Chromophobe renal cell carcinoma: a morphologic and immunohistochemical study of 45 cases

The aim of this study was to evaluate the morphological spectrum of chromophobe renal cell carcinoma (CRCC) and diagnostic utility of a panel of three immunohistochemical stains. All cases of CRCC reported between 2002 and 2012 in the Section of Histopathology, Aga Khan University Hospital, were retrieved. A total of 45 cases were identified. Slides were reviewed and immunohistochemical stains (CK7, CD117, and vimentin) were performed. Ages ranged from 18 to 90 years (mean, 48.5 years). Male-to-female ratio was 0.8:1. The tumor was located in the left kidney in 24 patients and the right kidney in 20 patients. The tumor size ranged from 3.5 to 22 cm (mean 10 cm). Histologically, 4 were classic, 22 were eosinophilic, 16 were mixed, and 3 were sarcomatoid type. Morphologic patterns included broad alveolar, solid, nested, tubular, tubulocystic, trabecular, papillary, and microglandular. Binucleation and perinuclear halos were seen in all cases. Nuclear grooves and pseudoinclusions were seen in 17 and 6 cases, respectively. Multinucleated cells were seen in 19 cases. Mitoses ranged from 1 to 11/10 HPFs (mean 3/10 HPFs). Hyalinized stroma was seen in 38 cases and calcification in 26 cases. Necrosis was seen in 18 cases. Palisading of smaller cells around the broad alveolar pattern was noted in 5 cases. The Furhman’s nuclear grade was I (11), II (26), III (5), and IV (3). Hale’s colloidal iron was positive in all cases. Immunohistochemical stain CK7 and CD117 were positive in 100% and 95.5% of cases respectively. Vimentin was negative in all cases, except in the sarcomatoid areas of 3 cases. In conclusion, chromophobe renal cell carcinoma has certain unique morphological features and immunohistochemical profile which help to distinguish it from conventional renal cell carcinoma and oncocytoma. We identified nuclear pseudoinclusions, microglandular pattern and palisading of smaller cells, which have not been reported earlier.     

Parent-child emotion communication,attachment, and affective narratives

Forty-four pre-schoolers (ages 4.3 to 5.8 years) and their primary caregivers participated in a study on the connections between parent-child emotion communication and a narrative assessment of pre-schoolers' attachment. Children completed the Separation Anxiety Test (SAT), a narrative assessment of children's responses to attachment-related separations (including self-reliance, avoidance, attachment and coherence scores). Several aspects of parent-child discussions of emotion-eliciting events were also assessed in the Emotion Communication Task. Results indicated that SAT coherence was positively related to SAT attachment and negatively related to SAT avoidance. Furthermore, SAT coherence was positively related to parental scaffolding and negatively related to parental and child negativity during the Emotion Communication Task. Parental scaffolding and child reciprocity were positively related to each other and, in general, were negatively related to parental and child negativity. Discussion focused on the potential contributions of children's interactions with caregivers to the development of children's attachment narratives and emotion-related understanding.     

Effects of cachaça,a typical Brazilian alcoholic beverage,on submandibular glands of rats: a histomorphometric and biochemical study

Objective

This study aimed to evaluate the effects of chronic consumption of cachaça, a Brazilian beverage containing alcohol, on submandibular glands (SM) of rats by using histomorphometric and biochemical parameters.

Materials and methods

Twenty-four male rats (40 days of age) were assigned into the following four groups (n = 6): two control groups for 75 days (C75) and 105 days (C105), and two experimental groups of cachaça ingestion with ascending concentrations for consecutive 75 days (CA75) and 105 days (CA105). On the right SM glands, the striated, granular and acini ducts were processed for histomorphometric analysis. The left SM glands were weighed and stored at − 80 °C, to evaluate through biochemical tests carried out by spectrophotometric methods, the functional activity of total acid phosphatase (TAP), tartrate-resistant acid phosphatase (TRAP), and alkaline phosphatase (ALP) and to determine the mucin levels.

Results

The absolute and relative weights of the SM glands in both experimental groups were reduced in relation to the controls (p < 0.05). The histomorphometric analysis showed a significant reduction of the acini area (p < 0.05) and non-relevant reduction of striated ducts (p > 0.05). The granular ducts did not show a significant increase of the area (p > 0.05). The TAP and TRAP activities were significantly decreased in the experimental groups (p < 0.05), while the ALP functional activity decreased moderately (p > 0.05). Mucin levels also had a significant reduction when compared with the control groups (p < 0.05).

