Molecular and physiologic changes in the SpaceX Inspiration4 civilian crew.

Human spaceflight has historically been managed by government agencies, such as the NASA Twins Study1, but new commercial spaceflight opportunities have opened spaceflight to a broader population. In 2021, the SpaceX Inspiration4 mission launched the first-ever all civilian crew to low Earth orbit, which included the youngest American astronaut (age 29), novel in-flight experimental technologies (handheld ultrasound imaging, smartwatch wearables, and immune profiling), ocular alignment measurements, and new protocols for in-depth, multi-omic molecular and cellular profiling. Here we report the primary findings from the 3-day spaceflight mission, which induced a broad range of physiological and stress responses, neurovestibular changes indexed by ocular misalignment, and altered neurocognitive functioning, some of which match long-term spaceflight2, but almost all of which did not differ from baseline (pre-flight) after return to Earth. Overall, these preliminary civilian spaceflight data suggest that short-duration missions do not pose a significant health risk, and moreover present a rich opportunity to measure the earliest phases of adaptation to spaceflight in the human body at anatomical, cellular, physiologic, and cognitive levels. Finally, these methods and results lay the foundation for an open, rapidly expanding biomedical database for astronauts3, which can inform countermeasure development for both private and government-sponsored space missions.

Comparing rare variants versus common in the pathogenesis of nonalcoholic fatty liver disease: a whole exome sequencing approach.

BACKGROUND/PURPOSE: Genome-wide association studies have reported the association of common variants with nonalcoholic fatty liver disease in genes, namely, PNPLA3/TM6SF2/MBOAT7/HSD17B13, across ethnicities. However, the approach does not identify rarer variants with a higher effect size. We therefore sequenced the complete exonic regions of patients with nonalcoholic steatohepatitis and controls to compare rare and common variants with a role in the pathogenesis. METHODS: This is a prospective study that recruited 54 individuals with/without fatty infiltration. Patients with biopsy-proven nonalcoholic steatohepatitis and persistently elevated liver enzymes were included. Controls were with normal CT/MR fat fraction. DNA was isolated from whole blood, amplified (SureSelectXT Human All Exon V5 + UTR kit) and sequenced (Illumina). Data were filtered for quality, aligned (hg19), and annotated (OpenCRAVAT). Pathogenic (Polyphen-2/SIFT/ClinVar) variants and variants reported to be associated with NAFLD based on published literature were extracted from our data and compared between patients and controls. RESULTS: The mean age of controls (N = 17) and patients (N = 37) was 46.88 ± 6.94 and 37.46 ± 13.34 years, respectively. A total of 251 missense variants out of 89 286 were classified as pathogenic. Of these, 106 (42.23%) were unique to the patients and remaining (n = 145; 57.77%) were found in both patients and controls. Majority (25/37; 67.57%) patients had a minimum of one or more rare pathogenic variant(s) related to liver pathology that was not seen in the controls. CONCLUSION: Elucidating the contribution of rare pathogenic variants would enhance our understanding of the pathogenesis. Including the rarer genes in the polygenic risk scores would enhance prediction power.

Enhanced resonances by waveguide wrapping of a bulbed microring resonator.

A high Q-factor novel bulb design, to the best of our knowledge, inspired by the well-studied pulley microring resonator (MRR), is demonstrated and compared with circle and racetrack MRRs at wavelengths of 1.45-1.65 µm. A wrapping of 60% around the ring showed a three times Q-factor increment (Q=828) compared to a standard circle MRR (Q=206) at a telecom wavelength of 1.55 µm with a fixed ring radius of 2 µm, while further increasing the wrapping at 80% shows a decrease in its Q-factor (Q=454). A comparison of the wavelength dependence of the bulb design with other typical MRR designs suggests that bulb designs are highly sensitive to wavelength and have very high Q-factors at lower wavelengths.

Overcoming chromoprotein limitations by engineering a red fluorescent protein.

