Low-cost photocatalytic membrane modified with green heterojunction TiO2/ZnO nanoparticles prepared from waste.
The combination of photocatalysis and membrane procedures represents a promising approach for water treatment. This study utilized green synthesis methods to produce TiO2 nanoparticles (NPs) using Pomegranate extract and ZnO nanoparticles using Tangerine extract. These nanoparticles were then incorporated into a polyvinyl chloride (PVC) nanocomposite photocatalytic membrane. Different devices were used to examine the properties of nanocomposite membranes. The prepared membranes' morphology was examined using atomic force microscopy (AFM) and field emission scanning electron microscopy (FESEM). The hydrophilicity of the membrane surface was assessed through the measurement of contact angle, while the crystal structure and chemical bonding were analyzed using Raman and Fourier transform infrared spectroscopy (FT-IR). The study also encompassed an examination of the mechanical properties. The hydrophilicity of the modified membrane exhibited a significant improvement. Additionally, there was an observed increase in both the pure water flux and rejection values. The photocatalytic activity of the membrane was found to be enhanced when exposed to sunlight as compared to when kept in the dark. The TiO2/ZnO nanocomposites membrane exhibited the highest level of photocatalytic degradation, achieving a rejection rate of 98.7% compared to the unmodified membrane. Therefore, it was determined that the TiO2/ZnO nanocomposites membrane exhibited superior performance to the other membranes assessed. The potential utility of our research lies in its application within the water treatment industry, specifically as an effective technique for modifying PVC membranes.


Inhibitory Effects of Pectinase-Treated Prunus Mume Fruit Concentrate on Colorectal Cancer Proliferation and Angiogenesis of Endothelial Cells.
Pectinase is a well-known enzyme used in the food processing industry to produce fruit juice and concentrate. This study evaluated the anticancer and antiangiogenesis activities of pectinase-treated Prunus mume fruit concentrate (PC) and its phenolic components. PC treatment (250 to 1,000 µg/mL) resulted in decreased proliferation of SW480 human colorectal cancer cells through S-phase cell cycle arrest; however, equivalent concentrations of PC did not show toxicity toward CRL-1539 colon normal cells. Furthermore, PC-induced caspase-dependent apoptosis in SW480 cells, which was characterized by accumulation of apoptotic cell population, cell shrinkage, formation of apoptotic bodies, upregulation of proapoptotic Bax, cleaved PARP, caspase-3, caspase-8, and caspase-9, and downregulation of antiapoptotic Bcl-2. Antiangiogenesis effects of PC were assessed using human umbilical vein endothelial cells (HUVECs). We found that PC did not inhibit HUVECs proliferation at concentrations of 500 to 1,500 µg/mL. In addition, treatment with PC at nontoxic concentrations (500 to 1,000 µg/mL) blocked vascular endothelial growth factor induced cell migration, invasion, capillary-like tube formation, and angiogenesis from rat aortic rings. HPLC-PDA analysis showed that there were at least four different phenolics including 5-HMF, neochlorogenic acid, protocatechuic acid, and syringic acid. Taken together, these results indicated that PC could be used as a good source of phenolic compounds with selective anticancer and antiangiogenesis activities. PRACTICAL APPLICATION: Pectinases are one of the well-known enzyme used in the part of food processing. Treatment of pectinase is a useful strategy to reduce viscosity, turbidity, and pulp particles in the production of fruit juice, extract, and concentrate. In the present study, we found that pectinase-treated P. mume fruit concentrate significantly suppresses colorectal cancer proliferation and angiogenesis of human umbilical vein endothelial cells. The significance of our findings is that pectinase-treated P. mume concentrate may be used as a commercial functional food material to inhibit colorectal cancer and angiogenesis.


Time to treat the tendon rupture induced by surgery: early hypertrophy of the patellar tendon graft site predicts strong quadriceps after ACLR with bone-patellar tendon-bone autograft.
Quadriceps dysfunction is ubiquitous after anterior cruciate ligament reconstruction, especially when using bone-patellar tendon-bone (BPTB) autografts. The role of patellar tendon hypertrophy after graft harvest on knee extensor strength is unknown. The purpose of this study was to determine the predictive ability of patellar tendon (PT) and quadriceps muscle (Quad) cross-sectional area (CSA) on knee extensor strength 1-2 months after ACLR using BPTB autografts. This is a cross-sectional analysis of a cohort 1-2 months after ACLR using BPTB autograft. Peak knee extensor torque, and PT and Quad CSA measured using ultrasound imaging, were collected in 13 males and 14 females. Simple linear regressions compared quadriceps strength index (QI) against limb symmetry index (LSI) in PT and Quad CSA. Multiple linear regressions with sequential model comparisons predicting peak knee extensor torque were performed for each limb. The base model included demographics. Quad CSA was added in the first model, then PT CSA was added in the second model. Both PT (p < 0.001, R2 = 0.693) and Quadriceps CSA (p = 0.013, R2 = 0.223) LSI had a positive linear relationship with QI. In the involved limb, addition of PT CSA significantly improved the model (R2 = 0.781, ΔR2 = 0.211, p for ΔR2 < 0.001). In the uninvolved limb, the addition of Quad CSA improved the model, but the addition of PT CSA did not. PT LSI was more predictive of QI than Quad CSA LSI. Involved limb PT CSA mattered more in predicting peak knee extensor torque than did Quad CSA, but in the uninvolved limb, Quad CSA was the most important predictor of peak knee extensor torque. Graft site patellar tendon hypertrophy is key for strong quadriceps early after ACLR. Early targeted loading via exercise to promote healing of the graft site patellar tendon may bring patients a step closer to winning their battle against quadriceps dysfunction. Level I.


