Pro-anorexia coaches prey on individuals with eating disorders.

OBJECTIVE: While studies have focused on pro-ana communities and pro-anorexia websites, no research has been conducted on the presence of pro-anorexia coaches within these communities. This study aimed to gain insight into the modus operandi of pro-anorexia coaches. METHOD: First, three fake profiles were used to attempt interaction with pro-anorexia coaches (n = 31). Second, an online questionnaire on experiences with pro-anorexia coaches was completed by 79 respondents. Third, a follow-up in-depth interview was conducted with 14 of these respondents. RESULTS: The results show that pro-anorexia coaches' behavior fits a five-staged model which has similarities to stages of online grooming. They focus on (1) building trust and developing a dependency relationship with the aim of (2) obtaining sexually explicit materials. Subsequently, they (3) increase pressure, (4) utilize blackmail methods with acquired content, and (5) groom respondents to meet in person. DISCUSSION: Pro-anorexia coaches deliberately abuse vulnerable young people who suffer from eating disorders to receive sexually explicit material or to meet face-to-face with a sexual intention. This study shows that the modus operandi of pro-ana coaches is similar to online grooming. Clinical professionals need to be aware of this practice to detect victims and potential victims in order to support and treat them. Prevention is invaluable to further combat pro-anorexia coaches and protect potential victims. PUBLIC SIGNIFICANCE: Individuals with an eating disorder are avid internet users. A minority frequent pro-anorexia websites and fora seeking help in losing weight. This study showed that pro-anorexia coaches prey on these individuals, often to obtain sexually explicit content. The modus operandi of pro-anorexia coaches shows similarities to online grooming. Awareness of this phenomenon and the way in which pro-anorexia coaches operate is valuable for clinicians, parents, and teachers.

Retinal ganglion cell loss and gliosis in the retinofugal projection following intravitreal exposure to amyloid-beta.

Pathological accumulations of amyloid-beta (Aß) peptide are found in retina early in Alzheimer's disease, yet its effects on retinal neuronal structure remain unknown. To investigate this, we injected fibrillized Aß1-42 protein into the eye of adult C57BL/6 J mice and analyzed the retina, optic nerve (ON), and the superior colliculus (SC), the primary retinal target in mice. We found that retinal Aß exposure stimulated microglial activation and retinal ganglion cell (RGC) loss as early as 1-week post-injection. Pathology was not limited to the retina, but propagated into other areas of the central nervous system. Microgliosis spread throughout the retinal projection (retina, ON, and SC), with multiplex protein quantitation demonstrating an increase in endogenously produced Aß in the ON and SC corresponding to the injected retinas. Surprisingly, this pathology spread to the opposite side, with unilateral Aß eye injections driving increased Aß levels, neuroinflammation, and RGC death in the opposite, un-injected retinal projection. As Aß-mediated microglial activation has been shown to propagate Aß pathology, we also investigated the role of the Aß-binding microglial scavenger receptor CD36 in this pathology. Transgenic mice lacking the CD36 receptor were resistant to Aß-induced inflammation and RGC death up to 2 weeks following exposure. These results indicate that Aß pathology drives regional neuropathology in the retina and does not remain isolated to the affected eye, but spreads throughout the nervous system. Further, CD36 may serve as a promising target to prevent Aß-mediated inflammatory damage.

Targeted therapies for ROS1-rearranged non-small cell lung cancer.

ROS1 gene fusions account for approximately 1-2% of all cases of non-small cell lung cancer (NSCLC). Similarly to anaplastic lymphoma kinase (ALK)-positive NSCLC, patients with ROS1+ NSCLC tend to have minimal smoking and be of the female sex. In most cases, adenocarcinoma is the dominant histology. The ROS1 gene has homology to ALK and this structural similarity formed the basis for utilizing ALK inhibitors for ROS1+ NSCLC. On the basis of impressive progression-free survival of 19.2 months from the PROFILE 1001 trial, crizotinib obtained Food and Drug Administration (FDA) approval as first-line therapy for treatment of ROS1+ NSCLC. Since then, there has been a growing appreciation of the incidence of brain metastases in ROS1+ NSCLC and rates of central nervous system progression on crizotinib. Additionally, appreciation of novel resistance mechanisms to crizotinib has led to the development of newer tyrosine kinase inhibitors (TKIs). In this review, we highlight known and emerging TKIs for the management of ROS1+ NSCLC.

Misdiagnosis of asthma in schoolchildren.

