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Evaluation of factors affecting time to achieve dry weight among hemodialysis patients using bioimpedance spectroscopy

Khan A, Khan AH, Adnan AS, Sulaiman SAS, Ahmad N, Gan SH

Ir J Med Sci, 2019 Feb;188(1):311-319.
PMID: 29680929 DOI: 10.1007/s11845-018-1813-2

BACKGROUND: Achieving and maintaining dry weight appears to be an effective strategy for controlling and maintaining normotension among hypertensive patients on hemodialysis (HD).
OBJECTIVE: The present study aimed to determine the time at which the majority of patients achieve postdialysis dry weight using bioimpedance spectroscopy (BIS).
METHODS: A total of 220 HD patients were prospectively assessed for fluid overload using the Fresenius body composition monitor (BCM). BCM readings were taken at 30 and 45 min postdialysis.
RESULTS: Among the 220 patients included in this study, 120 (54.5%) achieved a euvolemic state at 30 min, and 25 (11.4%) achieved it at 45 min according to the BCM. In the multivariate analysis, vascular access other than arteriovenous fistula (AVF) (OR = 0.286, p value = 0.049) and cardiovascular disease (OR = 0.384, p value = 0.026) had a statistically significant negative association and receiving HD at Hospital Universiti Sains Malaysia (HUSM) (OR = 2.705, p value = 0.008) had a statistically significant positive association with achieving a euvolemic state at 30 min.
CONCLUSION: This suggests that assessing the hydration status at 45 min postdialysis in all patients or in those with identified risk factors for not achieving a euvolemic state at 30 min will provide a relatively accurate assessment for most patients.
Antiphospholipid antibodies in epilepsy: A systematic review and meta-analysis

Islam MA, Alam F, Cavestro C, Calcii C, Sasongko TH, Levy RA, et al.

Autoimmun Rev, 2018 Aug;17(8):755-767.
PMID: 29885542 DOI: 10.1016/j.autrev.2018.01.025

BACKGROUND: Autoimmunity is believed to play an important causative role in the pathogenesis of epilepsy. There are evidences for the presence of autoantibodies in patients with epilepsy. To date, many studies have assessed the presence of antiphospholipid antibodies (aPLs) in epilepsy patients, though the relationship has been inconclusive.

AIMS: The aim of this systematic review and meta-analysis was to evaluate the presence of aPLs in epileptic patients as compared to healthy controls.

METHODS: Five electronic databases (PubMed, Web of Science, Embase, Scopus and Google Scholar) were searched systematically. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects model. Quality assessment was carried out by using the modified 9-star Newcastle-Ottawa Scale (NOS). L'Abbé plots were generated to visually inspect heterogeneity while publication bias was evaluated via visualization of contour- enhanced funnel plots, and Begg's and Egger's tests.

RESULTS: Based on the inclusion criteria, 14 studies were selected involving 1248 epilepsy patients and 800 healthy controls. The majority of epilepsy was categorised as generalised or partial and none had comorbidity with autoimmune diseases. Significant presence of both anticardiolipin (aCL) antibodies (OR: 5.16, 95% CI: 3.21-8.28, p 
Thrombotic management of antiphospholipid syndrome: towards novel targeted therapies

Islam MA, Alam F, Wong KK, Kamal MA, Gan SH

Curr Vasc Pharmacol, 2017;15(4):313-326.
PMID: 28056758 DOI: 10.2174/1570161115666170105120931

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis and/or pregnancy morbidity with persistent levels of antiphospholipid antibodies (aPLs). The development of thrombosis in APS is mediated by aPLs and contributes to the high mortality rate in APS patients. However, although APS has been reported for more than 30 years, there has been no optimal regimen for its prevention or for the management of thrombosis, mainly because the mainstay treatment strategies for managing APS are not targeted towards aPL-mediated thrombotic pathophysiology. Instead, the treatments commonly used are aimed at general thrombotic disorders. Warfarin is the most commonly used vitamin K antagonist (VKA), in addition to anti-platelet medications, such as aspirin and clopidogrel. Over the last decade, novel non-VKA oral anticoagulants, including rivaroxaban, apixaban and dabigatran, as well as immunomodulatory agents, such as rituximab, eculizumab, hydroxychloroquine, statins and sirolimus, have also been used. In this review, we discuss the current treatment strategies and future treatment outlook for thrombotic APS.
Alzheimer's Disease and Natural Products: Future Regimens Emerging from Nature

