L-1, and the mean residence time was 43.17 ± 8.04 h. The pharmacometrics simulation suggests that the venom toxins were instantly and rapidly absorbed into the extravascular compartment and slowly moved into the central compartment. Our study demonstrates that Nigerian N. nigricollis venom contains low molecular weight toxins that are well absorbed into the blood and deep tissues. The venom could be detected in rabbit blood 48 h after intramuscular envenoming.
  7. Hor JY, Asgari N, Nakashima I, Broadley SA, Leite MI, Kissani N, et al.
    Front Neurol, 2020;11:501.
    PMID: 32670177 DOI: 10.3389/fneur.2020.00501
    Neuromyelitis optica spectrum disorder (NMOSD) is an uncommon inflammatory disease of the central nervous system, manifesting clinically as optic neuritis, myelitis, and certain brain and brainstem syndromes. Cases clinically diagnosed as NMOSD may include aquaporin 4 (AQP4)-antibody-seropositive autoimmune astrocytopathic disease, myelin oligodendrocyte glycoprotein (MOG)-antibody-seropositive inflammatory demyelinating disease, and double-seronegative disease. AQP4-antibody disease has a high female-to-male ratio (up to 9:1), and its mean age at onset of ~40 years is later than that seen in multiple sclerosis. For MOG-antibody disease, its gender ratio is closer to 1:1, and it is more common in children than in adults. Its clinical phenotypes differ but overlap with those of AQP4-antibody disease and include acute disseminated encephalomyelitis, brainstem and cerebral cortical encephalitis, as well as optic neuritis and myelitis. Double-seronegative disease requires further research and clarification. Population-based studies over the past two decades report the prevalence and incidence of NMOSD in different populations worldwide. One relevant finding is the varying prevalence observed in different racial groups. Consistently, the prevalence of NMOSD among Whites is ~1/100,000 population, with an annual incidence of <1/million population. Among East Asians, the prevalence is higher, at ~3.5/100,000 population, while the prevalence in Blacks may be up to 10/100,000 population. For MOG-antibody disease, hospital-based studies largely do not observe any significant racial preponderance so far. This disorder comprises a significant proportion of NMOSD cases that are AQP4-antibody-seronegative. A recent Dutch nationwide study reported the annual incidence of MOG-antibody disease as 1.6/million population (adult: 1.3/million, children: 3.1/million). Clinical and radiological differences between AQP4-antibody and MOG-antibody associated diseases have led to interest in the revisions of NMOSD definition and expanded stratification based on detection of a specific autoantibody biomarker. More population-based studies in different geographical regions and racial groups will be useful to further inform the prevalence and incidence of NMOSD and their antibody-specific subgroups. Accessibility to AQP4-antibody and MOG-antibody testing, which is limited in many centers, is a challenge to overcome. Environmental and genetic studies will be useful accompaniments to identify other potential pathogenetic factors and specific biomarkers in NMOSD.
  8. Solomon SD, Ostrominski JW, Vaduganathan M, Claggett B, Jhund PS, Desai AS, et al.
    Eur J Heart Fail, 2024 Jun;26(6):1334-1346.
    PMID: 38733212 DOI: 10.1002/ejhf.3266
    AIMS: To describe the baseline characteristics of participants in the FINEARTS-HF trial, contextualized with prior trials including patients with heart failure (HF) with mildly reduced and preserved ejection fraction (HFmrEF/HFpEF). The FINEARTS-HF trial is comparing the effects of the non-steroidal mineralocorticoid receptor antagonist finerenone with placebo in reducing cardiovascular death and total worsening HF events in patients with HFmrEF/HFpEF.