BACKGROUND: A correct diagnosis of asthma is the cornerstone of asthma management. Few pediatric studies have examined the accuracy of physician-diagnosed asthma. OBJECTIVES: We determined the accuracy of parent reported physician-diagnosed asthma in children sampled from a community cohort. METHODS: Nested case-control study that recruited 203 children, aged 9-12, from a community-based sample. Three groups were recruited: asthma cases had a parental report of physician-diagnosed asthma, symptomatic controls had respiratory symptoms without a diagnosis of asthma, and asymptomatic controls had no respiratory symptoms. All participants were assessed and assigned a clinical diagnosis by one of three study physicians, and then completed spirometry, methacholine challenge, and allergy skin testing. The reference standard of asthma required a study physician's clinical diagnosis of asthma and either reversible bronchoconstriction or a positive methacholine challenge. Diagnostic accuracy, sensitivity and specificity were calculated for parent-reported asthma diagnosis compared to the reference standard. RESULTS: One hundred two asthma cases, 52 controls with respiratory symptoms but no asthma diagnosis, and 49 asymptomatic controls were assessed. Physician agreement for the diagnosis of asthma was moderate (kappa 0.46-0.81). Compared to the reference standard, 45% of asthma cases were overdiagnosed and 10% of symptomatic controls were underdiagnosed. Parental report of physician-diagnosed asthma had 75% sensitivity and 92% specificity for correctly identifying asthma. CONCLUSIONS: There is significant misclassification of childhood asthma when the diagnosis relies solely on a clinical history. This study highlights the importance of objective testing to confirm the diagnosis of asthma. Pediatr Pulmonol. 2017;52:293-302. © 2016 Wiley Periodicals, Inc.

Post-operative enteral immunonutrition for gynecologic oncology patients undergoing laparotomy decreases wound complications.

OBJECTIVES: The aim of this study is to determine if peri-operative immune modulating dietary supplements decrease wound complications in gynecologic oncology patients undergoing laparotomy. METHODS: In July 2013 we instituted a practice change and recommended pre- and post-operative oral immune modulating diets (IMDs) to patients undergoing laparotomy. We retrospectively compared patients who received IMDs to those who did not for the study period July 2012 to June 2014. Our outcome of interest was the frequency of Centers for Disease Control surgical site infections (CDC SSIs). RESULTS: Of the 338 patients who underwent laparotomy during the study period, 112 (33%) received IMDs post-operatively. There were 89 (26%) wound complications, including 69 (78%) CDC SSI class 1, 7(8%) class 2 and 13(15%) class 3. Patients receiving IMDs had fewer wound complications than those who did not (19.6% vs. 33%, p=0.049). After controlling for variables significantly associated with the development of a wound complication (ASA classification, body mass index (BMI), history of diabetes mellitus or pelvic radiation, length of surgery and blood loss) consumption of IMDs remained protective against wound complications (OR 0.45, CI 0.25-0.84, p=0.013) and was associated with a 78% reduction in the incidence of CDC SSI class 2 and 3 infections (OR=0.22, CI 0.05-0.95, p=0.044). CONCLUSIONS: Post-operative IMDs are associated with fewer wound complications in patients undergoing laparotomy for gynecologic malignancy and may reduce the incidence of CDC SSI class 2 and 3 infections.

Novel GCH1 variant in Dopa-responsive dystonia and Parkinson's disease.

BACKGROUND: GTP cyclohydrolase I (GCH1) mutations are the commonest cause of Dopa-responsive dystonia (DRD). Clinical phenotypes can be broad, even within a single family. METHODS: We present clinical, genetic and functional imaging data on a British kindred in which affected subjects display phenotypes ranging from DRD to Parkinson's disease (PD). Twelve family members were studied. Clinical examination, dopamine transporter (DAT) imaging, and molecular genetic analysis of GCH1 and the commonest known familial PD-related genes were performed. RESULTS: We have identified a novel missense variant, c.5A > G, p.(Glu2Gly), within the GCH1 gene in affected family members displaying a range of phenotypes. Two affected subjects carrying this variant had abnormal DAT imaging. These two with abnormal DAT imaging had a PD phenotype, while the remaining three subjects with the novel GCH1 variant had normal DAT imaging and a DRD phenotype. CONCLUSIONS: We propose that this GCH1 variant is pathogenic in this family and these findings suggest that similar mechanisms involving abnormal GTP cyclohydolase I may underlie both PD and DRD. GCH1 genetic testing should be considered in patients with PD and a family history of DRD.

All-cause mortality in hospitalized patients with infectious diarrhea: Clostridium difficile versus other enteric pathogens in Austria from 2008 to 2010.