Chromoproteins (CPs) are widely-used visual reporters of gene expression. We previously showed that, for coloration in Escherichia coli, CPs had to be overexpressed and that this caused large fitness costs with the most useful (darkly colored) CPs. These fitness costs were problematic because passage of plasmids encoding darkly colored CPs in liquid culture frequently resulted in loss of color due to mutations. Unexpectedly, an early variant of the monomeric red fluorescent protein 1 (mRFP1) gene that was codon-optimized for E. coli (abbreviated mRFP1E) was found here to be an ideal replacement for CP genes. When we subcloned mRFP1E in the same way as our CP genes, it produced a similarly dark color, yet affected E. coli fitness minimally. This finding facilitated testing of several hypotheses on the cause of CP cytotoxicities by gel electrophoresis and size-exclusion chromatography: toxicities correlated with the combination of amounts of expression, oligomerization and inclusion bodies, not isoelectric point. Finally, a semi-rational mutagenesis strategy created several mRFP1 protein variants with different colors without altering the fitness cost. Thus, these mutants and mRFP1E are suitable for comparative fitness costs between different strains of E. coli. We conclude that our new mRFP1E series overcomes prior limitations of CPs.

A Clinical Study on the Circadian Rhythm of Salivary Cortisol on Aggressive Periodontitis and Its Correlation with Clinical Parameters using Electrochemiluminescence Immunoassay Method.

AIM: Periodontal pathologies are gaining importance as there is a clear indication of bi-way control on general homeostasis of an individual. The study of HPA axis in various diseases has proved that there is evident vulnerability existing for any organism when the Cortisol diurnal rhythm is altered. The aim was to compare the diurnal rhythm of salivary cortisol in aggressive periodontitis with control patients. This study also compared various parameters like body mass index (BMI), waist circumference, Hamilton anxiety scale, OHI-S, clinical attachment loss in aggressive periodontitis. MATERIALS AND METHODS: 30 control patients were compared against 30 aggressive periodontitis patients in Salivary cortisol diurnal rhythm. It was estimated using the electrochemiluminescence (ECL) method on a 3 point analysis-Soon after waking up, 30 minutes after waking up, 1 hour before sleep to see the diurnal variation in aggressive periodontitis patients. The samples were transferred to CABRI labs to be frozen to -20°C. The analysis was done using Cobas e-411 autoanalyzer by Roche, USA. RESULTS: The average cortisol in aggressive patients was found to be higher compared to control patients and was found to be statistically significant with a p value of 0.012. Control group is moderately skewed left (negative skewness graph) while the aggressive p periodontitis patients showed moderately skewed right (+ve skewness graph). CONCLUSION: The cortisol awakening response seen in control patients is not observed in aggressive periodontitis. Instead of giving a surge, the cortisol showed a dip in the first 30 minutes followed by a gradual increase in aggressive periodontitis instead of decline as observed in normal patients. CLINICAL SIGNIFICANCE: The study will focus on the importance of cortisol circadian rhythm on periodontal health allowing the microorganism to create an environment of dysbiosis.

Stenotrophomonas maltophilia: More than Just a Colonizer!

Stenotrophomonas maltophilia is an emerging gram-negative pathogen that was previously labeled as a colonizer. Nowadays, with multiple antibiotic usage along with certain host factors, infections caused by this organism are getting attention. We hereby report two cases of ventilator-associated pneumonia in postoperative infants by Stenotrophomonas maltophilia in a cardiac intensive care unit (ICU). How to cite this article: Baidya A, Kodan P, Fazal F, Tsering S, Menon RP, Jorwal P, et al. Stenotrophomonas maltophilia: More than Just a Colonizer! Indian J Crit Care Med 2019;23(9):434-436.

An In Vitro Comparative Evaluation of Shear Bond Strengths of Veneering Porcelain and Different Core Materials.

AIM: The aim of the present study was to evaluate and compare the bond strengths of different core structures to veneering porcelain. MATERIALS AND METHODS: Sixty specimens were divided into 4 groups of 15 each. Specimen fabrication was done according to the International Organization for Standardization (ISO) specifications 9693:1999. Group 1 comprised core structure made of cast alloy, group 2 from sintered metal, group 3 from milled zirconia and group 4 milled zirconia without liner at the interface. The shear bond strengths were recorded and the values obtained were statistically examined. RESULTS: Highest values were recorded in group 3 and there were significant differences between groups 1 and 3 while groups 3 and 4 were not statistically different. This led us to imply that zirconia as a core structure provided maximum strengths and laser sintered metal came second. The results also pointed out that the role of the zirconia liner is not that crucial to attaining adequate strength. CONCLUSION: The present study concluded that zirconia and laser sintered metal are excellent core materials and feasible alternatives to cast alloy. We also concluded from our study that a zirconia liner did not affect the bond strength significantly and is not absolutely essential. CLINICAL SIGNIFICANCE: This study helps us to understand the role of materials used as core structures in enhancing the shear bond strength to veneer porcelains and also clarifies the role of a zirconia liner in the process.

