The Effect of Self-Reported Race on Noninvasive Prenatal Screening Test Characteristics.

OBJECTIVE: Low fetal fraction (FF) on cell-free DNA (cfDNA)-based noninvasive prenatal screening (NIPS) is a common etiology for indeterminate results. As maternal Black race is implicated as a risk factor for low FF and more indeterminate results, we sought to evaluate this association. STUDY DESIGN: This was a single-institution, retrospective cohort study of cfDNA-based NIPS performed between May 2017 and May 2022 with complete clinical data abstraction. We compared FF, indeterminate rates, and total cfDNA concentration among self-reported Black, White, and Other groups from NIPS results from 2017 to 2022 with full clinical data abstraction. Using linear regression and interaction testing, we evaluated associations between self-reported race, FF, indeterminate rate, and total cfDNA concentration. RESULTS: In total, 1,591 participants met the inclusion criteria; 70.8% (n = 1,126) self-identified as White, 6.9% (n = 110) as Black, and 22.3% (n = 355) self-identified with another race. Mean FF was not different between the White, Black, or Other groups (11.8 vs. 11.2 vs. 11.7%, respectively, p = 0.52). This remained true after adjusting for body mass index (BMI), gestational age (GA) at draw, and fetal sex (all p > 0.17). Interaction testing for FF and total cfDNA by race with BMI, GA at draw, and fetal sex demonstrated no effect modification. CONCLUSION: In our population, maternal self-identified race, particularly Black race, does not affect FF. Biological plausibility for race-based differences on clinical tests requires ongoing thoughtful consideration. KEY POINTS: · NIPS is widely used to screen for fetal aneuploidy.. · FF is an important test metric, and low FF is associated with adverse outcomes, like aneuploidy.. · In existing studies, Black race is implicated as a risk factor for lower FF.. · Our study found no differences in FF between groups by self-reported race.. · Biological plausibility for race-based differences on clinical tests requires ongoing consideration..

Prevalence of Cerebrovascular Accidents Among the US Population With Substance Use Disorders: A Nationwide Study.

Introduction Globally, stroke is one of the top ten causes of death. The incidence of stroke in patients aged 44 years and younger was noted to have risen over the past three decades. This rise in stroke diagnosis among young adults could be attributed to multiple reasons, including the rising prevalence of comorbidities like diabetes, hypertension, substance use disorders (SUDs), etc. Aim & objectives This study's primary aim was to evaluate the prevalence of stroke in the US population and the prevalence of SUDs amongst patients with a prior history of stroke. The secondary aim was to evaluate the association between Stroke and SUDs. Methods Our population was obtained from the National Health and Nutrition Examination Survey (NHANES) between the years 2013 to 2018. We identified respondents diagnosed with stroke using the questionnaire and the history of various SUDs amongst this population. The data were analyzed using SAS software (Version 9.4). We performed univariate analysis using the chi-square and Mann-Whitney test, and a p-value of <0.05 was considered statistically significant. Results Two hundred sixty-four thousand seven hundred forty (264,740) respondents were included in this study, and 10435 (3.94%) respondents were noted to have a history of stroke. The population subset with a stroke diagnosis was older (68 years vs. 51 years). Higher prevalence was noted among the female sex (52.14% females vs. 47.86% males), Non-Hispanic white ethnicity, followed by Non-Hispanic black & then other Hispanics (47.56% vs.25.47% vs. 7.82%), and those belonging to a lower annual household income of $0-$25,000 and $25,000-$65,000 ( 46.61% vs. 35.93% ). (p<0.0001). After adjusting for socio-demographics and coexisting comorbidities, e-cigarette [OR: 2.03; 95% CI: 2.03-2.03], cocaine [OR: 1.54; 95%CI:1.54-1.54], heroin [OR: 1.83; 95%CI: 1.83-1.83], marijuana or hashish [OR: 1.01; 95% CI: 1.01-1.01], were observed to have an association with higher odds of stroke than the population without a history of using these illicit drugs.  Conclusion Among respondents with a history of stroke, the use of cocaine was most prevalent, followed by marijuana/hashish, heroin, e-cigarettes, and injecting illegal drugs. The odds of having a stroke were two times higher in the population using an e-cigarette and higher among those using heroin, cocaine, and marijuana/ hashish. The Government should plan policy changes to treat SUDs in the USA, which could help reduce the stroke burden. Recall that bias and geographic variations in response rate by participants of the study were the limitations of our survey-based study.

