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Aim: Prostate biopsy can be prone to complications and thus should be avoided when unnecessary. Although the combination of magnetic resonance imaging (MRI), the prostate health index (PHI), and PHI density (PHID) has been shown to improve detection of clinically significant prostate cancer (csPCa), there is limited information available assessing its clinical utility. We sought to determine whether using PHID could enhance the detection of PCa on MRI ultrasound fusion-targeted biopsy (MRF-TB) compared to other biomarker cutoffs. Methods: Between June 2015 and December 2020, 302 men obtained PHI testing before MRF-TB at a single institution. We used descriptive statistics, multivariable logistic regression, and receiver operating characteristic curves to determine the predictive accuracy of PHID and PHI to detect ≥ Gleason grade group (GGG) 2 PCa and identify cutoff values. Results: Any cancer grade was identified in 75.5% of patients and ≥ GGG2 PCa was identified in 45% of patients. The median PHID was 1.05 [interquartile range (IQR) 0.59–1.64]. A PHID cutoff of 0.91 had a higher discriminatory ability to predict ≥ GGG2 PCa compared to PHI > 27, PHI > 36, and prostate specific-antigen (PSA) density > 0.15 (AUC: 0.707 vs. 0.549 vs. 0.620 vs. 0.601), particularly in men with Prostate Imaging Reporting and Data System (PI-RADS) 1–2 lesions on MRI (AUC: 0.817 vs. 0.563 vs. 0.621 vs. 0.678). At this cutoff, 35.0% of all the original biopsies could be safely avoided (PHID < 0.91 and no ≥ GGG2 PCa) and csPCa would be missed in 9.67% of patients who would have been biopsied. In patients with PI-RADS 1–2 lesions using a PHID cutoff of 0.91, 56.8% of biopsies could be safely avoided while missing 0 csPCa. Conclusions: These findings suggest that a PHID cutoff of 0.91 improves the selection of patients with elevated prostate-specific antigen who are referred for prostate biopsy, and potentially in patients with PI-RADS 1–2 lesions.

Purpose Nocturia significantly impacts patients’ quality of life but remains insufficiently evaluated and treated. The “Sleep C.A.L.M.” system categorizes the factors thought to collectively reflect most underlying causes of nocturia (Sleep disorders, Comorbidities, Actions [i.e., modifiable patient behaviors such as excess fluid intake], Lower urinary tract dysfunction, and Medications). The purpose of this study was to assess the association of nocturia with the Sleep C.A.L.M. categories using a nationally representative dataset. Methods Retrospective analysis of the National Health and Nutrition Examination Survey from 2013/14–2017/18 cycles was conducted. Pertinent questionnaire, laboratory, dietary, and physical examination data were used to ascertain the presence of Sleep C.A.L.M. categories in adults ≥20 years of age. Nocturia was defined as ≥2 nighttime voids. Results A total of 12,274 included subjects were included (51.6% female; median age, 49.0 years [interquartile range, 34.0–62.0 years]; 27.6% nocturia). Among subjects with nocturia, the prevalence of 0, ≥1, and ≥2 Sleep C.A.L.M. categories was 3.5% (95% confidence interval [CI], 2.8%–4.4%), 96.5% (95% CI, 95.6%–97.2%), and 81.2% (95% CI, 78.9%–83.3%), respectively. Compared to those with 0–1 Sleep C.A.L.M. categories, the adjusted odds of nocturia in subjects with 2, 3, and 4–5 Sleep C. A.L.M. categories were 1.77 (95% CI, 1.43–2.21), 2.33 (1.89–2.87), and 3.49 (2.81–4.35), respectively (P

Palliative care plays a crucial role in enhancing the quality of life for individuals facing serious illnesses, aiming to alleviate suffering and provide holistic support. With the advent of telehealth, there is a growing interest in leveraging technology to extend the reach and effectiveness of palliative care services. This article provides a comprehensive review of the evolution of telehealth, the current state of telemedicine in palliative care, and the role of telepharmacy and medication management. Herein we highlight the potential benefits, challenges, and future directions of palliative telemedicine. As the field continues to advance, the article proposes key considerations for future research, policy development, and clinical implementation, aiming to maximize the advantages of telehealth in assisting individuals and their families throughout the palliative care journey. The comprehensive analysis presented herein contributes to a deeper understanding of the role of telehealth in palliative care and serves as a guide for shaping its future trajectory.

Background: Opioid-induced constipation (OIC) is a pervasive and distressing side effect of chronic opioid therapy in patients with cancer pain, significantly impacting their quality of life. Peripherally acting μ-opioid receptor antagonists (PAMORAS) were developed for treatment-resistant OIC but most studies were conducted with non-cancer patients. Objective: to discuss two oral formulations of PAMORAs, naldemedine and naloxegol, and to review available evidence of the effectiveness of these drugs for OIC in cancer patients. Methods: a comprehensive search to identify primary literature for either naldemedine or naloxegol for OIC in cancer patients. Results: Only three prospective randomized, double-blind, placebo-controlled clinical trials for naldemedine enrolling cancer patients were identified; the results of a subgroup analysis of two of those studies and two non-interventional post marketing surveillance studies of these trials are also reported here. For naloxegol, only two randomized controlled trials were identified; both were unsuccessful in enrolling sufficient patients. An additional four prospective non-interventional observational studies with naloxegol were found that enrolled cancer patients. There were significantly higher rates of responders in the PAMORA groups than in the placebo groups. The most common side effect for both PAMORAs was diarrhea. Limitations: All studies were industry-funded, and given that only three trials were randomized controlled studies, the overall quality of the studies was lacking. Conclusion: Naldemedine or naloxegol appeared safe and useful in the treatment of OIC in cancer patients and may improve their quality of life. Larger-scale randomized placebo-controlled studies of PAMORAs in cancer patients would strengthen existing evidence.

Antenna arrays and spatial processing techniques are among the most effective countermeasures against interference. Here, we demonstrate a new array concept consisting of spatially-distributed subarrays that are small enough to fit inside the non-metallic parts of an automobile. This will facilitate concealed installation of these devices in bumpers or side mirrors, which is a strict requirement of the industry and preferred by the customers. Using beamforming algorithms, this array was proven to be robust against jammers in the L1 band. The large distances between the individual antenna elements resulted in a non-negligible baseband delay that violated the narrowband assumption and increased with bandwidth. Hence, this paper demonstrates the influence of a jammer in the L5 band. Space-time adaptive processing that allows for compensation of the delays was introduced and analyzed. Improvements in interference mitigation capabilities were assessed and compared to those of pure spatial state-of-the-art implementation. Real-life measurement data was used to ensure realistic results.