    METHODS AND RESULTS: Patients with symptomatic HF, left ventricular ejection fraction (LVEF) ≥40%, estimated glomerular filtration rate ≥ 25 ml/min/1.73 m2, elevated natriuretic peptide levels and evidence of structural heart disease were enrolled and randomized to finerenone titrated to a maximum of 40 mg once daily or matching placebo. We validly randomized 6001 patients to finerenone or placebo (mean age 72 ± 10 years, 46% women). The majority were New York Heart Association functional class II (69%). The baseline mean LVEF was 53 ± 8% (range 34-84%); 36% of participants had a LVEF <50% and 64% had a LVEF ≥50%. The median N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 1041 (interquartile range 449-1946) pg/ml. A total of 1219 (20%) patients were enrolled during or within 7 days of a worsening HF event, and 3247 (54%) patients were enrolled within 3 months of a worsening HF event. Compared with prior large-scale HFmrEF/HFpEF trials, FINEARTS-HF participants were more likely to have recent (within 6 months) HF hospitalization and greater symptoms and functional limitations. Further, concomitant medications included a larger percentage of sodium-glucose cotransporter 2 inhibitors and angiotensin receptor-neprilysin inhibitors than previous trials.

    CONCLUSIONS: FINEARTS-HF has enrolled a broad range of high-risk patients with HFmrEF and HFpEF. The trial will determine the safety and efficacy of finerenone in this population.

  9. Solomon SD, McMurray JJV, Vaduganathan M, Claggett B, Jhund PS, Desai AS, et al.
    N Engl J Med, 2024 Sep 01.
    PMID: 39225278 DOI: 10.1056/NEJMoa2407107
    BACKGROUND: Steroidal mineralocorticoid receptor antagonists reduce morbidity and mortality among patients with heart failure and reduced ejection fraction, but their efficacy in those with heart failure and mildly reduced or preserved ejection fraction has not been established. Data regarding the efficacy and safety of the nonsteroidal mineralocorticoid receptor antagonist finerenone in patients with heart failure and mildly reduced or preserved ejection fraction are needed.

    METHODS: In this international, double-blind trial, we randomly assigned patients with heart failure and a left ventricular ejection fraction of 40% or greater, in a 1:1 ratio, to receive finerenone (at a maximum dose of 20 mg or 40 mg once daily) or matching placebo, in addition to usual therapy. The primary outcome was a composite of total worsening heart failure events (with an event defined as a first or recurrent unplanned hospitalization or urgent visit for heart failure) and death from cardiovascular causes. The components of the primary outcome and safety were also assessed.

    RESULTS: Over a median follow-up of 32 months, 1083 primary-outcome events occurred in 624 of 3003 patients in the finerenone group, and 1283 primary-outcome events occurred in 719 of 2998 patients in the placebo group (rate ratio, 0.84; 95% confidence interval [CI], 0.74 to 0.95; P = 0.007). The total number of worsening heart failure events was 842 in the finerenone group and 1024 in the placebo group (rate ratio, 0.82; 95% CI, 0.71 to 0.94; P = 0.006). The percentage of patients who died from cardiovascular causes was 8.1% and 8.7%, respectively (hazard ratio, 0.93; 95% CI, 0.78 to 1.11). Finerenone was associated with an increased risk of hyperkalemia and a reduced risk of hypokalemia.

    CONCLUSIONS: In patients with heart failure and mildly reduced or preserved ejection fraction, finerenone resulted in a significantly lower rate of a composite of total worsening heart failure events and death from cardiovascular causes than placebo. (Funded by Bayer; FINEARTS-HF ClinicalTrials.gov number, NCT04435626.).

  10. Whittam DH, Karthikeayan V, Gibbons E, Kneen R, Chandratre S, Ciccarelli O, et al.
    J Neurol, 2020 Dec;267(12):3565-3577.
    PMID: 32623595 DOI: 10.1007/s00415-020-10026-y
    INTRODUCTION: While monophasic and relapsing forms of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) are increasingly diagnosed world-wide, consensus on management is yet to be developed.

    OBJECTIVE: To survey the current global clinical practice of clinicians treating MOGAD.

    METHOD: Neurologists worldwide with expertise in treating MOGAD participated in an online survey (February-April 2019).