TaqMan Array Card testing of participant-collected stool smears to determine the pathogen-specific epidemiology of travellers' diarrhoea†.

BACKGROUND: We assessed the compliance with self-collection of stool smears on Whatman® FTA® Elute Card (FTA Card) and detection of travellers' diarrhoea (TD)-associated pathogens by using a quantitative Polymerase Chain Reaction (PCR) assay [customized TaqMan® array card (TAC)] in a prospective, observational cohort of travellers. METHODS: Enrolled travellers documented symptoms on a travel diary and collected an FTA Card during a diarrhoeal episode, or at the end of travel if they remained asymptomatic. TAC testing was performed on FTA Cards from TD cases and 1:1 matched asymptomatic controls and 1:1 matched loose stool cases that did not meet TD criteria. Odds ratios were used to determine the association between detected pathogens and TD. RESULTS: Of 2456 travellers, 484 (19.7%) completed an illness diary and met TD criteria, and 257 (53.1%) collected an FTA Card during the TD episode. FTA Cards were stored for a median of 2 years at room temperature (IQR: 1-4 years) before extraction and testing. The overall TAC detection rate in TD cases was 58.8% (95% CI: 52.5-64.8). Enterotoxigenic Escherichia coli was the most common pathogen in TD cases (26.8%), and 3.5% of samples were positive for norovirus. The odds of detecting TD-associated pathogens in 231 matched cases and asymptomatic controls were 5.4 (95% CI: 3.6-8.1) and 2.0 (95% CI: 1.1-3.7) in 121 matched TD and loose stool cases (P < 0.05). Enteroaggregative E. coli was the most common pathogen detected in asymptomatic controls and loose stool cases. Detection of diarrhoeagenic E. coli, Shigella/enteroinvasive E. coli and Campylobacter spp. was significantly associated with TD. CONCLUSION: FTA Cards are a useful adjunct to traditional stool collection methods for evaluating the pathogen-specific epidemiology of TD in austere environments. Qualitative detection of pathogens was associated with TD. Measures to improve compliance and quality of FTA Card collection with decreased storage duration may further optimize detection.

Soybean oil and coconut oil enhance the absorption of chlorogenic acid in humans.

The effect of a mainly polyunsaturated oil (soybean oil) and a mainly medium chain triglyceride oil (coconut oil) on the absorption of the phenolic antioxidant chlorogenic acid (5-caffeoylquinic acid) was investigated using 90 healthy volunteers. Serum concentrations and the absorbed percentages of chlorogenic acid of volunteers who received chlorogenic acid without oils (0.006 ± 0.001 mg/ml, 5.7 ± 0.2%), chlorogenic acid with soybean oil (0.012 ± 0.001 mg/ml, 11.8 ± 1.3%), and chlorogenic acid with coconut oil (0.067 ± 0.014 mg/ml, 65.6 ± 18.1%) were significantly different from each other (p < .05). There was a strong positive correlation between the increase in serum and plasma antioxidant capacity and the absorption of chlorogenic acid. The major fatty acid of each of soybean oil and coconut oil also improved the permeability of chlorogenic acid in Caco-2 cell monolayers. The results suggest that the tested edible oils may improve the nutritional value of chlorogenic acid-containing foods by improving the absorption of chlorogenic acid. PRACTICAL APPLICATIONS: Small polar antioxidants such as phenolic acids and flavonoids are poorly absorbed through the intestinal epithelium. Chlorogenic acid was used in the present study as a model for small polar phenolic antioxidants. According to the present study, soybean oil with mainly polyunsaturated fatty acids and coconut oil with mainly medium chain fatty acids improve the absorption of these antioxidants. These findings suggest that proper planning of diets or food supplements containing phenolic antioxidants with medium chain or polyunsaturated fatty acid-rich edible oils may enhance the nutritional benefits expected from phenolic antioxidants.

