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Schizophrenia (SZ) detection enables effective treatment to improve the clinical outcome, but objective and reliable SZ diagnostics are still limited. An ideal diagnosis of SZ suited for robust clinical screening must address detection throughput, low invasiveness, and diagnosis accuracy. Herein, we built a multi-shelled hollow Cr 2 O 3 spheres (MHCSs) assisted laser desorption/ionization mass spectrometry (LDI MS) platform for the direct metabolic profiling of biofluids towards SZ diagnostics. The MHCSs displayed strong light absorption for enhanced ionization and microscale surface roughness with stability for the effective LDI of metabolites. We profiled urine and serum metabolites (~ 1 μL) with the enhanced LDI efficacy in seconds. We discriminated SZ patients (SZs) from healthy controls (HCs) with the highest area under the curve (AUC) value of 1.000 for the blind test. We identified four compounds with optimal diagnostic power as a simplified metabolite panel for SZ and demonstrated the metabolite quantification for clinic use. Our approach accelerates the growth of new platforms toward a precision diagnosis in the near future.

Introduction Infertility is mediated by several changes system‐wide. These changes are likely to cause other systems‐related pathologies, such as changes in systemic immune response, particularly inflammatory response can lead to cardiovascular diseases and breast cancer. Methods These morbidities can exist immediately or years after the diagnosis of infertility. Therefore, understanding the mechanism is important to move toward therapeutic interventions. Results Several extragonadal pathologies are reported due to infertility, as well as, how these might also contribute to reproductive disabilities. Detailed evidence are still not present that can give stronger result. Conclusion This review highlights some of the most frequent comorbidities that are seen in infertile women, hence requiring a need for complete clinical screening and care, as well as diagnosis and treatment in early stages., Several extragonadal pathologies are reported due to infertility, as well as how these might also contribute to reproductive disabilities. Women presenting subfertility or infertility need to be screened for abovementioned disorder. Adaptions in lifestyle might subsidize these effects.

OBJECTIVES The diagnosis of hematologic malignancies integrates multiple diagnostic and clinical disciplines. Historically, targeted (single-analyte) genetic testing has been used as reflex to initial prescreening by other diagnostic modalities including flow cytometry, anatomic pathology, and clinical cytogenetics. Given the wide range of mutations associated with hematologic malignancies a DNA/RNA-based NGS panel can provide a more effective and economical approach to comprehensive testing of patients as an initial, tier-1 screen. METHODS Using a cohort of 380 patients, we performed clinical validation of a gene panel designed to assess 40 genes (DNA), and 29 fusion driver genes with over 600 gene fusion partners (RNA), including sample exchange data across three clinical laboratories, and correlation with cytogenetic testing results. RESULTS The clinical validation of this technology demonstrated that its accuracy, sensitivity, and specificity are comparable to the majority of targeted single-gene approaches, while assessment of the initial patient cohort data demonstrated a high diagnostic yield of 50.5%. CONCLUSIONS Implementation of a tier-1 NGS-based protocol for gene panel screening provides a comprehensive alternative to targeted molecular testing in patients with suspected hematologic malignancies, with increased diagnostic yield, scalability, reproducibility, and cost effectiveness, making it ideally suited for implementation in clinical laboratories.

Objective To develop and conduct preliminary feasibility testing of a clinical screening instrument for early identification of COVID-19 infection in older people residing in residential aged care services (RACS). Methods A qualitative study was conducted using a multi-modal approach involving examination of existing literature and national guidelines for COVID-19 clinical screening, formulation of a discussion document with peer review and feasibility testing of a prototype screening tool. Results Existing COVID-19 clinical screening tools do not consider age-related impacts on clinical presentation. The qualitative analysis identified the important clinical elements to include were a lower threshold for temperature, occurrence of a recent fall and change in functional status. The new elements also had to be simple and feasible to implement. Overall feedback was positive with all participants recommending the use of the new tool. Conclusion A new screening tool for RACS residents was developed addressing the pathophysiological changes with ageing and atypical features of COVID-19 infection.

