Glutathione peroxidase (GPX1) - Selenocysteine metabolism preserves the follicular fluid's (FF) redox homeostasis via IGF-1- NMD cascade in follicular ovarian cysts (FOCs).

Follicular ovarian cysts (FOCs) are characterized by follicles in the ovaries that are >20 mm in diameter and persist for >10 days without the corpus luteum, leading to anovulation, dysregulation of folliculogenesis and subfertility in humans and livestock species. Despite their clinical significance, the precise impact of FOCs on oocyte reserve, maturation, and quality still needs to be explored. While FOCs are observed in both human and livestock populations, they are notably prevalent in livestock species. Consequently, livestock species serve as valuable models for investigating the molecular intricacies of FOCs. Thus, in this study, using goat FOCs, we performed integrated proteomic, metabolomic and functional analyses to demonstrate that oocyte maturation is hampered due to increased reactive oxygen species (ROS) in FOCs follicular fluid (FF) via downregulation of glutathione peroxidase (GPX1), a critical antioxidant seleno enzyme required to negate oxidative stress. Notably, GPX1 reduction was positively correlated with the FF's decline of free selenium and selenocysteine metabolic enzymes, O-phosphoryl-tRNA (Sec) selenium transferase (SEPSECS) and selenocysteine lyase (SCLY) levels. Adding GPX1, selenocysteine, or selenium to the culture media rescued the oocyte maturation abnormalities caused by FOCs FF by down-regulating the ROS. Additionally, we demonstrate that substituting GPX1 regulator, Insulin-like growth factor-I (IGF-1) in the in vitro maturation media improved the oocyte maturation in the cystic FF by down-regulating the ROS activity via suppressing Non-sense-mediated decay (NMD) of GPX1. In contrast, inhibition of IGF-1R and the target of rapamycin complex 1 (mTORC1) hampered the oocyte maturation via NMD up-regulation. These findings imply that the GPX1 regulation via selenocysteine metabolism and the IGF-1-mediated NMD may be critical for the redox homeostasis of FF. We propose that GPX1 enhancers hold promise as therapeutics for enhancing the competence of FOCs oocytes. However, further in vivo studies are necessary to validate these findings observed in vitro.

Evaluating the Quality of Life of Beneficiaries After Providing Financial Aid by a Multi-specialty Tertiary Care Hospital.

Background Financial aid programs offered by multi-specialty tertiary care hospitals play a crucial role in ensuring equitable access to healthcare. This study investigates the effect of financial aid on the quality of life (QoL) of beneficiaries, aiming to provide a comprehensive understanding of the multifaceted relationship between healthcare support and overall well-being. Aim The study's objectives included assessing changes in pre- and post-aid QoL, identifying influencing factors, understanding beneficiary experiences, and evaluating the effectiveness of financial aid programs. Methods The study adopted quantitative assessments through QoL questionnaires developed based on the WHO BREF questionnaire and insights obtained through interviews. A representative sample of beneficiaries was selected, informed consent was obtained, and an institutional ethical certificate was also obtained. Results The findings overwhelmingly support the alternative hypothesis. The alternative hypothesis was that after receiving financial support, recipients' quality of life would increase. Quantitative analysis revealed a statistically significant enhancement in the QoL of beneficiaries across physical, mental, and social well-being domains. The quality of life scores of patients before and after receiving the support was statistically tested using a paired t-test, and the quality of life score has improved significantly with a p-value of 4.156 × 10-28 (p value<0.001). The comparison of quality of life scores of the control group with the patient's group before getting the support was tested using an independent sample t-test and found to be non-significant (p=0.496), while a similar comparison between the control group and the patient's group after receiving the support was found to be statistically highly significant with a p-value of 8.721 × 10-28 (p-value<0.001). Conclusions This research demonstrates the substantial impact of financial aid on the QoL of beneficiaries in a multi-specialty tertiary care hospital setting. It underlines the importance of addressing economic barriers and providing patient-centered, holistic support. These insights have broader implications for healthcare policy and practice, promoting a more comprehensive approach to patient well-being.

Population assessment of the Endangered Kashmir Gray Langur (Semnopithecus ajax, Pocock 1928) using the double-observer method.

