Clonal analysis of micronodules in virus C-induced liver cirrhosis using laser capture microdissection (LCM) and HUMARA assay

Most hepatocellular carcinomas (HCC) arise from malignant transformation of regenerative cirrhotic nodules. Because HCC has a very poor prognosis, detection of these premalignant lesions may improve the management of patients with cirrhosis. In this regard, clonal analysis of liver micronodules should be of particular interest in order to differentiate polyclonal regenerative micronodules from monoclonal neoplastic potentially malignant micronodules. To address this issue, 112 micronodules from 15 cases of explanted liver cirrhosis were carefully microdissected from paraffin-embedded tissue using a laser capture microscopy system. Clonal analysis was performed by analyzing X-chromosome inactivation, as indicated by the methylation status of the human androgen receptor gene (HUMARA). For each microdissected micronodule, a large set of pathological features was evaluated and correlated with their clonal status. Clonal analysis showed that 57 micronodules (51%) were monoclonal and 55 (49%) were polyclonal. Prevalence of monoclonal nodules ranged from 25% to 71% according to cases. In all cases, mono- and polyclonal nodules were randomly distributed in the cirrhotic liver. Although the clonal status was not significantly affected by the presence or absence of macronodules in the adjacent liver, size of monoclonal micronodules was significantly larger than size of polyclonal micronodules (mean size of the monoclonal nodules: 3 + 0.1 mm vs mean size of the polyclonal nodules: 2.5 +/- 0.1 mm, p = 0.007). Among the elementary pathological features evaluated, only the presence of iron overload was correlated with a monoclonal status (p = 0.04). In conclusion, clonal analysis of liver cirrhosis shows that 51% of micronodules are monoclonal lesions, supporting the notion that liver cirrhosis is a multineoplastic lesion. Because monoclonality is a marker of neoplasia, cirrhosis with accumulation of monoclonal nodules may be carefully followed, and monoclonal nodules should be screened for additional markers to assess their biological behavior.     

High levels of estradiol impair spatial performance in the Morris water maze and increase 'depressive-like' behaviors in the female meadow vole

The present study investigated sex differences and the effect of a high level of estradiol in the female meadow vole on performance in the forced swim test (FST) and the Morris water maze in meadow voles. Female meadow voles were ovariectomized (OVX) and administered either vehicle (sesame oil) or estradiol for 2 days prior to performing the FST. Four days following the FST, all animals were run in the Morris water maze. Results indicated that estradiol-injected female meadow voles showed more 'depressive-like' behaviors in the FST (greater time spent immobile and less time spent swimming) than vehicle-treated female or male meadow voles. In addition, estradiol-treated females had impaired performance (greater latencies and distance swam to reach the hidden platform) than both vehicle-treated female and male meadow voles, consistent with previous data. Despite the fact that estradiol administration increased 'depressive-like' behaviors in the FST and impaired performance in the Morris water maze, there was no correlation between the two behaviors indicating that 'depressive-like' behaviors did not account for the differences seen in spatial performance in the Morris water maze. To our knowledge, this is the first demonstration in rodents indicating that estradiol-mediated changes in behavior in the FST is not indicative of subsequent performance in the Morris water maze.     

Leptin resistance in mice is determined by gender and duration of exposure to high-fat diet

Mice fed a high-fat diet are reported to be resistant to peripheral injections of leptin. We previously failed to induce leptin resistance in female mice fed a high-fat diet for 15 weeks. Therefore, we measured the responsiveness to peripheral infusions (10 microg/day) of leptin, and the responsiveness to third ventricle injections of leptin (1 microg) in male and female NIH Swiss mice fed low-fat (10% kcal) or high-fat (45% kcal) diets. Male and female 15-week-old mice that had been fed low- or high-fat diet from 10 days of age lost fat during a 13-day intraperitoneal infusion of leptin and lost weight in response to a single central injection of leptin. Fifteen-week-old male mice fed a high-fat diet for 5 weeks did not lose body fat during a peripheral infusion of leptin and did not lose weight in response to a central injection of leptin. Female mice fed high-fat diet for 5 weeks remained leptin-responsive. Weight loss was achieved without a significant voluntary decrease in food intake, suggesting that both peripherally and centrally administered leptin increases energy expenditure. These results demonstrate that the development of leptin resistance in NIH Swiss mice fed a high-fat diet is dependent upon the gender of the mice and either the duration of exposure to high-fat diet or the age at which the mice are first exposed to the diet.     

