Prevalence of HIV antibodies in transsexual and female prostitutes.

Human immunodeficiency virus (HIV) prevalence was studied in an unselected group of 216 female and transsexual prostitutes. Subjects were asked about age, biological sex, marital status, children, length of occupation, sexual practices, and drug abuse history. Blood was drawn on site. All 128 females who did not admit to drug abuse were seronegative; 2 of the 52 females (3.8%) who admitted to intravenous drug abuse were seropositive. In contrast, 11.1% of the 36 male transsexuals (including 3 out of 32 non-drug abusers) were seropositive. The results support the notion that vaginal transmission of HIV is less effective than anal transmission.     

Endocrinology: Ultrasonic control without hormone determination for ovulation induction in in-vitro fertilization/embryo transfer with gonadotrophin-releasing hormone analogue and human menopausal gonadotrophin

A total of 114 patients admitted to an in-vitro fertilization-embryotransfer programme for the first time, were randomly assignedto the study group or controls. Gonadotrophinreleasing hormoneanalogue (GnRHa) and human menopausal gonadotrophin (HMG) wereused for ovulation induction. The study patients were followedup merely by ultrasonography and the controls by ultrasonographyand serum determinations of oestradiol, progesterone and luteinizinghormone (LH). There was no significant difference in the durationand total amount of HMG used for ovulation induction (10.9 versus11.5 days and 34.8 versus 37.9 ampoules, respectively). Thenumber of oocytes retrieved (11.7 versus 13.4) and the numbersof embryos replaced (2.6 versus 2.8) and cryopreserved (1.9versus 3.3) were also similar. Pregnancy rates were similar.Pregnancy rate per ovum retrieval was 22.2 versus 25% and perembryo transfer 27.2 versus 26.5%. Oestradiol patterns werealso similar. The rate and severity of ovarian hyperstimulationsyndrome were virtually identical. We conclude that ‘ultrasound-only’monitoring of ovulation induction in IVF cycles treated by GnRHa-HMGin the long protocol is as effective and safe as the conventionalultrasound and hormone determination, but far simpler, swifterand more cost-effective     

Treatment of tongue thrust with hypnosis: two case histories

Tongue thrust is a relatively infrequent habit which can result in disruptive, permanent oral malocclusion, bone changes, and facial disharmony. The use of hypnotic phenomena can augment myofunctional therapy. Temperature control, glove anesthesia, relaxation, and imagery enhance demonstration of the proper way to swallow. The cornerstone of having the patient actually feel the contraction at the insertion of the masseter muscles provides an inner biofeedback which provides a very positive signal that the improper habit is being corrected. Hypnosis can then be used in the manner described to achieve a good clinical result.     

Prognostic Implications of Tumor Differentiation in Clinical T1N0 Gastric Adenocarcinoma

BackgroundCurrent guidelines recommend neoadjuvant chemotherapy in patients with locoregional gastric adenocarcinoma. Patients diagnosed with early stage gastric adenocarcinoma are usually managed with upfront surgical intervention. However, pathologic staging in a subset of these clinically staged patients identifies more advanced locoregional disease requiring adjuvant treatment. Therefore, identifying these patients prior to surgical intervention is critical to ensure employment of the appropriate treatment paradigm. The aim of the current study was to define patient characteristics associated with clinical understaging in early gastric cancer.MethodsUsing the National Cancer Database (2004–2014) we identified 3,892 individuals with clinical T1N0 gastric adenocarcinoma who underwent upfront definitive surgery, had negative surgical margins, and did not receive preoperative chemotherapy or radiotherapy. Patient characteristics were compared between those with pathologic stage T1N0 disease and those who were upstaged upon surgery.ResultsTwenty‐seven percent of clinical T1N0 gastric adenocarcinomas had a change in stage because of pathologically defined ≥T2 disease or positive lymph nodes. Individuals who were upstaged had a higher tumor grade compared with those with pathologic stage T1N0 disease. Specifically, 41.9% (530/1,264) of individuals with a poorly differentiated tumor were upstaged, compared with only 10.7% (70/656) with a well‐differentiated tumor. Approximately 75% of cases involved upstaging because of T misclassification. The highest percentage of upstaging was shown for tumors located at the fundus and body of the stomach.ConclusionUpstaging of clinical T1N0 gastric adenocarcinoma is characterized by higher tumor grade and is mostly a result of a change in T stage. These findings mandate thorough workup in order to identify patients with clinically staged T1N0 disease requiring preoperative chemotherapy.Implications for PracticeUpstaging of clinical T1N0 gastric adenocarcinoma is characterized by higher tumor grade and is mostly a result of a change in T stage. These findings mandate thorough workup in order to identify patients with clinically staged T1N0 disease requiring preoperative chemotherapy.     