Purpose The pathophysiology of nocturia and nocturnal polyuria (NP), conditions that become more prevalent with aging, may in part be explained by changes in hormones involved in water homeostasis. The purpose of this study was to analyze the impact of aging on urinary natriuretic peptides in nocturia and NP. Methods Patients aged ≥18 years completed 24-hour bladder diaries for assessment of nocturia and NP. They were divided into subgroups of ≥65 years old and

Background: Although the Decipher genomic classifier has been validated as a prognostic tool for several prostate cancer endpoints, little is known about its role in assessing the risk of biopsy reclassification for patients on active surveillance, a key event that often triggers treatment. Objective: To evaluate the association between Decipher genomic classifier scores and biopsy Gleason upgrading among patients on active surveillance. Design, setting, and participants: This was a retrospective cohort study among patients with low- and favorable intermediate-risk prostate cancer on active surveillance who underwent biopsy-based Decipher testing as part of their clinical care. Outcome measurements and statistical analysis: We evaluated the association between the Decipher score and any increase in biopsy Gleason grade group (GG) using univariable and multivariable logistic regression. We compared the area under the receiver operating characteristic curve (AUC) for models comprising baseline clinical variables with or without the Decipher score. Results and limitations: We identified 133 patients for inclusion with a median age of 67.7 yr and median prostate-specific of 5.6 ng/ml. At enrollment, 75.9% had GG1 and 24.1% had GG2 disease. Forty-three patients experienced biopsy upgrading. On multivariable logistic regression, the Decipher score was significantly associated with biopsy upgrading (odds ratio 1.37 per 0.10 unit increase, 95% confidence interval [CI] 1.05–1.79; p = 0.02). The Decipher score was associated with upgrading among patients with biopsy GG 1 disease, but not GG2 disease. The discriminative ability of a clinical model (AUC 0.63, 95% CI 0.51–0.74) was improved by integration of the Decipher score (AUC 0.69, 95% CI 0.58–0.80). Conclusions: The Decipher genomic classifier score was associated with short-term biopsy Gleason upgrading among patients on active surveillance. Patient summary: The results from this study indicate that among patients with prostate cancer undergoing active surveillance, those with higher Decipher scores were more likely to have higher-grade disease found over time. These findings indicate that the Decipher test might be useful for guiding the intensity of monitoring during active surveillance, such as more frequent biopsy for patients with higher scores.

Due to the low signal power of global navigation satellite signals, the receivers are prone to radio frequency interference. Employing multi-antenna arrays is one method to mitigate such effects, by incorporating spatial processing techniques. The large size of the uniform rectangular arrays prevents their use in applications where installation space is limited. Therefore, we proposed a new approach, namely to split one full array into a number of smaller, spatially distributed, sub-arrays to reduce their size and exploit available installation spaces. This concept challenges the distribution of the local oscillator and calibration signals to the respective sub-arrays. This paper compares qualitatively different design concepts for a satellite navigation receiver with two two-element sub-arrays, installed multiple wavelengths apart from each other, in support of establishing an optimal choice for our intended applications in the automotive sector in terms of electrical performance and required hardware and software efforts. In general, weighing the pros and cons of the different concepts, as discussed in the paper, will assist in optimizing the system design approach for a specific application.

Abstract Objective To evaluate in-vitro quality of paracetamol 500 mg tablet brands marketed in Saudi Arabia. Results Two reference (R1 and R2) and seven generic (G1-G7) brands were commercially available. Four brands were single-drug, containing paracetamol only (R1, G1-G3) and five contained additional active ingredients (R2, G4-G7). All brands were immediate-release. Weight variation (n = 20, range as percent difference from mean), active substance content (n = 20, mean (SD) as percent difference from label), breaking force (n = 10, mean (SD)), and friability (n = 20, as percent weight loss) ranged from 97 to 102%, 96.1% (2.9%) to 99.8% (1.1%), 9.9 (0.4) to 21.0 (0.9) kg, and 0.017% to 0.809%, respectively. Disintegration (water medium) time (n = 6, minute: second) ranged from 02:35–03:09 to 12:49–13:10. Dissolution (phosphate buffer, pH 5.8) profile showed a mean release at 30 min of 87% to 97% of label content, with seven brands passing stage-1 (≥ 85% for each of 6 test units) and two passing stage-2 (mean of 12 test units ≥ 85%) criteria. Despite statistically significant differences between R1 and R2 and some of their corresponding generic brands in active substance content, breaking force, and amount dissolved at 30 min, all nine brands met the pre-specified quality standards.

Background The coronavirus 2019 disease (COVID-19) has infected many individuals worldwide and continues to pose a significant threat to those with weakened immune systems. The data evaluating the clinical outcomes of patients with humoral immunodeficiencies that contract COVID-19 is limited and conflicting. Objective To describe the clinical outcomes of COVID-19 infections in patients with primary humoral immunodeficiency and compare results to current literature. Methods We conducted a retrospective cohort review on 15 patients with a humoral immunodeficiency defined as Common Variable Immunodeficiency, Specific Antibody Deficiency, or unspecified hypogammaglobulinemia, who contracted COVID-19. Severity scores were determined to evaluate the clinical outcomes of these patients. Results Of our 15-patient cohort, 33% of individuals with a humoral immunodeficiency infected with COVID-19 had moderate to severe disease, requiring hospitalization or resulting in death. COVID-19 mortality rate was found to be 7%. All 5 of our patients with severe COVID-19 infection had at least 1 comorbidity or risk factor. Conclusion Within our cohort of humoral immunodeficient patients infected with COVID-19, we found a higher rate of moderate to severe COVID-19 infection and worse clinical outcomes, particularly in patients with comorbidities or risk factors.

Purpose Low nocturnal urine production (NUP) may be sufficient to rule out global polyuria (GP) in men. This study determines the sensitivity of indices for nocturnal polyuria (NP), defined as nocturnal polyuria index (NPi; nocturnal urine volume/24-hour urine volume) ≥0.33 or NUP ≥90 mL/hr, for detecting GP in women. Methods Data were analyzed from 2 prospective protocols involving subjects recruited from a urology ambulatory care unit and a continence clinic. Women ≥18 years with nocturia were included if they met either of 2 common criteria for GP: (1) ≥40 mL/kg/24 hr or (2) ≥3,000 mL/24 hr. Results Thirty-one women were included (NPi, 28.6 [21.3–40.7]; NUP, 100.8 [68.3–135.8] mL/hr). At the ≥40 mL/kg/24-hr cutoff, 40% and 63% of women reporting ≥1 nocturnal void(s) (n=30) had NPi ≥0.33 and NUP ≥90 mL/hr, respectively. Additionally, 53% and 71% of subjects reporting ≥2 nocturnal voids (n=17) had NPi ≥0.33 and NUP ≥90 mL/hr, respectively. At the ≥3,000 mL/24-hr cutoff, 38% and 69% of women reporting ≥1 nocturnal void(s) (n=13) had NPi ≥0.33 and NUP ≥90 mL/hr, respectively, and 63% and 88% of subjects reporting ≥2 nocturnal voids (n=8) had NPi ≥0.33 and NUP ≥90 mL/hr, respectively. By extension, 37%–62% of women with nocturia and GP did not have NP by NPi ≥0.33 criteria, and 12%–37% did not have NP by NUP ≥90 mL/hr criteria. Conclusions Indices of excess nighttime urination do not reliably predict GP in women. A full-length voiding diary may be particularly important in the evaluation of women with nocturia. Nocturia in women merits further consideration as a distinct entity.