A bibliometric analysis of obstetrics and gynecology articles with highest relative citation ratios, 1980 to 2019.

BACKGROUND: The Relative Citation Ratio is a novel bibliometric tool that quantifies the impact of research articles. The objectives of this study were to identify the 100 obstetrics and gynecology articles with the highest relative citation ratios, evaluate how characteristics of these articles changed over time, and compare characteristics of these articles with top-cited obstetrics and gynecology articles. OBJECTIVE: We undertook a cross-sectional bibliometric study to examine the 100 obstetrics and gynecology articles with the highest relative citation ratios and the top 100 cited articles in the National Institutes of Health Open Citations Collection from 1980 to 2019. STUDY DESIGN: We identified every obstetrics and gynecology article published from 1980 to 2019 that was indexed in the National Institutes of Health Open Citations Collection. The top 100 articles with the highest relative citation ratios and the top 100 cited articles were selected for further review. Each article was evaluated using metrics of influence, translation, and other characteristics. We compared the top 100 articles with the highest relative citation ratios published from 1980 to 1999 versus 2000 to 2019 and characteristics of the top 100 articles with the highest relative citation ratios versus the top 100 top-cited articles (after excluding those on both lists). Means, standard deviations, and mean differences with corresponding 95% confidence intervals were calculated. Associations were expressed as relative risks (95% confidence interval). RESULTS: A total of 323,673 obstetrics and gynecology articles were published between 1980 and 2019. Among the top 100 articles with the highest relative citation ratios, most were observational studies (36%), reviews (26%), and consensus statements (21%). There were only 5 randomized clinical trials. Compared with the articles with the highest relative citation ratios published from 1980 to 1999, articles published from 2000 to 2019 were more likely about benign gynecology (relative risks, 1.3; 95% confidence interval, 0.6-2.8) and less likely about gynecology-oncology (relative risks, 0.6; 95% confidence interval, 0.2-1.9) and urogynecology (relative risks, 0.6; 95% confidence interval, 0.1-3.3). The articles after 2000 were more likely about systematic reviews (relative risks, 7.7; 95% confidence interval, 1.0-58.3) and consensus statements (relative risks, 5.1; 95% confidence intervals, 1.6-16.3) and were published as open access articles (relative risks, 1.3; 95% confidence interval, 0.9-2.0). There were 60 articles in common between the top 100 articles with the highest relative citation ratios and the top 100 cited articles. Compared with articles that were top cited (after excluding articles on both lists), articles with the highest relative citation ratios received fewer mean citations (266.9 [135.3] vs 514.3 [54.6]; mean differences, 247.4; 95% confidence interval, 201.5-293.3) but had higher numbers of citations per year (37.5 [4.1] vs 31.6 [8.1]; mean difference, -5.9; 95% confidence interval, -14.6 to -2.7). Compared with the articles with the highest relative citation ratios, top-cited articles were more likely to address gynecology topics (relative risk, 1.6; 95% confidence interval, 1.1-2.5), less likely to be randomized clinical trials (relative risk, 0.7; 95% confidence interval, 0.1-3.8), and less likely to be published as open access articles (relative risk, 0.52; 95% confidence interval, 0.31-0.86). CONCLUSION: The Relative Citation Ratio is a novel bibliometric tool that does not rely on absolute citation rates and provides unique insight into the dissemination of knowledge in obstetrics and gynecology. Nearly half of the influential obstetrics and gynecology articles identified with this metric would not have been recognized as citation classics by conventional bibliometric analysis.

Renal Safety of Intravenous Gadolinium-enhanced MRI in Patients Following Liver Transplantation.