Islam MA, Khandker SS, Alam F, Khalil MI, Kamal MA, Gan SH

Curr Top Med Chem, 2017;17(12):1408-1428.
PMID: 28049401 DOI: 10.2174/1568026617666170103163054

Alzheimer's disease (AD), which largely affects the elderly, has become a global burden. Patients with AD have both short- and long-term memory impairments. The neuronal loss in AD occurs due to abnormally folded amyloid beta proteins and aggregation of hyperphosphorylated tau proteins in the brain. Eventually, amyloid plaques and neurofibrillary tangles are formed, which subsequently disintegrate the neuronal transport system. There are several factors which are involved in AD pathogenesis, including oxidative stress, inflammation and the presence of metal ions. The modern therapies utilized for AD treatment have many adverse effects, driving the quest for more safe and effective medications. Many dietary components, including different types of fruits, vegetables, spices, and marine products as well as a Mediterranean diet, are a good source of antioxidants and have anti-inflammatory properties, with many showing substantial potential against AD pathogenesis. In this review, we discuss the potential of these foods for treating AD and opportunities for developing disease-targeted drugs from active compounds extracted from natural dietary products.
Therapeutic Suppression of Nonsense Mutation: An Emerging Target in Multiple Diseases and Thrombotic Disorders

Asiful Islam M, Alam F, Kamal MA, Gan SH, Wong KK, Sasongko TH

Curr Pharm Des, 2017;23(11):1598-1609.
PMID: 27875971 DOI: 10.2174/1381612823666161122142950

Nonsense mutations contribute to approximately 10-30% of the total human inherited diseases via disruption of protein translation. If any of the three termination codons (UGA, UAG and UAA) emerges prematurely [known as premature termination codon (PTC)] before the natural canonical stop codon, truncated nonfunctional proteins or proteins with deleterious loss or gain-of-function activities are synthesized, followed by the development of nonsense mutation-mediated diseases. In the past decade, PTC-associated diseases captured much attention in biomedical research, especially as molecular therapeutic targets via nonsense suppression (i.e. translational readthrough) regimens. In this review, we highlighted different treatment strategies of PTC targeting readthrough therapeutics including the use of aminoglycosides, ataluren (formerly known as PTC124), suppressor tRNAs, nonsense-mediated mRNA decay, pseudouridylation and CRISPR/Cas9 system to treat PTC-mediated diseases. In addition, as thrombotic disorders are a group of disease with major burdens worldwide, 19 potential genes containing a total of 705 PTCs that cause 21 thrombotic disorders have been listed based on the data reanalysis from the 'GeneCards® - Human Gene Database' and 'Human Gene Mutation Database' (HGMD®). These PTC-containing genes can be potential targets amenable for different readthrough therapeutic strategies in the future.
Fulltext Tualang Honey Protects the Rat Midbrain and Lung against Repeated Paraquat Exposure

Tang SP, Kuttulebbai Nainamohamed Salam S, Jaafar H, Gan SH, Muzaimi M, Sulaiman SA

Oxid Med Cell Longev, 2017;2017:4605782.
PMID: 28127418 DOI: 10.1155/2017/4605782

Paraquat (PQ) is a dopaminergic neurotoxin and a well-known pneumotoxicant that exerts its toxic effect via oxidative stress-mediated cellular injuries. This study investigated the protective effects of Tualang honey against PQ-induced toxicity in the midbrain and lungs of rats. The rats were orally treated with distilled water (2 mL/kg/day), Tualang honey (1.0 g/kg/day), or ubiquinol (0.2 g/kg/day) throughout the experimental period. Two weeks after the respective treatments, the rats were injected intraperitoneally with saline (1 mL/kg/week) or PQ (10 mg/kg/week) once per week for four consecutive weeks. After four weekly exposures to PQ, the glutathione peroxidase activity and the number of tyrosine-hydroxylase immunopositive neurons in the midbrain were significantly decreased in animals from group PQ (p < 0.05). The lungs of animals from group PQ showed significantly decreased activity of superoxide dismutase and glutathione-S-transferase. Treatment with Tualang honey ameliorated the toxic effects observed in the midbrain and lungs. The beneficial effects of Tualang honey were comparable to those of ubiquinol, which was used as a positive control. These findings suggest that treatment with Tualang honey may protect against PQ-induced toxicity in the rat midbrain and lung.
Dietary Phytochemicals: Natural Swords Combating Inflammation and Oxidation-Mediated Degenerative Diseases