Cortical hyperexcitability and disease spread in amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is characterized by focal disease onset with a predominantly contiguous pattern of disease spread. The pathophysiological mechanisms underlying disease progression in ALS have not been elucidated. Given that cortical hyperexcitability has been identified as an important pathogenic mechanism in ALS, the aim of the present study was to determine whether changes in cortical function could mediate disease spread in ALS. METHODS: Threshold-tracking transcranial magnetic stimulation was undertaken in 50 patients with sporadic ALS with recording of responses over both abductor pollicis brevis muscles, with results matched to clinical assessments and concurrent neurophysiological investigation of lower motor neuron function. Subsequently, patients were followed longitudinally to map patterns of clinical disease progression. RESULTS: Cortical dysfunction was evident over both motor cortices, with hyperexcitability more prominent over the dominant motor cortex, contralateral to the site of disease onset, with reduction of resting motor threshold (F = 3.83, P < 0.05), short-interval intracortical inhibition (F = 15.0, P < 0.0001) and cortical silent-period duration (F = 8.01, P < 0.01), along with an increase in motor evoked potential amplitude (F = 5.66, P < 0.01). In addition, patterns of cortical change were consistent with a contiguous pattern of disease progression. CONCLUSIONS: Cortical hyperexcitability appears to be more prominent over the dominant motor cortex, contralateral to the side of symptom onset, and contributes to a contiguous pattern of spread in sporadic ALS.

Brain functional connectome abnormalities in amyotrophic lateral sclerosis are associated with disability and cortical hyperexcitability.

BACKGROUND AND PURPOSE: The present study utilized a multimodal approach encompassing connectome networks combined with brain volume analysis, and assessment of cortical excitability to provide novel insights into amyotrophic lateral sclerosis (ALS) pathogenesis. METHODS: Magnetic resonance images were acquired using a 3.0-Tesla Signa HDx scanner (GE Healthcare, Milwaukee, WI, USA), using an eight-channel head coil. Magnetic resonance images for the resting-state scan were acquired using an echo-planar imaging magnetic resonance sequence, acquiring 40 contiguous axial/oblique slices. Structural magnetic resonance imaging three-dimensional T1-weighted images were acquired in the sagittal plane using three-dimensional spoiled gradient echo sequences. For structural imaging, a T1-weighted high-resolution (3.0-Tesla) magnetic resonance imaging scan was used. Cortical excitability was assessed by using the threshold-tracking transcranial magnetic stimulation paradigm. Network-based statistics and whole-brain functional topology (using graph theoretical approaches) assessed functional connectivity. RESULTS: Using a global network-based statistical analysis approach, functional connectivity was increased in 12 network edges connecting 14 nodes (P < 0.05) within the frontal, temporal, parietal and subcortical regions. Analysis of local connectedness disclosed dichotomous effects with reduced connectivity in frontal regions and increased connectivity in occipital regions in ALS. Cortical hyperexcitability was evident in patients with ALS, negatively correlated with functional connectivity changes in the pre-central gyrus (P < 0.01). Connectivity changes in the frontal regions were negatively associated with functional disability (P < 0.05). CONCLUSIONS: Multimodal assessment of cortical function in patients with ALS identified deficits in functional connectivity associated with cortical hyperexcitability that correlated with patient disability. Novel integration of functional brain assessment further contributes to the understanding of disease pathogenesis in ALS.

Cortical excitability changes distinguish the motor neuron disease phenotypes from hereditary spastic paraplegia.