BACKGROUND Excessive gingival display (EGD), or a gummy smile (GS), is a mucogingival deformity that can be of concern to patients. The prevalence of GS etiologies, such as altered passive eruption (APE) and hypermobile upper lip (HUL), has not been reported. The aim of this study was to assess the prevalence of APE and HUL in patients seeking to correct their GS, and to determine possible prevalence differences among patients with different gingival display (GD) levels. METHODS During clinical screening of patients interested in participating in a GS treatment study, GD diagnosis, GD level, and presence of APE and/or HUL were determined. Descriptive statistics were calculated for APE, HUL, and GD group prevalence. Fisher's exact test was used to determine difference in frequency of etiologies between GD groups. RESULTS Fifty-six patients were clinically screened (27.2 ± 7.2 years old; 85.7% females; 94.6% with GD, 5.4% without GD). Among patients having GD, 75.5% presented with GD≥4 mm and 24.5% with GD

Purpose A new multicontrast echo-planar imaging (EPI)-based sequence is proposed for brain MRI, which can directly generate six MR contrasts (T1 -FLAIR, T2 -w, diffusion-weighted (DWI), apparent diffusion coefficient (ADC), T2*-w, T2 -FLAIR) in 1 min with full brain coverage. This could enable clinical MR clinical screening in similar time as a conventional CT exam but with more soft-tissue information. Methods Eleven sequence modules were created as dynamic building blocks for the sequence. Two EPI readout modules were reused throughout the sequence and were prepended by other modules to form the desired MR contrasts. Two scan protocols were optimized with scan times of 55-75 s. Motion experiments were carried out on two volunteers to investigate the robustness against head motion. Scans on patients were carried out and compared to conventional clinical images. Results The pulse sequence is found to be robust against motion given its single-shot nature of each contrast. For excessive out-of-plane head motion, the T1 -FLAIR and T2 -FLAIR contrasts suffer from incomplete inversion. Despite lower signal-to-noise ratio (SNR) and resolution, the 1-min multicontrast EPI data show promising correspondence with conventional diagnostic scans on patients. Conclusion A 1 min multicontrast brain MRI scan based on EPI readouts has been presented in this feasibility study. Preliminary data show potential for clinical brain MRI use with minimal bore time for the patient. Such short examination time could be useful (e.g., for screening and acute stroke). The sequence may also help planning conventional brain MRI scans if run at the beginning of an examination. Magn Reson Med 79:3045-3054, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

An efficient electrochemical immunosensor can offer the potential for the detection of protein cancer biomarkers due to its high sensitivity, low cost and possible integration in compact analytical devices. In the last several years, researchers have developed various electrochemical immunoassay methods for the detection of protein cancer biomarkers. Significant progresses have been made in the study of electrochemical immunosensor that based on CNTs, especially in the fields of clinical screening and diagnosis of cancer field. This is because CNTs possess unique structural, mechanical and electronic properties that can decrease over-potential and improve the sensitivity of electrochemical immunosensor. This paper reviews recent advances in the different modified strategies of constructing electrochemical immunosensor based on CNTs for detecting protein cancer biomarkers. CNTs or CNTs hybrid nanomaterials modified electrodes have been firstly introduced as the sensing platforms for the detection of protein cancer biomarkers. On the other hand, CNTs or functional CNTs used as labels in sandwich-type electrochemical immunosensors have been systematically summarized. These novel strategies and the general principles could increase the sensitivity of the immunosensor, thereby overcoming the limitations of its application in the biosensing field.

Birth defects are a major cause of morbidity and mortality worldwide. There has been much progress in understanding the genetic basis of familial and syndromic forms of birth defects. However, the etiology of nonsydromic birth defects is not well-understood. Although there is still much work to be done, we have many of the tools needed to accomplish the task. Advances in next-generation sequencing have introduced a sea of possibilities, from disease-gene discovery to clinical screening and diagnosis. These advances have been fruitful in identifying a host of candidate disease genes, spanning the spectrum of birth defects. With the advent of CRISPR-Cas9 gene editing, researchers now have a precise tool for characterizing this genetic variation in model systems. Work in model organisms has also illustrated the importance of epigenetics in human development and birth defects etiology. Here we review past and current knowledge in birth defects genetics. We describe genotyping and sequencing methods for the detection and analysis of rare and common variants. We remark on the utility of model organisms and explore epigenetics in the context of structural malformation. We conclude by highlighting approaches that may provide insight into the complex genetics of birth defects.