Islam MA, Alam F, Solayman M, Khalil MI, Kamal MA, Gan SH

Oxid Med Cell Longev, 2016;2016:5137431.
PMID: 27721914

Cumulatively, degenerative disease is one of the most fatal groups of diseases, and it contributes to the mortality and poor quality of life in the world while increasing the economic burden of the sufferers. Oxidative stress and inflammation are the major pathogenic causes of degenerative diseases such as rheumatoid arthritis (RA), diabetes mellitus (DM), and cardiovascular disease (CVD). Although a number of synthetic medications are used to treat these diseases, none of the current regimens are completely safe. Phytochemicals (polyphenols, carotenoids, anthocyanins, alkaloids, glycosides, saponins, and terpenes) from natural products such as dietary fruits, vegetables, and spices are potential sources of alternative medications to attenuate the oxidative stress and inflammation associated with degenerative diseases. Based on in vitro, in vivo, and clinical trials, some of these active compounds have shown good promise for development into novel agents for treating RA, DM, and CVD by targeting oxidative stress and inflammation. In this review, phytochemicals from natural products with the potential of ameliorating degenerative disease involving the bone, metabolism, and the heart are described.
Fulltext Erratum to "Nonpharmacologic Interventions in Prevention and Treatment of Hypertension"

Erejuwa OO, Gan SH, Romani AMP, Kamal MA, Nammi S

Int J Hypertens, 2019 10 13;2019:2907675.
PMID: 31737360 DOI: 10.1155/2019/2907675

[This corrects the article DOI: 10.1155/2019/6709817.].
Implication of Physiological and Biochemical Variables of Prognostic Importance in Lead Exposed Subjects

Malik A, Ashraf MAB, Khan MW, Zahid A, Shafique H, Waquar S, et al.

Arch Environ Contam Toxicol, 2020 Apr;78(3):329-336.
PMID: 31620805 DOI: 10.1007/s00244-019-00673-2

The use of leaded gasoline adversely affects cardiovascular, nervous, and immune systems. Study projects to rule out different variables of prognostic importance in lead-exposed subjects. A total of 317 traffic wardens with 5 years of outdoor experience and Hb levels
'Non-criteria' neurologic manifestations of antiphospholipid syndrome: a hidden kingdom to be discovered

Islam MA, Alam F, Kamal MA, Wong KK, Sasongko TH, Gan SH

CNS Neurol Disord Drug Targets, 2016;15(10):1253-1265.
PMID: 27658514 DOI: 10.2174/1871527315666160920122750

Neurological manifestations or disorders associated with the central nervous system are among the most common and important clinical characteristics of antiphospholipid syndrome (APS). Although in the most recently updated (2006) APS classification criteria, the neurological manifestations encompass only transient ischemic attack and stroke, diverse 'non-criteria' neurological disorders or manifestations (i.e., headache, migraine, bipolar disorder, transverse myelitis, dementia, chorea, epileptic seizures, multiple sclerosis, psychosis, cognitive impairment, Tourette's syndrome, parkinsonism, dystonia, transient global amnesia, obsessive compulsive disorder and leukoencephalopathy) have been observed in APS patients. To date, the underlying mechanisms responsible for these abnormal neurological manifestations in APS remain unclear. In vivo experiments and human observational studies indicate the involvement of thrombotic events and/or high titers of antiphospholipid antibodies in the neuro-pathogenic cascade of APS. Although different types of neurologic manifestations in APS patients have successfully been treated with therapies involving anti-thrombotic regimens (i.e., anticoagulants and/or platelet antiaggregants), antineuralgic drugs (i.e., antidepressants, antipsychotics and antiepileptics) and immunosuppressive drugs alone or in combination, evidence-based guidelines for the management of the neurologic manifestations of APS remain unavailable. Therefore, further experimental, clinical and retrospective studies with larger patient cohorts are warranted to elucidate the pathogenic linkage between APS and the central nervous system in addition to randomized controlled trials to facilitate the discovery of appropriate medications for the 'non-criteria' neurologic manifestations of APS.
Beneficial roles of honey polyphenols against some human degenerative diseases: A review