Sialolipoma in minor salivary gland: case report and review of the literature.
Sialolipoma is a rare benign neoplasm characterized by a well-circumscribed mass composed of neoplastic mature adipose tissue and non-neoplastic salivary gland elements. A 72-year-old woman presented with a painless swelling located in the hard palate, which had been identified 15 days earlier. Microscopically, the tumor was well-circumscribed consisting of lobular proliferation of the lipomatous tissue with thin fibrous tissue septa containing clustered salivary gland elements. Both the glandular and adipose components were found in almost equal proportion. No atypia in the adipose tissue was observed. The definitive diagnosis was sialolipoma. The patient showed no signs of recurrence 8 months after surgical excision. Including the present case, 35 cases of sialolipoma have been reported in the English literature. Of these 35 cases, 16 cases were located in minor salivary glands. Gender was identified in 14 of these cases with 4 males (28.5%) and 10 females (71.5%). The age distribution was from 27 to 84 years (mean, 61.6 years) and the tumor size ranged from 0.9 to 4 cm (mean, 1.7 cm). The most frequently reported clinical presentation was of a painless swelling (56.3%).


Exposure to phenols, parabens and UV filters: Associations with loss-of-function mutations in the filaggrin gene in men from the general population.
Filaggrin is an epidermal protein that is important for normal skin barrier functions. Up to 10% of Europeans and Asians carry filaggrin gene (FLG) loss-of function mutations that appear to facilitate trans-epidermal penetration of certain chemicals. We previously showed that mutation carriers have higher internal exposure to certain phthalates, compared to controls, and hypothesized that they could have increased trans-epidermal penetration of other chemicals. We investigated exposure to non-persistent chemicals in young Danish men with and without FLG mutations. Concentrations of eight simple phenols, six parabens and nine UV filters were analysed in urine from 65 FLG loss-of-function mutation carriers and 130 non-carriers (controls). Regression analyses, controlling for urinary dilution and confounders, were performed to estimate associations between FLG mutation status and chemical concentrations in urine. FLG mutation carriers had 80% (13-180%) higher urinary concentrations of methyl paraben (MeP) and 91% (13-219%) higher concentrations of n-propyl paraben (n-PrP) than controls. For 13 compounds, levels were higher in FLG mutation carriers, although differences were only statistically significant for MeP and n-PrP. Combined statistical analysis of concentrations of all the 18 compounds that were detectable in >10% of subjects, suggested that concentrations were generally higher in mutation carriers (p=0.03). FLG loss-of-function mutation carriers have a higher internal exposure to some non-persistent chemicals, independently of atopic dermatitis. This may be due to increased trans-epidermal absorption and/or higher exposure, and mutation carriers may constitute a group susceptible to increased absorption of chemicals and topical medication.


Calcium Signal Profiles in Vascular Endothelium from Cdh5-GCaMP8 and Cx40-GCaMP2 Mice.
Studies in Cx40-GCaMP2 mice, which express calcium biosensor GCaMP2 in the endothelium under connexin 40 promoter, have identified the unique properties of endothelial calcium signals. However, Cx40-GCaMP2 mouse is associated with a narrow dynamic range and lack of signal in the venous endothelium. Recent studies have proposed many GCaMPs (GCaMP5/6/7/8) with improved properties although their performance in endothelium-specific calcium studies is not known. We characterized a newly developed mouse line that constitutively expresses GCaMP8 in the endothelium under the VE-cadherin (Cdh5-GCaMP8) promoter. Calcium signals through endothelial IP3 receptors and TRP vanilloid 4 (TRPV4) ion channels were recorded in mesenteric arteries (MAs) and veins from Cdh5-GCaMP8 and Cx40-GCaMP2 mice. Cdh5-GCaMP8 mice showed lower baseline fluorescence intensity, higher dynamic range, and higher amplitudes of individual calcium signals than Cx40-GCaMP2 mice. Importantly, Cdh5-GCaMP8 mice enabled the first recordings of discrete calcium signals in the intact venous endothelium and revealed striking differences in IP3 receptor and TRPV4 channel calcium signals between MAs and mesenteric veins. Our findings suggest that Cdh5-GCaMP8 mice represent significant improvements in dynamic range, sensitivity for low-intensity signals, and the ability to record calcium signals in venous endothelium.