BACKGROUND: Intravenous contrast-enhanced imaging is invaluable in diagnosing pathology following liver transplantation. Given the potential risk of contrast nephropathy associated with iodinated computed tomography contrast, alternate contrast modalities need to be examined, especially in the setting of renal insufficiency. The purpose of this study was to examine the renal safety of MRI with gadolinium following liver transplantation. METHODS: The study involved a retrospective analysis of 549 cases of abdominal MRI with low-dose gadobenate dimeglumine in liver transplant recipients at a single center. For each case, serum creatinine values before and after the MRI were compared. In addition, cases were analyzed for the development of nephrogenic systemic fibrosis. RESULTS: Pre-MRI creatinine values ranged from 0.32 to 6.57 mg/dL (median, 1.28 g/dL), with 191 cases having values ≥1.5 mg/dL (median, 1.86 g/dL). A comparison of the pre- and post-MRI creatinine values showed no significant difference, including those patients with pre-MRI values ≥1.5 mg/dL (mean change of -0.04 [95% confidence interval, -0.07 to -0.01; P = 0.004]). No cases of nephrogenic systemic fibrosis were noted. CONCLUSIONS: Our findings suggest that, irrespective of baseline renal function, MRI with gadobenate dimeglumine is a nonnephrotoxic imaging modality in liver transplant recipients. Importantly, this intravenous contrast-enhanced imaging modality can be considered in those posttransplant patients who have a contraindication to computed tomography contrast due to renal insufficiency.

Deep sequencing identified potential miRNAs involved in defence response, stress and plant growth characteristics of wild genotypes of cardamom.

Cardamom has long been used as a food flavouring agent and in ayurvedic medicines for mouth ulcers, digestive problems and even depression. Extensive occurrence of pests and diseases adversely affect its cultivation and result in substantial reductions in total production and productivity. Numerous studies revealed the significant role of miRNAs in plant biotic stress responses. In the current study, miRNA profiling of cultivar and wild cardamom genotypes was performed using an Ion Proton sequencer. We identified 161 potential miRNAs representing 42 families, including monocot/tissue-specific and 14 novel miRNAs in both genotypes. Significant differences in miRNA family abundance between the libraries were observed in read frequencies. A total of 19 miRNAs (from known miRNAs) displayed a twofold difference in expression between wild and cultivar genotypes. We found 1168 unique potential targets for 40 known miRNA families in wild and 1025 potential targets for 42 known miRNA families in cultivar genotypes. The differential expression analysis revealed that most miRNAs identified were highly expressed in cultivars and, furthermore, lower expression of miR169 and higher expression of miR529 in wild cardamom proved evidence that wild genotypes have stronger drought stress tolerance and floral development than cultivars. Potential targets predicted for the newly identified miRNAs from the miRNA libraries of wild and cultivar cardamom genotypes involved in metabolic and developmental processes and in response to various stimuli. qRT-PCR confirmed miRNAs were differentially expressed between wild and cultivar genotypes. Furthermore, four target genes were validated experimentally to confirm miRNA-mRNA target pairing using RNA ligase-mediated 5' Rapid Amplification of cDNA Ends (5'RLM-RACE) PCR.

Data on identification of conserved and novel miRNAs in Elettaria cardamomum.

Elettaria cardamomum (L.) Maton, or small cardamom referred as 'queen of spices', is a perennial herbaceous rhizomatous monocot of the family Zingiberaceae. Cardamom seeds and fruits are the economically significant parts and effectively used as a traditional medicine, food additive and flavoring agent. In the present study, using Ion Proton next generation sequencing technology we performed the small RNA sequencing, conserved and novel miRNA predictions of a wild and five cultivar genotypes of cardamom. Small RNA sequencing generated a total of 5,451,328 and 2,756,250 raw reads for wild and cultivar cardamom respectively. The raw data was submitted to SRA database of NCBI under the accession numbers and SRX2273863 (wild) and SRX2273862 (cultivars). The raw reads were quality filtered and predicted conserved and novel miRNAs for wild and cultivar cardamom. The predicted miRNAs, miRNA-targets and functional annotations might provide valuable insights into differences between wild progenitor and cultivated cardamom.

Diagnosis disclosure to adolescents living with HIV in rural Kenya improves antiretroviral therapy adherence and immunologic outcomes: A retrospective cohort study.