BACKGROUND AND PURPOSE: Cortical hyperexcitability has been identified as an important pathogenic mechanism in motor neuron disease (MND). The issue as to whether cortical hyperexcitability is a common process across the MND phenotypes, including amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS), remains unresolved. Separately, the clinical distinction between PLS and 'mimic disorders' such as hereditary spastic paraparesis (HSP) may be difficult, potentially delaying diagnosis. Consequently, the aim of the present study was to determine the nature and spectrum of cortical excitability changes across the MND phenotypes, and to determine whether the presence of cortical dysfunction distinguishes PLS from HSP. METHODS: Cortical excitability studies were undertaken on a cohort of 14 PLS, 82 ALS and 13 HSP patients with mutations in the spastin gene. RESULTS: Cortical hyperexcitability, as heralded by reduction of short interval intracortical inhibition (PLS 0.26%, -3.8% to 1.4%; ALS -0.15%, -3.6% to 7.0%; P < 0.01) and cortical silent period duration (CSPPLS 172.2 ± 5.4 ms; CSPALS 178.1 ± 5.1 ms; P < 0.001), along with an increase in intracortical facilitation was evident in ALS and PLS phenotypes, although appeared more frequently in ALS. Inexcitability of the motor cortex was more frequent in PLS (PLS 71%, ALS 24%, P < 0.0001). Cortical excitability was preserved in HSP. CONCLUSIONS: Cortical dysfunction appears to be an intrinsic process across the MND phenotypes, with cortical inexcitability predominating in PLS and cortical hyperexcitability predominating in ALS. Importantly, cortical excitability was preserved in HSP, thereby suggesting that the presence of cortical dysfunction could help differentiate PLS from HSP in a clinical setting.

Low-dose short-term hepatitis B immunoglobulin with high genetic barrier antivirals: the ideal post-transplant hepatitis B virus prophylaxis?

BACKGROUND: Low-dose hepatitis B immunoglobulin (HBIG) and nucleos(t)ides analogs (lamivudine/adefovir) used for the prevention of hepatitis B virus (HBV) recurrence after liver transplantation (LT) are associated with some risk of HBV recurrence and antiviral resistance. METHODS: The study cohort included 176 patients (at least >12 months follow-up) with HBV cirrhosis/hepatocellular carcinoma who received secondary prophylaxis with indefinite entecavir/tenofovir after living-donor LT (LDLT). All patients received 10,000 IU intravenous HBIG in anhepatic phase followed by 600-1000 IU intramuscularly daily for 7 days, weekly for 3 weeks, and then monthly, to keep antiHBs levels >100 mIU/mL for 1 year. Hepatitis B surface antigen (HBsAg) and HBV DNA were tested every 6 months. RESULTS: The study cohort is composed of 157 men and 19 women, mean age 47.9 ± 10.1 years, all HBsAg positive, 35 (19.8%) had HBV DNA >2000 IU/mL before LT. After LT, patients received entecavir (n = 126, 71.5%), tenofovir (n = 20, 11.3%), or a combination of entecavir and tenofovir (n = 30, 17% for 3 months), followed by entecavir alone. During follow-up of 43 (12-117) months, 2 patients (including 1 with non-compliance) had HBV recurrence. CONCLUSION: In a large cohort of LDLT recipients for HBV-related liver disease, use of low-dose short-term HBIG with high genetic barrier drugs results in a substantially lower incidence of HBV recurrence, even in high-risk patients.

Clinical risk factors for ovarian torsion.

Ovarian torsion is a relatively common gynaecological emergency, usually presenting as acute lower abdominal pain. The underlying pathophysiology involves torsion of the ovarian tissue on its pedicle leading to reduced venous return, stromal oedema, internal haemorrhage and infarction with the subsequent sequelae. It is not clear from looking at the literature which factors are responsible for the development of ovarian torsion and what are the odds of a particular clinical feature in determining the likelihood of developing ovarian torsion. In order to assess the likelihood of a particular clinical feature to be a risk factor for ovarian torsion, we studied the prevalence of each presenting clinical feature in the background population of women, for instance, looking at ovarian cysts and compared this with the odds of the feature occurring in the affected population of torsion patients. Thus we compared the odds of various clinical variables in ovarian torsion patients against the odds of the same feature occurring in the background population of women. Ovarian cysts are three times more common in ovarian torsion cohorts than in the general population. Evidence suggests that ovarian cysts are very common in the asymptomatic pregnant cohorts; however, they spontaneously resolve as the pregnancy progresses. Pregnancy is a risk factor for torsion (odds ratio: 18:1); however, it remains an uncommon event (0.167%). Tubal sterilisation practices vary according to geographical location and over chronology of the published literature. After considering the extremes of variation in tubal sterilisation practices, the risk of torsion increases by at least 8-fold following surgery. Hysterectomy with ovarian conservation is not a risk factor of torsion.