Global metabolic profiling currently achievable by untargeted mass spectrometry-based metabolomic platforms has great potential to advance our understanding of human disease states, including potential utility in the detection of novel and known inborn errors of metabolism (IEMs). There are few studies of the technical reproducibility, data analysis methods, and overall diagnostic capabilities when this technology is applied to clinical specimens for the diagnosis of IEMs. We explored the clinical utility of a metabolomic workflow capable of routinely generating semi-quantitative z-score values for ~900 unique compounds, including ~500 named human analytes, in a single analysis of human plasma. We tested the technical reproducibility of this platform and applied it to the retrospective diagnosis of 190 individual plasma samples, 120 of which were collected from patients with a confirmed IEM. Our results demonstrate high intra-assay precision and linear detection for the majority compounds tested. Individual metabolomic profiles provided excellent sensitivity and specificity for the detection of a wide range of metabolic disorders and identified novel biomarkers for some diseases. With this platform, it is possible to use one test to screen for dozens of IEMs that might otherwise require ordering multiple unique biochemical tests. However, this test may yield false negative results for certain disorders that would be detected by a more well-established quantitative test and in its current state should be considered a supplementary test. Our findings describe a novel approach to metabolomic analysis of clinical specimens and demonstrate the clinical utility of this technology for prospective screening of IEMs.

Background and aims The World Health Organization’s Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) has strong support as a clinical screening tool and research instrument, but has only been validated with adults. This study evaluated the ASSIST and ASSIST-Lite in an adolescent population.

Background Hypertrophic cardiomyopathy (HCM) causes significant morbidity and sudden death. First-degree relatives (FDR) of affected patients are at risk due to autosomal dominant inheritance. Guidelines recommend clinical screening, including echocardiography, for all FDR. Aim We sought to determine adherence to these guidelines, and whether a specialised HCM clinic improves screening rates. Method This 12-month prospective follow-up study obtained family pedigrees from all patients referred to the HCM Clinic @ The Alfred. The number of living FDR was determined, and whether they had previously been assessed by echocardiography. One year after a coordinated clinic-based family screening approach was instituted, the number of additionally screened FDR was recorded. Results Three hundred and eight living FDR of 61 HCM patients were identified. Of these, echocardiography had previously been performed in only 80 (26%), yielding 13 (16%) additional cases of HCM. Twelve months after attendance at our clinic, 51 additional FDR were screened (64% improvement) and 8 new cases of HCM were identified. Conclusions Recommended family screening for HCM is underperformed, resulting in missed opportunities to detect subclinical HCM. A coordinated approach through a specialised HCM clinic improves screening rates, thus referral to such a service should be considered for all patients with HCM and their families.

The aim of this study was to analyze gender differences in sagittal standing alignment at pre-peak height velocity age thereby applying a scientifically sound and practically oriented classification scheme for overall standing balance. The study population consisted of healthy boys (n = 639) and girls (n = 557) before pubertal peak growth. During subjects' habitual standing, sagittal plane measures of the spine, pelvis and lower limbs were collected using a clinical screening protocol. With each subject classified as one of three postural types (neutral, sway-back, or leaning-forward), differences in sagittal plane alignment were analyzed between sexes. The results revealed clear differences between genders in each of the postural types. Within the neutral and sway-back postural subgroups, boys presented more forward inclination of the trunk, more thoracic kyphosis and more pelvis backtilt compared with girls. Within the leaning-forward category, girls displayed more forward trunk lean, less thoracic kyphosis and more pelvic anteversion. A state of lumbar segmental hyperextension appeared to exist in female leaning-forward subjects. Our results reveal for the first time that sagittal standing alignment is different between prepubescent boys and girls when subjects are appropriately subclassified, and conversely represent a ‘wash-out effect’ when pooled. When the classification system is applied, gender-specificity in gravity line position is suggested, implying gender-related differences in lever arms and thus load. Present findings may add to our understanding of gender-specific biomechanical challenges posed by habitual posture, and may shed new light on sagittal standing alignment as a possible contributory factor in developmental spinal-pelvic disorders.

