Diabetes mellitus in midlife and the risk of dementia three decades later.
To examine the association between diabetes in midlife (1963-1968) and dementia more than three decades later (1999-2001). The authors characterized dementia using standard methods for 1,892 participants among 2,606 survivors of 10,059 participants in the Israeli Ischemic Heart Disease study, a longitudinal investigation of the incidence of and risk factors for cardiovascular disease among Jewish male civil servants in Israel. Face to face interviews were conducted with the 652 subjects identified as possibly demented by the Modified Telephone Interview for Cognitive Status. Logistic regression analysis was performed to assess the association of diabetes with dementia controlling for sociodemographic and cardiovascular variables compared to those with no cognitive impairment. Of 1,892 assessed subjects (mean age 82 at assessment), 309 (16.3%) had dementia. Diabetic subjects had significantly more dementia than non-diabetic subjects (chi2 = 7.54, df = 1, p = 0.006, OR 2.83 [95% CI = 1.40 to 5.71]). Those who survived to the time of this study were younger and healthier than those who died. Evidence for diabetes as a risk factor for dementia was found, similar to other epidemiologic studies. In contrast to the earlier studies, however, the authors linked diabetes in midlife to dementia more than three decades later in the very old survivors of a large male cohort.


A combined transcriptome and proteome analysis extends the allergome of house dust mite Dermatophagoides species.
House dust mites (HDMs) such as Dermatophagoides farinae and D. pteronyssinus represent major causes of perennial allergy. HDM proteomes are currently poorly characterized, with information mostly restricted to allergens. As of today, 33 distinct allergen groups have been identified for these 2 mite species, with groups 1 and 2 established as major allergens. Given the multiplicity of IgE-reactive mite proteins, potential additional allergens have likely been overlooked. To perform a comprehensive characterization of the transcriptomes, proteomes and allergomes of D. farinae and D. pteronyssinus in order to identify novel allergens. Transcriptomes were analyzed by RNA sequencing and de novo assembly. Comprehensive mass spectrometry-based analyses proteomes were combined with two-dimensional IgE reactivity profiling. Transcripts from D. farinae and D. pteronyssinus were assembled, translated into protein sequences and used to populate derived sequence databases in order to inform immunoproteomic analyses. A total of 527 and 157 proteins were identified by bottom-up MS analyses in aqueous extracts from purified HDM bodies and fecal pellets, respectively. Based on high sequence similarities (>71% identity), we also identified 2 partial and 11 complete putative sequences of currently undisclosed D. pteronyssinus counterparts of D. farinae registered allergens. Immunoprofiling on 2D-gels revealed the presence of unknown 23 kDa IgE reactive proteins in both species. Following expression of non-glycosylated recombinant forms of these molecules, we confirm that these new allergens react with serum IgEs from 42% (8/19) of HDM-allergic individuals. Using combined transcriptome and immunoproteome approaches, we provide a comprehensive characterization of D. farinae and D. pteronyssinus allergomes. We expanded the known allergen repertoire for D. pteronyssinus and identified two novel HDM allergens, now officially referred by the International Union of Immunological Societies (IUIS) Nomenclature Subcommittee as Der f 36 and Der p 36.


Skin problems in chronic kidney disease.
Skin disorders associated with chronic kidney disease (CKD) can markedly affect a patient's quality of life and can negatively impact their mental and physical health. Uremic pruritus, which is frequently encountered in patients with CKD, is considered to be an inflammatory systemic disease rather than a local skin disorder. Biomarkers of inflammation are increased in patients with uremic pruritus and an imbalance of the endogenous opioidergic system might be involved in the complex pathogenesis of the disease. Treatment options for uremic pruritus include emollients, topical capsaicin cream, ultraviolet B phototherapy, gabapentin, oral activated charcoal and nalfurafine, a kappa-opioid-receptor agonist. Calcific uremic arteriolopathy is triggered by an imbalance of promoters and inhibitors of vascular calcification, caused by the inflammatory changes that occur in uremia. Promising therapeutic strategies for calcific uremic arteriolopathy include bisphosphonates and intravenous sodium thiosulfate. Nephrogenic systemic fibrosis is a devastating condition associated with the use of gadolinium-based contrast agents in patients with CKD. At present, no therapies are available for this complication. Preventive measures include use of iodine-based contrast agents, particularly in patients with CKD stage 4 and 5. If gadolinium contrast is necessary, administration of low volumes of the more stable macrocyclic ionic types of gadolinium-based contrast agent is advocated. Hemodialysis following gadolinium exposure might offer benefits but evidence is lacking.


New insights into the regulation of the Saccharomyces cerevisiae UGA4 gene: two parallel pathways participate in carbon-regulated transcription.
The Saccharomyces cerevisiae UGA4 gene, which encodes the gamma-aminobutyric acid (GABA) and delta-aminolaevulinic acid (ALA) permease, is well known to be regulated by the nitrogen source. Its expression levels are low in the presence of a rich nitrogen source but are higher when a poor nitrogen source is used. In addition, GABA can induce UGA4 expression when cells are grown with proline but not when they are grown with ammonium. Although vast amounts of evidence have been gathered about UGA4 regulation by nitrogen, little is known about its regulation by the carbon source. Using glucose and acetate as rich and poor carbon source respectively, this work aimed to shed light on hitherto unclear aspects of the regulation of this gene. In poor nitrogen conditions, cells grown with acetate were found to have higher UGA4 basal expression levels than those grown with glucose, and did not show UGA4 induction in response to GABA. Analysis of the expression and subcellular localization of the transcription factors that regulate UGA4 as well as partial deletions and site-directed mutations of the UGA4 promoter region suggested that there are two parallel pathways that act in regulating this gene by the carbon source. Furthermore, the results demonstrate the existence of a new factor operating in UGA4 regulation.


A Study of Clinical Features and Risk Factors of Self-Referring Emergency Department Headache Patients: A Comparison with Headache Center Outpatients.
Nonlife-threatening headaches account for 3% of emergency department (ED) admissions, with social and economic negative consequences. We aim to investigate clinical features and risk factors of nonlife-threatening headache patients referring to ED versus those referring to headache outpatient clinics. During 6 months, we promptly reevaluated in our headache unit (HU) patients discharged from ED. We compared the clinical characteristics of patients who referred to ED with those of HU outpatients visited in the same time interval. Discriminant Function Analysis and Correspondence Analysis were used to determine risk factors for ED referral. We recruited 49 post-ED patients and 126 outpatients. The main reasons for ED admission were poor response to acute treatment and aura-related symptoms. Headache diagnoses made in ED were generally not confirmed later (overall concordance of 47%), except for cluster headache (CH) and migraine with aura (MA). ED patients complained higher headache intensity, longer duration, and prolonged aura compared to outpatients. Aura was the main risk factor associated with ED admission on statistical models, while less prominent risk factors were sex, age, and years from migraine onset. ED patients presented a more severe headache clinical phenotype compared with outpatients. Headache diagnosis remains difficult in the emergency setting and is more easily achieved for the headache forms with standout features, such as MA or CH. According to statistical models, the aura is the most important risk factor for ED admissions.


Comparison of three fluorosis indices in a Namibian community with twice optimum fluoride in the drinking water.
In Otjiwarongo, a town in Namibia with twice the optimum fluoride in the drinking water (1.56 ppm) the Dean (Dean, Arnold and Elvove, 1942), Thylstrup and Fejerskov (Thylstrup and Fejerskov, 1978) and TSIF (Horowitz et al, 1984) indices of fluorosis were compared in permanent teeth of the children aged 11 y living in the region. Fluorosis severety was skewed in all instances to lower scores within each index. With the Thylstrup and Fejerskov and TSIF indices it was possible to compare fluorosis by individual teeth; the former was significantly more sensitive in diagnosis (56 per cent vs 50 per cent prevalence). It is recommended that the aims of a fluorosis investigation be carefully detailed before selecting the fluorosis index to be used. If detailed information on individual teeth related to fluoride ingestion is needed the Thylstrup and Fejerskov index is recommended, especially in areas with raised fluoride intakes where it is anticipated that the fluorosis levels will be mainly in the low levels of severity.


A constraint-relaxation-recovery mechanism for stomatal dynamics.
Models of guard cell dynamics, built on the OnGuard platform, have provided quantitative insights into stomatal function, demonstrating substantial predictive power. However, the kinetics of stomatal opening predicted by OnGuard models were threefold to fivefold slower than observed in vivo. No manipulations of parameters within physiological ranges yielded model kinetics substantially closer to these data, thus highlighting a missing component in model construction. One well-documented process influencing stomata is the constraining effect of the surrounding epidermal cells on guard cell volume and stomatal aperture. Here, we introduce a mechanism to describe this effect in OnGuard2 constructed around solute release and a decline in turgor of the surrounding cells and its subsequent recovery during stomatal opening. The results show that this constraint-relaxation-recovery mechanism in OnGuard2 yields dynamics that are consistent with experimental observations in wild-type Arabidopsis, and it predicts the altered opening kinetics of ost2 H+ -ATPase and slac1 Cl- channel mutants. Thus, incorporating solute flux of the surrounding cells implicitly through their constraint on guard cell expansion provides a satisfactory representation of stomatal kinetics, and it predicts a substantial and dynamic role for solute flux across the apoplastic space between the guard cells and surrounding cells in accelerating stomatal kinetics.


Aldose reductase inhibitors for the prevention and treatment of diabetic peripheral neuropathy.
To assess the efficacy of aldose reductase inhibitors in the prevention, reversal or delay in the progression of diabetic peripheral neuropathy. The Cochrane Diabetes Group's database was searched and the citation lists of identified trials and previous reviews checked. Investigators identified as active in the field were approached for overlooked studies. Randomised controlled trials of aldose reductase inhibitors versus placebo, no treatment or other treatment in diabetic patients with or without clinical neuropathy. Nerve conduction velocity was the only end point measured in all trials. Treatment effect was evaluated in terms of nerve conduction velocity mean difference in median and peroneal motor and median and sural sensory nerves. 19 trials, testing 4 different aldose reductase inhibitors for between 4 to 208 weeks duration (median 24 weeks), met the inclusion criteria for the meta-analysis. A small but statistically significant reduction in decline of median and peroneal motor nerve conduction velocities was present in the treated group when compared to the control group (weighted mean 0.66 m/s 95% CI 0.18-1.14 m/s and 0.53 m/s 95% CI 0.02-1.04m/s respectively). No clear benefit of aldose reductase inhibitor treatment was observed in either of the sensory nerves. Although aldose reductase inhibitor treatment has been demonstrated to diminsh the reduction in motor nerve conduction velocity, the clinical relevance of such a change in this outcome measure is uncertain. There was no effect in terms of this outcome measure in the smaller sensory fibres, degeneration of which is primarily responsible for the most common neuropathic syndrome associated with diabetes, that of severe pain and loss of sensation in the extremity leading in some cases to ulceration and eventual amputation.


