Longitudinal study of the cascading effects of racial discrimination on parenting and adjustment among African American youth.

Attachment theory posits that parenting plays akey role in children's attachment and subsequent development. Given the normativity of racial discrimination on everyday life experiences of African American families, there is a need to integrate historical and socio-environmental processes in studies to understand how minoritized parents raise secure and stable children. Results from the current study revealed direct associations between mothers' reports of discrimination and heightened depression and anxiety. Maternal discriminatory experiences were indirectly associated with more negative parenting and compromised parent-child relationship quality, through mothers' psychological functioning. Elevated emotional and behavioral management problems among youth were directly associated with exposure to racial discrimination. Exposure to discrimination during middle childhood facilitated adapted or learned strategies to manage similar situations as youth transitioned into adolescence, with reduced patterns of depressive symptomology. No significant gender effects emerged. Implications for theoretical advancement and future research are provided.

Imaging pitfalls in paediatric posterior fossa neoplastic and non-neoplastic lesions.

Paediatric posterior fossa lesions can have much overlap in their clinical and radiological presentation. There are, however, a number of key imaging features that can help the reading radiologist to distinguish tumours from important tumour mimics which are often inflammatory or metabolic entities. This pictorial review provides a number of important cases that proved challenging on imaging and illustrates some common pitfalls when interpreting lesions in the posterior fossa in children. Not everything that is abnormal will be a tumour, but often other causes are overlooked and misinterpreted as tumours, leading to great morbidity for that child. This article highlights some lesions that were mistaken as tumours and will introduce the reader to less commonly seen pathologies which are important to consider on a differential list for this location.

Interactive influence of sex, stressor timing, and the BclI glucocorticoid receptor polymorphism on stress-induced alterations of long-term memory.

Certain susceptibility factors, such as genetic variants or specific physiological responses to stress, can dictate the effects of stress on learning and memory. Here, we examined the influence of the BclI polymorphism of the glucocorticoid receptor gene on the time-dependent effects of pre-learning stress on long-term memory. Healthy individuals were exposed to the socially evaluated cold pressor test or a control condition immediately or 30 min before word list learning. Participants' memory for the words was tested immediately and 24 h after learning, and saliva samples were collected to genotype participants for the BclI polymorphism and to assess cortisol responses to the stressor. Results revealed that stress immediately before learning enhanced memory, while stress 30 min before learning impaired memory; these effects were largely selective to males and non-arousing words. Additionally, stress, independent of when it was administered, enhanced memory in non-carriers of the BclI polymorphism, while impairing memory in carriers; these effects were largely selective to males and participants exhibiting a robust cortisol response to stress. These results provide further evidence for time-dependent effects of stress on long-term memory and suggest that carriers of the BclI polymorphism might be more sensitive to the negative effects of corticosteroids on learning.

FKBP5 polymorphisms influence pre-learning stress-induced alterations of learning and memory.

FK506 binding protein 51 (FKBP5) is a co-chaperone of heat shock protein 90 and significantly influences glucocorticoid receptor sensitivity. Single nucleotide polymorphisms (SNPs) in the FKBP5 gene are associated with altered hypothalamus-pituitary-adrenal (HPA) axis function, changes in the structure and function of several cognitive brain areas, and increased susceptibility to post-traumatic stress disorder, major depression, bipolar disorder and suicidal events. The mechanisms underlying these associations are largely unknown, but it has been speculated that the influence of these SNPs on emotional memory systems may play a role. In the present study, 112 participants were exposed to the socially evaluated cold pressor test (stress) or control (no stress) conditions immediately prior to learning a list of 42 words. Participant memory was assessed immediately after learning (free recall) and 24 h later (free recall and recognition). Participants provided a saliva sample that enabled the genotyping of three FKBP5 polymorphisms: rs1360780, rs3800373 and rs9296158. Results showed that stress impaired immediate recall in risk allele carriers. More importantly, stress enhanced long-term recall and recognition memory in non-carriers of the risk alleles, effects that were completely absent in risk allele carriers. Follow-up analyses revealed that memory performance was correlated with salivary cortisol levels in non-carriers, but not in carriers. These findings suggest that FKBP5 risk allele carriers may possess a sensitized stress response system, perhaps specifically for stress-induced changes in corticosteroid levels, which might aid our understanding of how SNPs in the FKBP5 gene confer increased risk for stress-related psychological disorders and their related phenotypes.