β-Myrcene Mitigates Colon Inflammation by Inhibiting MAP Kinase and NF-κB Signaling Pathways.
Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders that include Crohn's disease (CD) and ulcerative colitis (UC). The incidence of IBD is rising globally. However, the etiology of IBD is complex and governed by multiple factors. The current clinical treatment for IBD mainly includes steroids, biological agents and need-based surgery, based on the severity of the disease. Current drug therapy is often associated with adverse effects, which limits its use. Therefore, it necessitates the search for new drug candidates. In this pursuit, phytochemicals take the lead in the search for drug candidates to benefit from IBD treatment. β-myrcene is a natural phytochemical compound present in various plant species which possesses potent anti-inflammatory activity. Here we investigated the role of β-myrcene on colon inflammation to explore its molecular targets. We used 2% DSS colitis and TNF-α challenged HT-29 adenocarcinoma cells as in vivo and in vitro models. Our result indicated that the administration of β-myrcene in dextran sodium sulfate (DSS)-treated mice restored colon length, decreased disease activity index (DAI), myeloperoxidase (MPO) enzyme activity and suppressed proinflammatory mediators. β-myrcene administration suppressed mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) pathways to limit inflammation. β-myrcene also suppressed mRNA expression of proinflammatory chemokines in tumor necrosis factor-α (TNF-α) challenged HT-29 adenocarcinoma cells. In conclusion, β-myrcene administration suppresses colon inflammation by inhibiting MAP kinases and NF-κB pathways.


Clearance of mutant proteins as a therapeutic target in neurodegenerative diseases.
Accumulation and aggregation of disease-causing proteins is a hallmark of several neurodegenerative disorders such as Parkinson, Alzheimer, and Huntington diseases. One of the main goals of research in neurodegenerative disorders has been to improve clearance of these accumulated proteins. Using the example of Huntington disease, I discuss strategies to selectively activate cellular degradation machinery to improve clearance of the mutant protein and to identify therapeutic targets for the treatment of Huntington disease and related neurodegenerative disorders.


A survey of koala road kills in New South Wales.
Between 1984 and 1990, 75 koalas (Phascolarctos cinereus) from the central northern coast of New South Wales (Australia) were presented for necropsy due to motor vehicle accidents. The koalas consisted of 44 males and 31 females. Fifty one of these were between 2 and 7 yr (39 males and 12 females). The greater proportion of koalas, especially males, were struck by vehicles between June and December. The main injuries detected were head injuries (44), hemoperitoneum (16), limb injuries (16), hemothorax (15) and spinal injuries (7). Nine koalas were not dead at the time of the accident but died later following complications from the trauma. Twelve koalas had evidence of underlying disease at the time of accident. Ten of these had either conjunctivitis, cystitis, prostatitis, periovarian cysts, endometritis or a combination of the diseases. All 10 koalas still had good body condition. It is suggested that healthy young to middle-aged males are particularly prone to vehicular accidents during the mating period. This has implications for the management of local koala populations.


Refractory epilepsy is highly associated with severe dentoalveolar and maxillofacial injuries.
Dental intrusion and avulsion, crown fracture and mandibular fractures are important dentofacial complications in patients with epilepsy-related traumas. The objective of the present study was to describe the occurrence of orofacial injuries in patients with epilepsy. One hundred and nine consecutive patients (60 women; mean age 38.81 ± 14 years), treated for refractory epilepsy (45 with extratemporal epilepsy and 64 with temporal epilepsy) at the outpatient clinic of our University Hospital, were included in the present study. Orofacial injury occurring as a direct result of a seizure was determined by clinical examination and interview. In addition, seizure frequency, use of medication, and the occurrence and type of injury to other parts of the body, were documented. We employed regression analyses to investigate the association between teeth fractures and frequency of seizures. The majority of injuries were crown fractures (42 subjects), followed by mandibular fractures (eight subjects) and tooth avulsion (eight subjects). Sixteen patients had more than two fractured teeth. Patients with mandibular trauma also suffered concomitant injuries (teeth fracture, avulsion and dislocation). The number of fractured teeth was associated with seizure frequency (r(2) = 0.59, p < 0.001). The data suggest that there is an increased rate of dentoalveolar and maxillofacial injuries in patients with poorly controlled epileptic seizures.