Conclusions

Chronic consumption of cachaça can cause morphological changes associated with glandular atrophy, loss of biochemical functionality of phosphatases, and the reduction of mucin synthesis.

Clinical relevance

The consumption of cachaça can compromise the functions of the submandibular glands by altering their morphology and enzymatic activity.

     

Retinol-binding protein 4: a new marker of virus-induced steatosis in patients infected with hepatitis c virus genotype 1

Retinol-binding protein 4 (RBP4) is an adipocytokine associated with insulin resistance (IR). We tested serum levels of RBP4 to assess its link with steatosis in patients with genotype 1 chronic hepatitis C (CHC) or nonalcoholic fatty liver disease (NAFLD). Nondiabetic patients with CHC (n = 143) or NAFLD (n = 37) were evaluated by liver biopsy and anthropometric and metabolic measurements, including IR by the homeostasis model assessment. Biopsies were scored by Scheuer classification for CHC, and Kleiner for NAFLD. Steatosis was tested as a continuous variable and graded as absent-mild <30%, or moderate-severe > or =30%. Thirty nondiabetic, nonobese blood donors served as controls. RBP4 levels were measured by a human competitive enzyme-linked immunosorbent assay kit (AdipoGen). Mean values of RBP4 were similar in NAFLD and CHC (35.3 +/- 9.3 microg/L versus 36.8 +/- 17.6; P = 0.47, respectively), and both were significantly higher than in controls (28.9 +/- 12.1; P = 0.02 and P = 0.01, respectively). RBP4 was higher in CHC patients with steatosis than in NAFLD (42.1 +/- 19.7 versus 35.2 +/- 9.3; P = 0.04). By linear regression, RBP4 was independently linked to steatosis only (P = 0.008) in CHC, and to elevated body mass index (P = 0.01) and low grading (P = 0.04) in NAFLD. By linear regression, steatosis was independently linked to homeostasis model assessment score (P = 0.03) and high RBP4 (P = 0.003) in CHC. By logistic regression, RBP4 was the only variable independently associated with moderate-severe steatosis in CHC (odds ratio, 1.045; 95% confidence interval, 1.020 to 1.070; P = 0.0004), whereas waist circumference was associated with moderate-severe steatosis in NAFLD (odds ratio, 1.095; 95% confidence interval, 1.007 to 1.192; P = 0.03). CONCLUSION: In nondiabetic, nonobese patients with genotype 1 CHC, serum RBP4 levels might be the expression of a virus-linked pathway to steatosis, largely unrelated to IR.     

QSAR of clinically important EGFR mutant L858R/T790M pyridinylimidazole inhibitors

EGFR is a well‐established therapeutic target of clinical relevance in cancer. However, acquisition of secondary mutation (T790M) makes first‐generation inhibitors ineffective. Therefore, to circumvent the problem of resistance, new T790M/L858R (TMLR) double mutant inhibitors are required. In this study, fragment‐based QSAR models (GQSAR) were generated for pyridinylimidazole derivatives having biological activity against TMLR mutants. The GQSAR model developed using partial least squares regression via stepwise forward–backward variable selection technique showed best results as judged using statistical parameters (r², q², and pred_r²). Additionally, applicability domain of the model was verified using Williams plot, which indicated that the predicted data are reliable. The GQSAR provided site‐specific clues wherein modifications related to decreasing lipophilic character and rotatable bonds and increasing SaaCHE‐index are required for improving inhibitory activity. Overall, the study indicated that the presence of acrylamide at R5 is essential for covalent bond formation with Cys797 and occurrence of aromatic residue at R2 is required for occupying hydrophobic region next to Met790 gatekeeper residue. Based on this information, new derivatives were designed that show better inhibitory activity than the experimentally reported most active molecules. Thus, the model developed can be used to design new pyridinylimidazole derivatives with improved TMLR bioactivity.     

Evaluating the Connect with Pharmacy web-based intervention to reduce hospital readmission for older people

International Journal of Clinical Pharmacy - Background The patient transition from a hospital to a&nbsp;post-discharge healthcare setting has potential to disrupt continuity of medication...