Primates are among the most threatened taxa globally, therefore, there is a need to estimate and monitor their populations. Kashmir Gray Langur Semnopithecus ajax is an endangered species for which there is no population estimate. We used double-observer method to estimate its population size in the Kashmir region of North-Western Himalaya. We walked 1284 km across 31 survey blocks spanning all three divisions of Kashmir viz., North, Central, and South Kashmir, covering an area of 411 km2. We counted a minimum of 1367 individual langurs from 27 groups. The detection probability for observer 1 (0.719) and observer 2 (0.656) resulted in a population estimate of 1496 (95% confidence interval [CI] 1367-1899) across 30 groups (with a mean group size of 51), giving a density estimate of 3.64 (3.33-4.62) langurs/km². We found double-observer surveys to be suitable for the population estimation of langurs, and we make recommendations on how to effectively conduct primate surveys, especially in mountainous ecosystems. Our records extend the species distribution range beyond stated by the International Union for Conservation of Nature. Our findings also highlight that the Kashmir Himalaya is a stronghold of the species, where conservation efforts should focus.

Impact of mobile phone usage on dynamic postural control among South Indian college students.

BACKGROUND: Smartphones are a technical marvel that rapidly evolved to play an important role in our lives. One downside to smartphone use is that it significantly worsens posture. It is believed that using a smartphone while walking increases the risk of cognitive decline and the loss of dynamic balance needed to perform functional tasks. OBJECTIVE: The objective of the study was to determine the impact of smartphone usage on dynamic postural control among South Indian college students. METHODS: The study was carried out in a private college with 400 invited students through online social media platforms. The four-square step test and SAS-SV were used to determine the impact of smartphone usage on dynamic postural control. The students were informed about the study process. A total of 250 participants were included based on the inclusion criteria. RESULTS: There was a high percentage of agreement on smartphone usage on dynamic postural control measured with SAS-SV, revealing statistical significance with a mean value of 41.532 and SD of 10.010886. The four-square step test with a mean value of 22.5 and SD of 1.8995878 also proved significant impact. A positive correlation was found between smartphone usage and dynamic postural control, which was analysed using Pearson's correlation coefficient of 0.90130. CONCLUSION: A significant correlation was noted between mobile usage and dynamic balance. Smartphones can have a negative impact on dynamic balance by distracting users from their surroundings and increase the risk of falls.

Patient decision aids in mainstreaming genetic testing for women with ovarian cancer: A prospective cohort study.

OBJECTIVE: To evaluate patient preference for short (gist) or detailed/extensive decision aids (DA) for genetic testing at ovarian cancer (OC) diagnosis. DESIGN: Cohort study set within recruitment to the Systematic Genetic Testing for Personalised Ovarian Cancer Therapy (SIGNPOST) study (ISRCTN: 16988857). SETTING: North-East London Cancer Network (NELCN) population. POPULATION/SAMPLE: Women with high-grade non-mucinous epithelial OC. METHODS: A more detailed DA was developed using patient and stakeholder input following the principles/methodology of IPDAS (International Patients Decision Aids Standards). Unselected patients attending oncology clinics evaluated both a pre-existing short and a new long DA version and then underwent mainstreaming genetic testing by a cancer clinician. Appropriate inferential descriptive and regression analyses were undertaken. MAIN OUTCOME MEASURES: Satisfaction, readability, understanding, emotional well-being and preference for long/short DA. RESULTS: The mean age of patients was 66 years (interquartile range 11), and 85% were White British ethnicity. Of the participants, 74% found DAs helpful/useful in decision-making. Women reported higher levels of satisfaction (86% versus 58%, p < 0.001), right amount of information provided (76.79% versus49.12%, p < 0.001) and improved understanding (p < 0.001) with the long DA compared with the short DA. There was no statistically significant difference in emotional outcomes (feeling worried/concerned/reassured/upset) between 'short' and 'long' DA; 74% of patients preferred the long DA and 24% the short DA. Patients undergoing treatment (correlation coefficient (coef) = 0.603; 95% CI 0.165-1.041, p = 0.007), those with recurrence (coef = 0.493; 95% CI 0.065-0.92, p = 0.024) and older women (coef = 0.042; 95% CI 0.017-0.066, p = 0.001) preferred the short DA. Ethnicity did not affect outcomes or overall preference for long/short DA. CONCLUSIONS: A longer DA in OC patients has higher satisfaction without increasing emotional distress. Older women and those undergoing treatment/recurrence prefer less extensive information, whereas those in remission preferred a longer DA.