Transgenic Expression of Vitamin D Receptor in Gut Epithelial Cells Ameliorates Spontaneous Colitis Caused by Interleukin-10 Deficiency

Background

Vitamin D deficiency is common in patients with inflammatory bowel diseases. The vitamin D receptor (VDR) is a nuclear hormone receptor mediating the activity of vitamin D hormone. Our previous studies showed that intestinal epithelial VDR signaling inhibits colitis by protecting the mucosal epithelial barrier, and this activity is independent of non-epithelial immune VDR actions. Interleukin (IL)-10-deficient mouse is a chronic colitis model that develops colitis due to aberrant immune responses. Here we used IL-10 null (IL-10KO) model to assess the anti-colitic activity of epithelial VDR in the setting of an aberrant immune system.

Methods

We crossed IL-10KO mice with villin promoter-driven human (h) VDR transgenic (Tg) mice to generate IL-10KO mice that carry the hVDR transgene in intestinal epithelial cells (IL-10KO/Tg). IL-10KO and IL-10KO/Tg littermates were studied in parallel and followed for up to 25 weeks.

Results

By 25 weeks of age, accumulatively 79 % IL-10KO mice developed prolapse, whereas only 40 % IL-10KO/Tg mice did so (P < 0.001). Compared with IL-10KO mice, IL-10KO/Tg littermates showed markedly reduced mucosal inflammation in both small and large intestines, manifested by attenuation in immune cell infiltration and histological damage and a marked decrease in pro-inflammatory cytokine production. IL-10KO/Tg mice also showed reduced intestinal epithelial cell apoptosis as a result of diminished PUMA induction and caspase 3 activation.

Conclusion

These observations demonstrate that targeting hVDR expression to intestinal epithelial cells is sufficient to attenuate spontaneous colitis caused by an ill-regulated immune system, confirming a critical role of the epithelial VDR signaling in blocking colitis development.

     

Dietary intervention induces flow of changes within biomarkers of lipids, inflammation, liver enzymes, and glycemic control

ObjectiveTo determine how changes in lipids, liver enzymes, and inflammatory and glycemia markers intercorrelate during prolonged dietary intervention in obese participants with or without type 2 diabetes (T2D).MethodsWe examined the dynamics and intercorrelations among changes in biomarkers during the 2-y Dietary Intervention Randomized Controlled Trial (DIRECT) in 322 participants (including 46 with T2D; 52 y of age, body mass index 31 kg/m²) throughout rapid weight loss (0–6 mo) and weight-maintenance/regain (7–24 mo) phases.ResultsThe 2-y increase of high-density lipoprotein cholesterol was greater in participants with T2D (+9.41 versus+6.57 mg/dL, P < 0.05), although they tended to have smaller waist circumferences (?2.1 versus ?4.0 cm, P = 0.08). In models adjusted for age, sex, and weight loss, the 2-year decrease of triacylglycerols was associated with increases of low-density and high-density lipoprotein cholesterol. An increase of apolipoprotein A1 was associated with a decrease in high-sensitive C-reactive protein (P < 0.05 for all comparisons). Exclusively in participants with T2D, the 2-year decrease in triacylglycerols was further correlated with decreases in apolipoprotein B100 and liver enzymes, and a decrease in fasting glucose correlated with decreases in low-density lipoprotein cholesterol, apolipoprotein B100, and alanine aminotransferase (P < 0.05 for all comparisons). In the entire group, multivariate models adjusted for age, sex, intervention group, and 6-mo weight loss identified decreased high-sensitive C-reactive protein at 6 mo as an exclusive predictor of a greater decrease in triacylglycerols (β = 0.154, P = 0.008) and a greater increase in high-density lipoprotein cholesterol (β = ?0.452, P = 0.005) during the subsequent 18 mo.ConclusionsLong-term dietary intervention induces a flow of changes within biomarkers and the cross-talk is likely to be stronger in T2D. A decrease in systemic inflammation during the weight-loss phase may predict greater long-term improvement in lipids (www.ClinicalTrials.gov, identifier NCT00160108).     