Selective cell encapsulation, lysis, pico-injection and size-controlled droplet generation using traveling surface acoustic waves in a microfluidic device.
We generate droplets in a microfluidic device using a traveling surface acoustic wave (TSAW), and control droplet size by adjusting TSAW power and duration. We combine droplet production and fluorescence detection to selectively-encapsulate cells and beads; with this active method, the overwhelming majority of single particles or cells are encapsulated individually into droplets, contrasting the Poisson distribution of encapsulation number that governs traditional, passive microfluidic encapsulation. In addition, we lyse cells before selective encapsulation, and pico-inject new materials into existing droplets.


Dental Pulp Revascularization in a Replanted Avulsed Immature Maxillary Permanent Central Incisor.
An 8-year-old girl sustained an accidental traumatic avulsion of her right maxillary permanent central incisor. She arrived with her mother at a hospital dental clinic with the right maxillary central incisor tooth wrappe in a wet paper towel over 1 hour after the injury. Replantation was accomplished without root surface alteration or root canal intervention. Clinical and radiographic follow-up examinations for over 1 year revealed continued root growth and apical development of the replanted avulsed immature maxillary central incisor with no signs or symptoms of pulpal or periapical pathosis. Excellent outcomes were achieved for periodontal ligament reattachment without removal of the periodontal membrane and pulp revascularization without endodontic intervention.


Early Versus Routine Stoma Closure in Patients With Colorectal Resection: A Meta-Analysis of 7 Randomized Controlled Trials.
Background. A substantial proportion of patients undergoing colorectal surgery receive a temporary stoma, and the timing for stoma closure remains unclear. The aim of this study was to evaluate the safety and feasibility of early stoma closure (ESC) compared with routine stoma closure (RSC) after colorectal surgery. Methods. We comprehensively searched PubMed, Embase, and the Cochrane Library for randomized controlled trials that compared ESC and RSC after colorectal surgery. Results. A total of 7 randomized controlled trials with 814 enrolled patients were identified for this meta-analysis. There were no significant differences between the ESC and RSC groups regarding the complications of stoma closure (26.8% and 16.6%, respectively; odds ratio [OR]: 1.30; 95% confidence interval [CI]: 0.89-1.90; P = .17). A subgroup analysis was conducted by Clavien-Dindo grade of complication, and no significant difference was observed in any subgroup (P > .05). However, the ESC group had a significantly higher risk of wound complications than the RSC group (17.6% and 7.8%, respectively; OR: 2.61; 95% CI: 1.43-4.76; P = .002), and the RSC group had more cases of small bowel obstruction than the ESC group (3.1% and 8.4%, respectively; OR: 0.37; 95% CI: 0.15-0.87; P = .02). Conclusions. ESC is a safe and effective therapeutic approach in patients who have undergone colorectal surgery; it is associated with a reduced risk of bowel obstruction but a higher risk of wound complications.


[Clinical pathologic analysis on 3 724 cases of salivary gland tumors].
Objective: To investigate the incidence and proportion of salivary gland tumors in order to provide new thinking for clinical diagnosis and treatment. Methods: Collected 3 724 cases salivary gland tumors diagnosed by Pathology Department of Hospital of Stomatology, Jilin University from January 1961 to December 2016. The pathological diagnosis referred to the fourth edition of head and neck-salivary gland tumor histopathological classification standard of WHO. The database was established with Microsoft Excel and analyzed with SPSS 18.0. Made a retrospective analysis and comparison on the numbers of all cases in terms of types, site, gender and age and estimate the trend with the time interval of 8 years, and then make a judgement of the trend of salivary tumors. Results: The benign tumors were more common than the malignant among all periods, the proportion of all tumors was about 2.92∶1; The top three benign tumors were polymorphous adenoma [73.78% (2 046/2 773)], Warthin tumor [15.80% (438/2 773)] and base cell adenoma [8.37% (232/2 773)]. Polymorphous adenoma took up 54.94% (2 046/3 724) of all tumors. The top three malignant tumors were mucous epidermoid carcinoma [31.44% (299/951)], adenoid cystic carcinoma [26.92% (256/951)] and adenocarcinoma [11.88% (113/951)]. As for sex, male female ratio was 0.83∶1. As for site, the pathogenic site of tumors was mainly in parotid gland [63.75% (2 374/3 724)], followed by palatal gland [16.50% (615/3 724)], then submandibular gland [12.67% (472/3 724)]; As for age, the common age was between 51 and 60 years old [23.74% (884/3 724)], followed by 41 to 50 years old [21.56%(803/3 724)]. Conclusions: The incidence of benign and malignant salivary gland tumor increased in the 56 years. Females showed a higher incidence. The majority tumors occurred in parotid gland. The most common salivary gland tumor was pleomorphic adenoma and the most common malignant tumor was mucous epidermoid carcinoma. The most common age was in 51-60 years old period.


Effects of various sera on growth kinetics and collagen synthesis by keloid and normal dermal fibroblasts.
Fibroblasts derived from normal dermis and keloids were cultured in nutrient medium supplemented with fetal bovine serum, serum from keloid patients, and serum from age-, sex-, and race-matched nonkeloid formers. Cell numbers were determined at various times during the growth period, and collagen synthesis was analyzed on day 7. In lag phase, keloid-derived fibroblasts were significantly reduced in all sera compared with normal dermal fibroblasts. However, beyond day 2, the growth kinetics of both cell types were similar in keloid and control human sera. Furthermore, collagen synthesis relative to total protein synthesis (percent) was similar in keloid and control human sera. Although systemic factors have been implicated in the pathogenesis of keloids and other fibrotic diseases such as scleroderma and pulmonary fibrosis, this study demonstrates that serum from keloid patients does not contain a factor(s) that significantly modifies the in vitro growth kinetics or collagen synthesis of keloid-derived or normal dermal fibroblasts.


Short- and long-term readmission rates after infrainguinal bypass in a safety net hospital are higher than expected.
Readmission rates are expected to have an increasing effect on both the hospital bottom line and physician reimbursements. Safety net hospitals may be most vulnerable. We examined readmissions at 30 days, 90 days, and 1 year in a large safety net hospital to determine the magnitude and effect of short- and long-term readmission rates after lower extremity infrainguinal bypass in this setting. All nonemergent extremity infrainguinal bypass performed at a large safety net hospital between 2008 and 2016 were identified. Patient demographic, social, clinical, and procedural details were extracted from the electronic medical record. An analysis of patients readmitted at 30 days, 90 days, and 1 year was completed to determine the details of the readmission. A total of 350 patients undergoing extremity infrainguinal bypass were identified. The most frequent indication was tissue loss (57%), followed by claudication (25.6%), and rest pain (17.4%). Patient insurance carriers included Medicare (61.7%), Medicaid (25.4%), and private (13%). The distal target was the popliteal and tibial artery in 52.6% and 47.4% cases, respectively. The majority of bypasses used autologous vein (73.1%). In-hospital complications included pulmonary complications (4.3%), urinary tract infection (3.1%), acute renal failure (2%), graft occlusion (2%), myocardial infarction (1.7%), bleeding (1.4%), surgical wound complications (1.1%), and stroke (0.9%). The 30-day readmission rate was 30% with the most common reasons for readmission being surgical wound complications, nonsurgical foot/leg wounds, nonextremity infectious causes, cardiac ischemia, and congestive heart failure. The 90-day readmission rate was 49.4% and the most common reasons for readmission from 31 to 90 days were nonsurgical foot/leg wounds, graft complications, surgical wound complications, cardiac ischemia, and contralateral leg morbidity. The readmission rate within 1 year was 72.2%. Readmission causes from 91 days to 1 year included graft complications, contralateral leg morbidity, nonextremity infectious, nonsurgical foot/leg wounds, cardiac ischemia, and congestive heart failure. A tibial bypass target was associated with 30-day (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.06-2.69; P = .029) and 90-day (OR, 1.77; 95% CI, 1.14-2.74, P = .011) readmission. Nonprivate insurance (OR, 2.31; 95% CI, 1.17-4.57, P = .016), and critical limb ischemia (OR, 1.77; 95% CI, 1.14-2.74; P = .035) were associated with 1-year readmission. Short- and long-term readmission rates in a safety net setting are high. The 30-day rates in this study are higher than historically reported. This data sets baseline rates for 90-day and 1-year readmission for future analyses. Although the majority of short-term readmissions are related to the index procedure, long-term readmission rates are more frequently related to systemic comorbidities. Targeted patient interventions aimed at preventing the most common reasons for readmission may improve readmission rates, particularly among patients with nonprivate insurance. However, other risk factors, such as tibial target, may not be modifiable and a higher readmission rate may need to be accepted in this population.


[Age-related changes in the morphology and functional state of the heart].
The aim of this study was to assess age-related morpho-functional peculiarities of the heart on the basis of investigating the chrono-inotropic dependence of left ventricular [LV] myocardium. The results of this investigation are of importance for geriatric practice. They are necessary for determining the markers and elaborating the quantitative criteria of detecting the early stages of heart failure and finding the ways to its correction in elderly people. Twenty subjects aged 20-35 and forty four subjects aged 60-74 without clinical symptoms of cardiovascular pathology were investigated by means of stress-echocardiography. The indices of systolic and diastolic functions of the heart were studied by means of the transesophageal atrial electric pacing (TAEP) at baseline and at each frequency of pacing with the assessment of degree and type of LV myocardium hypertrophy. In all of the subjects investigated the results of TAEP were negative, i.e. they showed no signs of coronary insufficiency. In elderly people the increment values of contraction and relaxation velocity indices at the same pacing frequency were significantly lower (P < 0.05) in comparison with ones obtained in younger subjects. In elderly people a decrease of the maximal relaxation velocity occurred at submaximal age-related heart rate (on the average 135 beats/min) as compared to intermediate pacing frequencies whereas in younger subjects a further increment of this value continued. The LV hypertrophy developing with ageing plays on the one hand a compensatory role but on the other hand it deteriorates the diastolic function. The inefficiency of work of the old heart while pacing is an important factor limiting functional capabilities of the heart.