Diagnostic utility of cortical excitability studies in amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: The diagnosis of amyotrophic lateral sclerosis (ALS) relies on identification of a combination of upper and lower motor neuron signs. In order to improve the diagnostic sensitivity for ALS, Awaji criteria were developed, in part to better incorporate neurophysiological measures, although assessment of upper motor neuron dysfunction remained clinically based. Given that cortical hyperexcitability appears to be an early feature in ALS, the present study assessed the diagnostic utility of a threshold tracking transcranial magnetic stimulation technique as an aid to the research-based Awaji criteria in establishing an earlier diagnosis of ALS. METHODS: Prospective studies were undertaken on a cohort of 82 patients with suspected ALS and results were compared with 34 healthy controls. RESULTS: Short-interval intracortical inhibition (SICI) was significantly reduced in ALS patients (P < 0.0001), with a comparable reduction evident in the Awaji groups (SICIAWAJI POSSIBLE 1.3% ± 1.3%; SICIAWAJI PROBABLE/DEFINITE 1.4% ±1.7%). Central motor conduction time was significantly prolonged (P < 0.001), whereas the motor evoked potential amplitude (P < 0.05) and intracortical facilitation (P < 0.05) were increased. The frequency of transcranial magnetic stimulation abnormalities was similar across Awaji subgroups, and addition of transcranial magnetic stimulation abnormalities as a diagnostic category enabled reclassification of 88% of Awaji possible patients to Awaji probable/definite. CONCLUSIONS: Cortical excitability studies potentially facilitate an earlier diagnosis of ALS when combined with clinical and conventional neurophysiological findings, albeit in a research setting.

Tracking hybrid viability across life stages in a natural avian contact zone.

Hybrid inviability is an important post-zygotic reproductive barrier between species, but emerging signs of reduced viability can be difficult to study across the lifespan of natural hybrids. We use a combination of long-term monitoring, extra-pair paternity, and mitochondrial DNA identification in a natural hybrid zone of Ficedula flycatchers to detect emerging signs of intrinsic hybrid inviability across their entire lifespan. We evaluate possible evidence of Darwin's corollary to Haldane's rule, predicting asymmetries in inviability between hybrids resulting from reciprocal crosses, due to incompatible genetic factors with sex-specific inheritance patterns. We found higher hatching failure among mixed-species pairs, possibly indicating early developmental impairments associated with specific parental genetic combinations. Adult hybrids had a higher basal mortality rate than both parental species and different age-specific mortality trajectories. There were signs of differences in age-independent mortality rates between the reciprocal hybrid crosses: hybrids with a pied flycatcher mother experienced slightly increased mortality later in life. Using an exceptional dataset with many natural hybrids tracked across life stages, we provide evidence for several emerging signs of reduced hybrid viability. Incompatibilities between alleles located on autosomes and uniparentally inherited factors such as Z-linked and/or mitochondrial genes are strong candidates underlying intrinsic hybrid dysfunction in this system.

Automated Analysis of Nuclear Parameters in Oral Exfoliative Cytology Using Machine Learning.

BACKGROUND: As oral cancer remains a major worldwide health concern, sophisticated diagnostic tools are needed to aid in early diagnosis. Non-invasive methods like exfoliative cytology, albeit with the help of artificial intelligence (AI), have drawn additional interest. AIM: The study aimed to harness the power of machine learning algorithms for the automated analysis of nuclear parameters in oral exfoliative cytology. Further, the analysis of two different AI systems, namely convoluted neural networks (CNN) and support vector machine (SVM), were compared for accuracy. METHODS: A comparative diagnostic study was performed in two groups of patients (n=60). The control group without evidence of lesions (n=30) and the other group with clinically suspicious oral malignancy (n=30) were evaluated. All patients underwent cytological smears using an exfoliative cytology brush, followed by routine Hematoxylin and Eosin staining. Image preprocessing, data splitting, machine learning, model development, feature extraction, and model evaluation were done. An independent t-test was run on each nuclear characteristic, and Pearson's correlation coefficient test was performed with Statistical Package for the Social Sciences (SPSS) software (IBM SPSS Statistics for Windows, Version 28.0. IBM Corp, Armonk, NY, USA). RESULTS:  The study found substantial variations between the study and control groups in nuclear size (p<0.05), nuclear shape (p<0.01), and chromatin distribution (p<0.001). The Pearson correlation coefficient of SVM was 0.6472, and CNN was 0.7790, showing that SVM had more accuracy. CONCLUSION: The availability of multidimensional datasets, combined with breakthroughs in high-performance computers and new deep-learning architectures, has resulted in an explosion of AI use in numerous areas of oncology research. The discerned diagnostic accuracy exhibited by the SVM and CNN models suggests prospective improvements in early detection rates, potentially improving patient outcomes and enhancing healthcare practices.