Abstract Objective To evaluate in vitro quality of enteric-coated 50 mg diclofenac sodium tablet formulations on Saudi market. Results A reference and seven generic (G1-7) formulations were commercially available in December 2019/January 2020 and were assessed within 25–75% of manufacture-expiration period. Weight variation (range as% difference from mean, n = 20), active substance content (ASC, mean (SD) as% difference from label, n = 20), hardness (mean (SD), n = 10), and friability (% weight loss, n = 20) were 97–103%, 102.0% (3.4%), 15.4 (1.1) kg, and 0.24%, respectively, for the reference. For G2-7, they were ≤ ±5%, 98.6% (4.0%) to 109.9% (1.8%), 11.9 (0.9) to 18.3 (0.8) kg, and ≤ 0.00 to 0.75%, respectively. G1 ASC, hardness, and friability were 111.3% (1.7%), 20.1 (1.7) kg, and 1.10%, respectively. Disintegration time (n = 6) and dissolution profile (n = 8) were also determined. No formulation disintegrated or released ˃ 0.1% of label ASC in 0.1 N HCl for 2 h. The reference disintegrated in 15:00 min:seconds and released a mean (range) of 100% (99–103%) of label ASC by 45 min in phosphate buffer (pH = 6.8). G1-7 disintegrated in 8:53 to 20:37 min:seconds and released 81% (69–90%) (G1) to 109%. Except for borderline performance of G1, all formulations passed in vitro quality tests according to United States Pharmacopoeia.

The aim of the study was to develop and validate a practical assay of clinically relevant testosterone levels in human plasma and saliva. We performed ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis on Atlantis dC18 steel column using a mobile phase of 2-mM ammonium acetate and acetonitrile (20:80, v: v) that was delivered at 0.3 ml/min. After adding d3-testosterone as an internal standard (IS), we extracted plasma and salivary samples with methyl tert-butyl ether. Mass spectrometry was performed in electrospray positive-ion mode. Targeted ion transitions were examined at m/z 289.18 → 97.04 and 292.24 → 97.04 for testosterone and IS, respectively. We validated the method according to the US Food and Drug Administration guidelines. Elution times for testosterone and IS were both around 1.35 min. Testosterone level was linearly associated (r2 = 0.9975 and 0.9958) with peak area ratio of testosterone to IS between 0.5–50 ng/ml and 10–400 pg/ml in plasma and saliva, respectively. The coefficient of variation and bias were ≤12.6% and ≤±12.1% in plasma and ≤10.2% and ≤±5.3% in saliva. The extraction recovery of testosterone was ≥92% from plasma and ≥94% from saliva. Testosterone was stable (≥91%) for 24 h at room temperature and for 8 weeks at −20°C in both plasma and salivary samples. We report a simple, validated, UPLC-MS/MS assay that can be used to determine clinically relevant levels of testosterone in human plasma and saliva.

A simple and effective ultra-high-performance liquid chromatography assay linked to tandem mass spectrometry (UHPLC-MS/MS) for measuring cortisol and cortisone levels in human sweat has been developed and validated. A noninvasive world standard sweat collecting equipment was utilized to collect samples. The samples were analyzed using an Atlantis dC18 (2.1 × 100 mm, 3 μm) column with a 2 mM ammonium acetate and acetonitrile (1 : 1, v : v) mobile phase. In an isocratic condition, the mobile phase was delivered at a flow rate of 0.3 ml/minute. A positive electrospray ionization interface with multiple-reaction monitoring mode was used to provide simultaneous quantification of cortisol, cortisone, and internal standard at transitions of 363.11 to 121.00, 361.18 to 163.11, and 367.19 to 121.24, respectively. The method was validated for cortisol and cortisone determination over a concentration range of 0.5–50 ng/mL The detection limits for cortisol and cortisone in human sweat were 0.3 and 0.2 ng/ml, respectively. The interday coefficients of variation of cortisol and cortisone were ≤8.5% and ≤10.01%, whereas bias was in the range from −7.9% to 2.1% and from −4.3% to 3.0%, respectively. The assay was successfully applied to evaluate the cortisol-to-cortisone ratio in sweat samples collected from healthy adult volunteers.

There is a paucity of management recommendations for patients with aggressive Diffuse large B cell lymphoma (DLBCL) of the bladder. A 57-year-old male patient presented with lower urinary tract symptoms underwent flexible cystoscopy and then bladder tumor biopsy. Through immediate staging CT scan, tumor and bone biopsies he was diagnosed with a 16 cm Stage IVa high-grade DLBCL. He was treated with DA EPOCH with only a partial response and was transitioned to R-ICE. For rarer presentations of bladder cancer during diagnostic cystoscopy there should be no delay in tumor imaging and involving medical oncology in early treatment decision making.

In this study new sulphamethoxazole derivatives (S1–S4, S6–S12, and S14–S22) were designed and synthesized and their structures were fully characterized and validated using NMR, mass, and IR spectroscopy, as well as elemental analyses. All new derivatives (S1–S22) were assayed against human carbonic anhydrase (hCAs IX and XII) for their inhibitory activities. hCAs IX and XII were chosen due to the fact that CAIX expression is recognized as a hypoxia marker with a poor prognosis in breast cancer. When compared to Dorzolamide HCl as a standard reference, derivatives S2, S3, S8, S9, and S15 had the most effective inhibition with low IC50 values. The active compounds were further evaluated against hCAs I and II inhibitory activity and compounds S8, S9 and S15 showed the least inhibitory effect compared to the reference standard, acetazolamide, indicating that their effect in normal cells is the lowest. Cell viability tests for the selected compounds were carried out on MCF7 (normoxia and hypoxia) and on the normal breast cell line (MCF10a) with Staurosporine as a standard. The results showed that compound S15 had a highly potent cytotoxic effect. Furthermore, cell cycle analysis results showed that compound S15 triggered cell cycle arrest and apoptosis in G1/S of MCF7 cancer cells. Finally, molecular docking was performed to point out the possible explanation for the vital structural features and key-interactions exerted by our ligands with hCAs IX and XII that might share additional designs and highlight possible leads for a hopeful anticancer agent. Consequently, sulphamethoxazole Derivative S15 could be the potential lead for emerging selective cytotoxic compounds directing h CAs IX and XII.

