Nevin Manimala

Nat Commun. 2021 May 24;12(1):3051. doi: 10.1038/s41467-021-23094-z.

ABSTRACT

The vast preponderance of somatic mutations in a typical cancer are either extremely rare or have never been previously recorded in available databases that track somatic mutations. These constitute a hidden genome that contrasts the relatively small number of mutations that occur frequently, the properties of which have been studied in depth. Here we demonstrate that this hidden genome contains much more accurate information than common mutations for the purpose of identifying the site of origin of primary cancers in settings where this is unknown. We accomplish this using a projection-based statistical method that achieves a highly effective signal condensation, by leveraging DNA sequence and epigenetic contexts using a set of meta-features that embody the mutation contexts of rare variants throughout the genome.

PMID:34031376 | DOI:10.1038/s41467-021-23094-z

Transl Psychiatry. 2021 May 24;11(1):310. doi: 10.1038/s41398-021-01431-6.

ABSTRACT

Gene expression has provided promising insights into the pathophysiology of post-traumatic stress disorder (PTSD); however, specific regulatory transcriptomic mechanisms remain unknown. The present study addressed this limitation by performing transcriptome-wide RNA-Seq of whole-blood samples from 226 World Trade Center responders. The investigation focused on differential expression (DE) at the gene, isoform, and for the first time, alternative splicing (AS) levels associated with the symptoms of PTSD: total burden, re-experiencing, avoidance, numbing, and hyperarousal subdimensions. These symptoms were associated with 76, 1, 48, 15, and 49 DE genes, respectively (FDR < 0.05). Moreover, they were associated with 103, 11, 0, 43, and 32 AS events. Avoidance differed the most from other dimensions with respect to DE genes and AS events. Gene set enrichment analysis (GSEA) identified pathways involved in inflammatory and metabolic processes, which may have implications in the treatment of PTSD. Overall, the findings shed a novel light on the wide range of transcriptomic alterations associated with PTSD at the gene and AS levels. The results of DE analysis associated with PTSD subdimensions highlights the importance of studying PTSD symptom heterogeneity.

PMID:34031375 | DOI:10.1038/s41398-021-01431-6

Transl Psychiatry. 2021 May 24;11(1):311. doi: 10.1038/s41398-021-01437-0.

ABSTRACT

Posttraumatic stress disorder (PTSD) is associated with shortened lifespan and healthspan, which suggests accelerated aging. Emerging evidence suggests that methylation age may be accelerated in PTSD. It is important to examine whether transcriptional age is also accelerated because transcriptome is highly dynamic, associated with age-related outcomes, and may offer greater insight into the premature aging in PTSD. This study is the first reported investigation of the relationship between transcriptional age and PTSD. Using RNA-Seq data from our previous study on 324 World Trade Center responders (201 never had PTSD, 81 with current PTSD, and 42 with past PTSD), as well as a transcriptional age calculator (RNAAgeCalc) recently developed by our group, we found that responders with current PTSD, compared with responders without a PTSD diagnosis, showed accelerated transcriptional aging (p = 0.0077) after adjustment for chronological age and race. We compared our results to the epigenetic aging results computed from several epigenetic clock calculators on matching DNA methylation data. GrimAge methylation age acceleration was also associated with PTSD diagnosis (p = 0.0097), and the results remained significant after adjustment for the proportions of immune cell types. PhenoAge, Hannum, and Horvath methylation age acceleration were not reliably related to PTSD. Both epigenetic and transcriptional aging may provide biological insights into the mechanisms underpinning aging in PTSD.

PMID:34031357 | DOI:10.1038/s41398-021-01437-0

Med J Malaysia. 2021 May;76(3):401-413.

ABSTRACT

INTRODUCTION: Internet Addiction Disorder (IAD) is an umbrella term for various types of Internet-based behavioural addiction, whereas Internet Gaming Disorder (IGD) addresses a specific type of IAD that is postulated to be due to a lack of control in impulse inhibition. IGD is an area of concern in the Diagnostic and Statistics Manual of Mental Disorders (DSM-5), which can be objectively assessed by dysfunctional behaviour and the increasing time of being online, particularly during the COVID-19 pandemic. Electroencephalography (EEG) identifies amplitude changes in the evoked response potential (ERP) among IGDs, correlated with underlying comorbidities.