A comprehensive survey of collaborative biostatistics units in academic health centers.
The organizational structures of collaborative biostatistics units in academic health centers (AHCs) in the United States and their important contributions to research are an evolving and active area of discussion and inquiry. Collaborative biostatistics units may serve as a centralized resource to investigators across various disciplines or as shared infrastructure for investigators within a discipline (e.g., cancer), or a combination of both. The characteristics of such units vary greatly, and there has been no comprehensive review of their organizational structures described in the literature to date. This manuscript summarizes the current infrastructure of such units using responses from 129 leaders. Most leaders were over 45 years old, held doctoral degrees, and were on a 12-month appointment. Over half were tenured or on a tenure track and held primary appointments in a school of medicine. Career advancement metrics most important included being funded as co-investigator on NIH grants and being either first or second author on peer-reviewed publications. Team composition was diverse in terms of expertise and training, and funding sources were typically hybrid. These results provide a benchmark for collaboration models and evaluation and may be used by institutional administrators as they build, evaluate, or restructure current collaborative quantitative support infrastructure.


Is fibromyalgia a distinct clinical entity? The patient's evidence.
In the eyes of a person with fibromyalgia syndrome, their pain and other symptoms are real. By the time a patient seeks medical care for fibromyalgia, they will have probably endured criticism and misunderstandings about the invisible nature of their symptoms. Patients are genuinely disturbed that their bodies are not performing up to par, while at the same time, their family, friends and employers are placing demands on them that can't be met. No one would want to be placed in such a frustrating and painful predicament, so naturally this situation becomes the driving force for fibromyalgia patients who are seeking medical advice. Unfortunately, lack of understanding about the neurophysiology of chronic pain syndromes and the advent of evidence-based medicine leads to restricted care for patients who really need a physician's help. The best prescription for aiding people with fibromyalgia undoubtedly includes a physician with an open mind on treatment options.


Soft tissue changes after connective tissue grafts around immediately placed and restored dental implants in the esthetic zone: A systematic review and meta-analysis.
The aim of this systematic review and meta-analysis was to evaluate the soft tissue outcomes of connective tissue graft (CTG) combined with immediate implant placement and restoration (IIPR) in the esthetic zone. Following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement, randomized controlled trials (RCTs) were searched for in electronic databases and complemented by hand searching. The risk of bias was assessed using the Cochrane Collaboration's Risk of Bias tool and data were analyzed using statistical software. A total of 180 studies were identified, of which, four trials were included with 144 implant sites in 144 participants. Overall meta-analysis showed that CTG in conjunction with IIPR had a significantly greater gingival thickness than IIPR alone. The IIPR with CTG had less recession and higher esthetic pink score compared to IIPR group, but the difference was not statistically significant. No significant differences in implant failure rate were found between IIPR with and without CTG. The use of CTG in conjunction with IIPR in the esthetic zone significantly improved the thickness of the gingival tissues compared to IIPR without CTG. No significant differences were observed in the level of soft tissues around immediately placed implants with or without CTG. The use of connective tissue graft with IIPR can be considered to improve the soft tissue profile and minimize mucosal recession in esthetic zone.


[Clinicopathologic analysis and expression of cyclin D1 and p53 of ovarian borderline tumors and carcinomas].
To study the clinicopathological features and expression of cyclin D1 and p53 in epithelial ovarian tumors, and to investigate the correlation between pathogenesis of ovarian cancer and epithelial borderline tumors. Fifty four cases of ovarian borderline tumors and 45 cases of ovarian carcinomas from the People's Hospital, Peking University were reviewed retrospectively. The clinical data and pathological findings were analyzed. Immunohistochemical study of cyclin D1 and p53 was performed in all 99 cases. (1) In borderline tumors, the age of patients ranged from 14 - 82 (mean age = 42.5) years. International Federation of Gynecology and Obstetrics (FIGO) stage of borderline tumors was stage I in 48 cases, stage II in 3 cases, and stage III in 3 cases. In ovarian carcinomas, the age of patients ranged from 26 - 80 (mean age = 53.5) years. FIGO stage of carcinoma was stage I in 6 cases, stage II in 8 cases, stage III in 26 cases, and stage IV in 5 cases. In follow-up of 54 cases with borderline tumors the 5-year survival rate was 98% and of 45 cases with carcinomas a 5-year survival rate of 51% was noted. (2) In 54 cases of borderline tumors, mucinous types accounted for 56% (30/54) and serous types accounted for 30% (16/54). There were 5 cases with micropapillary pattern, 3 cases with peritoneal implants, 3 cases with lymph node involvement, 6 cases with microinvasion, one case with intraepithelial carcinoma, and one case with mural nodules. In 45 cases of carcinomas, serous carcinoma was the most (49%, 22/45). The remainder included 3 cases of mucinous types, 8 cases of endometrioid types, 6 cases of transitional cell types, 3 cases of mixed phenotype and 3 cases of undifferentiated types. (3) Overexpression of cyclin D1 and p53 was observed in 31% (14/45) and 56% (25/45) of ovarian carcinomas, respectively. There was a significant association between p53 overexpression and tumor grade. In the borderline tumor group, 69% (37/54) had overexpression of cyclin D1 and 6% (3/54) had overexpression of p53. There were significant differences in expression of cyclin D1 and p53 between conventional serous borderline tumors and high-grade serous carcinomas (cyclin D1: 91% vs 26%; p53: 0 vs 58%). However, micropapillary serous borderline tumors and low-grade serous carcinomas showed remarkably similar expression of cyclin D1 and p53. Epithelial ovarian borderline tumors are distinct from ovarian cancer in clinical progress and prognosis, and histological types. Overexpression of cyclin D1 is common in ovarian borderline tumors and low grade carcinomas. And overexpression of p53 is more common in high grade ovarian carcinomas. Conventional serous borderline tumors are distinct from high-grade serous carcinomas in pathogenesis. Micropapillary serous borderline ovarian tumors may be closely related to low grade serous carcinomas.


Timely Detection of Infants at Risk of Intrapartum Acidosis and Hypoxic-Ischemic Encephalopathy Using Cardiotocography.
This work aims to improve the intrapartum detection of fetuses with an increased risk of developing fetal acidosis or hypoxic-ischemic encephalopathy (HIE) using fetal heart rate (FHR) and uterine pressure (UP) signals. Our study population comprised 40,831 term births divided into 3 classes based on umbilical cord or early neonatal blood gas assessments: 374 with verified HIE, 3,047 with acidosis but no encephalopathy and 37,410 healthy babies with normal gases. We developed an intervention recommendation system based on a random forest classifier. The classifier was trained using classical and novel features extracted electronically from 20-minute epochs of FHR and UP. Then, using the predictions of the classifier on each epoch, we designed a decision rule to determine when to recommended intervention. Compared to the Caesarean rates in each study group, our system identified an additional 5.68% of babies who developed HIE (54.55% vs 60.23%, p < 0.01) with a specific alert threshold. Importantly, about 75% of these recommendations were made more than 200 minutes before birth. In the acidosis group, the system identified an additional 17.44% (37.15% vs 54.59%, p < 0.01) and about 2/3 of these recommendations were made more than 200 minutes before birth. Compared to the Caesarean rate in the healthy group, the associated false positive rate was increased by 1.07% (38.80% vs 39.87%, p<0.01).Clinical Relevance- This method recommended intervention in more babies affected by acidosis or HIE, than the intervention rate observed in practice and most often did so 200 minutes before delivery. This was early enough to expect that interventions would have clinical benefit and reduce the rate of HIE. Given the high burden associated with HIE, this would justify the marginal increase in the normal Cesarean rate.


Anti-inflammatory entrapment in polycaprolactone/silica hybrid material prepared by sol-gel route, characterization, bioactivity and in vitro release behavior.
A novel organic/inorganic hybrid material, based on poly(ε-caprolactone) (PCL) and silica (SiO₂), were synthesized by the sol-gel method. An anti-inflammatory agent (indomethacin) was incorporated into the hybrid material to verify its local controlled drug delivery system. The structure of the interpenetrating network was investigated by Fourier transform infrared spectroscopy. The morphology of the materials was studied by scanning electron microscopy. The structure of a molecular level dispersion was disclosed by atomic force microscopy. The bioactivity of the synthesized hybrid materials was revealed by the formation of a layer of hydroxyapatite on the surface of samples soaked in a simulated body fluid (SBF). Release kinetics in SBF were subsequently investigated. The amount of drug released was detected by UV-VIS spectroscopy. Pure anti-inflammatory agent exhibited linear release with time; in contrast, sol-gel silica entrapped drugs were released with a logarithmic time dependence starting with an initial burst effect followed by a gradual decrease. SiO₂/PCL (3, 6, 9 and 12 %wt) materials, prepared via sol-gel process, are organic/inorganic hybrid and bioactive materials. All the materials showed a good release and therefore could be used as drug delivery system.


[Differentiation, identification and development of database of T. aestivum L. varieties of Ukrainian selection on the basis of sequence-tagged analysis of microsatellite repeats].
Determination of the variety genotype is very important for the development of theory and practice of plant breeding and for right protection of a variety originator. In this reason attention is focused on the molecular markers generated by polymerase chain reaction. On the basis of STMS-analysis principles of identification and development of database, which reflect molecular-genetics peculiarities of some varieties of the Plant Breeding and Genetics Institute and other Ukrainian breeding organizations, are formulated. Allelic state at microsatellite loci and their distribution were investigated. Wheat varieties were ranged according to genetic distances, data on pedigree and cluster distribution of varieties obtained using computer programs were compared.


The hepatitis B virus X protein transactivates viral core gene expression in vivo.
The function of the X protein in the life cycle of mammalian hepadnaviruses is unclear. Based on tissue culture experiments it has been suggested that this protein represents a transcriptional transactivator which might be essential for the expression of the viral core gene. Here we have examined whether the activity of the human hepatitis B virus (HBV) core gene in vivo depends on X coexpression. To this end we compared core gene expression between four lineages of transgenic mice carrying the HBV core gene in cis arrangement with the X gene (cex lineage) and six lineages containing a modified construct in which the start codon of the X gene had been deleted (ce lineage). Whereas all cex lineages consistently exhibited a high-level hepatic core gene expression, the liver-specific core gene expression pattern of the ce lineages was heterogenous with four lineages virtually not expressing the core gene. This defect was due to a strongly reduced transcription since no core mRNA could be detected by Northern blotting. To test whether core gene expression could be restored by providing an intact X gene in trans, we crossbred mice of two lines which expressed no core mRNA or core protein with transgenic mice expressing the X-gene product under the transcriptional regulation of the liver-specific major-urinary-protein promoter/enhancer (MUP-X mice). The introduction of the MUP-X transgene induced core mRNA expression and core protein biosynthesis in the livers of the double-transgenic mice. This demonstrates that the X-gene product has the capacity to transactivate HBV core gene expression in vivo.