BACKGROUND: Clostridium difficile infection is the leading cause of gastroenteritis-associated deaths in the industrialized world, followed by infection with norovirus. METHODS: Using a cohort study design, we compared 90 inpatients with diarrhea due to C. difficile infection (CDI) with 180 inpatients with diarrhea due to other infectious agents (including 55% with norovirus infection) with respect to complications and all-cause mortality. The effects of age, severity of underlying diseases and additional infections were assessed by stratified analyses. RESULTS: Diarrhea recurrence occurred 8.9 (95%CI: 2.9-27.3) times more often in CDI independent of age and severity of comorbidities. The all-cause mortality in CDI patients pre-discharge and at 30 and 180 days, respectively, was 20.0%, 17.0% and 42.3% versus 7.2%, 6.7% and 22.5% in non-CDI diarrhea patients. Among those patients with low comorbidities, who were younger than 65 years and without additional infections, the all-cause pre-discharge, 30-day and 180-day mortality risks were significantly higher for the CDI diarrhea patients than the non-CDI diarrhea patients. This association was not observed among patients with an older age, more severe comorbidities or additional infections. CONCLUSION: CDI results in higher all-cause mortality than diarrhea due to other infectious agents in younger patients with low comorbidities.

Hospital-acquired Clostridium difficile infection: determinants for severe disease.

Risk factors of severity (need for surgical intervention, intensive care or fatal outcome) were analysed in hospital-acquired Clostridium difficile infection (CDI) in a 777-bed community hospital. In a prospective analytical cross-sectional study, age (≥ 65 years), sex, CDI characteristics, underlying diseases, severity of comorbidity and PCR ribotypes were tested for associations with severe CDI. In total, 133 cases of hospital-acquired CDI (mean age 74.4 years) were identified, resulting in an incidence rate of 5.7/10,000 hospital-days. A recurrent episode of diarrhoea occurred in 25 cases (18.8%) and complications including toxic megacolon, dehydration and septicaemia in 69 cases (51.9%). Four cases (3.0%) required ICU admission, one case (0.8%) surgical intervention and 22 cases (16.5%) died within the 30-day follow-up period. Variables identified to be independently associated with severe CDI were severe diarrhoea (odds ratio [OR] 3.64, 95% confidence interval [CI] 1.19-11.11, p=0.02), chronic pulmonary disease (OR 3.0, 95% CI 1.08-8.40, p=0.04), chronic renal disease (OR 2.9, 95% CI 1.07-7.81, p=0.04) and diabetes mellitus (OR 4.30, 95% CI 1.57-11.76, p=0.004). The case fatality of 16.5% underlines the importance of increased efforts in CDI prevention, in particular for patients with underlying diseases.

Glucocorticoids for the treatment of anaphylaxis: Cochrane systematic review.

BACKGROUND: Anaphylaxis is a serious hypersensitivity reaction that is rapid in onset and may result in death. A number of guidelines recommend glucocorticoids for the treatment of people experiencing anaphylaxis. OBJECTIVES: We sought to assess the benefits and harms of glucocorticoid treatment during episodes of anaphylaxis. METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 3), MEDLINE (Ovid) (1966 to September 2009), EMBASE (Ovid) (1988 to September 2009), CINAHL (EBSCOhost) (to September 2009) and The Science Citation Index Expanded (SCI-EXPANDED) (1945 to September 2009). We also searched the UK National Research Register and websites listing ongoing trials and contacted international experts in anaphylaxis in an attempt to locate unpublished material. We sought to include randomized and quasi-randomized controlled trials comparing glucocorticoids with any control (either placebo, adrenaline (epinephrine), an antihistamine, or any combination of these). Two authors independently assessed articles for inclusion. RESULTS: None of the 2496 reports identified satisfied the inclusion criteria. CONCLUSIONS: We conclude that there is no evidence from high-quality studies for the use of steroids in the emergency management of anaphylaxis. Therefore, we can neither support nor refute the use of these drugs for this purpose.

Systematics of early and middle Miocene Old World monkeys.

New information about the early cercopithecoids Prohylobates tandyi (Wadi Moghra, Egypt) and Prohylobates sp. indet. (Buluk and Nabwal, Kenya) is presented. Comparisons are made among all major collections of Early and Middle Miocene catarrhine monkeys, and a systematic revision of the early Old World monkeys is provided. Previous work involving the systematics of early Old World monkeys (Victoriapithecidae; Cercopithecoidea) has been hampered by a number of factors, including the poor preservation of Prohylobates material from North Africa and lack of comparable anatomical parts across collections. However, it is now shown that basal cercopithecoid species from both northern and eastern Africa can be distinguished from one another on the basis of degree of lower molar bilophodonty, relative lower molar size, occlusal details, symphyseal construction, and mandibular shape. Results of particular interest include: 1) the first identification of features that unambiguously define Prohylobates relative to Victoriapithecus; 2) confirmation that P. tandyi is incompletely bilophodont; and 3) recognition of additional victoriapithecid species.

