Immunophenotype of Atypical Polypoid Adenomyoma of the Uterus: Diagnostic Value and Insight on Pathogenesis

Atypical polypoid adenomyoma (APA) is a rare uterine lesion constituted by atypical endometrioid glands, squamous morules, and myofibromatous stroma. We aimed to assess the immunophenotype of the 3 components of APA, with regard to its pathogenesis and its differential diagnosis. A systematic review was performed by searching electronic databases from their inception to January 2019 for immunohistochemical studies of APA. Thirteen studies with 145 APA cases were included. APA glands appeared analogous to atypical endometrial hyperplasia (endometrioid cytokeratins pattern, Ki67≤50%, common PTEN loss, and occasional mismatch repair deficiency); the prominent expression of hormone receptors and nuclear β-catenin suggest that APA may be a precursor of "copy number-low," CTNNB1-mutant endometrial cancers. Morules appeared as a peculiar type of hyperdifferentiation (low KI67, nuclear β-catenin+, CD10+, CDX2+, SATB2+, p63-, and p40-), analogous to morular metaplasia in other lesions and distinguishable immunohistochemically from both conventional squamous metaplasia and solid cancer growth. Stroma immunphenotype (low Ki67, α-smooth-muscle-actin+, h-caldesmon-, CD10-, or weak and patchy) suggested a derivation from a metaplasia of normal endometrial stroma. It was similar to that of nonatypical adenomyoma, and different from adenosarcoma (Ki67 increase and CD10+ in periglandular stroma) and myoinvasive endometrioid carcinoma (h-caldesmon+ in myometrium and periglandular fringe-like CD10 pattern)

PIP5KIβ Selectively Modulates Apical Endocytosis in Polarized Renal Epithelial Cells

Localized synthesis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] at clathrin coated pits (CCPs) is crucial for the recruitment of adaptors and other components of the internalization machinery, as well as for regulating actin dynamics during endocytosis. PtdIns(4,5)P2 is synthesized from phosphatidylinositol 4-phosphate by any of three phosphatidylinositol 5-kinase type I (PIP5KI) isoforms (α, β or γ). PIP5KIβ localizes almost exclusively to the apical surface in polarized mouse cortical collecting duct cells, whereas the other isoforms have a less polarized membrane distribution. We therefore investigated the role of PIP5KI isoforms in endocytosis at the apical and basolateral domains. Endocytosis at the apical surface is known to occur more slowly than at the basolateral surface. Apical endocytosis was selectively stimulated by overexpression of PIP5KIβ whereas the other isoforms had no effect on either apical or basolateral internalization. We found no difference in the affinity for PtdIns(4,5)P2-containing liposomes of the PtdIns(4,5)P2 binding domains of epsin and Dab2, consistent with a generic effect of elevated PtdIns(4,5)P2 on apical endocytosis. Additionally, using apical total internal reflection fluorescence imaging and electron microscopy we found that cells overexpressing PIP5KIβ have fewer apical CCPs but more internalized coated structures than control cells, consistent with enhanced maturation of apical CCPs. Together, our results suggest that synthesis of PtdIns(4,5)P2 mediated by PIP5KIβ is rate limiting for apical but not basolateral endocytosis in polarized kidney cells. PtdIns(4,5)P2 may be required to overcome specific structural constraints that limit the efficiency of apical endocytosis. © 2013 Szalinski et al

What are we measuring? A critique of range of motion methods currently in use for Dupuytren's disease and recommendations for practice

Background: Range of motion is the most frequently reported measure used in practice to evaluate outcomes. A goniometer is the most reliable tool to assess range of motion yet, the lack of consistency in reporting prevents comparison between studies. The aim of this study is to identify how range of motion is currently assessed and reported in Dupuytren’s disease literature. Following analysis recommendations for practice will be made to enable consistency in future studies for comparability. This paper highlights the variation in range of motion reporting in Dupuytren’s disease. Methods: A Participants, Intervention, Comparison, Outcomes and Study design format was used for the search strategy and search terms. Surgery, needle fasciotomy or collagenase injection for primary or recurrent Dupuytren’s disease in adults were included if outcomes were monitored using range of motion to record change. A literature search was performed in May 2013 using subject heading and free-text terms to also capture electronic publications ahead of print. In total 638 publications were identified and following screening 90 articles met the inclusion criteria. Data was extracted and entered onto a spreadsheet for analysis. A thematic analysis was carried out to establish any duplication, resulting in the final range of motion measures identified. Results: Range of motion measurement lacked clarity, with goniometry reportedly used in only 43 of the 90 studies, 16 stated the use of a range of motion protocol. A total of 24 different descriptors were identified describing range of motion in the 90 studies. While some studies reported active range of motion, others reported passive or were unclear. Eight of the 24 categories were identified through thematic analysis as possibly describing the same measure, ‘lack of joint extension’ and accounted for the most frequently used. Conclusions: Published studies lacked clarity in reporting range of motion, preventing data comparison and meta-analysis. Percentage change lacks context and without access to raw data, does not allow direct comparison of baseline characteristics. A clear description of what is being measured within each study was required. It is recommended that range of motion measuring and reporting for Dupuytren’s disease requires consistency to address issues that fall into 3 main categories:- Definition of terms Protocol statement Outcome reportin