BACKGROUND & AIMS: Emphasis on adolescent HIV has increased worldwide as antiretroviral treatment has greatly extended life expectancies of HIV-positive children. Few evidence-based guidelines exist on the optimal time to disclose to an adolescent living with HIV (ALHIV); little is known about the medical effects of disclosure. This study looked to determine whether disclosure is associated with improved medical outcomes in ALHIV. Prior work has tended to be qualitative, cross-sectional, and with an emphasis on psychosocial outcomes. This paper addresses the adolescent cohort retrospectively (longitudinally), building upon what is already known about disclosure. METHODS: Retrospective, longitudinal clinical record reviews of ALHIV seen at Kericho District Hospital between April 2004 and November 2012 were performed. Patient demographics and clinical outcomes were systematically extracted. The student's t-test was used to calculate changes in mean CD4 count, antiretroviral therapy (ART), and cotrimoxazole adherence pre- vs. post-disclosure. Linear regression modelling assessed for trends in those clinical outcomes associated with age of disclosure. RESULTS: Ninety-six ALHIV (54 female, 42 male) were included; most (73%) entered care through the outpatient department. Nearly half were cared for by parents, and 20% experienced a change in their primary caregiver. The mean time in the study was 2.47 years; mean number of visits 10.97 per patient over the mean time in the study. Mean disclosure age was 12.34 years. An increase in mean ART adherence percentage was found with disclosure (0.802 vs. 0.917; p = 0.0015). Younger disclosure age was associated with significantly higher mean CD4 counts over the course of the study (p = 0.001), and a nonsignificant trend toward a higher mean ART adherence percentage (p = 0.055). CONCLUSION: ART adherence and improved immunologic status are both associated with disclosure of HIV infection to adolescent patients. Disclosure of an HIV diagnosis to an adolescent is an important means to improve HIV care.

Myofibromatosis: Utility of fine needle aspiration cytology in the diagnosis of an underreported entity.

Myofibromatosis (MFS) was recognized as a distinct form of childhood fibromatosis. Infantile myofibromatosis (IMF) is now identified as a solitary or multicentric tumor that predominantly occurs in neonates and infants. The adult counterpart of IMF, though of rare occurrence, is identified and is known as MFS. Morphological diagnosis of MFS is made by histopathological examination of the biopsy or surgically excised mass and confirmed on the basis of specific immunoprofile. We report a case of multicentric MFS occurring in an adolescent in whom diagnosis was suggested on the basis of fine needle aspiration cytology (FNAC) that avoided surgical excision of multiple nodules. The diagnosis was later confirmed on histopathological study and contributory immunohistochemical markers. Details of the clinical features and cytological diagnosis of the case are provided to diminish the paucity of available literature on FNAC diagnosis of the rare disease.

Transcriptome profiling of Elettaria cardamomum (L.) Maton (small cardamom).

Elettaria cardamomum (L.) Maton, known as 'queen of spices, is a perennial herbaceous monocot of the family Zingiberaceae, native to southern India. Cardamom is an economically valuable spice crop and used widely in culinary and medicinal purposes. In the present study, using Ion Proton RNA sequencing technology, we performed transcriptome sequencing and de novo transcriptome assembly of a wild and five cultivar genotypes of cardamom. RNA-seq generated a total of 22,811,983 (92 base) and 24,889,197 (75 base) raw reads accounting for approximately 8.21GB and 7.65GB of sequence data for wild and cultivar genotypes of cardamom respectively. The raw data were submitted to SRA database of NCBI under the accession numbers SRX1141272 (wild) and SRX1141276 (cultivars). The raw reads were quality filtered and assembled using MIRA assembler resulted with 112,208 and 264,161contigs having N50 value 616 and 664 for wild and cultivar cardamom respectively. The assembled unigenes were functionally annotated using several databases including PlantCyc for pathway annotation. This work represents the first report on cardamom transcriptome sequencing. In order to generate a comprehensive reference transcriptome, we further assembled the raw reads of wild and cultivar genotypes which might enrich the plant transcriptome database and trigger advanced research in cardamom genomics.

Prediction of Relapse After Discontinuation of Antipsychotic Treatment in Alzheimer's Disease: The Role of Hallucinations.