17-Beta-Hydroxysteroid Dehydrogenase 13 Loss of Function Does Not Confer Protection to Nonalcoholic Fatty Liver Disease in Indian Population.

Background: A splice variant in HSD17B13 gene is demonstrated to protect against nonalcoholic fatty liver disease (NAFLD), and mitigate the effect of Patatin-like phospholipase domain-containing 3 (PNPLA3-I148M). It is being explored as a putative drug target and in polygenic risk scores. Based on whole exome sequencing (WES) in our cohort of biopsy proven NAFLD and limited data on the variant in our ethnicity, we sought to explore its role. Methods: This is a cross-sectional study that recruited 1,020 individuals with ultrasound/biopsy-confirmed NAFLD and matched controls. Liver enzymes and lipid profiles were estimated (Beckman coulter LX750/DXH800); WES was performed in NAFLD patients and controls (Illumina; HiSeqX); HSD17B13-A-INS/I148M-PNPLA3 variants were genotyped (sequencing/qR T-PCR); HSD17B13 protein expression was estimated (immunohistochemistry); the Student's t-test/Mann-Whitney U/Chi-square test and odds ratio (95% confidence interval) were used. Results: There was no significant difference (Odds ratio = 0.76; 95% CI -0.57 to 1.03; P = 0.76) in the frequency of the rs72613567-A-INS between controls and patients (17.8% vs. 14.4%). No difference in the ALT (Alanine transaminase; 72.24 ± 65.13 vs. 73.70 ± 60.06; P = 0.51) and AST levels (Aspartate aminotransferase; 60.72 ± 55.59 vs. 61.63 ± 60.33; P = 0.91) between HSD17B13-wild and variant carriers were noted. Significantly elevated liver enzymes were seen in PNPLA3-148-variant/HSD17B13-wild compared with PNPLA3-148-variant/HSD17B13-variant (90.44 ± 59.0 vs. 112.32 ± 61.78; P = 0.02). No difference in steatosis (P = 0.51) between HSD17B13-wild and variant carriers was noted. No other variants in the intron-exon boundaries were identified. Although, protein expression differences were noted between wild and variant carriers, no difference in the extent of steatosis was seen. Conclusion: Our study reports lack of association of the splice variant with reduced risk of NAFLD, and mitigating the effect of PNPLA3 variant. Ethnicity-based validation must be carried out before including it in assessing protection against NAFLD.

Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function.

Positional cloning of hereditary deafness genes is a direct approach to identify molecules and mechanisms underlying auditory function. Here we report a locus for dominant deafness, DFNA36, which maps to human chromosome 9q13-21 in a region overlapping the DFNB7/B11 locus for recessive deafness. We identified eight mutations in a new gene, transmembrane cochlear-expressed gene 1 (TMC1), in a DFNA36 family and eleven DFNB7/B11 families. We detected a 1.6-kb genomic deletion encompassing exon 14 of Tmc1 in the recessive deafness (dn) mouse mutant, which lacks auditory responses and has hair-cell degeneration. TMC1 and TMC2 on chromosome 20p13 are members of a gene family predicted to encode transmembrane proteins. Tmc1 mRNA is expressed in hair cells of the postnatal mouse cochlea and vestibular end organs and is required for normal function of cochlear hair cells.

Recent Advances in Surface Plasmon Resonance (SPR) Technology for Detecting Ovarian Cancer Biomarkers.