Body piercing, which is prevalent in young adults, has been suggested to be associated with features usually related to posttraumatic stress disorder (PTSD) such as high-risk behaviours and psychopathological symptoms and might be motivated by a wish to deal with prior traumatic experiences. However, to date, no research has investigated the relationship between this practice and PTSD symptoms. The present research aims to investigate the possible relationship between body piercing and PTSD symptoms in French-speaking young adults. According to our results, having two or more body piercings was associated with a twofold increased risk for scoring above the cut-off score for PTSD on the PTSD checklist. Our findings suggest that two or more body piercings might serve as an identifiable marker for PTSD symptoms and may have important implications for clinical screening.

Background Screening for developmental dysplasia of the hip (DDH) after the neonatal period is controversial. Due to recent changes in the screening policy in England & Wales, routine clinical screening for DDH at the 8-month baby check is no longer recommended. Results This paper looks at the effectiveness of screening for DDH by health visitors in the Flintshire area. A total of 525 8-month baby checks were performed in our area in 2007. Thirty babies were referred to their general practitioner of which six were referred on to a specialist children's orthopaedic surgeon. None of these required treatment for DDH. One patient who was screened by the health visitor but not referred was later diagnosed with DDH. Conclusion Screening for DDH at 8 months using clinical examination by a trained health visitor has a high false-positive rate. This paper therefore supports the current UK National Screening Committee position.

The risk perception attitude (RPA) framework classifies people into 4 groups based on their perceptions of risk and personal efficacy: responsive (high risk, high efficacy), avoidance (high risk, low efficacy), proactive (low risk, high efficacy), and indifference (low risk, low efficacy). This study tested the central propositions from the RPA framework among a group of immigrant Indian women (N = 413) in the Washington, DC area in their propensity to pay attention to breast cancer information and engage in self-exams and clinical screening. Self-efficacy and knowledge about breast cancer were consistent predictors of these outcomes. Use of the RPA framework explained 16% to 27% of the variance. Implications for breast cancer prevention campaigns are discussed.

In a population of 340,000 in Southern Hame, Finland, there were 541 intellectually disabled adult males (> 16 years) known to the District Organisation for the Care of the Mentally Retarded in August 1993. Of these, 197 already had a confirmed etiological diagnosis, with 20 having the fragile X syndrome. The other 344 males were screened for the fragile X syndrome using a three-step method: a clinical checklist used by a specialist nurse, a clinical examination by a physician who was very familiar with the fragile X syndrome, and the FRAXA-locus gene test. Six new fragile X males were found. The minimum prevalence of the fragile X syndrome in the district was calculated to be 1:4400.

Sensitive, single volume detections of multiple diabetes antibodies can provide immunoprofiling and early screening of at-risk patients. To advance the state-of-the-art suspension assays for diabetes antibodies, porous hydrogel droplets are leveraged in microfluidic serpentine arrays to enhance reagent transport. This spatially multiplexed assay is applied to the detection of antibodies against insulin, glutamic acid decarboxylase, and insulinoma-associated protein 2. Optimization of assay protocol results in a shortened assay time of 2 h, with better than 20 pg mL Supporting Information detection limits across all three antibodies. Specificity and cross-reactivity tests show negligible background, nonspecific antibody-antigen, and nonspecific antibody-antibody bindings. Multiplexed detections are able to measure within 15% of target concentrations from low to high ranges. The technique enables quantifications of as little as 8000 molecules in each 500 µm droplet in a single volume, multiplexed assay format, a breakthrough necessary for the adoption of diabetes panels for clinical screening and monitoring in the future.

Blood biomarkers of omega-3 (ω3) fatty acids can be used as markers of optimal health and disease risk. Rapid, high-throughput and cost efficient fatty acid analyses would enable routine clinical screening for ω3 fatty acid status by health professionals. Clinical monitoring of ω3 fatty acid status of individuals would enable prevention strategies for cardiovascular disease and prenatal nutrition.