Börjeson-Forssman-Lehmann syndrome: delineating the clinical and allelic spectrum in 14 new families.

Börjeson-Forssman-Lehmann syndrome (BFLS) is an X-linked intellectual disability syndrome caused by variants in the PHF6 gene. We ascertained 19 individuals from 15 families with likely pathogenic or pathogenic PHF6 variants (11 males and 8 females). One family had previously been reported. Six variants were novel. We analysed the clinical and genetic findings in our series and compared them with reported BFLS patients. Affected males had classic features of BFLS including intellectual disability, distinctive facies, large ears, gynaecomastia, hypogonadism and truncal obesity. Carrier female relatives of affected males were unaffected or had only mild symptoms. The phenotype of affected females with de novo variants overlapped with the males but included linear skin hyperpigmentation and a higher frequency of dental, retinal and cortical brain anomalies. Complications observed in our series included keloid scarring, digital fibromas, absent vaginal orifice, neuropathy, umbilical hernias, and talipes. Our analysis highlighted sex-specific differences in PHF6 variant types and locations. Affected males often have missense variants or small in-frame deletions while affected females tend to have truncating variants or large deletions/duplications. Missense variants were found in a minority of affected females and clustered in the highly constrained PHD2 domain of PHF6. We propose recommendations for the evaluation and management of BFLS patients. These results further delineate and extend the genetic and phenotypic spectrum of BFLS.

Winter foraging ecology of stump-tailed macaques Macaca arctoides in the Hollongapar Gibbon Sanctuary, Assam, India.

Frugivorous primates in temperate and subtropical regions often experience a shortage or complete absence of fruits for several months of the year. We studied the foraging ecology of a group of stump-tailed macaques Macaca arctoides in a subtropical forest during winter, when fruit abundance was low. We conducted this study in the Hollongapar Gibbon Sanctuary, Assam, India, from December 2015 to April 2016. We estimated the time-activity budgets, diet, and habitat use of the study troop and also conducted vegetation sampling and phenological monitoring of the study area. The stump-tailed macaque troop spent about 73.2% of its time foraging and feeding, with seasonal differences in food species intake and in habitat use. Open degraded forests were primarily used in December, January, and February, when the macaques largely fed on shoots of the bamboo Schizostachyum polymorphum and roots of the herb Forrestia (= Amischotolype) mollissima, while they mostly utilised F. mollissima in canopy-covered, degraded forests in March and April. There was a major shift from a primary diet of fruits in the wet season, reported from earlier studies, to possibly relatively poorquality, but abundant, shoots and roots in winter. This suggests that the consumption of these poor-quality fallback food species is a key dietary adaptation of the macaques to periods of fruit scarcity. Although our preliminary study suggests that the feeding behaviour of the stump-tailed macaque in its subtropical semievergreen forest habitat appears to be similar to that of its congeneric species in temperate forests, further investigations are needed to firmly establish the observed foraging patterns of this vulnerable cercopithecine species in its last lowland rainforest refuge in northeastern India.

Probing excited state 1Hα chemical shifts in intrinsically disordered proteins with a triple resonance-based CEST experiment: Application to a disorder-to-order switch.