Highly flexible and stretchable sensors are becoming increasingly widespread due to their versatile applicability in human/robot monitoring sensors. Conductive polymeric composites have been regarded as potential candidates for such sensors, and carbon nanotubes (CNTs) are widely used to fabricate such composites. In the present study, CNT-embedded high flexible sensors were fabricated using a facile three-roll milling method, which mitigates the drawbacks of the conventional fabrication methods. CNTs content varied between 0.5 and 4.0 wt.%, and the percolation threshold range was obtained via conductivity/resistivity values of the fabricated sensors. Following this, the electrical stability of the sensors was examined against the various DC and AC signals. Furthermore, the fabricated sensors were stretched up to 500% strain, and their sensitivity against varying strain amplitudes was investigated in terms of the change in resistance and gauge factors. Lastly, the fabricated sensors were applied to human fingers for monitoring finger bending and releasing motions to validate their potential applications. The experimental results indicated that these sensors have a percolation threshold of around 2% CNTs content, and the sensors fabricated with 2 to 4% CNTs content showed measurable resistance changes against the applied strain amplitudes of 50–500%. Among these sensors, the sensor with 2% CNTs content showed the highest sensitivity in the studied strain range, exhibiting a resistance change and gauge factor of about 90% and 1.79 against 50% strain amplitude and about 18,500% and 37.07 against 500% strain amplitude, respectively. All these sensors also showed high sensitivity for finger motion detection, showing a resistance change of between 22 and 69%.

Recent work at the U.S. Naval Research Laboratory studied atmospheric turbulence on dynamic links with the goal of developing an optical anemometer and turbulence characterization system for unmanned aerial vehicle (UAV) applications. Providing information on the degree of atmospheric turbulence, as well as wind information and scintillation, in a low size, weight and power (SWaP) system is key for the design of a system that is also capable of adapting quickly to changes in atmospheric conditions. The envisioned system consists of a bi-static dynamic link between a transmitter (Tx) and a receiver (Rx), relying on a small UAV. In a dynamic link, the propagation distance between the Tx/Rx changes rapidly. Due to SWaP constraints, a monostatic system is challenging for such configurations, so we explored a system in which the Tx/Rx is co-located on a mobile platform (UAV), which has a mounted retroreflector. Beam divergence control is key in such a system, both for finding the UAV (increased beam divergence at the Tx) and for signal optimization at the Rx. This led us to the concept of using adaptive/active elements to control the divergence at the Tx but also to the implementation of an adaptive/active retroreflector in which the return beam divergence can be controlled in order to optimize the signal at the Rx. This paper presents the design, fabrication and characterization of a low SWaP adaptive retroreflector.

Summary: Understanding the cellular properties controlling neural stem and progenitor cell (NSPC) fate choice will improve their therapeutic potential. The electrophysiological measure whole-cell membrane capacitance reflects fate bias in the neural lineage but the cellular properties underlying membrane capacitance are poorly understood. We tested the hypothesis that cell surface carbohydrates contribute to NSPC membrane capacitance and fate. We found NSPCs differing in fate potential express distinct patterns of glycosylation enzymes. Screening several glycosylation pathways revealed that the one forming highly branched N-glycans differs between neurogenic and astrogenic populations of cells in vitro and in vivo. Enhancing highly branched N-glycans on NSPCs significantly increases membrane capacitance and leads to the generation of more astrocytes at the expense of neurons with no effect on cell size, viability, or proliferation. These data identify the N-glycan branching pathway as a significant regulator of membrane capacitance and fate choice in the neural lineage. : Flanagan and colleagues tested glycosylation contributions to a unique, fate-specific electrophysiological property of neural stem cells. They found the N-glycan branching pathway generating highly branched N-glycans associated with astrocyte fate. Enhanced branching shifted the electrophysiological property and fate potential of neural stem cells toward astrocytes, revealing the importance of N-glycan branching to neural stem cell differentiation. Keywords: neuron progenitor, astrocyte progenitor, glycosylation, biophysical, dielectrophoresis, membrane capacitance, mouse, branch, MGAT, L-PHA

Abstract Background The extents of generic-reference and generic-generic average bioequivalence and intra-subject variation of on-market drug products have not been prospectively studied on a large scale. Methods We assessed bioequivalence of 42 generic products of 14 immediate-release oral drugs with the highest number of generic products on the Saudi market. We conducted 14 four-sequence, randomized, crossover studies on the reference and three randomly-selected generic products of amlodipine, amoxicillin, atenolol, cephalexin, ciprofloxacin, clarithromycin, diclofenac, ibuprofen, fluconazole, metformin, metronidazole, paracetamol, omeprazole, and ranitidine. Geometric mean ratios of maximum concentration (Cmax) and area-under-the-concentration-time-curve, to last measured concentration (AUCT), extrapolated to infinity (AUCI), or truncated to Cmax time of reference product (AUCReftmax) were calculated using non-compartmental method and their 90% confidence intervals (CI) were compared to the 80.00%–125.00% bioequivalence range. Percentages of individual ratios falling outside the ±25% range were also determined. Results Mean (SD) age and body-mass-index of 700 healthy volunteers (28–80/study) were 32.2 (6.2) years and 24.4 (3.2) kg/m2, respectively. In 42 generic-reference comparisons, 100% of AUCT and AUCI CIs showed bioequivalence, 9.5% of Cmax CIs barely failed to show bioequivalence, and 66.7% of AUCReftmax CIs failed to show bioequivalence/showed bioinequivalence. Adjusting for 6 comparisons, 2.4% of AUCT and AUCI CIs and 21.4% of Cmax CIs failed to show bioequivalence. In 42 generic-generic comparisons, 2.4% of AUCT, AUCI, and Cmax CIs failed to show bioequivalence, and 66.7% of AUCReftmax CIs failed to show bioequivalence/showed bioinequivalence. Adjusting for 6 comparisons, 2.4% of AUCT and AUCI CIs and 14.3% of Cmax CIs failed to show bioequivalence. Average geometric mean ratio deviation from 100% was ≤3.2 and ≤5.4 percentage points for AUCI and Cmax, respectively, in both generic-reference and generic-generic comparisons. Individual generic/reference and generic/generic ratios, respectively, were within the ±25% range in >75% of individuals in 79% and 71% of the 14 drugs for AUCT and 36% and 29% for Cmax. Conclusions On-market generic drug products continue to be reference-bioequivalent and are bioequivalent to each other based on AUCT, AUCI, and Cmax but not AUCReftmax. Average deviation of geometric mean ratios and intra-subject variations are similar between reference-generic and generic-generic comparisons. Trial registration ClinicalTrials.gov identifier: NCT01344070 (registered April 3, 2011).