Epithelial Ovarian Cancer (EOC) is a leading cause of cancer-related deaths among women, mainly due to a lack of early detection and screening methods. Advanced immunoassay techniques, such as Luminex and proximity extension assay (PEA) technology, show promise in improving EOC detection by utilizing highly sensitive and specific multiplex panels to detect multiple combinations of biomarkers. However, these advanced immunoassay techniques have certain limitations, especially in validating the performance characteristics such as specificity, sensitivity, limit of detection (LOD), and dynamic range for each EOC biomarker within the panel. Implementing multiplexing in point-of-care (POC) biosensors can enhance EOC biomarker detection, with Surface Plasmon Resonance (SPR) being a versatile option among optical biosensors. There is no study on multiplex SPR biosensors specifically tailored for diagnosing EOC. Recent studies have shown promising results in the single detection of EOC biomarkers using SPR, with LOD for cancer antigen 125 (CA125) at 0.01 U/mL-1 and human epididymis protein 4 (HE4) at 1pM. This study proposes a potential roadmap for scientists and engineers in academia and industry to develop a cost effective yet highly efficient SPR biosensor platform for detecting EOC.

Geriatric Services Hub - A Collaborative Frailty Management Model between The Hospital and Community Providers.

BACKGROUND: Frailty is an important geriatric syndrome especially with ageing populations. Frailty can be managed or even reversed with community-based interventions delivered by a multi-disciplinary team. Innovation is required to find community frailty models that can deliver cost-effective and feasible care to each local context. OBJECTIVES: We share pilot data from our Geriatric Service Hub (GSH) which is a novel frailty care model in Singapore that identifies and manages frailty in the community, supported by a hospital-based multi-disciplinary team. METHODS: We describe in detail our GSH model and its implementation. We performed a retrospective data analysis on patient characteristics, uptake, prevalence of frailty and sarcopenia and referral rates for multi-component interventions. RESULTS: A total of 152 persons attended between January 2020 to May 2021. Majority (59.9%) were female and mean age was 81.0 ± 7.1 years old. One-fifth (21.1%) of persons live alone. Mean Charlson Co-morbidity Index was 5.2 ± 1.8. Based on the clinical frailty risk scale (CFS), 31.6% were vulnerable, 51.3% were mildly frail and 12.5% were moderately frail. Based on SARC-F screening, 45.3% were identified to be sarcopenic whilst 56.9% had a high concern about falling using the Falls-Efficacy Scale-International. BMD scans were done for 41.4% of participants, of which 58.7% were started on osteoporosis treatment. In terms of referrals to allied health professionals, 87.5% were referred for physiotherapy, 71.1% for occupational therapy and 50.7% to dieticians. CONCLUSION: The GSH programme demonstrates a new local model of partnering with community service providers to bring comprehensive population level frailty screening and interventions to pre-frail and frail older adults. Our study found high rates of frailty, sarcopenia and fear of falling in community-dwelling older adults who were not presently known to geriatric care services.

Geometrical Characterisation of TiO2-rGO Field-Effect Transistor as a Platform for Biosensing Applications.

The performance of the graphene-based field-effect transistor (FET) as a biosensor is based on the output drain current (Id). In this work, the signal-to-noise ratio (SNR) was investigated to obtain a high-performance device that produces a higher Id value. Using the finite element method, a novel top-gate FET was developed in a three-dimensional (3D) simulation model with the titanium dioxide-reduced graphene oxide (TiO2-rGO) nanocomposite as the transducer material, which acts as a platform for biosensing application. Using the Taguchi mixed-level method in Minitab software (Version 16.1.1), eighteen 3D models were designed based on an orthogonal array L18 (6134), with five factors, and three and six levels. The parameters considered were the channel length, electrode length, electrode width, electrode thickness and electrode type. The device was fabricated using the conventional photolithography patterning technique and the metal lift-off method. The material was synthesised using the modified sol-gel method and spin-coated on top of the device. According to the results of the ANOVA, the channel length contributed the most, with 63.11%, indicating that it was the most significant factor in producing a higher Id value. The optimum condition for the highest Id value was at a channel length of 3 µm and an electrode size of 3 µm × 20 µm, with a thickness of 50 nm for the Ag electrode. The electrical measurement in both the simulation and experiment under optimal conditions showed a similar trend, and the difference between the curves was calculated to be 28.7%. Raman analyses were performed to validate the quality of TiO2-rGO.