ADRA2B deletion variant influences time-dependent effects of pre-learning stress on long-term memory.

Extensive work over the past few decades has shown that certain genetic variations interact with life events to confer increased susceptibility for the development of psychological disorders. The deletion variant of the ADRA2B gene, which has been associated with enhanced emotional memory and heightened amygdala responses to emotional stimuli, might confer increased susceptibility for the development of post-traumatic stress disorder (PTSD) or related phenotypes by increasing the likelihood of traumatic memory formation. Thus, we examined whether this genetic variant would predict stress effects on learning and memory in a non-clinical sample. Two hundred and thirty-five individuals were exposed to the socially evaluated cold pressor test or a control condition immediately or 30min prior to learning a list of words that varied in emotional valence and arousal level. Participants' memory for the words was tested immediately (recall) and 24h after learning (recall and recognition), and saliva samples were collected to genotype participants for the ADRA2B deletion variant. Results showed that stress administered immediately before learning selectively enhanced long-term recall in deletion carriers. Stress administered 30min before learning impaired recognition memory in male deletion carriers, while enhancing recognition memory in female deletion carriers. These findings provide additional evidence to support the idea that ADRA2B deletion variant carriers retain a sensitized stress response system, which results in amplified effects of stress on learning and memory. The accumulating evidence regarding this genetic variant implicates it as a susceptibility factor for traumatic memory formation and PTSD-related phenotypes.

Blunted cortisol response to acute pre-learning stress prevents misinformation effect in a forced confabulation paradigm.

Research examining the effects of stress on false memory formation has been equivocal, partly because of the complex nature of stress-memory interactions. A major factor influencing stress effects on learning is the timing of stress relative to encoding. Previous work has shown that brief stressors administered immediately before learning enhance long-term memory. Thus, we predicted that brief stress immediately before learning would decrease participants' susceptibility to subsequent misinformation and reduce false memory formation. Eighty-four male and female participants submerged their hand in ice cold (stress) or warm (no stress) water for 3min. Immediately afterwards, they viewed an 8-min excerpt from the Disney movie Looking for Miracles. The next day, participants were interviewed and asked several questions about the video, some of which forced them to confabulate responses. Three days and three weeks later, respectively, participants completed a recognition test in the lab and a free recall test via email. Our results revealed a robust misinformation effect, overall, as participants falsely recognized a significant amount of information that they had confabulated during the interview as having occurred in the original video. Stress, overall, did not significantly influence this misinformation effect. However, the misinformation effect was completely absent in stressed participants who exhibited a blunted cortisol response to the stress, for both recognition and recall tests. The complete absence of a misinformation effect in non-responders may lend insight into the interactive roles of autonomic arousal and corticosteroid levels in false memory development.

Implementation of CFD modeling in the performance assessment and optimization of secondary clarifiers: the PVSC case study.

The water industry and especially the wastewater treatment sector has come under steadily increasing pressure to optimize their existing and new facilities to meet their discharge limits and reduce overall cost. Gravity separation of solids, producing clarified overflow and thickened solids underflow has long been one of the principal separation processes used in treating secondary effluent. Final settling tanks (FSTs) are a central link in the treatment process and often times act as the limiting step to the maximum solids handling capacity when high throughput requirements need to be met. The Passaic Valley Sewerage Commission (PVSC) is interested in using a computational fluid dynamics (CFD) modeling approach to explore any further FST retrofit alternatives to sustain significantly higher plant influent flows, especially under wet weather conditions. In detail there is an interest in modifying and/or upgrading/optimizing the existing FSTs to handle flows in the range of 280-720 million gallons per day (MGD) (12.25-31.55 m(3)/s) in compliance with the plant's effluent discharge limits for total suspended solids (TSS). The CFD model development for this specific plant will be discussed, 2D and 3D simulation results will be presented and initial results of a sensitivity study between two FST effluent weir structure designs will be reviewed at a flow of 550 MGD (∼24 m(3)/s) and 1,800 mg/L MLSS (mixed liquor suspended solids). The latter will provide useful information in determining whether the existing retrofit of one of the FSTs would enable compliance under wet weather conditions and warrants further consideration for implementing it in the remaining FSTs.