The influence of perioperative risk factors and therapeutic interventions on infection rates after spine surgery: a systematic review.
Systematic review. The objectives of this systematic review were to determine the patient and perioperative risk factors that contribute to infections after spine surgery and to examine the level of evidence to support the use of therapeutic interventions to reduce infection rates. Infection continues to be one of the most common and feared complications after spine surgery. As such, it is used as a sentinel event for quality assurance processes. It is clear that the causes of infections after spine surgery are multifactorial and numerous patient- and procedure-related factors have been proposed as contributory elements. In addition, numerous perioperative adjuncts have been suggested to reduce infection rates. A systematic review of the English-language literature (published between January 1990 and June 2009) was undertaken to identify articles examining risk factors associated with and adjunct treatment measures for preventing surgical-site infections. Two independent reviewers assessed the level of evidence quality using the Grading of Recommendations Assessment, Development, and Evaluation criteria, and disagreements were resolved by consensus. Of the 127 articles identified, 32 met the criteria to undergo full-text review. Individual patient, operative, and perioperative variables have been identified that are associated with increased infection rates (i.e., older age, obesity, diabetes, malnutrition, higher American Society of Anesthesiologists score, posterior approaches, and blood transfusions) but these variables have not been combined to provide individual patient risks based on a composite of factors (e.g., risk stratification). Of the surgical adjuncts investigated, only irrigation with dilute betadine solution showed moderate support for reducing infection rates. It is clear that the causes of postoperative spinal site infections are multifactorial and related to a complex interplay of patient and procedural influences. Because of these complexities, for any individual and surgical procedure, predictable infection rates likely exist that do not extrapolate to 0. Although we have identified factors associated with increased infection rates, further studies will be required to allow multifactorial risk stratification for individual patients and to further investigate the use of therapeutic adjuncts.


LeVeen vs Denver peritoneovenous shunts for intractable ascites of cirrhosis. A randomized, prospective trial.
Peritoneovenous shunts (PVSs) have provided salutary effects on medically recalcitrant ascites, functional renal impairment, nutritional derangements, ventilatory embarrassment, and locomotion potential in patients with cirrhosis. While the LeVeen (LPVS) and Denver (DPVS) PVSs are most frequently implanted in such patients, postoperative complications of bleeding gastroesophageal varices, sepsis, and shunt occlusion occur with notable frequency. Addressing primarily the complication of PVS occlusion, a randomized prospective trial of LPVSs and DPVSs was conducted in cirrhotic patients with refractory ascites. From July 1, 1982 to July 1, 1984, 26 initial PVSs were implanted for hepatic-related intractable ascites. Twenty-two patients were eligible for randomization (cirrhosis, sterile ascites, initial PVS, total bilirubin level less than or equal to 6.0 mg/dL, prothrombin time less than or equal to 5-s prolongation, serum creatinine level less than or equal to 2.0 mg/dL [creatinine clearance rate greater than or equal to 20 mL/min], absence of recent [less than 30 days] bleeding gastroesophageal varices, or absent spontaneous encephalopathy). Twelve LPVSs and ten DPVSs were implanted; however, one patient with a DPVS was found to have hepatic polycystic disease and was excluded from analysis. All patients were followed up until death or Jan 1, 1985. The PVS patency determinations included contrast shuntography, technetium Tc 99m albumin scintigraphy, sequential manual compression (DPVS), and operative or autopsy observation. Using the Kaplan-Meier actuarial analysis, the LPVS patency proved to be highly superior to that of the DPVS, while survival was not significantly different. As LPVS and DPVS complications other than patency are comparable, the LPVS is preferred for its superior patency in cirrhotic patients with intractable ascites.


Predicting Pouch of Douglas Obliteration Using Ultrasound and Laparoscopic Video Sets: An Interobserver and Diagnostic Accuracy Study.
To investigate the diagnostic accuracy and interobserver agreement among sonologists when assessing offline ultrasound (US) video sets of the "sliding sign" and among gynecologic surgeons when assessing corresponding laparoscopic video sets to predict pouch of Douglas (POD) obliteration and to compare the performance of the groups. A diagnostic and reproducibility study was conducted, including 15 observers in 4 groups: (1) senior sonologists, (2) junior sonologists, (3) general gynecologists, and (4) advanced laparoscopists. The sonologists viewed 25 offline preoperative US video sets of the sliding sign, and the surgeons viewed the corresponding intraoperative laparoscopic videos of the same patients. Each observer was asked to classify POD obliteration in the video sets and was compared to the reference standard POD state determined at real-time laparoscopy by a single investigator (G.C.). The interobserver correlation and diagnostic accuracy were evaluated among the 15 observers and 4 groups. The Cohen κ coefficient and Fleiss κ coefficient were used for the analysis. The overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for senior sonologists were 93.3%, 100%, 89.6%, 84.4%, and 100%, respectively; for junior sonologists, 70.0%, 88.9%, 59.4%, 55.2%, and 90.5%; for general gynecologists, 75.2%, 88.1%, 78.1%, 69.8%, and 91.9%; and for advanced laparoscopists, 82.4%, 91.9%, 90.8%, 82.9%, and 95.8%. The overall agreement between senior sonologists was almost perfect (Fleiss κ = 0.876); for junior sonologists and general gynecologists, it was moderate (Fleiss κ = 0.589 and 0.528); and for advanced laparoscopists, it was substantial (Fleiss κ = 0.652). Interobserver agreement was superior among senior sonologists. Prediction of POD obliteration using offline US videos by senior sonologists is comparable to offline assessments of laparoscopic videos by advanced laparoscopists for prediction of POD obliteration.


Disinfection alternatives for contact surfaces and toys at child care centers.
Child care surfaces are vehicles for disease-causing organisms. Disinfectant procedures prevent microbial dispersion. This study reports the effectiveness of CITRUS Farm Edition® (CFE), Clorox® GreenWorks™ (CGW) and Clorox® Anywhere® (CA) against Salmonella Typhimurium and Staphylococcus aureus inoculated (1 ml of 9Log(10) CFU/ml) on a high chair and ball toy. Disinfectants were sprayed and bacteria recovered from surfaces by sponge method. Exposing an inoculated high chair to CA resulted in the highest reduction of S. aureus (3.92 Log(10)) and S. Typhimurium (3.22 Log(10)). CGW reduced S. aureus and S. Typhimurium by 2.84 and 2.12 Log(10) from the inoculated high chair, while the inoculated ball toy showed a 2.50 and 1.80 Log(10) reduction, respectively. CFE showed the lowest reduction with 1.42 and 1.53 Log(10) of S. aureus and S. Typhimurium from the inoculated ball toy. CA was the best disinfectant no matter which bacteria or surface was analyzed. Emphasis on the effectiveness of disinfectant products is needed to be included in child care center infection control programs.


Crawling wounded: molecular genetic insights into wound healing from Drosophila larvae.
For animals, injury is inevitable. Because of this, organisms possess efficient wound healing mechanisms that can repair damaged tissues. However, the molecular and genetic mechanisms by which epidermal repair is accomplished remain poorly defined. Drosophila has become a valuable model to study epidermal wound healing because of the comprehensive genetic toolkit available in this organism and the similarities of wound healing processes between Drosophila and vertebrates. Other reviews in this Special Issue cover wound healing assays and pathways in Drosophila embryos, pupae and adults, as well as regenerative processes that occur in tissues such as imaginal discs and the gut. In this review, we will focus on the molecular/genetic control of wound-induced cellular processes such as inflammation, cell migration and epithelial cell-cell fusion in Drosophila larvae. We will give a brief overview of the three wounding assays, pinch, puncture, and laser ablation, and the cellular responses that ensue following wounding. We will highlight the actin regulators, signaling pathways and transcriptional mediators found so far to be involved in larval epidermal wound closure and what is known about how they act. We will also discuss wound-induced epidermal cell-cell fusion and possible directions for future research in this exciting system.


Effects of concomitant glucocorticoids in TOZURA, a common-framework study programme of subcutaneous tocilizumab in rheumatoid arthritis.
This post hoc analysis of the TOZURA study programme evaluated the efficacy and safety of subcutaneous tocilizumab (TCZ-SC) as monotherapy or with concomitant conventional synthetic DMARDs (csDMARDs) in patients with RA categorized by baseline glucocorticoid (GC) use. TOZURA was a multinational, open-label, single-arm, common-framework study programme (11 protocols, 22 countries) in patients with moderate to severe RA in whom csDMARDs or biologic therapies had failed or who were MTX naïve. Patients received once-weekly TCZ-SC 162 mg for ⩾24 weeks as monotherapy or in combination with csDMARDs and/or oral GC use (⩽10 mg/day prednisone or equivalent), which was to be continued unchanged for 24 weeks. Treatment subgroups were defined by baseline GC use and analysed for efficacy and safety. Of 1804 patients who received TCZ-SC, 145 received monotherapy + GC, 208 received monotherapy without GC, 730 received combination therapy + GC and 721 received combination therapy without GC. The median GC dose in both GC subgroups was 5 mg/day. The proportion of patients who achieved clinical remission, defined as DAS in 28 joints using ESR <2.6, increased similarly from baseline to week 24 in all subgroups. Improvements in patient-reported outcomes were similar in all subgroups. Overall adverse event profiles were generally similar between subgroups, with some slight numerical differences between GC and non-GC subgroups. The incremental efficacy benefits of TCZ-SC as monotherapy and in combination with csDMARDs were similar between patients with and without previous and continued oral GC treatment, with generally similar safety profiles. ClinicalTrials.gov, http://www.clinicaltrials.gov, NCT01941940, NCT01941095, NCT01951170, NCT01987479, NCT01988012, NCT01995201, NCT02001987, NCT02011334, NCT02031471, NCT02046603, NCT02046616.