Hossen MS, Ali MY, Jahurul MHA, Abdel-Daim MM, Gan SH, Khalil MI

Pharmacol Rep, 2017 Dec;69(6):1194-1205.
PMID: 29128800 DOI: 10.1016/j.pharep.2017.07.002

Honey contains many active constituents and antioxidants such as polyphenols. Polyphenols are phytochemicals, a generic term for the several thousand plant-based molecules with antioxidant properties. Many in vitro studies in human cell cultures as well as many animal studies confirm the protective effect of polyphenols on a number of diseases such as cardiovascular diseases (CVD), diabetes, cancer, neurodegenerative diseases, pulmonary diseases, liver diseases and so on. Nevertheless, it is challenging to identify the specific biological mechanism underlying individual polyphenols and to determine how polyphenols impact human health. To date, several studies have attempted to elucidate the molecular pathway for specific polyphenols acting against particular diseases. In this review, we report on the various polyphenols present in different types of honey according to their classification, source, and specific functions and discuss several of the honey polyphenols with the most therapeutic potential to exert an effect on the various pathologies of some major diseases including CVD, diabetes, cancer, and neurodegenerative diseases.
Computational algorithmic and molecular dynamics study of functional and structural impacts of non-synonymous single nucleotide polymorphisms in human DHFR gene

Alam MS, Saleh MA, Mozibullah M, Riham AT, Solayman M, Gan SH

Comput Biol Chem, 2021 Dec;95:107587.
PMID: 34710812 DOI: 10.1016/j.compbiolchem.2021.107587

Human dihydrofolate reductase (DHFR) is a conserved enzyme that is central to folate metabolism and is widely targeted in pathogenic diseases as well as cancers. Although studies have reported the fact that genetic mutations in DHFR leads to a rare autosomal recessive inborn error of folate metabolism and drug resistance, there is a lack of an extensive study on how the deleterious non-synonymous SNPs (nsSNPs) disrupt its phenotypic effects. In this study, we aim at discovering the structural and functional consequences of nsSNPs in DHFR by employing a combined computational approach consisting of ten recently developed in silico tools for identification of damaging nsSNPs and molecular dynamics (MD) simulation for getting deeper insights into the magnitudes of damaging effects. Our study revealed the presence of 12 most deleterious nsSNPs affecting the native phenotypic effects, with three (R71T, G118D, Y122D) identified in the co-factor and ligand binding active sites. MD simulations also suggested that these three SNPs particularly Y122D, alter the overall structural flexibility and dynamics of the native DHFR protein which can provide more understandings into the crucial roles of these mutants in influencing the loss of DHFR function.
Frontiers of monoclonal antibodies: Applications in medical practices

Ghagane SC, Puranik SI, Gan SH, Hiremath MB, Nerli RB, Ravishankar MV

Hum Antibodies, 2017;26(3):135-142.
PMID: 29060935 DOI: 10.3233/HAB-170331

With the flourishing of innovation in drug discovery into a new era of personalized therapy, the use of monoclonal antibodies (mAbs) in the treatment of various ailments lies at the forefront. Major improvements in genetic sequencing and biomedical techniques as well as research into mAbs emphasize on determining new targets for advanced therapy while maximizing efficacy for clinical application. However, a balance has to be achieved concerning developing a target with low toxicity combined with high specificity and versatility, to allow a specific antibody to facilitate several biotic effects, ranging from neutralization of virus mechanisms to modulation of immune response and maintaining low global economic cost. Presently, there are approximately 30 mAbs' permitted for therapeutic use with many more being tested in clinical trials. Nevertheless, the heavy cost of mAbs' production, stowage and management as well as the subsequent hindrances to their development are outweighed by mAbs' clinical advantages. Compared to conventional drugs, since mAbs use as pharmacologic iotas have specific physical features and modes of action, they should be considered as a discrete therapeutic category. In this review, the history of mAb generation and the innovative technological applications of mAbs that has advanced in clinical practices is reviewed.
Coexistence of antiphospholipid antibodies and cephalalgia