Over 40% of eukaryotic proteomes and 15% of bacterial proteomes are predicted to be intrinsically disordered based on their amino acid sequence. Intrinsically disordered proteins (IDPs) exist as heterogeneous ensembles of interconverting conformations and pose a challenge to the structure-function paradigm by apparently functioning without possessing stable structural elements. IDPs play a prominent role in biological processes involving extensive intermolecular interaction networks and their inherently dynamic nature facilitates their promiscuous interaction with multiple structurally diverse partner molecules. NMR spectroscopy has made pivotal contributions to our understanding of IDPs because of its unique ability to characterize heterogeneity at atomic resolution. NMR methods such as Chemical Exchange Saturation Transfer (CEST) and relaxation dispersion have enabled the detection of 'invisible' excited states in biomolecules which are transiently and sparsely populated, yet central for function. Here, we develop a 1Hα CEST pulse sequence which overcomes the resonance overlap problem in the 1Hα-13Cα plane of IDPs by taking advantage of the superior resolution in the 1H-15N correlation spectrum. In this sequence, magnetization is transferred after 1H CEST using a triple resonance coherence transfer pathway from 1Hα (i) to 1HN(i + 1) during which the 15N(t1) and 1HN(t2) are frequency labelled. This approach is integrated with spin state-selective CEST for eliminating spurious dips in CEST profiles resulting from dipolar cross-relaxation. We apply this sequence to determine the excited state 1Hα chemical shifts of the intrinsically disordered DNA binding domain (CytRN) of the bacterial cytidine repressor (CytR), which transiently acquires a functional globally folded conformation. The structure of the excited state, calculated using 1Hα chemical shifts in conjunction with other excited state NMR restraints, is a three-helix bundle incorporating a helix-turn-helix motif that is vital for binding DNA.

Characterization of immune responses to two and three doses of the adenoviral vectored vaccine ChAdOx1 nCov-19 and the whole virion inactivated vaccine BBV152 in a mix-and-match study in India.

Infections with SARS-CoV-2 variants and declining immunity after primary vaccination, encouraged the use of booster doses. Some countries changed their immunization programmes to boost with vaccines different from the ones in their original schedule, based on results from immunogenicity and effectiveness studies. This study reports immunological analysis of samples collected in a phase 4 randomized trial, where participants who had previously received two primary doses of ChAdOx1 nCov-19 (ChAd) or inactivated BBV152 vaccine were randomized to receive either ChAd or BBV152 booster and further categorized as: Group 1 (two primary doses of ChAd - ChAd booster), Group 2 (two primary doses of ChAd - BBV152 booster), Group 3 (two primary doses of BBV152 - ChAd booster), and Group 4 (two primary doses of BBV152 - BBV152 booster). SARS-CoV-2 specific cellular and humoral responses at day 0 (pre-boost samples 12-36 weeks after the second primary dose), and at day 28 post booster, were measured in a subset of participants (ChAd recipients, n = 37 and BBV152 recipients, n = 36). Additionally, on day180 post-booster humoral responses were assessed for the entire cohort (N = 378). Primary vaccination with 2 doses of BBV152 generated higher memory-B cells (median% 0.41 vs 0.35) and cytokine producing CD8-Tcells (median% 0.09 vs 0.04) while lower anti-spike IgG levels (medianAU/ml: 12,433 vs 27,074) as compared to ChAd. Irrespective of the primary vaccine received, ChAd boosted individuals generated higher memory-B cell frequencies and anti-spike IgG levels as compared to BBV152 booster. The percentage ACE-2 inhibition against Omicron and its sub-variants was higher in Group 3 (median > 60 %) as compared to other groups (median < 25 %). At day180 post booster the hierarchy of the antibody amounts was Group 1 âˆ¼ Group 2 âˆ¼ Group 3 > Group 4. Sustained humoral and robust cellular immune response to SARS-CoV-2 can be obtained with ChAd booster irrespective of the primary vaccination regimen. The trial is registered with ISRTCN (CTRI/2021/08/035648).

Range restricted old and young lineages show the southern Western Ghats to be both a museum and a cradle of diversity for woody plants.

The Western Ghats (WG) mountain chain is a global biodiversity hotspot with high diversity and endemicity of woody plants. The latitudinal breadth of the WG offers an opportunity to determine the evolutionary drivers of latitudinal diversity patterns. We examined the spatial patterns of evolutionary diversity using complementary phylogenetic diversity and endemism measures. To examine if different regions of the WG serve as a museum or cradle of evolutionary diversity, we examined the distribution of 470 species based on distribution modelling and occurrence locations across the entire region. In accordance with the expectation, we found that the southern WG is both a museum and cradle of woody plant evolutionary diversity, as a higher proportion of both old and young evolutionary lineages are restricted to the southern WG. The diversity gradient is likely driven by high geo-climatic stability in the south and phylogenetic niche conservatism for moist and aseasonal sites. This is corroborated by persistent lineage nestedness at almost all evolutionary depths (10-135 million years), and a strong correlation of evolutionary diversity with drought seasonality, precipitation and topographic heterogeneity. Our results highlight the global value of the WG, demonstrating, in particular, the importance of protecting the southern WG-an engine of plant diversification and persistence.