Relative right versus left frontal EEG in neonates

Although infants have been noted to have greater relative right or left frontal EEG as early as the neonatal period, other ways in which these newborns differ have not been reported. In this study, 48 newborns were divided on the basis of greater relative right versus greater relative left frontal EEG to determine whether these groups differed in other ways at the neonatal period including behavior, physiology, and biochemistry. We also were interested in whether these EEG patterns were related to any prenatal maternal variables including mood states (depression, anxiety, anger) and biochemistry as well as fetal activity. The greater relative right frontal EEG newborns had mothers with lower prenatal and postnatal serotonin and higher postnatal cortisol levels. The mothers of the greater relative right frontal EEG newborns also had greater relative right frontal EEG activation and lower vagal tone. The greater relative right frontal EEG newborns themselves had elevated cortisol levels, showed a greater number of state changes during sleep/wake behavior observations, and performed less optimally on the Brazelton Neonatal Behavior Assessment (T. B. Brazelton, 1973) including the habituation, motor, range of state, excitability, and depressive symptoms scales. These data suggest that greater relative right frontal EEG newborns may be at greater risk for developmental problems than those with greater relative left frontal EEG activation. In addition, a discriminant function analysis correctly classified 67% of the newborns' EEGs by prenatal maternal variables, suggesting that these might be used to target pregnant women for prenatal intervention.     

Key Informants’ Perspectives on Childhood Obesity in Vietnam: A Qualitative Study

Maternal and Child Health Journal - Vietnam’s post-war globalization, economic development, and urbanization have contributed to a nutrition transition from traditional diets to...     

Identification and Validation of Nutrient State-Dependent Serum Protein Mediators of Human CD4+ T Cell Responsiveness

Intermittent fasting and fasting mimetic diets ameliorate inflammation. Similarly, serum extracted from fasted healthy and asthmatic subjects’ blunt inflammation in vitro, implicating serum components in this immunomodulation. To identify the proteins orchestrating these effects, SOMAScan technology was employed to evaluate serum protein levels in healthy subjects following an overnight, 24-h fast and 3 h after refeeding. Partial least square discriminant analysis identified several serum proteins as potential candidates to confer feeding status immunomodulation. The characterization of recombinant IGFBP1 (elevated following 24 h of fasting) and PYY (elevated following refeeding) in primary human CD4⁺ T cells found that they blunted and induced immune activation, respectively. Furthermore, integrated univariate serum protein analysis compared to RNA-seq analysis from peripheral blood mononuclear cells identified the induction of IL1RL1 and MFGE8 levels in refeeding compared to the 24-h fasting in the same study. Subsequent quantitation of these candidate proteins in lean versus obese individuals identified an inverse regulation of serum levels in the fasted subjects compared to the obese subjects. In parallel, IL1RL1 and MFGE8 supplementation promoted increased CD4⁺ T responsiveness to T cell receptor activation. Together, these data show that caloric load-linked conditions evoke serological protein changes, which in turn confer biological effects on circulating CD4⁺ T cell immune responsiveness.     

Congenital Thumb-Index Web Space Deficiency

Background: There are several congenital hand differences that cause thumb-index (TI) web space deficiency. There is a knowledge gap in the literature about the hand differences that are associated with TI web space deficiency. We aimed to identify these congenital differences and the various specific reconstructive surgical procedures that are used for these conditions. Methods: We conducted a retrospective chart review of children treated operatively over a period of 30 years for congenital TI web space deficiency by the senior author (G.M.R.). We gathered data on demographics and associated congenital hand differences and compiled a list of all surgical procedures performed for the web space and the ipsilateral upper extremity. Results: We included 71 patients (77 hands) with 12 congenital hand differences (62 developmental and 9 spastic). The total number of upper extremity operations, (ie), anesthetics performed for these patients was 186, averaging 2.6 settings and 7.5 procedures for each patient. Cutaneous reconstructive procedures included first dorsal metacarpal artery pedicle flaps (49 patients), 4-flap Z-plasties (15), and transposition flaps (13). In addition, 16 different thumb reconstructive procedures were necessary. Ten patients required revision of their TI web space procedures for recurrence. Conclusions: The prevalence of TI web space deficiency is underappreciated. These patients often have multiple musculoskeletal anomalies of the hand and upper extremity that should be ruled out and require surgical treatment to optimize hand function. Consideration should be given to performing more than one procedure in one setting when possible.     

Gay Community Involvement and Condomless Anal Sex Among Sexual Minority Men in the USA

Archives of Sexual Behavior - Sexual minority men (SMM) remain disproportionately burdened by sexually transmitted infections. Although gay community involvement has been theorized to be protective...