Effect of pre-exercise ingestion of α-lactalbumin on subsequent endurance exercise performance and mood states.
This study investigated the effect of pre-exercise α-lactalbumin ingestion on subsequent endurance exercise performance, muscle pain and mood states. In a two-stage cross-over counterbalance design, eleven male endurance runners (age: 31 (se 2) years, height: 169·5 (se 4·4) cm, weight: 63·6 (se 5·1) kg, V̇O2max: 58·8 (se 6·3) ml/kg per min) consumed two solutions (carbohydrate+α-lactalbumin, CA; carbohydrate+whey protein isolate, CW) 2 h before a self-paced 21-km run. Creatine kinase, IL-6, muscle pain, pressure pain threshold (PPT) and mood states were assessed 2 h before exercise, immediately before exercise (Pre-ex0) and immediately after exercise (Post-ex0). No difference was found in 21-km running performance between two trials (CA v. CW: 115·85 (se 5·20) v. 118·85 (se 5·51) min, P=0·48). Compared with CW, CA led to higher PPT at Pre-ex0 (41·77 (se 2·27) v. 35·56 (se 2·10) N/cm2, P<0·01) and Post-ex0 (38·76 (se 3·23) v. 35·30 (se 3·55) N/cm2, P=0·047). Compared with CW, CA reduced the feeling of fatigue at Post-ex0 (P<0·01); CA also reduced salivary cortisol levels at Post-ex0 (0·72 (se 0·07) v. 0·83 (se 0·13) ng/ml, P<0·01). In conclusion, the ingestion of α-lactalbumin did not improve the 21-km time-trial performance. However, compared with the pre-exercise ingestion of whey protein, that of α-lactalbumin led to superior results during similar levels of endurance exercise: it elevated PPT and reduced the feeling of fatigue and the cortisol levels.


Traction Bronchiectasis/Bronchiolectasis is Associated with Interstitial Lung Abnormality Mortality.
To investigate if the presence and severity of traction bronchiectasis/bronchiolectasis are associated with poorer survival in subjects with ILA. The study included 3,594 subjects (378 subjects with ILA and 3,216 subjects without ILA) in AGES-Reykjavik Study. Chest CT scans of 378 subjects with ILA were evaluated for traction bronchiectasis/bronchiolectasis, defined as dilatation of bronchi/bronchioles within areas demonstrating ILA. Traction bronchiectasis/bronchiolectasis Index (TBI) was assigned as: TBI = 0, ILA without traction bronchiectasis/bronchiolectasis: TBI = 1, ILA with bronchiolectasis but without bronchiectasis or architectural distortion: TBI = 2, ILA with mild to moderate traction bronchiectasis: TBI = 3, ILA and severe traction bronchiectasis and/or honeycombing. Overall survival (OS) was compared among the subjects in different TBI groups and those without ILA. The median OS was 12.93 years (95%CI; 12.67 - 13.43) in the subjects without ILA; 11.95 years (10.03 - not reached) in TBI-0 group; 8.52 years (7.57 - 9.30) in TBI-1 group; 7.63 years (6.09 - 9.10) in TBI-2 group; 5.40 years (1.85 - 5.98) in TBI-3 group. The multivariable Cox models demonstrated significantly shorter OS of TBI-1, TBI-2, and TBI-3 groups compared to subjects without ILA (P < 0.0001), whereas TBI-0 group had no significant OS difference compared to subjects without ILA, after adjusting for age, sex, and smoking status. The presence and severity of traction bronchiectasis/bronchiolectasis are associated with shorter survival. The traction bronchiectasis/bronchiolectasis is an important contributor to increased mortality among subjects with ILA.


Yellow fever vaccine-associated viscerotropic disease (YEL-AVD) and corticosteroid therapy: eleven United States cases, 1996-2004.
During 1996 through 2004, 29 cases of yellow fever vaccine-associated viscerotropic disease (YEL-AVD) have been reported worldwide; 17 were fatal. Stress-dose corticosteroid (SDS) therapy has recently been found to improve survival among patients with septic shock but benefit for the treatment of YEL-AVD patients in septic shock is unknown. We retrospectively reviewed medical records of 11 U.S. YEL-AVD cases reported to the Vaccine Adverse Event Reporting System (VAERS) from 1996 through 2004. Four of 11 case-patients received SDS; 3 of these 4 (75%) survived. Seven patients did not receive SDS and 2 (29%) survived. Altered mental status was documented on admission for 5 of the 11 patients; 4 of these 5 did not receive SDS and died, whereas one received SDS and survived. The use of stress-dose steroids might be a factor that influenced the survival of these YEL-AVD patients and should be further evaluated in the management of both YEL-AVD and wild-type yellow fever septic shock.


A facile deposition of silver onto the inner surface of a glass capillary tube for micro-surface-enhanced Raman scattering measurements.
Silver can be deposited very efficiently onto glass substrates using only ethanolic solutions of AgNO3 and butylamine. This paper reports that the inner surface of a glass capillary can also be coated evenly with silver by shaking it after soaking in ethanolic solutions of AgNO3 and butylamine; the silver deposited outside the capillary can be easily wiped off with cotton wool before drying. The grain size of the silver deposited onto the inner surface can be readily controlled within the range from 20 to 100 nm by varying the relative molar ratio of butylamine and AgNO3 used as reactants. Due to its nanoaggregated structure, the Ag coated capillary is a very efficient surface-enhanced Raman scattering (SERS) active substrate, particularly usable in the microanalysis of chemicals; the detection limit of adenine is as low as 1.0x10(-7) M based on a signal-to-noise (S/N) ratio of 3. Since the proposed method is cost-effective and is suitable for the mass production of Ag coated capillaries, we fully expect it to play a significant role in the development of SERS based microchip analyzers and even in the fabrication of Ag coated hollow glass waveguides.


Neutrophil-dependent decrease in early wound margin strength.
We evaluated the effect of neutropenia or administration of a serine proteinase inhibitor on the early suture-holding capacity of intestinal anastomoses in rats. One group of rats was treated with antineutrophil serum, and another group received the soybean trypsin inhibitor. Controls received inactivated serum or saline. Anastomotic suture-holding capacity (breaking strength), myeloperoxidase activity, and collagen were measured 0 and 72 hours after surgery. Suture-holding capacity decreased by 70% in controls and 35% in soybean trypsin inhibitor-treated rats, but remained on level with immediate postoperative strength in neutropenic rats, where low myeloperoxidase levels reflected effective wound margin neutropenia. Collagen content and solubility were similar in all groups. These findings indicate that reduction in early wound margin strength is neutrophil dependent, and that neutrophil serine proteinases are important mediators in that process.


What's New in Cleft Palate and Velopharyngeal Dysfunction Management?
After studying this article, the participant should be able to: 1. Have a clear understanding of the evolution of concepts of velopharyngeal dysfunction, especially as it relates to patients with a cleft palate. 2. Explain the subjective and objective evaluation of speech in children with velopharyngeal dysfunction. 3. On the basis of these diagnostic findings, be able to classify types of velopharyngeal dysfunction. 4. Develop a safe, evidence-based, patient-customized treatment plan for velopharyngeal dysfunction founded on objective considerations. Velopharyngeal dysfunction is improper function of the dynamic structures that work to control the velopharyngeal sphincter. Approximately 30 percent of patients having undergone cleft palate repair require secondary surgery for velopharyngeal dysfunction. A multidisciplinary team using multimodal instruments to evaluate velopharyngeal function and speech should manage these patients. Instruments may include perceptual speech analysis, video nasopharyngeal endoscopy, multiview speech videofluoroscopy, nasometry, pressure-flow, and magnetic resonance imaging. Velopharyngeal dysfunction may be amenable to surgical or nonsurgical treatment methods or a combination of each. Nonsurgical management may include speech therapy or prosthetic devices. Surgical interventions could include palatal re-repair with repositioning of levator veli palatini muscles, posterior pharyngeal flap, sphincter pharyngoplasty, or soft palate or posterior wall augmentation. Treatment interventions should be based on objective assessment and rating of the movement of lateral and posterior pharyngeal walls and the palate to optimize speech outcomes. Treatment should be tailored to specific anatomical and physiologic findings and the overall needs of the patient.


Meta-analysis of the effects of cognitive-behavioral therapy for binge-eating-type disorders on abstinence rates in nonrandomized effectiveness studies: Comparable outcomes to randomized, controlled trials?
The efficacy of cognitive-behavioral therapy (CBT) for eating disorders is well-established. The extent to which CBT tested in controlled research settings generalizes to real-world circumstances is unknown. We conducted a meta-analysis of nonrandomized studies of CBT for eating disorders, with three aims: (a) to estimate the prevalence of patients who achieve binge-purge abstinence after CBT in routine practice; (b) to compare these estimates with those derived from two recent meta-analyses of randomized controlled trials (RCTs) of CBT for bulimia nervosa (BN) and binge-eating disorder (BED); (c) to examine whether the degree of clinical representativeness of studies was associated with effect sizes. Twenty-seven studies, mainly involving BN, were included. Pooled event rates were calculated using random effects models. The percentage of treatment completers who achieved abstinence at post-treatment was 42.1% (95% CI = 34.7-50.0). The intention-to-treat (ITT) estimate was lower (34.6% [95% CI = 29.3-40.4]). However, abstinence rates varied across diagnoses, such that the completer and ITT analysis abstinence estimates were larger for BED samples (completer = 50.2%, 95% CI = 29.4-70.9; ITT = 47.2%, 95% CI = 29.8-65.2) than for BN (completer = 37.4%, 95% CI = 29.1-46.5; ITT = 29.8%, 95% CI = 24.9-35.3) and atypical eating disorder samples (completer = 37.8%, 95% CI = 20.2-59.3; ITT = 28.8%, 95% CI = 18.2-42.4). No relationship between the degree of clinical representativeness and the effect size was observed, and our estimates were highly comparable to those observed in recent meta-analyses of RCTs. Findings suggest that CBT for eating disorder can be effectively delivered in real-world settings. This study provides evidence for the generalizability of CBT from controlled research settings to routine clinical services.


Uterine cellular leiomyomata with chromosome 1p deletions represent a distinct entity.
This study aimed to determine whether 1p deletion defines a subset of cellular leiomyomata (CL), which is a hypercellular variant of uterine leiomyomata that may have delayed malignant potential, and to correlate this genetic change with clinical and pathologic characteristics including those present in uterine sarcomas. Available CL cases at the Mayo Clinic (n = 101) and variant cases reported in another article (n = 16) were identified. Each case with sufficient tissue that met histologic criteria for CL when reviewed by a single pathologist underwent interphase fluorescence in situ hybridization to determine the presence of 1p deletion. Clinical characteristics of women with confirmed CL were compared on the basis of 1p deletion status using univariate analysis. Of the Mayo Clinic cohort of histologically confirmed CL, 23% had deletion of 1p. Women with this subset of CL, when compared to those without 1p deletion, were more likely to be postmenopausal (P = .049) and their uteri tended to be heavier (P = .039) with a larger dominant leiomyoma (P = .030). The pathologic features associated with 1p deletion were high cellularity (P = .036) and hyaline necrosis (P = .047), which remained significant after inclusion of the CL cases from a previously published series. Deletion of 1p occurs in approximately one-quarter of CL cases. This genetic alteration is potentially associated with clinicopathologic features that are present in uterine sarcomas, which suggests a distinct clinical entity that may have malignant potential. Our findings are particularly pertinent considering the increased preference for uterine-sparing options in leiomyoma treatment, suggesting assessment of 1p deletion status in CL may influence clinical surveillance decisions.