Middle Ear Muscle Reflex in Normal-Hearing Individuals with Occupational Noise Exposure.

Objectives: Noise-induced cochlear synaptopathy is studied extensively in animal models. The diagnosis of synaptopathy in humans is challenging and the roles of many noninvasive measures in identifying synaptopathy are being explored. The acoustic middle ear muscle reflex (MEMR) can be considered as a vital tool since noise exposure affects the low-spontaneous rate fibers that play an important role in elicitation of MEMR. The present study aimed at measuring MEMR threshold and MEMR strength. Design: The study participants were divided into two groups. All the participants had normal-hearing thresholds. The control group consisted of 25 individuals with no occupational noise exposure whereas noise exposure group had 25 individuals who were exposed to occupational noise of 85 dBA for a minimum period of 1 year. MEMR threshold and strength was assessed for pure tones (500 Hz and 1000 Hz) and broadband noise. Results: The results showed that the MEMR threshold was similar in both the groups. MEMR strength was reduced in noise exposure group compared to control group. Conclusions: The results of the study suggest that MEMR strength could be used as a sensitive measure in identifying cochlear synaptopathy with careful consideration of the stimulus characteristics.

Personalized recurrence risk assessment following the birth of a child with a pathogenic de novo mutation.

Following the diagnosis of a paediatric disorder caused by an apparently de novo mutation, a recurrence risk of 1-2% is frequently quoted due to the possibility of parental germline mosaicism; but for any specific couple, this figure is usually incorrect. We present a systematic approach to providing individualized recurrence risk. By combining locus-specific sequencing of multiple tissues to detect occult mosaicism with long-read sequencing to determine the parent-of-origin of the mutation, we show that we can stratify the majority of couples into one of seven discrete categories associated with substantially different risks to future offspring. Among 58 families with a single affected offspring (representing 59 de novo mutations in 49 genes), the recurrence risk for 35 (59%) was decreased below 0.1%, but increased owing to parental mixed mosaicism for 5 (9%)-that could be quantified in semen for paternal cases (recurrence risks of 5.6-12.1%). Implementation of this strategy offers the prospect of driving a major transformation in the practice of genetic counselling.

The Experimental Infection of Goats with Small Ruminant Morbillivirus Originated from Barbary Sheep.

Peste des Petits Ruminants (PPR) is a transboundary contagious disease in domestic small ruminants. Infections with the small ruminant morbillivirus (SRMV) were regularly found in wildlife, with unknown roles in PPR epidemiology. In order to access infection dynamics and virulence, we infected German Edelziege goats intranasally with a SRMV isolate that originated from Barbary sheep from an outbreak in the United Arab Emirates. Six goats were infected with cell culture-isolated SRMV, and two goats were kept in contact. Goats were daily monitored, and clinical score was recorded. EDTA blood, nasal, conjunctival and rectal swab samples were collected for the detection of SRMV genome load and serum for serological analysis. Short incubation period in infected (4 to 5 dpi) as well as in contact goats (9 dpi) was followed by typical clinical signs related to PPR. The highest viral load was detectable in conjunctival and nasal swab samples with RT-qPCR and rapid pen-side test. Specific antibodies were detected at 7 dpi in infected and 14 dpi in contact goats. In general, high virulence and easy transmission of the virus originated from wildlife in domestic goats was observed. The virus isolate belongs to Asian lineage IV, genetically related to Chinese and Mongolian strains.

Expanding the phenotype of TAB2 variants and literature review.