OBJECTIVE: In Alzheimer's disease, antipsychotic medications are often used for a period, with relief of symptoms, and then discontinued, after which relapse may occur. The authors sought to determine which neuropsychiatric symptoms predict relapse. METHOD: In the Antipsychotic Discontinuation in Alzheimer's Disease trial, 180 patients with Alzheimer's disease and symptoms of agitation or psychosis were treated with risperidone for 16 weeks, after which patients who responded (N=110) were randomly assigned to continue risperidone for 32 weeks, to continue risperidone for 16 weeks followed by switch to placebo for 16 weeks, or to receive placebo for 32 weeks. As reported previously, discontinuation of risperidone was associated with a two- to fourfold increased risk of relapse over 16-32 weeks. In planned post hoc analyses, the authors examined associations between the 12 symptom domains in the Neuropsychiatric Inventory (NPI) and relapse in the first 16-week phase after randomization. RESULTS: Compared with patients with mild hallucinations or no hallucinations, patients with severe hallucinations as a presenting symptom at baseline had a higher likelihood of relapse (hazard ratio=2.96, 95% CI=1.52, 5.76). This effect was present for the subgroup with auditory hallucinations, but not the subgroup with visual hallucinations. Among patients with baseline hallucinations, 13 of 17 (76.5%) who discontinued risperidone relapsed, compared with 10 of 26 (38.5%) who continued risperidone (p<0.02). This group difference remained significant for severe (77.8%) compared with mild (36%) hallucinations. NPI domain scores after the initial open-treatment phase were not associated with relapse. CONCLUSIONS: Patients with severe baseline hallucinations were more likely to relapse after randomization, and the presence of baseline hallucinations was associated with a higher risk of relapse after discontinuation of risperidone compared with continued risperidone treatment. For patients with hallucinations, particularly auditory hallucinations, antipsychotic discontinuation should be approached cautiously because of high relapse risk.

Intraspecific variations in cardamom (Elettaria cardamomum Maton): assessment of genomic diversity by flow cytometry, cytological studies and ISSR analysis.

BACKGROUND: The main goal of the work was to analyse intraspecific variation in Elettaria cardamomum Maton (cardamom) using genome size, cytological studies and molecular marker data. Nuclear DNA content and molecular marker details furnish data on genome size and genetic diversity respectively among the studied accessions and both complement each other for evolutionary and taxonomic studies. RESULTS: The relative 2C genome size and total number of base pairs of cardamom was determined through flow cytometric analysis using propidium iodide staining. The nuclear DNA content was estimated in various sections of the species representing individuals from wild and cultivar genotypes following Zea mays L. CE-777 (2C = 5.43 pg) as internal reference standard. Chromosome number from growing root tip was examined following standard protocols. Twenty-six ISSR primers that generated polymorphic bands were used for genetic diversity analysis of the thirty accessions of cardamom. Estimated nuclear 2C DNA content ranged from 2.57 to 3.22 pg demonstrating 1.25-fold variation. The mean amount of 2C nuclear DNA of the cardamom was calculated as 2.87 pg which is equivalent of 2806 Mbp as the diploid genome size. The chromosome number was found to be 2n = 48. Among the thirty accessions of cardamom studied using ISSR markers, C53 (feral from Bonacaud) showed a very prominent level of genetic diversity and was lowest for C96 (Avinash-I, a released variety from Indian Institute of Spices Research, Kozhikode). CONCLUSION: These analyses revealed the existence of genetic variability within the studied cardamom accessions. The plant specimens also differed significantly in their genome size. However, the genetic variability parameters did not show any correlation with genome size.

Leishmaniasis in a patient with HIV co-infection: Diagnosis on fine needle aspiration cytology.

Leishmaniasis is a vector borne parasitic disease caused by obligate intracellular protozoa Leishmania and is transmitted by the bite of sand fly. The disease typically presents in visceral, cutaneous and mucocutaneous forms and is endemic in some states of India. Cases with atypical presentation are seen when patient has co- infection with HIV. We report a case of Leishmaniasis occurring in a HIV seropositive expectant mother diagnosed initially on fine needle aspiration cytology. The patient was resident of non endemic area and had presented with isolated cervical lymphadenopathy and fever without spleenomegaly. Characteristic morphological features of Leishmania seen in the fine needle aspiration smears from the neck nodes were identified and definitive diagnosis of Leishmaniasis could be given. Cytological features were not suggestive of any other disease. Timely diagnosis of the disease facilitated proper management in our patient.