In the functional 3D-printing field, poly(vinylidene fluoride-co-trifluoroethylene) (PVDF-TrFE) has been shown to be a more promising choice of material over polyvinylidene fluoride (PVDF), due to its ability to be poled to a high level of piezoelectric performance without a large mechanical strain ratio. In this work, a novel presentation of in situ 3D printing and poling of PVDF-TrFE is shown with a d33 performance of up to 18 pC N−1, more than an order of magnitude larger than previously reported in situ poled polymer piezoelectrics. This finding paves the way forward for pressure sensors with much higher sensitivity and accuracy. In addition, the ability of in situ pole sensors to demonstrate different performance levels is shown in a fully 3D-printed five-element sensor array, accelerating and increasing the design space for complex sensing arrays. The in situ poled sample performance was compared to the performance of samples prepared through an ex situ corona poling process.

Blinding mitigates several sources of bias which, if left unchecked, can quantitively affect study outcomes. Blinding remains under-utilized, particularly in non-pharmaceutical clinical trials, but is often highly feasible through simple measures. Although blinding is generally viewed as an effective method by which to eliminate bias, blinding does also pose some inherent limitations, and it behooves clinicians and researchers to be aware of such caveats. This article will review general principles for blinding in clinical trials, including examples of useful blinding techniques for both pharmaceutical and non-pharmaceutical trials, while also highlighting the limitations and potential consequences of blinding. Appropriate reporting on blinding in trial protocols and manuscripts, as well as future directions for blinding research, will also be discussed.

علم التخَلُّق هو دراسة التعديلات النوكليوتيدية المورَّثة التي تعمل كآلية تنظيمية دون تغيير التسلسل النيوكليوتيدي للجينوم. تؤثر إشارات خارجية مثل البيئة، ونمط الحياة، والتغذية، والإجهاد والعوامل النفسية على آليات التخَلُّق. وتتوافق هذه الآلية مع المعلومات الجينية التي تلعب دورا مهما في حياة الفرد قبل الولادة وبعدها. لقد كشفت الدراسات الأخيرة في علم التخَلُّق إمكانات علم التخَلُّق في توضيح آليات أمراض مختلفة لم يتم فهمها سابقا بشكل كامل. ناقشنا في هذا الاستعراض آليات التخَلُّق الأساسية ودورها في الصحة والمرض. إضافة إلى ذلك فقد تم وصف الانحرافات في التنظيم التخلُّقي التي تم تسجيلها لبعض الأمراض البشرية الشائعة. وأخيرا، تتناول الورقة بعض الأساليب في علم التخَلُّق، التي تكمن بها القدرة على العلاج الموجَّه للأمراض.

Summary: Background: Poor development in young children in developing countries is a major problem. Child development experts are calling for interventions that aim to improve child development to be integrated into health services, but there are few robust evaluations of such programmes. Previous small Bangladeshi trials that used individual play sessions with mothers and their children (at home or in clinics), which were predominantly run by employed women, found moderate improvements on child development. We aimed to integrate an early childhood development programme into government clinics that provide primary health care and to evaluate the effects of this intervention on child cognition, language, and motor development, growth, and behaviour in a subsample of the children. Methods: In this open-label cluster-randomised controlled trial, we recruited individuals from community clinics in Narsingdi district, Bangladesh. These clinics were randomly selected from a larger sample of eligible clinics, and they were assigned (1:1) to either deliver an intervention of 25 sessions, in which mothers of eligible children were shown how to support their child's development through play and interactions, or to deliver no intervention (control group). Participants were underweight children, defined as a weight-for-age Z score of −2 SDs of the WHO standard, who were aged 5–24 months and who lived near the clinic (defined as a walk of less than 30 min). Government health workers ran these sessions at the clinics as part of their routine work, and mothers and children attended fortnightly in pairs (instead of individual weekly home visits that were specified in the original programme). A subsample of children from each clinic was randomly selected for impact evaluation, and these children were assessed on the Bayley Scales of Infant and Toddler Development for their cognitive, language, and motor performance and for their behaviour with Wolke's ratings, before and after implementation of the intervention. The primary outcomes were the performance of this evaluation subsample on the Bayley and Wolke scales and their anthropometric measurements (weight, length or height, and head circumference) after 1 year of the intervention. This study is registered with ClinicalTrials.gov, number NCT02208531. Findings: Between Nov 29, 2014, and April 30, 2015, 12 054 children in 90 clinics were screened, and between six and 25 underweight children were enrolled from each clinic. From the 2423 (20%) underweight children, we excluded 656 (27%) children who lived more than 30-min walking distance from the community clinics, and 30 (1%) children whose mothers did not consent to participate. We therefore enrolled 1737 (72%) children from these 90 clinics. After randomisation, the control group clinics included 878 (51%) children (who all received no intervention) and the intervention group clinics included 859 (49%) children (who all received the child development programme sessions). Eight children from each clinic (360 [41%] children from the control group clinics and 358 [42%] children from the intervention group clinics) were randomly selected for inclusion in the evaluation subsample. Between Feb 24, 2016, and Sept 7, 2016, 344 (96%) children in control group clinics and 343 (96%) children in intervention group clinics were assessed for the primary outcome. 16 (5%) children in the control group clinics and 15 (4%) children in the intervention group clinics did not provide all data and were not included in final analyses. An intention-to-treat analysis showed that the intervention significantly improved children's cognition (effect size 1·3 SDs, 95% CI 1·1 to 1·5; p=0·006), language (1·1 SDs, 0·9 to 1·2; p=0·01), and motor composite scores (1·2 SDs, 1·0 to 1·3; p=0·006) and behaviour ratings (ranging from 0·7 SDs, 0·5 to 0·9; p=0·02; to 1·1 SDs, 1·0 to 1·2; p=0·007), but the intervention had no significant effect on growth (p values ranged from 0·05 to 0·74). Three (1%) children in the intervention group died, but their deaths were not related to the intervention. Interpretation: The extent and range of benefits of our intervention are encouraging. Health workers ran most of the sessions effectively and attendance was good, which is promising for scale-up of the intervention model. However, researchers trained and supervised the health workers, and the next step will be to determine whether the Bangladeshi ministry of health can perform these tasks. In future programmes, more attention needs to be paid to the nutrition of the children. Funding: Grand Challenges Canada (Saving Brains).