Islam MA, Alam F, Gan SH, Cavestro C, Wong KK

Cephalalgia, 2018 03;38(3):568-580.
PMID: 28952322 DOI: 10.1177/0333102417694881

Background The occurrence of antiphospholipid antibodies (aPLs) and headache comorbidity in the presence or absence of underlying autoimmune diseases remains unclear. Aim The aim of this review was to summarize the relationship between headache and aPLs based on evidences from cohort studies and case reports, in addition to examining the treatment strategies that resolved headache in aPLs-positive individuals.
Methods A comprehensive literature search was conducted through PubMed, ISI Web of Science and Google Scholar. A total of 559 articles were screened and the appropriate articles were selected based on quality and level of evidence.
Results Cohort studies (n = 27) from Europe, North America and Asia demonstrated comorbidity of aPLs and headache in antiphospholipid syndrome, systemic lupus erythematosus (SLE) and neuropsychiatric SLE patients. Significantly higher association between migraine and aPLs was observed (n = 170/779; p
Fulltext Trigeminal neuralgia, glossopharyngeal neuralgia, and myofascial pain dysfunction syndrome: an update

Khan M, Nishi SE, Hassan SN, Islam MA, Gan SH

Pain Res Manag, 2017;2017:7438326.
PMID: 28827979 DOI: 10.1155/2017/7438326

Neuropathic pain is a common phenomenon that affects millions of people worldwide. Maxillofacial structures consist of various tissues that receive frequent stimulation during food digestion. The unique functions (masticatory process and facial expression) of the maxillofacial structure require the exquisite organization of both the peripheral and central nervous systems. Neuralgia is painful paroxysmal disorder of the head-neck region characterized by some commonly shared features such as the unilateral pain, transience and recurrence of attacks, and superficial and shock-like pain at a trigger point. These types of pain can be experienced after nerve injury or as a part of diseases that affect peripheral and central nerve function, or they can be psychological. Since the trigeminal and glossopharyngeal nerves innervate the oral structure, trigeminal and glossopharyngeal neuralgia are the most common syndromes following myofascial pain dysfunction syndrome. Nevertheless, misdiagnoses are common. The aim of this review is to discuss the currently available diagnostic procedures and treatment options for trigeminal neuralgia, glossopharyngeal neuralgia, and myofascial pain dysfunction syndrome.
Fulltext Presence of anticardiolipin antibodies in patients with dementia: A systematic review and meta-analysis

Islam MA, Alam F, Kamal MA, Gan SH, Sasongko TH, Wong KK

Front Aging Neurosci, 2017;9:250.
PMID: 28824414 DOI: 10.3389/fnagi.2017.00250

Growing evidences are supporting towards the involvement of antiphospholipid antibodies [aPLs e.g., lupus anticoagulant (LA), anticardiolipin (aCL) and anti-β2-glycoprotein I (anti-β2-GPI) antibodies] in various neurological manifestations including migraine, epilepsy and dementia in the presence or absence of autoimmune diseases such as antiphospholipid syndrome or systemic lupus erythematosus. The aim of this systematic review and meta-analysis was to assess the presence of aPLs in dementia patients without a diagnosis of any autoimmune disease. Electronic databases (e.g., PubMed, Web of Science, Scopus, ScienceDirect and Google Scholar) were searched without any year or language restrictions and based on the inclusion criteria, nine prospective case-control studies assessing only aCL were included involving 372 dementia patients and 337 healthy controls. No studies were found to assess the presence of both LA or anti-β2-GPI. The study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects model. We observed the prevalence of aCL in dementia was higher (32.80%) than that of controls (9.50%) e.g., 3.45 times higher risk of presenting with dementia than the controls, and significant presence of aCL antibodies was detected in dementia patients compared to controls (OR: 4.94, 95% CI: 2.66 - 9.16, p < 0.00001; I2 = 32%, p = 0.16). Publication bias was not observed from Egger's (p = 0.081) and Begg's tests (p = 0.180). Based on the study quality assessment using modified Newcastle-Ottawa Scale for case-control studies, seven of nine studies were of high methodological quality scoring ≥ 7 (median value). In summary, aCL antibodies were significantly present in dementia patients suggesting that aCL antibodies are generated due to the autoimmune-derived effects of dementia or there might be a potential causative role of this autoantibody in dementia pathogenesis.
Fulltext Short-term renal outcomes following acute kidney injury among dengue patients: A follow-up analysis from large prospective cohort