On traits, situations, and their integration: a developmental perspective.
The question of whether the person or the situation is largely responsible for behavior has plagued psychology intermittently for the last half century. Studies of the heritability, stability, and consensual validity of traits have clearly demonstrated the existence of traits. However, there is continuing controversy about the role of traits and situations in the enterprise of personality psychology. The goal of this article is to describe how insights yielded from adopting a developmental approach can foster the successful integration of the person and the situation across the life span. Five key lessons are described: (a) age matters--studying different age groups can lead to biases for and against traits and situations; (b), if age matters, time matters more--longitudinal and within-participant designs demonstrate that traits and situations are reciprocally related; (c) examine multiple types of change--focusing on one type, such as mean-level change, can lead to inappropriate conclusions about the merits of persons or situations; (d) be sensitive to levels of analysis--the relative breadth of persons and situations may determine the relative influence of the two; (e) pay attention to process--process models lead inextricably to transactional explanations.


[Post-partum thyroiditis].
In the post-partum period the immune alterations are associated with the multiple autoimmune diseases relapse. After birth, immune-tolerance variation slowly disappear, and is observed a return to a normal state - after an exacerbation period - of autoimmune reactivity, during which a great increase in T cells and autoantibodies is observed. In this period - 3 to 9 months after birth - the thyroid autoimmune disease relapses or reappears. The reactivation of the immune system in the post-partum period unchains an acute phase of celular destruction which characterizes the post-partum thyroiditis.


An endogenous monocarboxylate transport in Xenopus laevis oocytes.
We investigated the existence of an endogenous system for lactate transport in Xenopus laevis oocytes. (36)Cl-uptake studies excluded the involvement of a DIDS-sensitive anion antiporter as a possible pathway for lactate movement. L-[(14)C]lactate uptake was unaffected by superimposed pH gradients, stimulated by the presence of Na(+) in the incubating solution, and severely reduced by the monocarboxylate transporter inhibitor p-chloromercuribenzenesulphonate (pCMBS). Transport exhibited a broad cation specificity and was cis inhibited by other monocarboxylates, mostly by pyruvate. These results suggest that lactate uptake is mediated mainly by a transporter and that the preferred anion is pyruvate. [(14)C]pyruvate uptake exhibited the same pattern of functional properties evidenced for L-lactate. Kinetic parameters were calculated for both monocarboxylates, and a higher affinity for pyruvate was revealed. Various inhibitors of monocarboxylate transporters reduced significantly pyruvate uptake. These studies demonstrate that Xenopus laevis oocytes possess a monocarboxylate transport system that shares some functional features with the members of the mammalian monocarboxylate cotransporters family, but, in the meanwhile, exhibits some particular properties, mainly concerning cation specificity.


Acute compartment syndrome after intramedullary nailing of isolated radius and ulna fractures in children.
There exist varying reports in the literature regarding the incidence of compartment syndrome (CS) after intramedullary (IM) fixation of pediatric forearm fractures. A retrospective review of the experience with this treatment modality at our institution was performed to elucidate the rate of postoperative CS and identify risk factors for developing this complication. In this retrospective case series, we reviewed the charts of all patients treated operatively for isolated radius and ulnar shaft fractures from 2000 to 2009 at our institution and identified 113 patients who underwent IM fixation of both-bone forearm fractures. There were 74 closed fractures and 39 open fractures including 31 grade I fractures, 7 grade II fractures, and 1 grade IIIA fracture. If the IM nail could not be passed easily across the fracture site, a small open approach was used to aid reduction. CS occurred in 3 of 113 patients (2.7%). CS occurred in 3 of 39 (7.7%) of the open fractures compared with none of 74 closed fractures (P=0.039), including 45 closed fractures that were treated within 24 hours of injury. An open reduction was performed in all of the open fractures and 38 (51.4%) of the closed fractures. Increased operative time was associated with developing CS postoperatively (168 vs. 77 min, P<0.001). CS occurred within the first 24 postoperative hours in all 3 cases. CS was an uncommon complication after IM fixation of pediatric diaphyseal forearm fractures in this retrospective case series. Open fractures and longer operative times were associated with developing CS after surgery. None of 45 patients who underwent IM nailing of closed fractures within 24 hours of injury developed CS; however, 51.4% of these patients required a small open approach to aid reduction and nail passage. We believe that utilizing a small open approach for reduction of one or both bones, thereby avoiding the soft-tissue trauma of multiple attempts to reduce the fracture and pass the nail, leads to decreased soft-tissue trauma and a lower rate of CS. We recommend a low threshold for converting to open reduction in cases where closed reduction is difficult.