A simple ultraperformance liquid chromatography-tandem mass spectrometry assay for measurement of cortisol level in human saliva was developed and validated. Saliva samples containing cortisol were spiked with tolperisone as internal standard (IS) and extracted with a mixture of methyl tert-butyl ether and hexane (8:2, v:v). After solvent evaporation, residue was reconstituted in 100 μl mobile phase. Analysis was performed on Atlantis dC18 column (2.1 × 100 mm, 3 μm particle size) with a mobile phase composed of acetonitrile and 2 mM ammonium acetate (50:50, v:v) and delivered at a flow rate of 0.3 ml/minute. Mass spectrometry acquisition was performed with multiple reaction monitoring in positive-ion mode for cortisol and IS (m/z: 363.1 → 121.0 and 246.0 → 97.9, respectively). Retention times of cortisol and IS were about 1.35 and 2.45 minutes, respectively. The relationship between cortisol level and peak area ratio of cortisol to IS was linear in the range of 0.5-100 ng/ml. Intra- and interday coefficient of variation and bias were ≤ 9.0% and ≤12.0%, respectively. Mean extraction recoveries of cortisol and IS from saliva samples were 92% and 94%, respectively. Using the method, cortisol was found to be ≥ 86% stable in processed (24 hours at room temperature or 48 hours at -20°C) and ≥ 91% stable in unprocessed (24 hours at room temperature or 20 weeks at -20°C) saliva samples. Further, the method was successfully applied to determine daily cortisol profile in saliva samples of a healthy volunteer.

Sensitivity, which denotes the proportion of subjects correctly given a positive assignment out of all subjects who are actually positive for the outcome, indicates how well a test can classify subjects who truly have the outcome of interest. Specificity, which denotes the proportion of subjects correctly given a negative assignment out of all subjects who are actually negative for the outcome, indicates how well a test can classify subjects who truly do not have the outcome of interest. Positive predictive value reflects the proportion of subjects with a positive test result who truly have the outcome of interest. Negative predictive value reflects the proportion of subjects with a negative test result who truly do not have the outcome of interest. Sensitivity and specificity are inversely related, wherein one increases as the other decreases, but are generally considered stable for a given test, whereas positive and negative predictive values do inherently vary with pre-test probability (e.g., changes in population disease prevalence). This article will further detail the concepts of sensitivity, specificity, and predictive values using a recent real-world example from the medical literature.

Background: Primary small cell carcinoma of the kidney (PSCCK) is exceedingly rare and data on disease characteristics and outcomes are sparse. This study examines a nationally-representative cancer registry to better characterize PSCCK. Methods: We queried the National Cancer Database to identify patients with histology-confirmed PSCCK from 2004 to 2015. Adjusted Cox proportional hazards regression and Kaplan–Meier analyses were employed to assess predictors of mortality and estimate median survival time, respectively. Results: A total of 110 patients were included (47:53% female:male, 77% ≥60 years of age, 86% Caucasian). Significant predictors of mortality included female sex, age 60–69 years, treatment at an Integrated Network Cancer Program, stage cM1, and lack of surgical and chemoradiotherapy treatment. Independent protective factors were high socioeconomic status and treatment at an Academic Research Program. The estimated median overall survival time was 9.31 (95% CI 7.28–10.98) months for all patients. No differences in estimated survival time were observed across individual treatment modalities among those patients who underwent treatment (p = 0.214). Conclusions: PSCCK is an aggressive malignancy with a median survival time of less than one year. Future studies that correlate clinical tumor staging with specific treatment modalities are needed to optimize and individualize management.

Background: A renewed interest has emerged in the use of bolus or intravenous (IV) infusion of phenylephrine for management of hypotension during spinal anesthesia (SA) for caesarean section to achieve optimal maternal and neonatal outcome. The aim of our study was to investigate the efficacy of using three different phenylephrine infusion regimens to maintain maternal baseline blood pressure during SA for caesarean delivery. Materials and Methods: Ninety parturients undergoing SA for elective caesarean delivery received an IV infusion of phenylephrine in one of three different concentration ratios. The groups contained a potency equivalent of 100 μg/min, 80μg/min, and 60 μg/min infusion doses. The infusions were adjusted to maintain systolic blood pressure (SBP) near the baseline until uterine incision. Hemodynamic changes in mother and umbilical cord blood gases were compared. Results: As concentration of phenylephrine increased, following significant trends were noticed: in group A, 10/29 (34.5%) patients had hypotension as compared to 2/28 (7.4%) patients in group B and 4/28 (14.3%) patients in group C. On the other hand, we found that the incidence of hypertension and bradycardia was higher in groups B (22/28; 4/28) and C (26/28; 10/28) as compared to those in group A (3/29; 2/29), respectively. Neonatal acid-base status in all three groups was favorable. Conclusions: As the concentration of phenylephrine increased, the tendency for SBP to be above the baseline increased, along with an incidence of bradycardia. Therefore, we conclude that low dose infusion regimens of phenylephrine, i.e. between 60 μg/min and 80 μg/min, will be more effective in prevention of hypotension during SA for caesarean delivery.

Objective: To determine the delay in diagnosis of various types of congenital heart defects in children and factors associated with such delay. Patients and Methods: For this observational study, 354 patients having congenital heart disease (CHD) presenting for the first time to the Department of Cardiology, Children's Hospital, Lahore, Pakistan, between January 1, 2015 and June 30, 2015, were enrolled after obtaining informed verbal consent from the guardian of each child. Demographical profile and various factors under observation were recorded. Results: Among the 354 enrolled children (M: F 1.7:1) with age ranging from 1 to 176 months (median 24 months), 301 (85.1%) had delayed diagnosis of CHD (mainly acyanotic 65.3%), with median delay (8 months). Main factors for delay were delayed first consultation to a doctor (37.2%) and delayed diagnosis by a health professional (22.5%). Other factors included delayed referral to a tertiary care hospital (13.3%), social taboos (13.0%), and financial constraints (12.3%). Most children were delivered outside hospital settings (88.7%). Children with siblings less than two (40%) were less delayed than those having two or more siblings (60%, P < 0.001). Conclusion: Diagnosis of congenital heart defect was delayed in majority of patients. Multiple factors such as lack of adequately trained health system and socioeconomic constraints were responsible for the delay. There is a need to develop an efficient referral system and improve public awareness in developing countries for early diagnosis and management of such children.