Dental microwear texture analysis of two families of subfossil lemurs from Madagascar.

This study employs dental microwear texture analysis to reconstruct the diets of two families of subfossil lemurs from Madagascar, the archaeolemurids and megaladapids. This technique is based on three-dimensional surface measurements utilizing a white-light confocal profiler and scale-sensitive fractal analysis. Data were recorded for six texture variables previously used successfully to distinguish between living primates with known dietary differences. Statistical analyses revealed that the archaeolemurids and megaladapids have overlapping microwear texture signatures, suggesting that the two families occasionally depended on resources with similar mechanical properties. Even so, moderate variation in most attributes is evident, and results suggest potential differences in the foods consumed by the two families. The microwear pattern for the megaladapids indicates a preference for tougher foods, such as many leaves, while that of the archaeolemurids is consistent with the consumption of harder foods. The results also indicate some intraspecific differences among taxa within each family. This evidence suggests that the archaeolemurids and megaladapids, like many living primates, likely consumed a variety of food types.

FBXO7 mutations cause autosomal recessive, early-onset parkinsonian-pyramidal syndrome.

BACKGROUND: The combination of early-onset, progressive parkinsonism with pyramidal tract signs has been known as pallido-pyramidal or parkinsonian-pyramidal syndrome since the first description by Davison in 1954. Very recently, a locus was mapped in a single family with an overlapping phenotype, and an FBXO7 gene mutation was nominated as the likely disease cause. METHODS: We performed clinical and genetic studies in two families with early-onset, progressive parkinsonism and pyramidal tract signs. RESULTS: An FBXO7 homozygous truncating mutation (Arg498Stop) was found in an Italian family, while compound heterozygous mutations (a splice-site IVS7 + 1G/T mutation and a missense Thr22Met mutation) were present in a Dutch family. We also found evidence of expression of novel normal splice-variants of FBXO7. The phenotype associated with FBXO7 mutations consisted of early-onset, progressive parkinsonism and pyramidal tract signs, thereby matching clinically the pallido-pyramidal syndrome of Davison. The parkinsonism exhibits varying degrees of levodopa responsiveness in different patients. CONCLUSIONS: We conclusively show that recessive FBXO7 mutations cause progressive neurodegeneration with extrapyramidal and pyramidal system involvement, delineating a novel genetically defined entity that we propose to designate as PARK15. Understanding how FBXO7 mutations cause disease will shed further light on the molecular mechanisms of neurodegeneration, with potential implications also for more common forms of parkinsonism, such as Parkinson disease and multiple system atrophy.

A genome-wide linkage scan in a Dutch family identifies a premature ovarian failure susceptibility locus.

BACKGROUND: Premature ovarian failure (POF) is characterized by elevated gonadotrophins and amenorrhea before the age of 40 years and occurs approximately in 1% of women. POF etiology is highly heterogeneous with a wide spectrum of etiological pathogenic mechanisms including genetic causes. These mostly involve numerical, structural or monogenic defects on the X-chromosome. Mutations in a small number of autosomal genes (such as FOXL2 and NOBOX) have been identified as a cause of POF. However, in most cases, the disease underlying mechanisms are largely unknown. METHODS: We performed a genome-wide linkage analysis in a relatively large Dutch family with seven patients suffering from POF, showing a dominant pattern of inheritance. A genome-wide analysis, using 50K single nucleotide polymorphism arrays, was combined with conventional parametric linkage analysis. RESULTS: We identified three genomic regions on chromosomes 5, 14 and 18 yielding suggestive linkage (multipoint LOD score of 2.4 for each region). After inclusion of one elder unaffected family member, only the region on chromosome 5 remains as a putative POF locus. In addition, we investigated a second family (three living patients over three generations) for the regions on chromosome 5, 14 and 18. Haplotype analysis supported only the locus on chromosome 5q14.1-q15. CONCLUSION: We performed the first genome-wide linkage search in familial POF and identified a region on chromosome 5q14.1-q15, which may harbor a novel POF susceptibility gene.

Implementing and optimising an Electronic Library of Health Care in Belgium: results of a pilot study.