Global access to antibiotics without prescription in community pharmacies: a systematic review and meta-analysis

Objective: To estimate the proportion of over-the-counter antibiotic requests or consultations that resulted in non-prescription supply of antibiotics in community pharmacies globally. Methods: We systematically searched EMBASE, Medline and CINAHL databases for studies published from January 2000 to September 2017 reporting the frequency of non-prescription sale and supply of antibiotics in community pharmacies across the world. Additional articles were identified by checking reference lists and a Google Scholar search. A random effects meta-analysis was conducted to calculate pooled estimates of non-prescription supply of antibiotics. Results: Of the 3302 articles identified, 38 studies from 24 countries met the inclusion criteria and were included in the review. All the included countries with the exception of one, classified antibiotics as prescription-only medicines. The overall pooled proportion of non-prescription supply of antibiotics was 62% (95% CI 53 – 72). The pooled proportion of non-prescription supply of antibiotics following a patient request was 78% (95% CI 59 - 97) and based on community pharmacy staff recommendation was 58% (95% CI 48 – 68). The regional supply of non-prescription antibiotics was highest in South America, 78% (95% CI 72 - 84). Antibiotics were commonly supplied without a prescription to patients with symptoms of urinary tract infections (68%, 95% CI 42 – 93) and upper respiratory tract infections (67%, 95% CI 55 - 79). Fluoroquinolones and Penicillins respectively were the most commonly supplied antibiotic classes for these indications. Conclusion: Antibiotics are frequently supplied without prescription in many countries. This overuse of antibiotics could facilitate the development and spread of antibiotic resistance

Acute cholecystitis with massive upper gastrointestinal bleed: A case report and review of the literature

BACKGROUND: Cystic artery pseudoaneurysm is a rare complication following cholecystitis. Its presentation with upper gastrointestinal hemorrhage (UGIH) is even rarer. Thirteen patients with cystic artery pseudoaneurysm have been reported in the literature but only 2 of them presented with UGIH alone. CASE PRESENTATION: We report a 43-year-old woman who developed a cystic artery pseudoaneurysm following an episode of acute cholecystitis. She presented with haematemesis and melaena associated with postural symptoms. Upper gastrointestinal endoscopy revealed a duodenal ulcer with adherent clots in the first part of the duodenum. Ultrasonography detected gallstones and a pseudoaneurysm at the porta hepatis. Selective hepatic angiography showed two small pseudoaneurysms in relation to the cystic artery, which were selectively embolized. However, the patient developed abdominal signs suggestive of gangrene of the gall bladder and underwent an emergency laparotomy. Cholecystectomy with common bile duct exploration along with repair of the duodenal rent, and pyloric exclusion and gastrojejunostomy was done. CONCLUSION: This case illustrates the occurrence of a rare complication (pseudoaneurysm) following cholecystitis with an unusual presentation (UGIH). Cholecystectomy, ligation of the pseudoaneurysm and repair of the intestinal communication is an effective modality of treatment

Clinical-pathological study on β-APP, IL-1β, GFAP, NFL, Spectrin II, 8OHdG, TUNEL, miR-21, miR-16, miR-92 expressions to verify DAI-diagnosis, grade and prognosis