Diffusion-weighted magnetic resonance imaging (MRI) can detect ischemia within minutes of onset, but its ability to reliably detect hyperacute cerebral hemorrhage is unknown. The present study characterized diffusion-weighted, T2-weighted, and contrast-enhanced T1-weighted MRI appearances of hemorrhagic transformation within 5 hours of onset in experimental embolic stroke. Apparent diffusion coefficients and MRI signal characteristics were noted within corresponding regions of hemorrhage observed on gross pathology. Apparent diffusion coefficients were significantly increased within hemorrhagic lesions, but were still within the expected range for bland ischemia. The appearance of the hemorrhagic lesions on diffusion-weighted MRI was also very heterogeneous and not very useful for clinical screening. Other MRI modalities should be investigated, but computed tomography remains the only widely available clinical method of reliably detecting cerebral hemorrhage.

Global metabolic profiling currently achievable by untargeted mass spectrometry-based metabolomic platforms has great potential to advance our understanding of human disease states, including potential utility in the detection of novel and known inborn errors of metabolism (IEMs). There are few studies of the technical reproducibility, data analysis methods, and overall diagnostic capabilities when this technology is applied to clinical specimens for the diagnosis of IEMs. We explored the clinical utility of a metabolomic workflow capable of routinely generating semi-quantitative z-score values for ~900 unique compounds, including ~500 named human analytes, in a single analysis of human plasma. We tested the technical reproducibility of this platform and applied it to the retrospective diagnosis of 190 individual plasma samples, 120 of which were collected from patients with a confirmed IEM. Our results demonstrate high intra-assay precision and linear detection for the majority compounds tested. Individual metabolomic profiles provided excellent sensitivity and specificity for the detection of a wide range of metabolic disorders and identified novel biomarkers for some diseases. With this platform, it is possible to use one test to screen for dozens of IEMs that might otherwise require ordering multiple unique biochemical tests. However, this test may yield false negative results for certain disorders that would be detected by a more well-established quantitative test and in its current state should be considered a supplementary test. Our findings describe a novel approach to metabolomic analysis of clinical specimens and demonstrate the clinical utility of this technology for prospective screening of IEMs. Electronic supplementary material The online version of this article (doi:10.1007/s10545-015-9843-7) contains supplementary material, which is available to authorized users.

Purpose: A study was carried out on 105 patients referred for cataract surgery at the Princess Alexandra Eye Pavilion Edinburgh. The aim of the study was to a) examine criteria significant for referral in current practice. b) explore the implications of a greater emphasis to QoL critera Methods: Three categories of variable were assessed – visual function (visual acuity,contrast sensitivity); cataract morphology ( oxford grading system, stray light meter) and quality of life (QoL - vf14, Sparrow scales). Referral procedures followed current clinical practice. A follow up on 30 patients was carried out 3 months after surgery. Results: 78% of patients were referred for surgery and of these 77% were first eyes. The main discriminators for surgery in current practice for all patients and those with Snellen

A total of 576 transcutaneous bilirubin measurements were performed on 336 Japanese full-term breast-fed newborn infants during the first twelve days of life. Our present study revealed that transcutaneous bilirubin measurements obtained from the forehead, chest, and sternum correlated well with serum bilirubin concentrations measured by AO bilirubinometer (0.910-0.922, p less than 0.001, n = 576). The 95% confidence limits were +/- 3.04 mg/dl for the forehead, +/- 2.85 mg/dl for the chest, and +/- 2.84 mg/dl for the sternum readings. The overall mean of values from the forehead, chest and sternum, when compared with individual means, was found to correlate better with serum bilirubin concentrations (r = 0.930, p less than 0.001, n = 576) and improve the 95% confidence limits to +/- 2.68 mg/dl. These results demonstrated that the accuracy and reliability of TcB measurement could be increased further with multiple site measurement. The study clearly indicates that transcutaneous bilirubinometry is useful for clinical screening of serum bilirubin levels in Japanese full-term newborn infants.