    RESULTS: Fifty-two responses were received (response rate 60.5%) from 86 invited experts, comprising adult (78.8%, 41/52) and paediatric (21.2%, 11/52) neurologists in 22 countries. All treat acute attacks with high dose corticosteroids. If recovery is incomplete, 71.2% (37/52) proceed next to plasma exchange (PE). 45.5% (5/11) of paediatric neurologists use IV immunoglobulin (IVIg) in preference to PE. Following an acute attack, 55.8% (29/52) of respondents typically continue corticosteroids for ≥ 3 months; though less commonly when treating children. After an index event, 60% (31/51) usually start steroid-sparing maintenance therapy (MT); after ≥ 2 attacks 92.3% (48/52) would start MT. Repeat MOG antibody status is used by 52.9% (27/51) to help decide on MT initiation. Commonly used first line MTs in adults are azathioprine (30.8%, 16/52), mycophenolate mofetil (25.0%, 13/52) and rituximab (17.3%, 9/52). In children, IVIg is the preferred first line MT (54.5%; 6/11). Treatment response is monitored by MRI (53.8%; 28/52), optical coherence tomography (23.1%; 12/52) and MOG antibody titres (36.5%; 19/52). Regardless of monitoring results, 25.0% (13/52) would not stop MT.

    CONCLUSION: Current treatment of MOGAD is highly variable, indicating a need for consensus-based treatment guidelines, while awaiting definitive clinical trials.

  11. Rahman MA, Das P, Lam L, Alif SM, Sultana F, Salehin M, et al.
    BMC Public Health, 2024 Jul 11;24(1):1848.
    PMID: 38992680 DOI: 10.1186/s12889-024-19365-1
    BACKGROUND: The ongoing global crisis of Higher Education (HE) institutions during the post-COVID-19 pandemic period has increased the likelihood of enduring psychological stressors for staff. This study aimed to identify factors associated with job insecurity, burnout, psychological distress and coping amongst staff working at HE institutions globally.

    METHODS: An anonymous cross-sectional study was conducted in 2023 with staff at HE institutions across 16 countries. Job insecurity was measured using the Job Insecurity Scale (JIS), burnout using the Perceived Burnout measure question, psychological distress using the Kessler Psychological Distress Scale (K10), and coping using the Brief Resilient Coping Scale. Multivariable logistic regression with a stepwise variable selection method was used to identify associations.

    RESULTS: A total of 2,353 staff participated; the mean age (± SD) was 43(± 10) years and 61% were females. Most staff (85%) did not feel job insecurity, one-third (29%) perceived burnout in their jobs, more than two-thirds (73%) experienced moderate to very high levels of psychological distress, and more than half (58%) exhibited medium to high resilient coping. Perceived job insecurity was associated with staff working part-time [Adjusted Odds Ratio 1.53 (95% Confidence Intervals 1.15-2.02)], having an academic appointment [2.45 (1.78-3.27)], having multiple co-morbidities [1.86 (1.41-2.48)], perceived burnout [1.99 (1.54-2.56)] and moderate to very high level of psychological distress [1.68 (1.18-2.39)]. Perceived burnout was associated with being female [1.35 (1.12-1.63)], having multiple co-morbidities [1.53 (1.20-1.97)], perceived job insecurity [1.99 (1.55-2.57)], and moderate to very high levels of psychological distress [3.23 (2.42-4.30)]. Staff with multiple co-morbidities [1.46 (1.11-1.92)], mental health issues [2.73 (1.79-4.15)], perceived job insecurity [1.61 (1.13-2.30)], and perceived burnout [3.22 (2.41-4.31)] were associated with moderate to very high levels of psychological distress. Staff who perceived their mental health as good to excellent [3.36 (2.69-4.19)] were more likely to have medium to high resilient coping.

    CONCLUSIONS: Factors identified in this study should be considered in reviewing and updating current support strategies for staff at HE institutions across all countries to reduce stress and burnout and improve wellbeing.

  12. Perrone G, Giuffrida M, Abu-Zidan F, Kruger VF, Livrini M, Petracca GL, et al.
    World J Emerg Surg, 2024 Apr 16;19(1):14.
    PMID: 38627831 DOI: 10.1186/s13017-024-00543-w
    BACKGROUND: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA.

    METHODS: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up.

    RESULTS: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P 

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