TAB2 is a gene located on chromosome 6q25.1 and plays a key role in development of the heart. Existing literature describes congenital heart disease as a common recognized phenotype of TAB2 gene variants, with evidence of a distinct syndromic phenotype also existing beyond this. Here we describe 14 newly identified individuals with nine novel, pathogenic TAB2 variants. The majority of individuals were identified through the Deciphering Developmental Disorders study through trio whole exome sequencing. Eight individuals had de novo variants, the other six individuals were found to have maternally inherited, or likely maternally inherited, variants. Five individuals from the same family were identified following cardiac disease gene panel in the proband and subsequent targeted familial gene sequencing. The clinical features of this cohort were compared to the existing literature. Common clinical features include distinctive facial features, growth abnormalities, joint hypermobility, hypotonia, and developmental delay. Newly identified features included feeding difficulties, sleep problems, visual problems, genitourinary abnormality, and other anatomical variations. Here we report 14 new individuals, including novel TAB2 variants, in order to expand the emerging syndromic clinical phenotype and provide further genotype-phenotype correlation.

Mortality Prediction in the ICU: The Daunting Task of Predicting the Unpredictable.

How to cite this article: Kumar AAK. Mortality Prediction in the ICU: The Daunting Task of Predicting the Unpredictable. Indian J Crit Care Med 2022;26(1):13-14.

Effects of Spatial Training Paradigms on Auditory Spatial Refinement in Normal-Hearing Listeners: A Comparative Study.

BACKGROUND AND OBJECTIVES: This study compared the effectiveness of two spatial training programs using real and virtual sound sources in refining spatial acuity skills in listeners with normal hearing. SUBJECTS AND METHODS: The study was conducted on two groups of 10 participants each; groups I and II underwent spatial training using real and virtual sound sources, respectively. The study was conducted in three phases: pre-training, training, and post-training phases. At the pre- and post-training phases, the spatial acuity of the participants was measured using real sound sources through the localization test, and virtual sound sources through the virtual acoustic space identification (VASI) test. The thresholds of interaural time difference (ITD) and interaural level difference (ILD) were also measured. In the training phase, Group I participants underwent localization training using loudspeakers in free field, while participants in Group II were subjected to virtual acoustic space (VAS) training using virtual sound sources from headphones. Both the training methods consisted of 5-8 sessions (20 min each) of systematically presented stimuli graded according to duration and back attenuation (for real source training) or number of VAS locations (for virtual source training). RESULTS: Results of independent t-scores comparing the spatial learning scores (pre vs. post-training) for each measure showed differences in performance between the two groups. Group II performed better than Group I on the VASI test, while the Group I out-performed Group II on the ITD. Both groups improved equally on the localization test and ILD. CONCLUSIONS: Based on the present findings, we recommend the use of VAS training as it has practical implications due to its cost effectiveness, need for minimal equipment, and end user usefulness.

Quaternary ammonium substituted pullulan accelerates wound healing and disinfects Staphylococcus aureus infected wounds in mouse through an atypical 'non-pore forming' pathway of bacterial membrane disruption.

The emergence of multi-drug resistant pathogens has fueled the search for alternatives to the existing line of antibiotics that can eradicate pathogens without inducing resistance development. Here, we report the accelerated wound healing and disinfection potential of a non-amphiphilic quaternized fungal exopolysaccharide, pullulan, without resistance generation in pathogens. The quaternary ammonium substituted pullulan (CP) derivatives showed excellent bactericidal activity against both Gram negative (MBC90 = 1.5 µg mL-1) and Gram positive (MBC90 = 0.25 µg mL-1) bacteria at very low concentrations without showing any toxicity towards mammalian cells. A combined approach of atomistic molecular dynamics simulation and experimental assays revealed that CP exerts a membrane directed bactericidal action through an atypical "non-pore forming" pathway which is not yet established for any known antibacterial polysaccharides. This involves an increase in membrane roughness, disorder among anionic lipid tails, formation of localized anionic lipid clusters and membrane depolarization, finally leading to physical disruption of the membrane integrity. Moreover, CP also displayed biofilm eradication abilities and emerged as an excellent therapeutic material for disinfection and healing of infected wounds. The present work shows the potential of exploiting polysaccharides as next-generation broad-spectrum antimicrobials and provides a platform for further development of rationally designed pullulan-based functional materials for biomedical applications.

Implementation of Multigene Germline and Parallel Somatic Genetic Testing in Epithelial Ovarian Cancer: SIGNPOST Study.