Hypertension is one of the most important factors responsible for cardiovascular ailments worldwide. It has been observed that herbal products and alternative herbal therapies played a significant role in decreasing hypertension. The aim of the current study is to provide significant ethnopharmacological information, both qualitative and quantitative on medicinal plants related to hypertension from Northern Pakistan. The documented data were quantitatively analyzed for the first time in this area. A total of 250 participants were interviewed through semi-structured discussions and questionnaires. Quantitative indices including FC (Frequency citation), FIV (Family importance value), RFC (Relative frequency of citation) and DCI (Disease Consensus index) were calculated. A total of 192 plant species, belonging to 77 families were reported to be used in treatment of hypertension in Northern Pakistan. The most dominant life form reported was herbs (54%), with decoction (72 reports) and leaves (55.1%) were commonly utilized plant part. Highest FIV was recorded in Lamiaceae (327 FIV). RFC ranged from 0.08 to 1.08% while DCI varied from 0.233 to 0.000. In this study original data was compared with thirty one previous national and international published papers from neighboring region to compare the medicinal uses and obtain some novel plant species. About 42% of the medicinal plant species were reported for the first time in treatment of hypertension in comparison to these 31 published papers. Different phytochemical activities of antihypertensive plants were also reported from literature. This research work documents the traditional knowledge of medicinal plants usage and provides baseline in designing clinical trials and pharmacological analysis for treatment of hypertension.

BACKGROUND: Vitamin D deficiency is common in many countries, including Saudi Arabia. Various population-level preventive measures have been implemented, including milk fortification with vitamin D. OBJECTIVES: The main objective of the study was to determine vitamin D levels in fortified low fat cow milk on the Saudi Arabian market and to compare it with the label claims. DESIGN: Cross-sectional study. SETTING: Academic research center. MATERIALS AND METHODS: Five milk batches from five major producers were purchased in five replicates from five major retail stores in Riyadh, Saudi Arabia. We used a validated liquid chromatography assay to measure vitamin D levels. All samples were producer labeled to contain 400 IU/L (10 ng/mL) vitamin D and were analyzed within the first 40% of their validity period. Intra-batch, inter-batch, and inter-producer variations were determined as a coefficient of variation. MAIN OUTCOME MEASURES: Intra-batch, inter-batch and inter-producer variations in vitamin D level. RESULTS: Overall, mean (SD) measured vitamin D level was 10.2 (1.6) with a range of 7.1–13.9 ng/mL. In 25 of 125 samples (20%), the vitamin D level was outside ± 20% of the label claim (10.4% under-fortified, 9.6% over fortified). Intra-batch, inter-batch, and intra-producer variations were 1.6–20.8%, 8.2–20.8%, and 16.1%, respectively. CONCLUSIONS: Vitamin D content in fortified low fat cow milk on the Riyadh market matches label claim in 85% of the samples of major retailers. Variations from label claim in 15% of the samples are small and may not be clinically important. LIMITATIONS: This study was limited to five major retailers in the Riyadh area and did not examine full-fat or non-fat milk samples.

Although considerable research has been directed at developing materials for ballistic protection, considerably less has been conducted to address non-firearm threats. Even fewer studies have examined the incorporation of particle-laden elastomers with textiles for spike, knife, and needle protection. We report on a new composite consisting of ultra-high-molecular-weight polyethylene (UHMWPE) fabric impregnated with nanoparticle-loaded elastomer, specifically designed for spike- and needle-resistant garments. Failure analysis and parametric studies of particle-loading and layer-count were conducted using a mixture of SiC and polyurethane at 0, 30, and 50 wt.%. The maximum penetration resistance force of a single-layer of uncoated fabric increased up to 218−229% due to nanoparticle loading. Multiple-layer stacks of coated fabric show up to 57% and 346% improvement in spike puncture and hypodermic needle resistance, respectively, and yet were more flexible and 21−55% thinner than a multiple-layer stack of neat fabric (of comparable areal density). We show that oxygen-plasma-treatment of UHMWPE is critical to enable effective coating.

Privacy has been found to be the major impediment and hence the area to be worked out for the provision of Location Based Services in the wide sense. With the emergence of smart, easily portable, communicating devices, information acquisition is achieving new domains. The work presented here is an extension of the ongoing work towards achieving privacy for the present day emerging communication techniques. This work emphasizes one of the most effective real-time privacy enhancement techniques called Mix-Zones. In this paper, we have presented a model of a secure road network with Mix-Zones getting activated on the basis of spatial as well as temporal factors. The temporal factors are ascertained by the amount of traffic and its flow. The paper also discusses the importance of the number of Mix-Zones a user traverses and their mixing effectiveness. We have also shown here using our simulations which are required for the real-time treatment of the problem that the proposed transient Mix-Zones are part of a viable and robust solution towards the road network privacy protection of the communicating moving objects of the present scenario.

The ovary receives a finite pool of follicles during fetal life. Atresia remains the major form of follicular expenditure at all stages since development of ovary. The follicular reserve, however, declines at an exponential rate leading to accelerated rate of decay during the years preceding menopause. We examined if diminished follicle reserve that characterizes ovarian aging impacts the attrition rate. Premature ovarian aging was induced in rats by intra-embryonic injection of galactosyltransferase-antibody on embryonic day 10. On post-natal day 35 of the female litters, either a wedge of fat (sham control) or a wild type ovary collected from 25-day old control rats, was transplanted under the ovarian bursa in both sides. Follicular growth and atresia, and ovarian microenvironment were evaluated in the follicle-deficient host ovary and transplanted ovary by real time RT-PCR analysis of growth differentiation factor-9, bone morphogenetic protein 15, and kit ligand, biochemical evaluation of ovarian lipid peroxidation, superoxide dismutase (SOD) and catalase activity, and western blot analysis of ovarian pro- and anti-apoptotic factors including p53, bax, bcl2, and caspase 3. Results demonstrated that the rate of follicular atresia, which was highly preponderant in the follicle-deficient ovary of the sham-operated group, was significantly prevented in the presence of the transplanted ovary. As against the follicle-deficient ovary of the sham-operated group, the follicle-deficient host ovary as well as the transplanted ovary in the ovary-transplanted group exhibited stimulated follicle growth with increased expression of anti-apoptotic factors and down regulation of pro-apoptotic factors. Both the host and transplanted ovaries also had significantly lower rate of lipid peroxidation with increased SOD and catalase activity. We conclude that the declining follicular reserve is perhaps the immediate thrust that increases the rate of follicle depletion during the final phase of ovarian life when the follicle reserve wanes below certain threshold size.