Health care practitioners are expected to incorporate results from the best available, scientific information into their daily clinical decision-making process. Useful formats of evidence for practitioners include selected reviews, abstracts in which research results are discussed, "quick answer", evidence-based website including for example diagnostic and therapeutic algorithms, drugs prescription and non-drug therapy. An increasing amount of practitioners has access to the World Wide Web, either at home or at the office. However, easy and cheap access to objective and high quality research results is limited. Many practitioners lack the skills to efficiently navigate complicated medical databases. In 2003 an 'Electronic Library of Health Care' was introduced in Belgium. The main goal of the electronic library is to provide a gateway to scientific evidence to Belgian health care practitioners from different disciplines. This paper presents the results of a pilot project to implement the library in the field. It also describes recent developments and adjustments that increased the efficacy of this gateway to evidence.

Advanced oocyte cryopreservation will not undermine the practice of ethical egg sharing.

The fear that the ethics and practice of egg sharing will be undermined by the growing success of oocyte cryopreservation is not based on published evidence. Separate contracts and directed counselling of donors and recipients as required by law in the UK provide protection against potential pitfalls with egg sharing. The cost and waiting time for egg donation might even fall should oocyte cryopreservation become a practicable procedure.

The G6055A (G2019S) mutation in LRRK2 is frequent in both early and late onset Parkinson's disease and originates from a common ancestor.

BACKGROUND: Mutations in the gene Leucine-Rich Repeat Kinase 2 (LRRK2) were recently identified as the cause of PARK8 linked autosomal dominant Parkinson's disease. OBJECTIVE: To study recurrent LRRK2 mutations in a large sample of patients from Italy, including early (<50 years) and late onset familial and sporadic Parkinson's disease. RESULTS: Among 629 probands, 13 (2.1%) were heterozygous carriers of the G2019S mutation. The mutation frequency was higher among familial (5.1%, 9/177) than among sporadic probands (0.9%, 4/452) (p<0.002), and highest among probands with one affected parent (8.7%, 6/69) (p<0.001). There was no difference in the frequency of the G2019S mutation in probands with early v late onset disease. Among 600 probands, one heterozygous R1441C but no R1441G or Y1699C mutations were detected. None of the four mutations was found in Italian controls. Haplotype analysis in families from five countries suggested that the G2019S mutation originated from a single ancient founder. The G2019S mutation was associated with the classical Parkinson's disease phenotype and a broad range of onset age (34 to 73 years). CONCLUSIONS: G2019S is the most common genetic determinant of Parkinson's disease identified so far. It is especially frequent among cases with familial Parkinson's disease of both early and late onset, but less common among sporadic cases. These findings have important implications for diagnosis and genetic counselling in Parkinson's disease.

The hands and feet of Archaeolemur: metrical affinities and their functional significance.

Recent expeditions to Madagascar have recovered abundant skeletal remains of Archaeolemur, one of the so-called "monkey lemurs" known from Holocene deposits scattered across the island. These new skeletons are sufficiently complete to permit reassembly of entire hands and feet--postcranial elements crucial to drawing inferences about substrate preferences and positional behavior. Univariate and multivariate analysis of intrinsic hand and foot proportions, phalangeal indices, relative pollex and hallux lengths, phalangeal curvature, and distal phalangeal shape reveal a highly derived and unique morphology for an extinct strepsirrhine that diverges dramatically from that of living lemurs and converges in some respects on that of Old World monkeys (e.g., mandrills, but not baboons or geladas). The hands and feet of Archaeolemur are relatively short (extremely so relative to body size); the carpus and tarsus are both "long" relative to total hand and foot lengths, respectively; phalangeal indices of both the hands and feet are low; both pollex and hallux are reduced; the apical tufts of the distal phalanges are very broad; and the proximal phalanges are slightly curved (but more so than in baboons). Overall grasping capabilities may have been compromised to some extent, and dexterous handling of small objects seems improbable. Deliberate and noncursorial quadrupedalism was most likely practiced on both the ground and in the trees. A flexible locomotor repertoire in conjunction with a eurytopic trophic adaptation allowed Archaeolemur to inhabit much of Madagascar and may explain why it was one of the latest surviving subfossil lemurs.

Helicobacter cinaedi bacteremia presenting as macules in an afebrile patient with X-linked agammaglobulinemia.

We describe a 54-year-old man with X-linked agammaglobulinemia (XLA) and Helicobacter cinaedi bacteremia, who presented with tender, hyper-pigmented skin macules without increased local warmth or fever. We propose that this presentation may be a characteristic early sign of bacteremia caused by H. cinaedi and related organisms in otherwise healthy immunocompromised patients. This case demonstrates the importance of a high index of suspicion for H. cinaedi bacteremia in immunocompromised patients with unexplained skin lesions.