Mallhi TH, Khan AH, Adnan AS, Sarriff A, Khan YH, Gan SH

PLoS One, 2018;13(2):e0192510.
PMID: 29481564 DOI: 10.1371/journal.pone.0192510

BACKGROUND: Despite myriad improvements in the care of dengue patients, acute kidney injury (AKI) remained least appreciated intricacy of dengue infection. Exiting literature does not provide any information on renal outcomes among dengue patients surviving an episode of AKI.
METHODS: Dengue patients who developed AKI were followed up for post-discharge period of three months and renal recovery was assessed by using recovery criteria based on different thresholds of serum creatinine (SCr) and estimated glomerular filtration rates (eGFR).
RESULTS: Out of the 526 dengue participants, AKI was developed in 72 (13.7%) patients. Renal recovery was assessed among AKI survivors (n = 71). The use of less (±50% recovery to baseline) to more (±5% recovery to baseline) stringent definitions of renal recovery yielded recovery rates from 88.9% to 2.8% by SCr and 94.4% to 5.6% by eGFR, as renal function biomarkers. At the end of study, eight patients had AKI with AKIN-II (n = 7) and AKIN-III (n = 1). Approximately 50% patients (n = 36/71) with AKI had eGFR primitive to CKD stage 2, while 18.3% (n = 13/71) and 4.2% (n = 3/71) patients had eGFR corresponding to advanced stages of CKD (stage 3 & 4). Factors such as renal insufficiencies at hospital discharge, multiple organ involvements, advance age, female gender and diabetes mellitus were associated with poor renal outcomes.
CONCLUSIONS: We conclude that dengue patients with AKI portend unsatisfactory short-term renal outcomes and deserve a careful and longer follow-up, especially under nephrology care.
Genetic risk factors in thrombotic primary antiphospholipid syndrome: A systematic review with bioinformatic analyses

Islam MA, Khandker SS, Alam F, Kamal MA, Gan SH

Autoimmun Rev, 2018 Mar;17(3):226-243.
PMID: 29355608 DOI: 10.1016/j.autrev.2017.10.014

BACKGROUND: Antiphospholipid Syndrome (APS) is an autoimmune multifactorial disorder. Genetics is believed to play a contributory role in the pathogenesis of APS, especially in thrombosis development and pregnancy morbidity. In the last 20 years, extensive research on genetic contribution on APS indicates that APS is a polygenic disorder, where a number of genes are involved in the development of its clinical manifestations.

AIMS: The aim of this systematic review is to evaluate the genetic risk factors in thrombotic primary APS. Additionally, to assess the common molecular functions, biological processes, pathways, interrelations with the gene encoded proteins and RNA-Seq-derived expression patterns over different organs of the associated genes via bioinformatic analyses.

METHODS: Without restricting the year, a systematic search of English articles was conducted (up to 4th September 2017) using Web of Science, PubMed, Scopus, ScienceDirect and Google Scholar databases. Eligible studies were selected based on the inclusion criteria. Two researchers independently extracted the data from the included studies. Quality assessment of the included studies was carried out using a modified New-Castle Ottawa scale (NOS).

RESULTS: From an initial search result of 2673 articles, 22 studies were included (1268 primary APS patients and 1649 healthy controls). Twenty-two genes were identified in which 16 were significantly associated with thrombosis in primary APS whereas six genes showed no significant association with thrombosis. Based on the NOS, 14 studies were of high quality while 6 were low quality studies. From the bioinformatic analyses, thrombin-activated receptor activity (q = 6.77 × 10-7), blood coagulation (q = 2.63 × 10-15), formation of fibrin clot (q = 9.76 × 10-10) were the top hit for molecular function, biological process and pathway categories, respectively. With the highest confidence interaction score of 0.900, all of the thrombosis-associated gene encoded proteins of APS were found to be interconnected except for two. Based on the pathway analysis, cumulatively all the genes affect haemostasis [false discovery rate (FDR) = 1.01 × 10-8] and the immune system [FDR = 9.93 × 10-2]. Gene expression analysis from RNA-Seq data revealed that almost all the genes were expressed in 32 different tissues in the human body.