The management of recurrent pregnancy loss (RPL) still remains a great challenge, and women with polycystic ovarian syndrome (PCOS) are at a greater risk for spontaneous abortion. Treatment with low-molecular-weight heparin (LMWH) has become an accepted treatment option for women with RPL; however, the subgroup of women, who are likely to respond to LMWH, has not been precisely identified. The present study evaluated the efficacy of LMWH with reference to PCOS and associated metabolic phenotypes including hyperhomocysteinemia (HHcy), insulin resistance (IR) and obesity. This prospective observational study was conducted at Institute of Reproductive Medicine, Kolkata, India. A total of 967 women with history of 2 or more consecutive first trimester abortions were screened and 336 were selected for the study. The selected patients were initially divided on the basis of presence or absence of PCOS, while subsequent stratification was based on HHcy, IR and/or obesity. The subjects had treatment with aspirin during one conception cycle and aspirin-LMWH combined anticoagulant therapy for the immediate next conception cycle, if the first treated cycle was unsuccessful. Pregnancy salvage was the sole outcome measure. The overall rate of pregnancy salvage following aspirin therapy was 43.15%, which was mostly represented by normohomocysteinemic women, while the salvage rate was lower in the HHcy populations irrespective of the presence or absence of PCOS, IR, or obesity. By contrast, aspirin-LMWH combined therapy could rescue 66.84% pregnancies in the aspirin-failed cases. Logistic regression analyses showed that HHcy remained a significant factor in predicting salvage rates in the PCOS, IR, and obese subpopulations controlled for other confounding factors. With regard to pregnancy salvage, combined anticoagulant therapy with aspirin and LMWH conferred added benefit to those with HHcy phenotype.

Recurrent pregnancy loss (RPL) in polycystic ovary syndrome (PCOS), which occurs in ∼50% of total pregnancies is a frequent obstetric complication. Among the several hypotheses, insulin resistance (IR), obesity and hyperhomocysteinemia (HHcy) play significant role/s in RPL. This study was conducted to assess the link between elevated levels of homocysteine and IR in PCOS-associated women with RPL in Kolkata, India. A retrospective study was conducted of one hundred and twenty six PCOS women (

Correspondence noise is a major factor limiting direction discrimination performance in random-dot kinematograms. In the current study we investigated the influence of correspondence noise on Dmax, which is the upper limit for the spatial displacement of the dots for which coherent motion is still perceived. Human direction discrimination performance was measured, using 2-frame kinematograms having leftward/rightward motion, over a 200-fold range of dot-densities and a four-fold range of dot displacements. From this data Dmax was estimated for the different dot densities tested. A model was proposed to evaluate the correspondence noise in the stimulus. This model summed the outputs of a set of elementary Reichardt-type local detectors that had receptive fields tiling the stimulus and were tuned to the two directions of motion in the stimulus. A key assumption of the model was that the local detectors would have the radius of their catchment areas scaled with the displacement that they were tuned to detect; the scaling factor k linking the radius to the displacement was the only free parameter in the model and a single value of k was used to fit all of the psychophysical data collected. This minimal, correspondence-noise based model was able to account for 91% of the variability in the human performance across all of the conditions tested. The results highlight the importance of correspondence noise in constraining the largest displacement that can be detected.

Clinical evidence suggests an association between galactosaemia and premature ovarian insufficiency (POI); however, the mechanism still remains unresolved. Experimental galactose toxicity in rats produces an array of ovarian dysfunction including ovarian development with deficient follicular reserve and follicular resistance to gonadotrophins that characterize the basic tenets of human POI. The present investigation explores if galactose toxicity in rats attenuates the bioactivity of gonadotrophins or interferes with their receptor competency, and accelerates the rate of follicular atresia. Pregnant rats were fed isocaloric food-pellets supplemented with or without 35% D-galactose from day-3 of gestation and continuing through weaning of the litters. The 35-day old female litters were autopsied. Serum galactose-binding capacity, galactosyltransferase (GalTase) activity, and bioactivity of FSH and LH together with their receptor competency were assessed. Ovarian follicular atresia was evaluated in situ by TUNEL. The in vitro effects of galactose were studied in isolated whole follicles in respect of generation of reactive oxygen species (ROS) and expression of caspase 3, and in isolated granulosa cells in respect of mitochondrial membrane potential, expression of p53, and apoptosis. The rats prenatally exposed to galactose exhibited significantly decreased serum GalTase activity and greater degree of galactose-incorporation capacity of sera proteins. LH biopotency and LH-FSH receptor competency were comparable between the control and study population, but the latter group showed significantly attenuated FSH bioactivity and increased rate of follicular atresia. In culture, galactose increased follicular generation of ROS and expression of caspase 3. In isolated granulosa cells, galactose disrupted mitochondrial membrane potential, stimulated p53 expression, and induced apoptosis in vitro; however co-treatment with either FSH or estradiol significantly prevented galactose-induced granulosa cell p53 expression. We conclude that the ovotoxic effects of galactose involves attenuation of FSH bioactivity that renders the ovary resistant to gonadotrophins leading to increased granulosa cell expression of p53 and follicular atresia.

BackgroundAlthough the Decipher genomic classifier has been validated as a prognostic tool for several prostate cancer endpoints, little is known about its role in assessing the risk of biopsy reclassification for patients on active surveillance, a key event that often triggers treatment.ObjectiveTo evaluate the association between Decipher genomic classifier scores and biopsy Gleason upgrading among patients on active surveillance.Design setting and participantsThis was a retrospective cohort study among patients with low- and favorable intermediate-risk prostate cancer on active surveillance who underwent biopsy-based Decipher testing as part of their clinical care.Outcome measurements and statistical analysisWe evaluated the association between the Decipher score and any increase in biopsy Gleason grade group (GG) using univariable and multivariable logistic regression. We compared the area under the receiver operating characteristic curve (AUC) for models comprising baseline clinical variables with or without the Decipher score.Results and limitationsWe identified 133 patients for inclusion with a median age of 67.7 yr and median prostate-specific of 5.6 ng/ml. At enrollment, 75.9% had GG1 and 24.1% had GG2 disease. Forty-three patients experienced biopsy upgrading. On multivariable logistic regression, the Decipher score was significantly associated with biopsy upgrading (odds ratio 1.37 per 0.10 unit increase, 95% confidence interval [CI] 1.05-1.79; p = 0.02). The Decipher score was associated with upgrading among patients with biopsy GG 1 disease, but not GG2 disease. The discriminative ability of a clinical model (AUC 0.63, 95% CI 0.51-0.74) was improved by integration of the Decipher score (AUC 0.69, 95% CI 0.58-0.80).ConclusionsThe Decipher genomic classifier score was associated with short-term biopsy Gleason upgrading among patients on active surveillance.Patient summaryThe results from this study indicate that among patients with prostate cancer undergoing active surveillance, those with higher Decipher scores were more likely to have higher-grade disease found over time. These findings indicate that the Decipher test might be useful for guiding the intensity of monitoring during active surveillance, such as more frequent biopsy for patients with higher scores.