Advancing Keloid Treatment: A Novel Multimodal Approach to Ear Keloids.
Management of keloids of the pinna, in particular, those located in the helix and antihelix and lobule that occur as complications of ear piercing. Retrospective analysis of 49 patients treated with extralesional surgical excision of keloids localized to the ear followed by the application of autologous platelet-rich plasma (PRP) to wound site and postoperative in-office superficial radiation therapy (SRT). Radiation protocol consisted of 1 to 3 fractions, with cumulative dosage ranging from 1,300 to 1,800 cGy. Average follow-up was 24 months to assess for evidence of recurrence and adverse side effects. Fifty ear keloids were treated with this method, age from 15 to 66 (mean = 32, SD = 16) of which 14 were male and 35 female. Almost 30% (n = 14) of patients acknowledged the source of injury that led to the development of the keloid was ear piercing. Treatment protocol achieved a 94% success rate with 3 patients who reported recurrence. Surgical excision combined with intraoperative PRP, adjuvant postoperative in-office SRT achieved a 94% nonrecurrence rate on follow-up over a 2-year period. Outcomes provide preliminary, albeit, strong evidence to support this multimodal method as a viable alternative in the management of keloids localized to the ear.


The transcriptional coactivator Cbp regulates self-renewal and differentiation in adult hematopoietic stem cells.
The transcriptional coactivator Cbp plays an important role in a wide range of cellular processes, including proliferation, differentiation, and apoptosis. Although studies have shown its requirement for hematopoietic stem cell (HSC) development, its role in adult HSC maintenance, as well as the cellular and molecular mechanisms underlying Cbp function, is not clear. Here, we demonstrate a gradual loss of phenotypic HSCs and differentiation defects following conditional ablation of Cbp during adult homeostasis. In addition, Cbp-deficient HSCs reconstituted hematopoiesis with lower efficiency than their wild-type counterparts, and this response was readily exhausted under replicative stress. This phenotype relates to an alteration in cellular fate decisions for HSCs, with Cbp loss leading to an increase in differentiation, quiescence, and apoptosis. Genome-wide analyses of Cbp occupancy and differential gene expression upon Cbp deletion identified HSC-specific genes regulated by Cbp, providing a molecular basis for the phenotype. Finally, Cbp binding significantly overlapped at genes combinatorially bound by 7 major hematopoietic transcriptional regulators, linking Cbp to a critical HSC transcriptional regulatory network. Our data demonstrate that Cbp plays a role in adult HSC homeostasis by maintaining the balance between different HSC fate decisions, and our findings identify a putative HSC-specific transcriptional network coordinated by Cbp.


Impairment of perceptual closure in autism for vertex- but not edge-defined object images.
One of the characteristics of autism spectrum disorder (ASD) is atypical sensory processing and perceptual integration. Here, we used an object naming task to test the significance of deletion of vertices versus extended contours (edges) in naming fragmented line drawings of natural objects in typically developing and ASD children. The basic components of a fragmented image in perceptual closure need to be integrated to make a coherent visual perception. When vertices were missing and only edges were visible, typically developing and ASD subjects performed similarly. But typically developing children performed significantly better than ASD children when only vertex information was visible. These results indicate impairment of binding vertices but not edges to form a holistic representation of an object in children with ASD.


The Aalborg Bolt-Connected Drain (ABCD) study: a prospective comparison of tunnelled and bolt-connected external ventricular drains.
Acutely increased intracranial pressure (ICP) is frequently managed by external ventricular drainage (EVD). This procedure is life-saving but marred by a high incidence of complications. It has recently been indicated that bolt-connected external ventricular drainage (BC-EVD) compared to the standard technique of tunnelled EVD (T-EVD) may result in less complications. To prospectively sample and compare two cohorts by consecutive allocation to either BC-EVD or T-EVD from the introduction of the BC-EVD technique in our department and 12 months onward. Patients undergoing ventriculostomy between the 1st of March 2017 and the 28th of February 2018 were considered for inclusion. The neurosurgeon on-call sovereignly set the indication and decided on EVD type (BC-EVD or T-EVD), consequently resulting in two cohorts as 3/7 senior neurosurgeons on call were open to the use of BC-EVD, while 4/7 were reluctant to use this technique. Data was continuously collected using patient records, including results of cerebrospinal fluid (CSF) culturing and available CT/MRI-scans. Recorded complications included CSF leakage, accidental discontinuation, placement-related intracranial haemorrhage, malfunction, migration, infection and revision. Forty-nine EVDs (32 T-EVDs/17 BC-EVDs) were included; 19/32 (59.4%) T-EVDs and 3/17 (17.6%) BC-EVDs were found to have complications (p = 0.007). The relative risk of complications when using T-EVD was 3.4 times that of BC-EVD. Ventriculostomy by BC-EVD compared to T-EVD reduces incidence and risk of complications and should be the first choice in EVD placement. That said, T-EVD has a role in paediatric patients and for intraoperatively and occipitally placed EVDs.