Cognitive Profile of C9orf72 in Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.

This review article focuses on the cognitive profile associated with the C9orf72 gene with GGGGCC (G4C2) hexanucleotide repeat expansions that is commonly found in both familial and sporadic forms of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) in order to aid clinicians in the screening process. In this growing clinical continuum between FTD and ALS, understanding and recognizing a neurocognitive profile is important for diagnosis. Key features of this profile include executive dysfunction with memory impairment and language deficits as the disease progresses. Behaviorally, patients are prone to disinhibition, apathy, and psychosis. With the discovery of this mutation, studies have begun to characterize the different phenotypes associated with this mutation in terms of epidemiology, clinical presentation, imaging, and pathology. Greater awareness and increased surveillance for this mutation will benefit patients and their families in terms of access to genetic counseling, research studies, and improved understanding of the disease process.

Phase 1 and pharmacodynamic trial of everolimus in combination with cetuximab in patients with advanced cancer.

BACKGROUND: Preclinical and clinical studies suggest mTOR (mammalian target of rapamycin) inhibitors may have metabolic and antiangiogenic effects, and synergize with epidermal growth factor pathway inhibitors. Therefore, a phase 1/pharmacodynamic trial of everolimus with cetuximab was performed. METHODS: A total of 29 patients were randomized to a run-in of oral everolimus (30, 50, or 70 mg) or cetuximab (400 mg/m(2) loading, 250 mg/m(2) maintenance) weekly, followed by the combination in this dose-escalation study. Primary endpoints were phase 2 dose and toxicity characterization. [(18)F]Fluorodeoxyglucose positron emission tomography (FDG-PET) was performed as a pharmacodynamic marker of mTOR inhibition, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was performed as an indicator of tumor perfusion changes, at 3 time points. RESULTS: Everolimus and cetuximab were tolerable at full doses, with an expected toxicity profile. Dose-limiting toxicities in the everolimus 70 mg group included grade 3 skin toxicity in 2 patients, and mucositis in 1 patient. Of 16 patients evaluable for response, 5 had stable disease lasting 4 to 19 months. Mean change in maximum standardized uptake value (SUV(max)) for those treated initially with everolimus was -24% (2% to -54%), and with cetuximab was -5% (-23 to 36%). The K(trans) measured by DCE-MRI did not decrease, regardless of run-in drug. CONCLUSIONS: Everolimus and cetuximab can be safely administered at standard doses, and are associated with prolonged disease control. The recommended phase 2 dose of oral weekly everolimus is 70 mg in combination with standard cetuximab. Imaging studies reveal that metabolic inhibition by everolimus alone and in combination with cetuximab predominates over changes in tumor perfusion in this patient population.

A Study of VO2 Max and Body Fat Percentage in Female Athletes.

INTRODUCTION: Aerobic capacity of athletes is an important element of success in sports achievements. It is generally considered the best indicator of cardio respiratory endurance and athletic fitness. Body fat percentage affects VO2 max and thus the cardiovascular status of the athletes. The present study was undertaken to assess the VO2 max and body fat percentage in athletes. The secondary objective of the study was to study the relationship between VO2 max and body fat percentage. MATERIALS AND METHODS: Twenty five female athletes of age group 17-22years were selected for the study. VO2 max was determined by Queen's college step test and body fat percentage by skin fold calipers. The VO2 max and body fat percentage were determined in non athletes of same age group for comparison. The statistical analysis was done by Student's t-test and Pearson correlation test. OBSERVATION AND RESULTS: The mean VO2 max in athletic group was 39.62 ± 2.80 ml/kg/min. In non-athletic group, VO2 max was 23.54 ± 3.26 ml/kg/min. The mean body fat percentage in athletes was 24.11 ± 1.83% and in non-athletes it was 29.31 ± 3.86%.The difference in VO2 max and body fat percentage was statistically significant in our study. The VO2 max and body fat percentage in both the groups showed negative correlation by Pearson test but, was not statistically significant. CONCLUSION: The present study showed a statistically significant higher VO2 max in female athletes. The study showed a negative correlation between VO2 max and body fat percentage but was not statistically significant.