Pleural and Pericardial Effusion With COVID-19 and Systemic Lupus Erythematosus and Its Recurrence: A Case Study.

As a chronic autoimmune disease, systemic lupus erythematosus (SLE) primarily affects young women and does not discriminate against any particular organs. In December 2019, coronavirus disease 2019 (COVID-19) spread worldwide, with many speculations of cardiac involvement in the pathogenesis of infection. Moreover, in cases where cardiac symptoms were described, they consisted solely of chest pain or a general deterioration in health if the patient presented with pleural effusion or pericardial effusion. Our patient, a 25-year-old Hispanic woman, initially complained of chest pain, cough, and shortness of breath. After being admitted, she noticed growing dyspnea and mild discomfort on the right side of her chest. The patient had both SLE and COVID-19 and had developed pleural and pericardial effusions. After two days in culture, nothing had grown from the fluid samples. In addition, measures of brain natriuretic peptide and total creatine kinase fell within the normal range. Considering the investigational findings, pericardiocentesis was performed. After the procedure, the patient's condition improved, and she was discharged. The patient continued taking CellCept® 1,500 mg and Plaquenil 200 mg and started taking colchicine. Her daily prednisone dose was increased to 40 milligrams. She felt well initially; however, after two weeks of follow-up, the pericardial effusion recurred, and pericardiocentesis was performed again. The patient was discharged in stable condition after a two-day hospital stay. After treatment of both initial and recurrent effusions, the patient's cardiac symptoms were resolved, and blood pressure became stable. We hypothesize that there may be other unreported cases of COVID-19-related viral pericarditis, pericardial effusion, and pericardial tamponade that could be caused by a combination of COVID-19 and a pre-existing condition, mainly autoimmune disorders. Due to the lack of clarity surrounding typical COVID-19 manifestations, it is crucial to record all cases of this unique illness and analyze any increased incidence of pericarditis, pericardial effusion, and pericardial tamponade in the public.

Characteristics of chronic hepatitis B patients who underwent liver biopsies.

Significant liver disease has been reported in chronic hepatitis B patients with normal alanine aminotransferase (ALT) but most studies performed biopsies on selected patients only. The aims of this study were to determine the rate of liver biopsy, characteristics of patients who underwent a biopsy and factors associated with significant liver disease in a cohort of such patients. Records of patients with chronic hepatitis B during a 10-year period were reviewed. Significant liver disease was defined as Knodell HAI ≥ 7 and/or Ishak fibrosis ≥ 3. Of 743 patients, 55.7% were Asian, 56.4% were men, and the mean age was 43.1 years. One hundred and ninety-three (26%) had undergone a biopsy. Biopsied patients were more likely to be men, HBeAg positive, and had lower platelet and higher alkaline phosphatase, bilirubin, ALT and hepatitis B virus (HBV) DNA. Significant liver disease was observed in 20% of patients who had normal ALT at presentation, 14% of those with normal ALT at the time of biopsy and in none of the patients with persistently normal ALT. Patients with normal ALT who were biopsied had higher HBV DNA and higher ALT than those not biopsied. Multivariate analysis showed that low albumin at the time of biopsy and HBV DNA >5 log(10) copies/mL were predictors of significant liver disease. Significant liver disease is rare in patients with chronic HBV and persistently normal ALT and liver histology of chronic HBV infected patients with normal ALT cannot be generalized to other patients with normal ALT that were not biopsied.

The Alarmone (p)ppGpp Regulates Primer Extension by Bacterial Primase.