Parents of children with neuromuscular disease (N = 16), cystic fibrosis (N = 16), and renal disease (N = 11) were compared with parents of control subjects matched by age to the clinical cases; the instrument used was the Questionnaire on Resources and Stress (QRS). The three clinical groups exhibited different patterns of stressful response, consistent with the nature of their illnesses and the requirements for care imposed on the families. Parents of children with neuromuscular disease reported a wide spectrum of problems, both qualitatively and quantitatively different from those experienced in the other two clinical samples. Parents of children with cystic fibrosis also experienced extensive stress, but less than anticipated. Parents of children with renal disease reported stress in only a few areas, in keeping with the nature of the disease. The relationship between severity of functional impairment from cystic fibrosis and QRS scales was examined and found to be equivocal. The 285-item and 66-item versions of the QRS were compared and judged to be appropriate for different situations (research vs. clinical screening).

Inclusion of a mental status examination in research and clinical screening instruments lengthens the protocol, thereby adding to the difficulty of using instruments addressing all relevant issues under study without taxing participants. The purpose of the present study was to evaluate the possibility of substituting a subset of items from the widely used Mini-Mental State Examination (MMSE) for the entire examination in order to reduce the time needed to screen for cognitive status. Study data came from a health study of 783 community-dwelling, white females, 65 years of age and over, selected randomly from a 20-census-tract area of northeast Baltimore. Results indicate that seven MMSE items can be used to reliably predict total MMSE scores. Because of an age X education interaction in the prediction of total MMSE scores, four age X education-specific predictive equations were developed. These four equations are most useful for predicting continuous MMSE scores rather than for categorizing individuals according to impaired versus unimpaired status. A short form of the MMSE and four age X education-specific scoring equations are presented and their potential utility discussed.

Analysis of sulfamethazine (SMZ) kinetics in man has revealed complexities including wide intersubject variability. In our study, an attempt was made to assess the potential influence of changes in nonmetabolic parameters (absorption and urinary elimination rate constants) on the markers of acetylation capacity normally used in clinical screening procedures to determine phenotype. Seven normal subjects were classified as slow (SA) or fast acetylators (FA) according to their metabolic rate constant for SMZ (Km), plasma SMZ half-life, and percentage of N-acetyl SMZ in a 6-hr blood sample (PI6), a 5- to 6-hr urine collection (UI5--6), or a 6-hr total urine collection (UI6). Computer simulations were applied to baseline SMZ kinetic data from these subjects, varying nonmetabolic kinetic parameters over experimentally defined ranges singly, or in parallel with 1 or more of the other parameters. The simulations indicate that all the usual phenotyping procedures were sensitive to changes in absorption and urinary elimination rate constants. While these predictions require experimental confirmation, results show that the PI6 method is least sensitive to such changes, suggesting this method may minimize errors in phenotyping screening.

SUMMARY A D(+) xylose absorption test has been standardised for use in the horse. A dose of 2 g. xylose/Kg. body-weight is required to produce a maximum plasma xylose level of 30 mg./100ml. after two hours. There are limitations to the procedure being used as a routine clinical screening test of small intestinal dysfunction in the horse. RESUME On a standardise un test d'absorption du D(+) xylose pour le cheval. Une dose de 2 gr de xylose par kilo de poids vif est necessaire pour produire une elevation du xylose plasmatique jusqu'a 30 mg par 100 ml apres deux heures. Il y a des limitations a l'emploi de cette methode pour l'exploration de routine des dysfonctionnements de l'intestin grele chez le cheval. ZUSAMMENFASSUNG Ein D(+)Xylose-Absorptionstest wurde fur die Verwendung beim Pferd standardisiert. Eine Dosis von 2 g. Xylose/kg. Korpergewicht wird benotigt, um eine maximale Plasmakonzentration von 30 mg./100 ml. nach 2 Stunden zu erreichen. Die Grenze des Tests fur den routinemassigen Einsatz als Screening-Test fur Dunndarmdysfunktionen beim Pferd werden aufgezeigt.