Depression and chronic pain in the elderly: links and management challenges.
Aging is an inevitable process and represents the accumulation of bodily alterations over time. Depression and chronic pain are highly prevalent in elderly populations. It is estimated that 13% of the elderly population will suffer simultaneously from the two conditions. Accumulating evidence suggests than neuroinflammation plays a critical role in the pathogenesis of both depression and chronic pain. Apart from the common pathophysiological mechanisms, however, the two entities have several clinical links. Their management is challenging for the pain physician; however, both pharmacologic and nonpharmacologic approaches are available and can be used when the two conditions are comorbid in the elderly patients.


Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD.
Strains of transmissible spongiform encephalopathies are distinguished by differing physicochemical properties of PrPSc, the disease-related isoform of prion protein, which can be maintained on transmission to transgenic mice. 'New variant' Creutzfeldt-Jakob disease (CJD) has strain characteristics distinct from other types of CJD and which resemble those of BSE transmitted to mice, domestic cat and macaque, consistent with BSE being the source of this new disease. Strain characteristics revealed here suggest that the prion protein may itself encode disease phenotype.


The passage of trimethylamine across rat and human skin.
Trimethylamine is a volatile low molecular weight tertiary aliphatic amine that has known toxicity and the potential for human exposure from industrial and environmental sources is considerable. It is generally believed that absorption across the skin is an unimportant route of entry but there is little, if any, supporting evidence for this assumption. Passage across rat and human skin has been investigated employing excised skin circles in an in vitro diffusion cell apparatus. Trimethylamine was found to penetrate readily when applied to the epidermal surface of skin at three different dose levels (0.1, 1.0 and 10 mg per skin membrane 0.32 cm2). The apparent dermal flux was calculated as 3.40 +/- 1.60, 58.3 +/- 30.6 and 265.0 +/- 155.0 microg/cm2/h for rat and 0.98 +/- 0.75, 9.21 +/- 3.06 and 92.7 +/- 31.9 microg/cm2/h for human at the three dose levels, respectively. Both rat and human skin was able to act as a reservoir, with the trimethylamine not remaining in the stratum corneum but passing through. When presented to the underneath of rat and human skin circles, both [U-14C]-trimethylamine and [U-14C]-trimethylamine N-oxide were able to pass from the dermis to the epidermis. Small but detectable amounts of trimethylamine were oxidised to its N-oxide during passage through the skin.


Neonatal di-(2-ethylhexyl)phthalate exposure induces permanent alterations in secretory CRH neuron characteristics in the hypothalamus paraventricular region of adult male rats.
Corticotrophin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN) play a critical role in the modulation of the hypothalamic-pituitary-adrenal (HPA) axis. Early-life exposure to di-(2-ethylhexyl) phthalate (DEHP) has been associated with an increased risk of developing psychiatric disorders in adulthood. The present work was designed to explore the impact of neonatal exposure to DEHP on adult PVN CRH neuronal activity. DEHP or vehicle was given to male rat pups from PND16 to PND22. Then, anxiety-like behaviors, serum corticosterone and testosterone, immunohistochemistry, western blotting, fluorescence in situ hybridization and acute ex vivo slice electrophysiological recordings were used to evaluate the influence of DEHP on adult PVN secretory CRH neurons. Neonatal DEHP-exposed rats exhibited enhanced anxiety-like behaviors in adults, with an increase in CORT. Secretory CRH neurons showed higher spontaneous firing activity but could be inhibited by GABAAR blockers. CRH neurons displayed fewer firing spikes, prolonged first-spike latency, depolarizing shifts in GABA reversal potential and strengthened GABAergic inputs, as indicated by increases in the frequency and amplitude of sIPSCs. Enhancement of GABAergic transmission was accompanied by upregulated expression of GAD67 and downregulated expression of GABABR1, KCC2 and GAT1. These findings suggest that neonatal exposure to DEHP permanently altered the characteristics of secretory CRH neurons in the PVN, which may contribute to the development of psychiatric disorders later in life.


Diagnostic problems and advances in inflammatory bowel disease.
This review summarizes current diagnostic problems and advances with regard to patterns of inflammation and dysplasia in ulcerative colitis and Crohn's disease. Ulcerative colitis and Crohn's disease have a variety of characteristic but non-specific pathologic features. In approximately 5% of inflammatory bowel disease cases, a definite diagnosis of ulcerative colitis or Crohn's disease cannot be established, in which case the term "indeterminate" colitis is used. Most cases of indeterminate colitis are related to fulminant colitis, a condition in which the classic features of ulcerative colitis or Crohn's disease may be obscured by severe ulceration with early superficial fissuring ulceration, transmural lymphoid aggregates, and relative rectal sparing. Approximately 20% of patients with indeterminate colitis develop severe pouch complications, which is intermediate in frequency between ulcerative colitis (8-10%) and Crohn's disease (30-40%). In order to establish a diagnosis of ulcerative colitis or Crohn's disease, it is important to evaluate pathologic material in conjunction with clinical, laboratory, radiologic, and endoscopic features and to recognize the variety of changes that may be seen in fulminant ulcerative colitis. There are a number of exceptions to the classic principles of inflammatory bowel disease pathology that may lead to diagnostic confusion. For instance, apparent skip lesions on biopsy analysis may occur in patients with ulcerative colitis in the following settings; long term oral or topical therapy, focal ascending colon, cecum and/or appendiceal involvement in patients with left sided ulcerative colitis, upper gastrointestinal involvement in patients with ulcerative colitis, and at initial presentation of ulcerative colitis in pediatric patients. In all of these circumstances, the finding of patchy disease and/or rectal sparing should not be misinterpreted as either evidence against a diagnosis of ulcerative colitis, or as representing skip areas characteristic of Crohn's disease. Patients with ulcerative colitis and Crohn's disease are at increased risk for the development of dysplasia and carcinoma. Recent studies suggest that given a similar duration and extent of disease, patients with Crohn's disease have a similar risk of dysplasia and cancer as patients with ulcerative colitis. Dysplasia in ulcerative colitis may be classified as flat or elevated (dysplasia associated lesion or mass [DALM]). Patients with flat high grade dysplasia are generally treated with colectomy. However, there is recent evidence to suggest that patients with flat low grade dysplasia, particularly if detected at the time of initial endoscopic exam, or if its multifocal or synchronous, should also be treated with colectomy. Elevated lesions in ulcerative colitis (DALM) are subdivided into "adenoma-like" and "non-adenoma-like" lesions based on their endoscopic appearance. Recent data suggests that adenoma-like lesions, regardless of the grade of dysplasia, or the location of the lesion (i.e., inside or outside areas of established colitis) may be treated adequately by polypectomy if there are no other areas of flat dysplasia in the patient. Although there are some histologic and molecular features that can help differentiate sporadic adenomas from adenoma-like polypoid dysplastic lesions related to ulcerative colitis, none of these adjunctive techniques can help distinguish these lesions definitively in any single patient. Patients with a non-adenoma-like DALM, (irregular, broad based, or strictured lesion) should be treated with colectomy because of the high probability of adenocarcinoma. The surveillance and treatment options for patients with flat and elevated dysplasia in ulcerative colitis are reviewed in detail.


Barbiturate protection in acute experimental spinal cord ischemia.
Ischemia is the pathophysiological mechanism in many types of spinal cord injury. In the present study, the infrarenal segment of the aorta was occluded for 25 minutes to produce spinal cord infarction in rabbits. Paraplegia occurred in 100% of control animals. Thiopental administered before aortic occlusion resulted in paraplegia in only 40% of animals so treated (p less than 0.01). Histological study of the spinal cord demonstrated infarction of the gray matter in all paraplegic animals, whereas the microscopic appearance was normal in animals without neurological deficit. The protective influence of thiopental therapy in spinal cord ischemia was demonstrated.


Elevated expression of the serine-arginine protein kinase 1 gene in ovarian cancer and its role in Cisplatin cytotoxicity in vitro.
Alternatively spliced variants of several oncogenes and tumor suppressors have been shown to be important for their tumorigenicity. In the present study we have tested whether serine-arginine protein kinase 1 (SRPK1), a major regulator of splicing factors, is involved in ovarian cancer progression and plays a role in chemo-sensitivity. By Western blot analyses, SRPK1 protein was found to be overexpressed in 4 out of 6 ovarian cancer cell lines as compared with an immortalized ovarian surface epithelial cell line; and in 55% of ovarian tumor samples as compared with non-neoplastic ovarian tissue samples. Reduction of SRPK1 expression using small interfering RNA (siRNA) encoding small hairpin RNA in ovarian cancer cells led to (i) reduced cell proliferation rate, slower cell cycle progression and compromised anchorage-independent growth and migration ability in vitro, (ii) decreased level of phosphorylation of multiple serine-arginine proteins, and P44/42MAPK and AKT proteins, and (iii) enhanced sensitivity to cisplatin. Together, these results suggest that elevated SRPK1 expression may play a role in ovarian tumorigenesis and SRPK1 may be a potential target for ovarian cancer therapy.


Adenylate cyclase 5 is required for melanophore and male pattern development in the guppy (Poecilia reticulata).
Guppies (Poecilia reticulata) are colorful fish that have attracted the attention of pigmentation researchers for almost a century. Here, we report that the blond phenotype of the guppy is caused by a spontaneous mutation in the guppy ortholog of adenylate cyclase 5 (adcy5). Using double digest restriction site-associated DNA sequencing (ddRADseq) and quantitative trait locus (QTL) mapping, we linked the blond phenotype to a candidate region of 118 kb, in which we subsequently identified a 2-bp deletion in adcy5 that alters splicing and leads to a premature stop codon. We show that adcy5, which affects life span and melanoma growth in mouse, is required for melanophore development and formation of male orange pigmentation traits in the guppy. We find that some components of the male orange pattern are particularly sensitive to loss of Adcy5 function. Our work thus reveals a function for Adcy5 in patterning of fish color ornaments.