Primase is an essential component of the DNA replication machinery, responsible for synthesizing RNA primers that initiate leading and lagging strand DNA synthesis. Bacterial primase activity can be regulated by the starvation-inducible nucleotide (p)ppGpp. This regulation contributes to a timely inhibition of DNA replication upon amino acid starvation in the Gram-positive bacterium Bacillus subtilis. Here, we characterize the effect of (p)ppGpp on B. subtilis DnaG primase activity in vitro. Using a single-nucleotide resolution primase assay, we dissected the effect of ppGpp on the initiation, extension, and fidelity of B. subtilis primase. We found that ppGpp has a mild effect on initiation, but strongly inhibits primer extension and reduces primase processivity, promoting termination of primer extension. High (p)ppGpp concentration, together with low GTP concentration, additively inhibit primase activity. This explains the strong inhibition of replication elongation during starvation which induces high levels of (p)ppGpp and depletion of GTP in B. subtilis. Finally, we found that lowering GTP concentration results in mismatches in primer base pairing that allow priming readthrough, and that ppGpp reduces readthrough to protect priming fidelity. These results highlight the importance of (p)ppGpp in protecting replisome integrity and genome stability in fluctuating nucleotide concentrations upon onset of environmental stress.

Institutional racism in public health contracting: Findings of a nationwide survey from New Zealand.

Public institutions within New Zealand have long been accused of mono-culturalism and institutional racism. This study sought to identify inconsistencies and bias by comparing government funded contracting processes for Maori public health providers (n = 60) with those of generic providers (n = 90). Qualitative and quantitative data were collected (November 2014-May 2015), through a nationwide telephone survey of public health providers, achieving a 75% response rate. Descriptive statistical analyses were applied to quantitative responses and an inductive approach was taken to analyse data from open-ended responses in the survey domains of relationships with portfolio contract managers, contracting and funding. The quantitative data showed four sites of statistically significant variation: length of contracts, intensity of monitoring, compliance costs and frequency of auditing. Non-significant data involved access to discretionary funding and cost of living adjustments, the frequency of monitoring, access to Crown (government) funders and representation on advisory groups. The qualitative material showed disparate provider experiences, dependent on individual portfolio managers, with nuanced differences between generic and Maori providers' experiences. This study showed that monitoring government performance through a nationwide survey was an innovative way to identify sites of institutional racism. In a policy context where health equity is a key directive to the health sector, this study suggests there is scope for New Zealand health funders to improve their contracting practices.

Changing trends in postoperative cataract care: impact of electronic patient records in optometrist-delivered shared care.

BACKGROUND: This study evaluates a community optometrist-delivered postoperative care scheme in patients discharged from the hospital ophthalmology department following uncomplicated cataract surgery. AIM: The aim of this study is to assess the efficacy of electronic patient records (EPR) in facilitating co-managed cataract care. METHODS: We performed a retrospective analysis of a prospectively maintained Medisoft EPR database of postoperative cataract review data at a single centre, Sligo University Hospital (SUH), which serves a large and predominantly rural catchment area. All patients undergoing cataract surgery at SUH from October 2012 to September 2013 were included in this study. A total of 39 optometric practices, all with access to the Medisoft EPR software, participated in this pilot co-management scheme. RESULTS: One thousand four hundred and twenty-two cataract surgeries were performed in SUH (55% female, 45% male); 1011 patients (71%) were discharged to the community on the day of cataract surgery. Complete postoperative feedback (i.e. data on refraction, visual acuity and intraocular pressure) was available in 97% of these patients compared to 50% of patients reviewed in the hospital. Patients followed up by optometrists were twice as likely to have complete postoperative clinical details (RR = 1.934, 95% CI: 1.759-2.126, p < 0.0001). Overall, 65% of operations were performed on first eyes. Hospital doctors were more likely to document requirement for second eye surgery compared to community optometrists (RR = 1.434, 95% CI: 1.302-1.580, p < 0.0001). CONCLUSIONS: Optometrists provided an excellent postoperative care service with superior postoperative feedback rates compared to hospital doctors. EPRs facilitate a postoperative shared-care pathway that is of high quality and efficiency with major economic advantages.

Increased food intake after starvation enhances sleep in Drosophila melanogaster.