CONCLUSION: According to our systematic review, 16 genes contribute significantly in patients with thrombotic primary APS when compared with controls. Bioinformatic analyses of these genes revealed their molecular interconnectivity in protein levels largely by affecting blood coagulation and immune system. These genes are expressed in 32 different organs and may pose higher risk of developing thrombosis anywhere in the body of primary APS patients.
Fulltext The Role of microRNAs in Alzheimer's Disease and Their Therapeutic Potentials

Miya Shaik M, Tamargo IA, Abubakar MB, Kamal MA, Greig NH, Gan SH

Genes (Basel), 2018 Mar 21;9(4).
PMID: 29561798 DOI: 10.3390/genes9040174

MicroRNAs (miRNAs) are short, endogenous, non-coding RNAs that post-transcriptionally regulate gene expression by base pairing with mRNA targets. Altered miRNA expression profiles have been observed in several diseases, including neurodegeneration. Multiple studies have reported altered expressions of miRNAs in the brains of individuals with Alzheimer's disease (AD) as compared to those of healthy elderly adults. Some of the miRNAs found to be dysregulated in AD have been reported to correlate with neuropathological changes, including plaque and tangle accumulation, as well as altered expressions of species that are known to be involved in AD pathology. To examine the potentially pathogenic functions of several dysregulated miRNAs in AD, we review the current literature with a focus on the activities of ten miRNAs in biological pathways involved in AD pathogenesis. Comprehensive understandings of the expression profiles and activities of these miRNAs will illuminate their roles as potential therapeutic targets in AD brain and may lead to the discovery of breakthrough treatment strategies for AD.
Fulltext Clinical pharmacists' intervention on pain management in cancer patients (PharmaCAP trial): study protocol for a randomized controlled trial

Shrestha S, Blebil AQ, Teoh SL, Sapkota S, Kc B, Paudyal V, et al.

J Pharm Policy Pract, 2023 Jan 24;16(1):14.
PMID: 36694232 DOI: 10.1186/s40545-022-00505-0

INTRODUCTION: Evidence-based services to support cancer patients with pain via clinical pharmacy services are currently lacking. Therefore, there is a need to undertake a randomized controlled trial (RCT) to explore the effectiveness of clinical pharmacists (CPs)' input into the multidisciplinary team (MDT) in providing better therapeutic outcomes for cancer pain management.
OBJECTIVES: The main aim of this pilot RCT is to determine the feasibility and preliminary efficacy of integrating CPs into the MDT for cancer pain management on the clinical outcomes of cancer patients experiencing pain.
METHODS: This study protocol outlines two-armed multicenter pilot RCT. Cancer patients suffering from pain will be randomly allocated to receive either clinical pharmacy services, i.e., PharmaCAP trial intervention from the CP, or the usual standard care (i.e., control group). Patients will be recruited consecutively from two hospitals in Kathmandu valley, Nepal. The outcomes will be assessed at baseline (pre-intervention) and 4 weeks post-intervention. The primary feasibility outcomes will include eligibility rate, recruitment rate, willingness to participate, acceptability of screening procedures and random allocation, possible contamination between the groups, intervention fidelity and compliance, treatment satisfaction, and patient understanding of the provided interventions. Subsequently, the primary clinical outcome, i.e., pain intensity of cancer patients, will be assessed. The secondary clinical outcomes will include health-related quality of life (HRQoL), anxiety, depression, adverse drug reactions, and patient medication compliance following the integration of CP into the healthcare team.
DISCUSSION: The feasibility and potential for integrating CP involvement in MDT to improve clinical outcomes of cancer patients with pain will be evaluated through the PharmaCAP trial.
TRIAL REGISTRATION: ClinicalTrials.gov NCT05021393. Registered on 25th August 2022.

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