We present findings of a cancer multidisciplinary-team (MDT) coordinated mainstreaming pathway of unselected 5-panel germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 and parallel somatic BRCA1/BRCA2 testing in all women with epithelial-OC and highlight the discordance between germline and somatic testing strategies across two cancer centres. Patients were counselled and consented by a cancer MDT member. The uptake of parallel multi-gene germline and somatic testing was 97.7%. Counselling by clinical-nurse-specialist more frequently needed >1 consultation (53.6% (30/56)) compared to a medical (15.0% (21/137)) or surgical oncologist (15.3% (17/110)) (p < 0.001). The median age was 54 (IQR = 51-62) years in germline pathogenic-variant (PV) versus 61 (IQR = 51-71) in BRCA wild-type (p = 0.001). There was no significant difference in distribution of PVs by ethnicity, stage, surgery timing or resection status. A total of 15.5% germline and 7.8% somatic BRCA1/BRCA2 PVs were identified. A total of 2.3% patients had RAD51C/RAD51D/BRIP1 PVs. A total of 11% germline PVs were large-genomic-rearrangements and missed by somatic testing. A total of 20% germline PVs are missed by somatic first BRCA-testing approach and 55.6% germline PVs missed by family history ascertainment. The somatic testing failure rate is higher (23%) for patients undergoing diagnostic biopsies. Our findings favour a prospective parallel somatic and germline panel testing approach as a clinically efficient strategy to maximise variant identification. UK Genomics test-directory criteria should be expanded to include a panel of OC genes.

Effect of Quiet and Noise on P300 Response in Individuals with Auditory Neuropathy Spectrum Disorder

Abstract Introduction Auditory neuropathy spectrum disorder (ANSD) is a clinical condition in which individuals have normal cochlear responses and abnormal neural responses. There is a lack of evidence in the literature regarding the neural discrimination skill in individuals with ANSD, especially when the signal is presented in the presence of noise. Objectives The present study was performed with the aim to investigate auditory discrimination skill, in quiet and in the presence of noise, in individuals with ANSD and to compare the findings with normal-hearing individuals. Methods A total of 30 individuals with normal hearing sensitivity and 30 individuals with ANSD in the age range of 15 to 55 years old, with the mean age of 27.86 years old, were the participants. P300 response was recorded from both groups using syllable pairs /ba/-/da/ in oddball paradigm and the syllable /da/ in repetitive paradigm in quiet and at +10 dB signal-to-noise ratio (SNR). Results There was significant prolongation in latency and reaction time, and reduction in amplitude of P300 response and sensitivity in both groups with the addition of noise. The topographic pattern analysis showed activation of the central-parietal-occipital region of the brain in individuals with ANSD, whereas activation of the central-parietal region was observed in individuals with normal hearing. The activation was more diffused in individuals with ANSD compared with that of individuals with normal hearing. Conclusion The individuals with ANSD showed a significantly more adverse effect of noise on the neural discrimination skill than the normal counterpart.

Effect of Quiet and Noise on P300 Response in Individuals with Auditory Neuropathy Spectrum Disorder.

Introduction Auditory neuropathy spectrum disorder (ANSD) is a clinical condition in which individuals have normal cochlear responses and abnormal neural responses. There is a lack of evidence in the literature regarding the neural discrimination skill in individuals with ANSD, especially when the signal is presented in the presence of noise. Objectives The present study was performed with the aim to investigate auditory discrimination skill, in quiet and in the presence of noise, in individuals with ANSD and to compare the findings with normal-hearing individuals. Methods A total of 30 individuals with normal hearing sensitivity and 30 individuals with ANSD in the age range of 15 to 55 years old, with the mean age of 27.86 years old, were the participants. P300 response was recorded from both groups using syllable pairs /ba/-/da/ in oddball paradigm and the syllable /da/ in repetitive paradigm in quiet and at +10 dB signal-to-noise ratio (SNR). Results There was significant prolongation in latency and reaction time, and reduction in amplitude of P300 response and sensitivity in both groups with the addition of noise. The topographic pattern analysis showed activation of the central-parietal-occipital region of the brain in individuals with ANSD, whereas activation of the central-parietal region was observed in individuals with normal hearing. The activation was more diffused in individuals with ANSD compared with that of individuals with normal hearing. Conclusion The individuals with ANSD showed a significantly more adverse effect of noise on the neural discrimination skill than the normal counterpart.