MATERIALS AND METHODS: A scoping review was performed to elaborate on the research regarding resting-state EEG and task-based EEG, particularly for Go/No-go paradigms pertaining to subjects with IAD or specifically IGD. The role of EEG was identified in its diagnostic capability to identify the salient changes that occurred in the response to reward network and the executive control network, using restingstate and task-based EEG. The implication of using EEG in monitoring the therapy for IAD and IGD was also reviewed.

RESULTS: EEG generally revealed reduced beta waves and increased theta waves in addicts. IGD with depression demonstrated increased theta and decreased alpha waves. Whereas increased P300, a late cognitive ERP component, was frequently associated with impaired excessive allocation of attentional resources of the IAD towards addiction-specific cues. IGD had increased whole brain delta waves at baseline, which showed significant reduction post therapy.

CONCLUSION: EEG can identify distinct neurophysiological changes among Internet Addiction Disorder and Internet Gaming Disorder that are akin to substance abuse disorders.

PMID:34031341

Med J Malaysia. 2021 May;76(3):395-400.

ABSTRACT

INTRODUCTION: Microbes in the human gut impact holistic health. Modifiable events can steer immunity through commensal microbial action. This protects from acute diseases and lays foundation for enduring health benefits. Timely modulation of immune development by correct feeding choices negate consequences of microbial dysequilibrium.

MATERIALS AND METHODS: Review and critical analysis of relevant literature integrated to the core understanding of facets of microbial existence in the gut , their roles in early immunity , and impact on health were done. Known deficiencies in newborn immunity integrated to the actions of microbes in human milk permitted some conclusions to be drawn through logical extrapolations.

RESULTS: Deficiencies in early immunity can, at least partially, be surmounted by an optimal gut microbial milieu provided for by human milk which also enhances gut immunity and holistic health.

LIMITATIONS: This is a narrative review and articles chosen were subjectively analysed for suitability according to relevance, however, analysis by statistical methods was not done.

CONCLUSIONS: There are clear pathways linking gut microbes, intestinal epithelia, microbial metabolites and early immune maturation. The immature immune system is guided towards proper development and maturation by breastmilk factors and milk microbes for immediate and enduring holistic health. Utilising this knowledge, research must be energised on possible mutualistic benefits of gut microbes to counter the current health challenges. The counselling of breastfeeding must not overlook the unique microbial environment endowed by the mother as a gift of health.

PMID:34031340

Med J Malaysia. 2021 May;76(3):369-374.

ABSTRACT

INTRODUCTION: Twenty-seven adult patients, skin type III -V with mild to moderate acne, were recruited. IPL at wavelengths range of 420 – 600nm with triple pulses was administered every two weeks for a total of 3 sessions. Assessment of acne severity and improvement of treatment was based on Global Acne Grading System (GAGS), scoring before and after treatment for each session and patient satisfaction’s using a 5-item Likert scale range at the end of session three.

RESULTS: Of the 27 patients, 77.8% were female. Their ages group ranged from 18 to 35 years, and all patients had skin type III or IV. There were 14 mild acne patients and 13 moderate ones. There was a statistically significant improvement in mean acne severity score from 18.1± 4.3 at baseline to 14.3 ± 4.6 after two weeks post-IPL and 12.3 ± 4.9 after four weeks post-IPL. The result on satisfaction level of patients showed ‘satisfied’ in 3 patients, “very satisfied” in 5 patients; and, half of the patients (11) answered “fair” at the end of the study. Most patients tolerated well the procedure, and only 5 patients developed either post-inflammatory hyperpigmentation or skin hyperpigmentation.

CONCLUSION: The IPL of wavelength of 400-600nm offers effective, safe, and well-tolerated treatment of mild to moderate acne lesions in Malaysians with skin types III-IV. The majority of subjects had a fair score on treatment satisfaction. It is recommended that reasonable expectations for clinical results be addressed with patients before hands to prevent over-expectation.

PMID:34031336

Med J Malaysia. 2021 May;76(3):360-368.

ABSTRACT

INTRODUCTION: The effective connectivity (EC) when the brain is resting and how a neuronal system exerts influence over other regions of the brain, in different groups of subjects are still being investigated. Limited information was seen about the relationship between precuneus (PRE) which is a wellknown resting state hub with supramarginal gyrus (SMG) in healthy subjects (HS) and temporal lobe epilepsy (TLE) participants.