Evaluation of the research norms of scientists and administrators responsible for academic research integrity.
The professional integrity of scientists is important to society as a whole and particularly to disciplines such as medicine that depend heavily on scientific advances for their progress. To characterize the professional norms of active scientists and compare them with those of individuals with institutional responsibility for the conduct of research. A mailed survey consisting of 12 scenarios in 4 domains of research ethics. Respondents were asked whether an act was unethical and, if so, the degree to which they considered it unethical and to select responses and punishments for the act. A total of 924 National Science Foundation research grantees in 1993 or 1994 in molecular or cellular biology and 140 representatives from the researchers' institutions to the US Department of Health and Human Services Office of Research Integrity. Percentage of respondents considering an act unethical and the mean malfeasance rating on a scale of 1 to 10. A total of 606 research grantees and 91 institutional representatives responded to the survey (response rate of 69% of those who could be contacted). Respondents reported a hierarchy of unethical research behaviors. The mean malfeasance rating was unrelated to the characteristics of the investigator performing the hypothetical act or to its consequences. Fabrication, falsification, and plagiarism received malfeasance ratings higher than 8.6, and virtually all thought they were unethical. Deliberately misleading statements about a paper or failure to give proper attribution received ratings between 7 and 8. Sloppiness, oversights, conflicts of interest, and failure to share were less serious still, receiving malfeasance ratings between 5 and 6. Institutional representatives proposed more and different interventions and punishments than the scientists. Surveyed scientists and institutional representatives had strong and similar norms of professional behavior, but differed in their approaches to an unethical act.


Suicide gene therapy with adenoviral delivery of HSV-tK gene for patients with local recurrence of prostate cancer after hormonal therapy.
We conducted a Phase I study of in situ herpes simplex virus thymidine kinase (HSV-tk) plus ganciclovir (GCV) gene therapy, which was approved by the Japanese government as the first prostate cancer gene therapy trial. Major inclusion criteria were local recurrence of prostate cancer after hormonal therapy and no metastasis. Adv.HSV-tk was injected directly into the prostate in escalating doses from 10(9) to 10(10) infection units, followed by intravenous administration of GCV for 14 days. Eight patients received nine courses of this gene therapy. The detection of vector DNA in blood/urine was only transient and no remarkable adverse events were observed in any patient. With regard to clinical response, significant prolongation of the median serum prostate-specific antigen (PSA) doubling time from 2.9 to 6.2 months (P = 0.041) was detected. In five patients (six injections), a clear decrease of PSA values was observed. One patient showed repeated clinical response after repeated injections. Serum cytokine analysis showed no notable changes after treatment. Fluorescence-activated cell sorting analysis also showed no influence on phenotypic distribution in peripheral blood samples, except for an increasing trend of CD8(+)/HLA-DR(+) after therapy. This study confirmed the safety profile and possibility of clinical response at the surrogate marker level in a clinical trial of HSV-tk gene therapy for hormone-refractory prostate cancer.


Middle-aged couples' exchanges of support with aging parents: patterns and association with marital satisfaction.
We examined the context of intergenerational support exchanges with aging parents and its association with middle-aged couples' marital satisfaction. A sample of 197 middle-aged couples reported support they gave to and received from their parents (n = 440). Results indicated that couples provided more total support to and received more from their parents as a function of number of living parents, but the amount of support each parent received ('parent-adjusted support') was lower when there were more living parents. The amount of support given to and received from parents had no association with the couple's marital satisfaction, but discrepancies in support given to and received from parents did have a significant association with marital satisfaction. Husbands who gave more support to their living parent(s) than their wives reported lower marital satisfaction. A similar effect on marital satisfaction was found for wives who gave more support to their living parents than their husbands. These findings contrast with caregiving studies where amount of support affected marital satisfaction and suggest that inequalities in involvement with parents may be a critical dimension in marriages of midlife adults.


The relationship between cognitive-ability saturation and subgroup mean differences across predictors of job performance.
The authors quantify the conventional wisdom that predictors' correlations with cognitive ability are positively related to subgroup mean differences. Using meta-analytic and large-N data from diverse predictors, they found that cognitive saturation correlates .84 with predictors' artifact-corrected Black-White d values and .95 with predictors' artifact-corrected Hispanic-White d values. The authors also investigate the extent to which d values are associated with the use of assessor-based scoring and with predictor domains in which differential investment is likely to occur. As a practical application of these findings, they present a procedure to forecast mean differences on a new predictor based on its cognitive saturation and other attributes. They also present a Bayesian framework that allows one to integrate regression-based forecasts with observed d values to achieve more precise estimates of mean differences. The proposed forecasting techniques based on the relationship between mean differences and cognitive saturation can help to mitigate the difficulties inherent in computing precise local estimates of mean differences. (PsycINFO Database Record


Mesoporous silica nanoparticles grafted with a light-responsive protein shell for highly cytotoxic antitumoral therapy.
A novel phototriggered drug delivery nanocarrier, which exhibits very high tumor cytotoxicity against human tumoral cells, is presented. This device is based on mesoporous silica nanoparticles decorated with a biocompatible protein shell cleavable by light irradiation. The proteins that compose the protein shell (avidin, streptavidin and biotinylated transferrin) act as targeting and capping agents at the same time, avoiding the use of redundant systems. The light responsive behavior is provided by a biotinylated photocleavable cross-linker covalently grafted on the mesoporous surface, which suffers photocleavage by UV radiation (366 nm). Human tumoral cells incubated in the presence of a very low particle concentration enter into the apoptotic stage after a short irradiation time. Thus, the system described here could be applied to the treatment of exposed tumors that affect the skin, oesophagus, and stomach, among others, and are easily accessible for light irradiation.


FDG PET/CT radiomics for predicting the outcome of locally advanced rectal cancer.
The aim of this study was to investigate the prognostic value of baseline 18F-FDG PET/CT textural analysis in locally-advanced rectal cancer (LARC). Eighty-six patients with LARC underwent 18F-FDG PET/CT before treatment. Maximum and mean standard uptake values (SUVmax and SUVmean), metabolic tumoral volume (MTV), total lesion glycolysis (TLG), histogram-intensity features, as well as 11 local and regional textural features, were evaluated. The relationships of clinical, pathological and PET-derived metabolic parameters with disease-specific survival (DSS), disease-free survival (DFS) and overall survival (OS) were assessed by Cox regression analysis. Logistic regression was used to predict the pathological response by the Dworak tumor regression grade (TRG) in the 66 patients treated with neoadjuvant chemoradiotherapy (nCRT). The median follow-up of patients was 41 months. Seventeen patients (19.7%) had recurrent disease and 18 (20.9 %) died, either due to cancer progression (n = 10) or from another cause while in complete remission (n = 8). DSS was 95% at 1 year, 93% at 2 years and 87% at 4 years. Weight loss, surgery and the texture parameter coarseness were significantly associated with DSS in multivariate analyses. DFS was 94 % at 1 year, 86 % at 2 years and 79 % at 4 years. From a multivariate standpoint, tumoral differentiation and the texture parameters homogeneity and coarseness were significantly associated with DFS. OS was 93% at 1 year, 87% at 2 years and 79% after 4 years. cT, surgery, SUVmean, dissimilarity and contrast from the neighborhood intensity-difference matrix (contrastNGTDM) were significantly and independently associated with OS. Finally, RAS-mutational status (KRAS and NRAS mutations) and TLG were significant predictors of pathological response to nCRT (TRG 3-4). Textural analysis of baseline 18F-FDG PET/CT provides strong independent predictors of survival in patients with LARC, with better predictive power than intensity- and volume-based parameters. The utility of such features, especially coarseness, should be confirmed by larger clinical studies before considering their potential integration into decisional algorithms aimed at personalized medicine.


Cutting edge: NKp80 uses an atypical hemi-ITAM to trigger NK cytotoxicity.
The human NK cell receptor NKp80 stimulates cytotoxicity upon engagement of its genetically linked ligand AICL. However, the mechanisms underlying NKp80-mediated signaling are unknown. In this study, we dissected NKp80 signaling using the NK cell line NK92MI. We demonstrated that NKp80, but not NKp80 mutated at tyrosine 7 (NKp80/Y7F), is tyrosine phosphorylated. Accordingly, NKp80/Y7F, but not NKp80/Y30F or NKp80/Y37F, failed to induce cytotoxicity. NKp80 phosphopeptides comprising the hemi-ITAM-like sequence surrounding tyrosine 7 bound Lck- and Syk-family kinases; accordingly, cross-linking of NKp80, but not NKp80/Y7F, induced Syk phosphorylation. Moreover, inhibition of Syk kinase, but not ZAP-70 kinase, impaired cytotoxic responses through NKp80. Atypical residues in the hemi-ITAM-like motif of NKp80 cause an altered stoichiometry of phosphorylation but did not substantially affect NK cytotoxicity. Altogether, these results show that NKp80 uses an atypical hemi-ITAM and Syk kinase to trigger cellular cytotoxicity.


Identification of three novel mutations [-41 (A>C), codon 24 (-G), and IVS-I-109 (-T)], in a study of beta-thalassemia alleles in the Isfahan region of Iran.
Beta-thalassemia (beta-thal) is one of the most common autosomal recessive disorders in Iran, with more than 15,000 registered cases of thalassemia major in the country. Iran has a multiethnic society and knowledge of the mutation spectrum and regional distribution is an essential requirement for health planning and a prenatal diagnosis program. We have determined the spectrum of mutations in patients from the Isfahan region of Iran. A study of 190 chromosomes revealed 24 different mutations, including three novel ones: -41 (A>C), IVS-I-109 (-T) and codon 24 (-G). The most common mutation was IVS-II-1 (G>A) (20.5%), followed by IVS-I-5 (G>C) (11%). The findings for the Isfahan region confirm the extremely heterogeneous nature of the molecular basis of beta-thal in Iran. The results show that a strategy of using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) for 14 of the most common mutations and DNA sequencing for the rare mutations can be used for prenatal diagnosis of beta-thal in this region.


Gustatory perception and behavior in Drosophila melanogaster.
The sense of taste is essential for the survival of virtually all animals. Considered a 'primitive sense' and present in the form of chemotaxis in many bacteria, taste is also a sense of sophistication in humans. Regardless, taste behavior is a crucial activity for the world's most abundant (insects) and most successful (mammals) inhabitants, providing a means of discrimination between nutrient-rich substrates, such as sugars and amino acids, from harmful, mostly bitter-tasting chemicals present in many plants. In this review, we present an update on progress in understanding taste perception in the model fruit fly Drosophila melanogaster. An introduction to the fly's taste system will be presented first, followed by a description of relevant behavioral assays developed to quantify taste perception at the organismal level and a short overview of electrophysiological studies performed on taste cells. The focal point will be the recent molecular-genetic investigations of the gustatory receptor (Gr) genes, which is complemented by a comparison between Drosophila and mammalian taste perception and transduction. Finally, we provide a perspective on the future of Drosophila taste research, including three specific proposals that seem uniquely applicable to this exquisite model system and cannot, at least currently, be pursued elsewhere.