Cellular hypersensitivity to gluten derived peptides in coeliac disease.
Wheat gluten derived antigens have been tested for their ability to inhibit the migration of leucocytes from healthy subjects and patients with coeliac disease. Three preparations of a water soluble fraction (Frazer's fraction III, FIII) of partial peptic tryptic digests of wheat gluten had different effects in a direct (one stage) assay. Subfractions B and B2 caused migration inhibition of leucocytes from patients with treated coeliac disease but not of leucocytes from healthy volunteers or patients with Crohn's disease or ulcerative colitis. This migration inhibition seems to be specific for gluten fractions because maize zein fraction B, beta-lactoglobulin and ovalbumin did not cause it. The sensitivity of coeliac leucocytes to fraction B is not related to factors present in coeliac serum as the migration of leucocytes from healthy individuals preincubated with coeliac sera was not inhibited. Puromycin diminished inhibition by fraction B, which was active at 1.2 micrograms/ml in an indirect (two stage) migration inhibition assay; this is consistent with a process involving elaboration of lymphokine(s). More highly purified fractions of B2, P1-P4 were prepared by reverse phase high performance liquid chromatography (HPLC) and showed differing potency in direct and indirect assays, with P4 being the most active fraction. Inhibition of migration by gluten derived peptides appears to result from the release of lymphokine by leucocytes specifically from coeliac patients.


Point-of-care screenings at the University of Minnesota: mechanism for civic engagement.
OBJECTIVES To describe Wellness Initiative of the Northland (WIN) screening events; present participant results from those events; discuss the benefits of pharmacist-conducted, community-based point-of-care (POC) testing to medically underserved patients and to the profession of pharmacy; and describe logistical considerations in launching disease screening services. SETTING Pharmacist-led community health fairs in a variety of settings, including shopping malls, churches, community pharmacies, senior residence facilities, critical-access hospitals, and clinics. PRACTICE DESCRIPTION Disease screenings for economically disadvantaged residents of northeastern Minnesota and northwest Wisconsin, held between 2005 and 2012, through WIN. PRACTICE INNOVATION Mobile POC screenings for dyslipidemia, diabetes, hypertension, and osteoporosis. MAIN OUTCOME MEASURE Percentage of screenings with out-of-range readings. RESULTS Since 2005, WIN screenings have served more than 2,000 individuals, providing 4,152 POC screenings. Out-of-range readings were obtained for 40.3% of fingerstick cholesterol tests, 24.8% of fingerstick blood glucose tests, 24.3% of blood pressure tests, and 38.7% of quantitative ultrasound heel bone density readings. CONCLUSION Community-conducted POC testing functions both as an important public health service and a mechanism by which pharmacists and student pharmacists can become involved in civic engagement.


The development of papillary serous carcinoma of the peritoneum subsequent to endometrial carcinoma: a case report and review of the literature.
Metachronous papillary serous carcinoma of the peritoneum (PSCP) after endometrial carcinoma (EC) is an extremely rare condition. Only three patients have been reported in the English literature. We present the fourth patient who had a more aggressive and fatal clinical course. A 79-year-old multiparous woman complained of progressive abdominal pain and distension after 5 years, subsequent to total abdominal hysterectomy and bilateral salpingo-oophorectomy for endometrioid type EC. Serum CA-125 level being followed routinely rose above 500 IU/mL. Abdominal and pelvic computed tomography demonstrated ascites, omental thickening, and nodularity. Paracentesis showed malignant cells resembling papillary adenocarcinoma. Omentectomy and bilateral pelvic lymphadenectomy were performed as cytoreductive surgery. The histologic slides of the totally sampled ovaries obtained from the first operation were reexamined and the corresponding paraffin blocks were re-sectioned but no tumor was detected. The microscopic appearance of the tumor in the omentum differed from that of the previous EC. Immunohistochemically, while the tumor showed reactivity for low and high molecular weight cytokeratin (CK) cocktail, epithelial membrane antigen, CK7, CA-125, and Ber-EP4, the immunostains for calretinin, monoclonal carcinoembryonic antigen, and CK20 were negative. On the basis of these results and the criteria proposed by the Gynecologic Oncology Group, the tumor was diagnosed as metachronous PSCP developed after EC, which corresponded to stage IIIC according to FIGO criteria for ovarian carcinoma. The patient received two cycles of carboplatin and paclitaxel and died 2 months after the cytoreductive surgery.


Bioethicsing.
This article describes the components of a unique 9 month required course in bioethics for 3rd year medical students at the American University of Beirut. The blended (hybrid) learning format emphasizes three innovative learning activities: the bioethics documentary, edutainment games, and the bioethics log book. Sample student responses are included as well as an outline of limitations.