Feeding and sleep are highly conserved, interconnected behaviors essential for survival. Starvation has been shown to potently suppress sleep across species; however, whether satiety promotes sleep is still unclear. Here we use the fruit fly, Drosophila melanogaster, as a model organism to address the interaction between feeding and sleep. We first monitored the sleep of flies that had been starved for 24 h and found that sleep amount increased in the first 4 h after flies were given food. Increased sleep after starvation was due to an increase in sleep bout number and average sleep bout length. Mutants of translin or adipokinetic hormone, which fail to suppress sleep during starvation, still exhibited a sleep increase after starvation, suggesting that sleep increase after starvation is not a consequence of sleep loss during starvation. We also found that feeding activity and food consumption were higher in the first 10-30 min after starvation. Restricting food consumption in starved flies to 30 min was sufficient to increase sleep for 1 h. Although flies ingested a comparable amount of food at differing sucrose concentrations, sleep increase after starvation on a lower sucrose concentration was undetectable. Taken together, our results suggest that increased food intake after starvation enhances sleep and reveals a novel relationship between feeding and sleep.

Mechanism of glomerular hyperfiltration after a protein meal in humans. Role of hormones and amino acids.

OBJECTIVES: Previous studies demonstrated that protein meals and amino acid (AA) infusions increase glomerular filtration rate (GFR) and renal plasma flow (RPF) and that somatostatin (SRIH) infusion inhibits these increments. We tested whether a single AA such as alanine could increase GFR and RPF and whether the changes in GFR and RPF could be explained on the basis of changes in glucagon, growth hormone (GH), and insulin. RESEARCH DESIGN AND METHODS: In the first experiment, alanine was infused with or without SRIH in five normal subjects. In the second experiment, five other subjects were infused with SRIH on three separate occasions. In a control study, insulin, glucagon, and GH were given at replacement doses; in a hyperglucagonemia study, glucagon was given at a rate of 0.2 microgram.kg-1.h-1 (hypoglucagonemia); and in a high GH study, GH was given at a rate of 2 micrograms.kg-1.h-1. GFR and RPF were measured using insulin and para-aminohippurate, respectively. RESULTS: Alanine increased GFR and RPF, whereas SRIH inhibited these changes (P < 0.05). Hyperglucagonemia or high GH with or without insulin failed to increase RPF or GFR. CONCLUSIONS: A single AA such as alanine increases GFR and RPF, and this increase is dependent on a factor inhibited by SRIH. Although GH, glucagon, and insulin are factors inhibited by SRIH, none of these factors explains the changes in RPF and GFR in our acute studies.

Post-learning stress enhances long-term memory and differentially influences memory in females depending on menstrual stage.

Most work has shown that post-learning stress enhances long-term memory; however, there have been recent inconsistencies in this literature. The purpose of the present study was to examine further the effects of post-learning stress on long-term memory and to explore any sex differences that may exist. Male and female participants learned a list of 42 words that varied in emotional valence and arousal level. Following encoding, participants completed a free recall assessment and then submerged their hand into a bath of ice cold (stress) or lukewarm (no stress) water for 3 min. The next day, participants were given free recall and recognition tests. Stressed participants recalled more words than non-stressed participants 24h after learning. Stress also enhanced female participants' recall of arousing words when they were in the follicular, but not luteal, phase. These findings replicate previous work examining post-learning stress effects on memory and implicate the involvement of sex-related hormones in such effects.

Spontaneous remission of the nephrotic syndrome in diabetic nephropathy.

A 28 year old woman, with diabetes since age 18, had the nephrotic syndrome, hypertension and renal insufficiency. The initial renal biopsy specimen revealed diffuse glomerulosclerosis with early nodular changes. After an initial decline in renal function, her creatinine clearance progressively improved and has remained normal. Within 2 years she had a spontaneous remission of the nephrotic syndrome despite the presence of more pronounced nodular glomerular lesions. Although the renal hemodynamic functions were normal, certain tubular functions were impaired. Since we found no etiology for the nephrotic syndrome other than diabetic glomerulopathy, the complete remission of the nephrotic syndrome and improvement in renal function were very unusual events.

Renal involvement in Refsum's disease.