Trichothiodystrophy: a systematic review of 112 published cases characterises a wide spectrum of clinical manifestations.
Trichothiodystrophy (TTD) is a rare, autosomal recessive disease, characterised by brittle, sulfur deficient hair and multisystem abnormalities. A systematic literature review identified 112 patients ranging from 12 weeks to 47 years of age (median 6 years). In addition to hair abnormalities, common features reported were developmental delay/intellectual impairment (86%), short stature (73%), ichthyosis (65%), abnormal characteristics at birth (55%), ocular abnormalities (51%), infections (46%), photosensitivity (42%), maternal pregnancy complications (28%) and defective DNA repair (37%). There was high mortality, with 19 deaths under the age of 10 years (13 infection related), which is 20-fold higher compared to the US population. The spectrum of clinical features varied from mild disease with only hair involvement to severe disease with profound developmental defects, recurrent infections and a high mortality at a young age. Abnormal characteristics at birth and pregnancy complications, unrecognised but common features of TTD, suggest a role for DNA repair genes in normal fetal development.


Is Human Walking a Network Medicine Problem? An Analysis Using Symbolic Regression Models with Genetic Programming.
Human walking is typically assessed using a sensor placed on the lower back or the hip. Such analyses often ignore that the arms, legs, and body trunk movements all have significant roles during walking; in other words, these body nodes with accelerometers form a body sensor network (BSN). BSN refers to a network of wearable sensors or devices on the human body that collects physiological signals. Our study proposes that human locomotion could be considered as a network of well-connected nodes. While hypothesizing that accelerometer data can model this BSN, we collected accelerometer signals from six body areas from ten healthy participants performing a cognitive task. Machine learning based on genetic programming was used to produce a collection of non-linear symbolic models of human locomotion. With implications in precision medicine, our primary finding was that our BSN models fit the data from the lower back's accelerometer and describe subject-specific data the best compared to all other models. Across subjects, models were less effective due to the diversity of human sizes. A BSN relationship between all six body nodes has been shown to describe the subject-specific data, which indicates that the network-medicine relationship between these nodes is essential in adequately describing human walking. Our gait analyses can be used for several clinical applications such as medical diagnostics as well as creating a baseline for healthy walking with and without a cognitive load.


Influenza in 1918: recollections of the epidemic in Philadelphia.
When the great influenza epidemic struck Philadelphia in 1918, the author was just starting his third year at the University of Pennsylvania School of Medicine. After a single lecture on influenza, classes for the third and fourth year students were suspended while he and his mates manned an emergency hospital, in which they worked under little or no medical supervision and in the presence of an alarming patient mortality. This essay describes what happened in the hospital, and in the city as a whole, during the pandemic. Certain features of the clinical course of most patients permit the hope that modern therapy will prevent a repetition of the horrendous mortality.


Split-Mouth Comparison of Splinted and Nonsplinted Prostheses on Short Implants: 3-Year Results.
To compare splinted and individual restorations supported by short implants featuring an internal connection utilizing a split-mouth design. Splinted and nonsplinted implant crowns were prospectively compared in 18 patients. After verifying the need for at least two consecutive implants bilaterally, computed tomography scans were made, virtual planning was done, and qualifying patients were enrolled. Implants were placed using a two-stage surgical approach. After 3 to 5 months, patients were randomly restored with splinted prostheses on their left or right side. Nonsplinted restorations were made for contralateral sides. Radiographs were taken at prostheses seating and yearly exams. Radiographic bone levels were analyzed and compared (SAS 9.4) to determine differences between splinted and nonsplinted implants. Complications such as screw loosening, screw breakage, or porcelain fracture were assessed at recalls. Eighteen patients (9 men and 9 women) with an age range from 49 to 76 years (mean = 56 years), received ≥ 4 implants in symmetrical posterior locations. Implants (n = 82) ranged in length from 6 to 11 mm with 70 implants ≤ 9 mm and 38 implants = 6 mm. At the time of this report, 3-year examinations and bone level comparisons were completed on 15 patients. One patient was lost to follow-up, one deviated from study protocol by smoking, and one was splinted on both sides due to repeated screw breakage. Screw loosening occurred in five patients on their nonsplinted side. These were 6-mm implants except for one patient. Porcelain chipping occurred for one patient on the splinted side. One 6-mm-length nonsplinted implant was lost after loading; this implant was successfully replaced after grafting. This patient had a total of six implants placed; ongoing bone level measurements included two pairs of implants only. For all implants combined, there was no significant difference (P > .05) at 1, 2, or 3 years for mean bone change around splinted and nonsplinted implants. However, length was identified as a significant factor (P = .0039). Further analysis revealed statistically significant differences between splinted and nonsplinted for 6-mm length implants at 24 (P = .0061) and 36 (P = .0144) months. A gain in mean bone level of 0.41 and 0.37 mm was observed for nonsplinted implants at 24 and 36 months compared with baseline. Bone levels for the splinted 6-mm implants were not statistically different from baseline measurements (P > .05). Results of this prospective 3-year study of splinted ipsilateral and nonsplinted contralateral implants in 15 patients show: (1) peri-implant bone levels around splinted and nonsplinted implants were not statistically different for implants greater than 6 mm in length; (2) nonsplinted 6-mm implants revealed a gain in bone at 24 and 36 months compared with baseline; (3) all screw loosening only occurred on the nonsplinted side for 5 of 15 patients; and (4) implant loss after loading occurred for one 6-mm nonsplinted implant.


Clinical manifestations of dengue in relation to dengue serotype and genotype in Malaysia: A retrospective observational study.
Malaysia experienced an unprecedented dengue outbreak from the year 2014 to 2016 that resulted in an enormous increase in the number of cases and mortality as compared to previous years. The causes that attribute to a dengue outbreak can be multifactorial. Viral factors, such as dengue serotype and genotype, are the components of interest in this study. Although only a small number of studies investigated the association between the serotype of dengue virus and clinical manifestations, none of these studies included analyses on dengue genotypes. The present study aims to investigate dengue serotype and genotype-specific clinical characteristics among dengue fever and severe dengue cases from two Malaysian tertiary hospitals between 2014 and mid-2017. A total of 120 retrospective dengue serum specimens were subjected to serotyping and genotyping by Taqman Real-Time RT-PCR, sequencing and phylogenetic analysis. Subsequently, the dengue serotype and genotype data were statistically analyzed for 101 of 120 corresponding patients' clinical manifestations to generate a descriptive relation between the genetic components and clinical outcomes of dengue infected patients. During the study period, predominant dengue serotype and genotype were found to be DENV 1 genotype I. Additionally, non-severe clinical manifestations were commonly observed in patients infected with DENV 1 and DENV 3. Meanwhile, patients with DENV 2 infection showed significant warning signs and developed severe dengue (p = 0.007). Cases infected with DENV 2 were also commonly presented with persistent vomiting (p = 0.010), epigastric pain (p = 0.018), plasma leakage (p = 0.004) and shock (p = 0.038). Moreover, myalgia and arthralgia were highly prevalent among DENV 3 infection (p = 0.015; p = 0.014). The comparison of genotype-specific clinical manifestations showed that DENV 2 Cosmopolitan was significantly common among severe dengue patients. An association was also found between genotype I of DENV 3 and myalgia. In a similar vein, genotype III of DENV 3 was significantly common among patients with arthralgia. The current data contended that different dengue serotype and genotype had caused distinct clinical characteristics in infected patients.


A novel phosphoprotein analysis scheme for assessing changes in premalignant and malignant breast cell lines using 2D liquid separations, protein microarrays and tandem mass spectrometry.
An analysis of phosphorylation changes that occur during cancer progression would provide insights into the molecular pathways responsible for a malignant phenotype. In this study we employed a novel coupling of 2D-liquid separations and protein microarray technology to reveal changes in phosphoprotein status between premalignant (AT1) and malignant (CA1a) cell lines derived from the human MCF10A breast cell lines. Intact proteins were first separated according to their isoelectric point and hydrophobicities, then arrayed on SuperAmine glass slides. Phosphoproteins were detected using the universal, inorganic phospho-sensor dye, ProQ Diamond. Using this dye, out of 140 spots that were positive for phosphorylation, a total of 85 differentially expressed spots were detected over a pH range of 7.2 to 4.0. Proteins were identified and their peptides sequenced by mass spectrometry. The strategy enabled the identification of 75 differentially expressed phosphoproteins, from which 51 phosphorylation sites in 27 unique proteins were confirmed. Interestingly, the majority of differentially expressed phosphorylated proteins observed were nuclear proteins. Three regulators of apoptosis, Bad, Bax and Acinus, were also differentially phosphorylated in the two cell lines. Further development of this strategy will facilitate an understanding of the mechanisms involved in malignancy progression and other disease-related phenotypes.


[Chronic diarrhea with uncommon etiology].
Chronic diarrhea is a common syndrome. An etiological diagnosis is often reached through clinical history, physical examination and simple tests. In some cases, when the etiology is not found, the syndrome is called functional diarrhea, even though established criteria are often not fulfilled. We present the case of a patient with diarrhea for several months. The most common causes were ruled out through clinical history, physical examination, radiographic studies and laboratory tests, and the patient was diagnosed with functional diarrhea. Three months later, the patient presented a neck mass, and biopsy revealed medullary carcinoma of the thyroid. A review of recommendations for the systematic evaluation of chronic diarrhea is presented. A general approach should include careful history taking characteristics of diarrhea (onset, associated symptoms, epidemiological factors, iatrogenic causes such as laxative ingestion), a thorough physical examination with special attention to the anorectal region, and routine laboratory tests (complete blood count and serum chemistry). In addition, stool analysis including electrolytes (fecal osmotic gap), leukocytes, fecal occult blood, excess stool fat and laxative screening can yield important objective information to classify the diarrhea as: osmotic (osmotic gaps > 125 mOsm/Kg), secretory (osmotic gaps < 50 mOsm/Kg), inflammatory or steatorrheic. At this point in the evaluation, a specific diagnosis may be made. However, if diagnosis is not reached further specific examinations should be performed for each of the 4 types of diarrhea described above. A systematic approach to the evaluation of chronic diarrhea is warranted. Medullary thyroid carcinoma and other endocrine syndromes causing chronic diarrhea are very rare. Measurement of serum peptide concentrations should only be performed when clinical presentation and findings in stool or radiographic studies suggest this etiology.