Direct comparison of Dll1- and Dll4-mediated Notch activation levels shows differential lymphomyeloid lineage commitment outcomes.
In the thymus, Notch signaling is essential for T lymphopoiesis, with Delta-like (Dll)4 uniquely involved in this process. However, using cocultures, either Dll4 or Dll1 were shown to support T lymphopoiesis. To address which Dll is more effective at inducing hematopoietic progenitor cells to give rise to T lineage cells in vitro, we generated OP9 cells expressing a series of incrementally discrete and equivalent levels of Dll1 or Dll4. In keeping with previous findings, OP9 cells expressing high levels of either Dll1 or Dll4 gave rise to T lineage cells with similar efficacy, and prevented the differentiation of B and myeloid-lineage cells. However, at limiting levels, Dll4 maintained its ability to inhibit B lineage choice and induce T lineage commitment and differentiation at lower levels than Dll1. This manifest property of Dll4 is evident despite lower levels of steady-state surface expression than Dll1 on OP9 cells. The heightened effectiveness of Dll4 over Dll1 also corresponded to the induction of Notch target genes, and inhibition of B and myeloid-specific transcription factors. Furthermore, we show that OP9 cells expressing levels of Dll4 equivalent to those present in thymic epithelial cells, as expected, gave rise to T lineage cells, but were also permissive for the differentiation of myeloid cells; whereas, still inhibiting B lymphopoiesis. Our findings show that Dll4 expressed at physiological levels on OP9 cells is functionally distinct from similarly expressed levels of Dll1, illustrating the unique properties of Dll4 in supporting the combined T lineage and specific myeloid-lineage outcomes that underpin its function within the thymus.


Maternal effects as generators of evolutionary change: a reassessment.
Despite being a center of debate in biology for centuries, the connection between the generation of novel adaptive variation and its inheritance remains a contentious issue. In evolutionary and behavioral ecology, assigning natural and sexual selection a creative and anticipatory role unmasks the need to explicitly consider the link between a trait's functional importance and its inheritance and results in confusion about selection as an adaptive modifier of development versus selection as a passive filter of already produced forms. In developmental genetics, an emphasis on regulatory versus coding aspects of molecular evolutionary change overlooks the fundamental question of the origination of an inherited developmental toolkit and assignment of its regulatory functions. Because maternal effects, by definition, combine developmental induction of functionally important changes and their inheritance, they bridge the origin and evolution of organismal adaptability, at least on short time scales. The explosion of empirical studies of maternal effects raises a question--are maternal effects ubiquitous but short-term adjusters and fine-tuners of an evolved form with only secondary importance for evolutionary change? Or are they a particularly clear example of a stage in a continuum of inheritance systems that accumulates, internalizes, and passes on the most consistent and adaptive organism-environment interactions? Here I place recent empirical studies of avian maternal effects into the evolutionary framework of variation, selection, and inheritance to examine whether maternal effects provide a window into evolutionary processes.


Taking health status into account when setting capitation rates: a comparison of risk-adjustment methods.
To compare performance of different health status measures for risk-adjusting capitation rates. Cross-sectional study. Health status measures derived from 1 year were used to predict resources for that year and the next. Group-network health maintenance organization in Minnesota. Sample of 18- to 64-year-old (n=3825) and elderly (aged > or = 65 years; n=1955) members enrolled in a network-model health maintenance organization in Minnesota. Total expenditures in the year concurrent with the health status survey (July 1991 through June 1992) and total expenditures in the year following the survey (July 1992 through June 1993). Capitation adjustment based on demographic measures performed least well. Both self-reported health status measures and diagnoses predicted future expenditures twice as well as demographics. When predicting costs for groups of patients rather than individuals, the demographic model worked well for average groups but tended to overpredict healthier groups and underpredict sicker groups. Ambulatory Care Groups based on diagnoses performed better than self-reported health status both in the retrospective models and across healthier and sicker groups. Without risk adjustment, capitation rates are likely to overpay or underpay physicians for certain patient groups. It is possible to improve prediction using health status measures for risk adjustment. When selection bias is suspected and administrative data are available, we recommend a risk-adjustment method based on diagnostic information. If diagnostic data are not available, we recommend a system based on simple self-reported measures, such as chronic conditions, rather than complex functional status measures.


Brightness alters Heidelberg retinal flowmeter measurements in an in vitro model.
The Heidelberg Retinal Flowmeter (HRF), a laser Doppler flowmetry device, has captured interest as a research and clinical tool for measurement of ocular blood flow. Concerns remain about the range and accuracy of the values that it reports. An in vitro blood-flow model was constructed to provide well-controlled laminar flow through a glass capillary for assessment by HRF. A change in material behind the glass capillary was used to simulate changing brightness conditions between eyes. Velocities reported by the HRF correlated linearly to true velocities below 8.8 mm/sec. Beyond 8.8 mm/sec, HRF readings fluctuated randomly. True velocity and HRF reported velocities were highly correlated, with r = 0.967 (P < 0.001) from 0.0 mm/sec to 2.7 mm/sec mean velocity using a light background, and r = 0.900 (P < 0.001) from 2.7 mm/sec to 8.8 mm/sec using a darker background. However, a large change in the y-intercept occurred in the calibration curve with the background change. The HRF may report velocities inaccurately because of varying brightness in the fundus. In the present experiment, a darker background produced an overreporting of velocities. An offset, possibly introduced by a noise correction routine, apparently contributed to the inaccuracies of the HRF measurements. Such offsets vary with local and global brightness. Therefore, HRF measurements may be error prone when comparing eyes. When used to track perfusion in a single eye over time, meaningful comparison may be possible if meticulous care is taken to align vessels and intensity controls to achieve a similar level of noise correction between measurements.