Renal hemodynamic and tubular functions were measured in a patient with Refsum's disease before and after 12 weeks of twice-weekly plasmaphereses. Percutaneous renal biopsy was performed before initiation of plasmapheresis. These studies were performed to (1) define the nature of the renal lesions and the effects of phytanic acid accumulation on renal functions, and (2) assess the effects of lowering the plasma phytanic acid level on renal functions. The patient, a 39 year old woman, had lipiduria, glycosuria, cylindruria, minimal proteinuria and mild azotemia initially. Renal lesions consist of extensive vacuolization and mitochondrial changes of the tubular epithelial cells, vacuolization of the visceral epithelial cells of the glomeruli, and slight to moderate mesangial sclerosis. The impaired renal hemodynamic function and various tubular functions improved following plasmaphereses associated with reduction of plasma phytanic acid. Over-all clinical improvement was also evident.

Synthesis and biological activity of a series of potent fluoromethyl ketone inhibitors of recombinant human calpain I.

Calpain I, an intracellular cysteine protease, has been implicated in the neurodegeneration following an episode of stroke. In this paper, we report on a series of potent dipeptide fluoromethyl ketone inhibitors of recombinant human calpain I (rh calpain I). SAR studies revealed that while calpain I tolerates a variety of hydrophobic groups at the P1 site, Leu at P2 is preferred. However, the nature of the N-terminal capping group has a significant effect on the inhibitory activity of this series of compounds. Compound 4e [(1,2,3,4-tetrahydroisoquinolin-2-yl)carbonyl-Leu-D,L-Phe-CH2F+ ++], having a tetrahydroisoquinoline containing urea as the N-terminal capping group, is the most potent dipeptide fluoromethyl ketone inhibitor of calpain I (with a second-order rate constant for inactivation of 276,000 M-1 s-1) yet reported; tripeptide 4k (Cbz-Leu-Leu-D,L-Phe-CH2F) is equipotent. A number of compounds presented in this study displayed excellent selectivity for calpain I over cathepsins B and L, two related cysteine proteases. Compounds which exhibited good inhibitory activity in the assay against isolated rh calpain I also inhibited intracellular calpain I in a human cell line. Thus, in an intact cell assay, compounds 4e and 4k inhibited calpain I with IC50 values of 0.2 and 0.1 microM, respectively. Finally, we also disclose the first example of fluorination of a dipeptide enol silyl ether to generate the corresponding dipeptide fluoromethyl ketone.

Percutaneous nephrostomy - recovered renal-function in 50 obstetric and gynecologic patients undergoing percutaneous nephrostomy.

Percutaneous nephrostomy (PN) will rapidly correct renal failure due to ureteral obstruction. Complications of the procedure are few and the procedure can be quickly accomplished on an outpatient basis using local anesthesia. A retrospective review of fifty patients who underwent PN led to derivation of a formula which predicts the expected degree of correction of renal function. Measurement of renal intracalyceal pressures at the time of PN was not helpful in predicting-outcome.

HER-2/neu gene amplification by FISH predicts poor survival in Barrett's esophagus-associated adenocarcinoma.

The HER-2/neu oncogene is localized to chromosome 17q and shares significant homology with the epidermal growth factor receptor. HER-2/neu protein overexpression has been associated with poor prognosis in a variety of tumors, but its significance in Barrett's esophagus-associated adenocarcinoma (BEAd) is unknown. Therefore, the aim of this study was to evaluate the prevalence and prognostic value of HER-2/neu gene amplification by fluorescence in situ hybridization (FISH) in 63 cases of BEAd. Routinely processed tissue sections from resection specimens of 63 patients with BEAd (M/F ratio, 10:1; mean age, 63 years) were assayed for HER-2/neu gene amplification by FISH using the Ventana unique sequence probe (Ventana Medical Systems, Inc, Tuscon, AZ). FISH results were correlated with the pathological features of the tumors and with patient survival. Clinical follow-up data were available for 54 patients (mean follow-up, 31 months [range, 1 to 152 months]). The HER-2/ neu gene was amplified in 12 of 63 (19%) cases. The presence of HER-2/neu gene amplification showed a trend toward a correlation with depth of tumor invasion (P = .07), lymph node metastasis (P = .13), and pathological stage (P = .14), but did not correlate with any of the other pathological features, such as degree of differentiation or tumor size. On both univariate and multivariate analysis, HER-2/neu gene amplification was associated with shortened survival (P = .03). HER-2/neu oncogene amplification, as determined by FISH, correlates with shortened patient survival and independently predicts poor outcome in patients with BEAd.