Traumatic brain injury (TBI) is one of the most important death and disability cause, involving substantial costs, also in economic terms, when considering the young age of the involved subject. Aim of this paper is to report a series of patients treated at our institutions, to verify neurological results at six months or survival; in fatal cases we searched for βAPP, GFAP, IL-1β, NFL, Spectrin II, TUNEL and miR-21, miR-16, and miR-92 expressions in brain samples, to verify DAI diagnosis and grade as strong predictor of survival and inflammatory response. Concentrations of 8OHdG as measurement of oxidative stress was performed. Immunoreaction of β-APP, IL-1β, GFAP, NFL, Spectrin II and 8OHdG were significantly increased in the TBI group with respect to control group subjects. Cell apoptosis, measured by TUNEL assay, were significantly higher in the study group than control cases. Results indicated that miR-21, miR-92 and miR-16 have a high predictive power in discriminating trauma brain cases from controls and could represent promising biomarkers as strong predictor of survival, and for the diagnosis of postmortem traumatic brain injury

Admission to acute care hospitals for adolescent substance abuse: a national descriptive analysis

BACKGROUND: Use of alcohol and illicit drugs by adolescents remains a problem in the U.S. Case identification and early treatment can occur within a broad variety of healthcare and non-healthcare settings, including acute care hospitals. The objective of this study is to describe the extent and nature of adolescent admissions to the acute inpatient setting for substance abuse (SA). We use the Agency for Healthcare Research and Quality (AHRQ) 2000 Healthcare Cost and Utilization Project Kids Inpatient Database (HCUP-KID) which includes over 2.5 million admissions for youth age 20 and under to 2,784 hospitals in 27 states in the year 2000. Specifically, this analysis estimates national number of admissions, mean total charges, and mean lengths of stay for adolescents between the ages of 12 and 17 admitted to an acute care hospital for the following diagnostic categories from the AHRQ's Clinical Classifications Software categories: "alcohol-related mental disorders" and "substance-related mental disorders". Frequency and percentage of total admissions were calculated for demographic variables of age, gender and income and for hospital characteristic variables of urban/rural designation and children's hospital designation. RESULTS: SA admissions represented 1.25 percent of adolescent admissions to acute care hospitals. Nearly 90 percent of the admission occurred in non-Children's hospitals. Most were for drug dependence (38%) or non-dependent use of alcohol or drugs (35%). Costs were highest for drug dependence admissions. Nearly half of admissions had comorbid mental health diagnoses. Higher rates of admission were seen in boys, in older adolescents, and in "self-pay" patients. Alcohol and drug rehabilitation/detoxification, alone or in combination with psychological and psychiatric evaluation and therapy, was documented for 38 percent of admissions. Over 50 percent of cases had no documentation of treatment specific to substance use behavior. CONCLUSION: General acute care hospitals have a significant and important opportunity to recognize, treat, and refer adolescents with substance abuse problems. These results suggest that inpatient facilities should develop and implement policies and processes to ensure that adolescent substance abusers admitted to their institutions receive appropriate care during the admission and appropriate referral to community care resources

The Circum-Galactic Medium of Massive Spirals. II. Probing the Nature of Hot Gaseous Halo around the Most Massive Isolated Spiral Galaxies

We present the analysis of the XMM-Newton data of the Circum-Galactic Medium of MASsive Spirals (CGM-MASS) sample of six extremely massive spiral galaxies in the local universe. All the CGM-MASS galaxies have diffuse X-ray emission from hot gas detected above the background extending \sim (30\mbox{--}100)\,\mathrm{kpc} from the galactic center. This doubles the existing detection of such extended hot CGM around massive spiral galaxies. The radial soft X-ray intensity profile of hot gas can be fitted with a β-function, with the slope typically in the range of \beta =0.35\mbox{--}0.55. This range, as well as those β values measured for other massive spiral galaxies, including the Milky Way (MW), are in general consistent with X-ray luminous elliptical galaxies of similar hot gas luminosity and temperature, and with those predicted from a hydrostatic-isothermal gaseous halo. Hot gas in such a massive spiral galaxy tends to have temperature comparable to its virial value, indicating the importance of gravitational heating. This is in contrast to lower mass galaxies, where hot gas temperature tends to be systematically higher than the virial one. The ratio of the radiative cooling to free fall timescales of hot gas is much larger than the critical value of ~10 throughout the entire halos of all the CGM-MASS galaxies, indicating the inefficiency of gas cooling and precipitation in the CGM. The hot CGM in these massive spiral galaxies is thus most likely in a hydrostatic state, with the feedback material mixed with the CGM, instead of escaping out of the halo or falling back to the disk. We also homogenize and compare the halo X-ray luminosity measured for the CGM-MASS galaxies and other galaxy samples and discuss the "missing" galactic feedback detected in these massive spiral galaxies