Recurrent Nocardia Sepsis in a Patient With Sickle Cell Anemia Receiving Continuous Deferoxamine.

Nocardia species are ubiquitous soil-borne organisms that most commonly cause invasive disease in patients with defective cell-mediated immunity. We report a case of recurrent Nocardia sepsis in a patient with sickle cell disease and chronic iron overload, who was undergoing high-dose infusions of deferoxamine through a central venous catheter.

Platelets and erythrocyte-bound platelets bind infectious HIV-1 in plasma of chronically infected patients.

Chronic HIV-1 infection is associated with persistent viremia in most patients, but it remains unclear how free virus may survive the potential hostile effects of plasma. We investigated whether sites might exist on the surfaces of circulating blood cells for protection of infectious HIV-1 particles. Red blood cells (RBC) either from blood of uninfected normal individuals, or from blood obtained without EDTA from chronically infected HIV-1 patients, invariably contained a small number of RBC having attached platelets as determined by flow cytometry, light microscopy, and immunofluorescence microscopy. After mixing normal RBC with platelet-rich plasma, discrete populations of RBC, platelets, and complexes of platelets attached to RBC were purified by fluorescence-activated cell sorting. Upon incubation of purified cells or platelets with HIV-1 followed by washing and co-incubation with CD4-positive peripheral blood mononuclear cells (PBMC), platelets, and platelet-RBC complexes, but not platelet-free RBC, caused infection of PBMC. Infection was prevented by pre-treating the platelet-RBC complexes with EDTA. Plasma and RBC (comprising a RBC/platelet-RBC mixture) from chronically infected patients with low viral loads were also co-incubated with PBMC ex vivo to determine the presence of infectious HIV-1. All freshly isolated plasmas from the HIV-1-infected donors, obtained in the absence of anticoagulant, were noninfectious. Interestingly, the RBC from most of the patients caused cell-cell infection of PBMC that was prevented by stripping the RBC with EDTA. A monoclonal antibody to DC-SIGN partially inhibited cell-cell HIV-1 infection of PBMC by normal RBC pre-incubated with platelets and HIV-1. We conclude: (a) platelet-free EDTA-free plasma from chronically infected HIV-1 patients, although containing viral RNA, is an environment that lacks detectable infectious HIV-1; (b) platelets and platelet-RBC complexes, but not purified RBC, bind infectious HIV-1; (c) DC-SIGN, and possibly other C-type lectins, may represent binding sites for infectious HIV-1 on platelets and platelet-RBC complexes.

A population of selected renal cells augments renal function and extends survival in the ZSF1 model of progressive diabetic nephropathy.

New treatment paradigms that slow or reverse progression of chronic kidney disease (CKD) are needed to relieve significant patient and healthcare burdens. We have shown that a population of selected renal cells (SRCs) stabilized disease progression in a mass reduction model of CKD. Here, we further define the cellular composition of SRCs and apply this novel therapeutic approach to the ZSF1 rat, a model of severe progressive nephropathy secondary to diabetes, obesity, dyslipidemia, and hypertension. Injection of syngeneic SRCs into the ZSF1 renal cortex elicited a regenerative response that significantly improved survival and stabilized disease progression to renal structure and function beyond 1 year posttreatment. Functional improvements included normalization of multiple nephron structures and functions including glomerular filtration, tubular protein handling, electrolyte balance, and the ability to concentrate urine. Improvements to blood pressure, including reduced levels of circulating renin, were also observed. These functional improvements following SRC treatment were accompanied by significant reductions in glomerular sclerosis, tubular degeneration, and interstitial inflammation and fibrosis. Collectively, these data support the utility of a novel renal cell-based approach for slowing renal disease progression associated with diabetic nephropathy in the setting of metabolic syndrome, one of the most common causes of end-stage renal disease.