Adhesion of sickle neutrophils and erythrocytes to fibronectin

The pathophysiology of vaso-occlusive crisis in sickle cell disease involves interactions among blood cells, plasma proteins, and vessel wall components. The initial goal of this work was to quantify the adhesion of sickle red blood cells (RBCs) to fibronectin immobilized on glass under both static and dynamic shear stress conditions. High-power microscopic inspection of static assay plates showed striking numbers of adherent neutrophils as well as RBCs. Sickle neutrophils and RBCs were significantly more adherent to fibronectin than the corresponding normal cells in static adhesion assays. Adhesion of both sickle neutrophils and sickle RBCs in dynamic adhesion assays was promoted by a period of static incubation preceding initiation of shear stress conditions. Adherent neutrophils remained attached at shear stresses up to 51 dyne/cm2; most adherent RBCs were attached at shear stresses up to 13 dyne/cm2, but detached at a shear stress of 20 dyne/cm2. Sickle neutrophil adhesion was enhanced significantly by autologous plasma. Elevated levels of plasma interleukin-6 (IL-6; but not IL-1 or IL-8) were found in 6 of 9 sickle cell disease samples examined, and elevated levels of tumor necrosis factor were found in 2 of 9 samples. Plasma IL- 6 levels correlated positively with both the number of sickle neutrophils adherent to fibronectin and the ability of sickle plasma to enhance adhesion of normal neutrophils to fibronectin. These data suggest possible roles for neutrophil activation and for fibronectin in mediating sickle neutrophil and RBC adhesion.     

Use of a fluorescent cholesterol derivative to measure lateral mobility of cholesterol in membranes.

N1-Cholesterylcarbamoyl-N8-(4-nitrobenzo-2-oxa-1,3-diazole)-3,6-dioxaoctyl-1,8-diamine (NBD-Chol), a new fluorescent derivative of cholesterol, was incorporated into L-alpha-dimyristoylphosphatidylcholine (Myr2PtdCho)-based liposomes. The lateral mobility of this derivative, as well as that of N-(4-nitrobenzo-2-oxa-1,3-diazole)phosphatidylethanolamine (NBD-PtdEtn), was measured by fluorescence recovery after photobleaching techniques. In Myr2PtdCho liposomes, the diffusion coefficients (D) of the two probes are the same within experimental error below (D, approximately equal to 2 X 10(-10) cm2 X sec-1) and above (D, approximately equal to 2 X 10(-8) cm2 X sec-1) the main phase transition temperature of the bulk lipid (Tm). There is, however, a distinct difference between the mobilities of the derivatives at concentrations of added cholesterol between 5 and 20 mol % at temperatures below the main phase transition. Under these conditions, the diffusion coefficient of NBD-Chol is approximately twice that of NBD-PtdCho, a result consistent with the idea that cholesterol undergoes a lateral phase separation in these membranes at concentrations less than 20 mol %. At cholesterol concentrations greater than 20 mol % or temperatures above the Tm, the D values of the two probes are identical. The lateral mobility of a cholesterol derivative has thus been monitored directly in cholesterol-containing membranes.     

Focal cortical dysfunction and blood-brain barrier disruption in patients with Postconcussion syndrome.

Postconcussion syndrome (PCS) refers to symptoms and signs commonly occurring after mild head injury. The pathogenesis of PCS is unknown. The authors quantitatively analyzed EEG recordings, localized brain sources for abnormal activity, and correlated it with imaging studies. Data from 17 patients with neurologic symptomatology consistent with ICD-10 criteria for PCS was analyzed. Normalized quantitative EEG (QEEG) revealed significantly higher power in the delta band and lower power in the alpha band compared with matched controls. The generators for the abnormal rhythms were focally localized in neocortical regions. Brain computerized tomography and/or MRI did not reveal focal abnormality at the time of diagnosis. Single photon emission computed tomography (SPECT) after 99mTc-ethylcysteinate dimer administration showed a focal reduction in perfusion in 85% (n = 11) of the patients, and abnormal blood-brain barrier (BBB) after 99mTc-diethylenetriaminepentaacetic acid administration in 73% (n = 8). In 75% of these patients, low-resolution brain electromagnetic tomography analysis showed that the generators for abnormal rhythms were closely related to the anatomic location of the BBB lesion. These data point to focal cortical dysfunction in conjunction with BBB disruption and hypoperfusion as a possible mechanism of pathogenesis in at least some PCS patients, and offer QEEG and SPECT as important tools in evaluating these patients.