MATERIALS AND METHODS: Fourteen HS and 14 TLE patients with age and gender matched underwent resting state functional magnetic resonance imaging (rsfMRI) scanning using a 3-Tesla MRI machine to investigate the EC and percentage of amplitude fluctuation (PerAF) involving SMG and PRE. The rsfMRI data were analysed using Statistical Parametric Mapping (SPM12) and Spectral Dynamic Causal Modelling (spDCM) from which causal models were specified, estimated and inferred.

RESULTS: Model with bidirectional connections between PRE and SMG was chosen as the winning model. The EC from PRE to SMG is positive but the EC from SMG to PRE is negative in both hemispheres and in HS and TLE. Based on the findings from the EC analysis, there is an excitatory effect shown by PRE to SMG connection indicating a dominant role of PRE over SMG in both groups.

CONCLUSION: There is important evidence showing that PRE might also have influence on areas outside resting state network and the influence changes in the presence of brain abnormality.

PMID:34031335

Med J Malaysia. 2021 May;76(3):346-352.

ABSTRACT

INTRODUCTION: Colorectal cancer (CRC) is one of the major causes of cancer-related mortality in Malaysia. Early screening has proven to be effective in reducing mortality due to CRC. The Malaysian CRC Clinical Practice Guidelines (2017) recommends that immunochemical faecal occult blood test (iFOBT) as the best non-invasive method for screening CRC in asymptomatic or average risk population. Outcome data on CRC screening program in the community is scarce. This study was to evaluate the prevalence and determinants of CRC among patients attending a public primary care health centre who underwent the screening program.

MATERIALS AND METHODS: Reviews of CRC Screening Registry and medical case record were conducted on patients who underwent CRC screening program at Klinik Kesihatan Mahmoodiah, Johor Bahru (KKMJB) from 2016 to 2018 period. Sociodemographic data, clinical profile of patients, iFOBT results and colonoscopy outcomes were extracted for analysis. Descriptive and inferential statistics were performed using IBM SPSS version 25.

RESULTS: Out of 591 registered patients, 584 were included for analysis. Majority of the screened individuals were males (2016-2017) compared to females (2018). Chinese were most screened individuals in 2016 [94 (46.8%)] and 2017[87 (61.7%)]. Percentage of patients with appropriate indicators for screening and underwent colonoscopy for positive iFOBT were highest recorded in 2018 (74.7%, 58.8% respectively). Prevalence of CRC among those screened with iFOBT was 1 per cent for 2017 and 2018. Adherence to annual screening with iFOBT ranged between 1.1% (2016)- 2.2% (2018). Significant association observed between gender and iFOBT results, χ2(df)= 4.747, p=0.029 (2018). Median age and ethnicity were not significantly associated with iFOBT results (p>0.05) CONCLUSION: Screening for CRC among average risk groups in primary care should focus on recruiting female patients/clients as an organised activity. Prevalence of CRC detected from screening with iFOBT was 1 per cent. CRC screening programs should focus on proportion of iFOBT positive patients progressing to receive definitive colonoscopy and complying to annual surveillance screening.

PMID:34031333

JAAPA. 2021 Jun 1;34(6):40-43. doi: 10.1097/01.JAA.0000750972.64581.b0.

ABSTRACT

OBJECTIVE: Employment analyses demonstrate that physician assistants (PAs) exhibit role flexibility in US medicine. The next step in understanding this labor-shifting observation is to know at what career stage it first occurs.

METHODS: Using matriculate data linked to the American Academy of PAs (AAPA) census survey data, a longitudinal analysis of seven graduate cohorts revealed that one-third of PAs changed specialty roles at least once during their first decade of employment.

RESULTS: From this series, it appears that new PAs spend about 3.4 years in their first job, on average, before they decide to move to another medical or surgical field. In examining PAs who changed their clinical role during this time period, 28% shifted from primary care to another medical or specialty role. Overall, the PA career movement to nonprimary care specialties increased substantially.

CONCLUSIONS: These findings support observations that PAs provide an adaptive role in a dynamic and changing medical workforce.

PMID:34031313 | DOI:10.1097/01.JAA.0000750972.64581.b0

Acad Med. 2021 Jun 1;96(6):774-776. doi: 10.1097/ACM.0000000000004048.

NO ABSTRACT

PMID:34031298 | DOI:10.1097/ACM.0000000000004048