The family 42 carbohydrate-binding module of family 54 alpha-L-arabinofuranosidase specifically binds the arabinofuranose side chain of hemicellulose.
Alpha-L-arabinofuranosidase catalyses the hydrolysis of the alpha-1,2-, alpha-1,3-, and alpha-1,5-L-arabinofuranosidic bonds in L-arabinose-containing hemicelluloses such as arabinoxylan. AkAbf54 (the glycoside hydrolase family 54 alpha-L-arabinofuranosidase from Aspergillus kawachii) consists of two domains, a catalytic and an arabinose-binding domain. The latter has been named AkCBM42 [family 42 CBM (carbohydrate-binding module) of AkAbf54] because homologous domains are classified into CBM family 42. In the complex between AkAbf54 and arabinofuranosyl-alpha-1,2-xylobiose, the arabinose moiety occupies the binding pocket of AkCBM42, whereas the xylobiose moiety is exposed to the solvent. AkCBM42 was found to facilitate the hydrolysis of insoluble arabinoxylan, because mutants at the arabinose binding site exhibited markedly decreased activity. The results of binding assays and affinity gel electrophoresis showed that AkCBM42 interacts with arabinose-substituted, but not with unsubstituted, hemicelluloses. Isothermal titration calorimetry and frontal affinity chromatography analyses showed that the association constant of AkCBM42 with the arabinose moiety is approximately 10(3) M(-1). These results indicate that AkCBM42 binds the non-reducing-end arabinofuranosidic moiety of hemicellulose. To our knowledge, this is the first example of a CBM that can specifically recognize the side-chain monosaccharides of branched hemicelluloses.


Colonization resistance: The deconvolution of a complex trait.
Carbapenemase-producing Enterobacteriaceae are an emerging threat to hospitals worldwide, and antibiotic exposure is a risk factor for developing fecal carriage that may lead to nosocomial infection. Here, we review how antibiotics reduce colonization resistance against Enterobacteriaceae to pinpoint possible control points for curbing their spread. Recent work identifies host-derived respiratory electron acceptors as a critical resource driving a post-antibiotic expansion of Enterobacteriaceae within the large bowel. By providing a conceptual framework for colonization resistance against Enterobacteriaceae, these mechanistic insights point to the metabolism of epithelial cells as a possible target for intervention strategies.


Efficiency of hydrogen peroxide in improving disinfection of ICU rooms.
The primary objective of this study was to determine the efficiency of hydrogen peroxide (H₂O₂) techniques in disinfection of ICU rooms contaminated with multidrug-resistant organisms (MDRO) after patient discharge. Secondary objectives included comparison of the efficiency of a vaporizator (HPV, Bioquell) and an aerosolizer using H₂O₂, and peracetic acid (aHPP, Anios) in MDRO environmental disinfection, and assessment of toxicity of these techniques. This prospective cross-over study was conducted in five medical and surgical ICUs located in one University hospital, during a 12-week period. Routine terminal cleaning was followed by H₂O₂ disinfection. A total of 24 environmental bacteriological samplings were collected per room, from eight frequently touched surfaces, at three time-points: after patient discharge (T0), after terminal cleaning (T1) and after H₂O₂ disinfection (T2). In total 182 rooms were studied, including 89 (49%) disinfected with aHPP and 93 (51%) with HPV. At T0, 15/182 (8%) rooms were contaminated with at least 1 MDRO (extended spectrum β-lactamase-producing Gram-negative bacilli 50%, imipenem resistant Acinetobacter baumannii 29%, methicillin-resistant Staphylococcus aureus 17%, and Pseudomonas aeruginosa resistant to ceftazidime or imipenem 4%). Routine terminal cleaning reduced environmental bacterial load (P <0.001) without efficiency on MDRO (15/182 (8%) rooms at T0 versus 11/182 (6%) at T1; P = 0.371). H₂O₂ technologies were efficient for environmental MDRO decontamination (6% of rooms contaminated with MDRO at T1 versus 0.5% at T2, P = 0.004). Patient characteristics were similar in aHPP and HPV groups. No significant difference was found between aHPP and HPV regarding the rate of rooms contaminated with MDRO at T2 (P = 0.313). 42% of room occupants were MDRO carriers. The highest rate of rooms contaminated with MDRO was found in rooms where patients stayed for a longer period of time, and where a patient with MDRO was hospitalized. The residual concentration of H₂O₂ appears to be higher using aHPP, compared with HPV. H₂O₂ treatment is efficient in reducing MDRO contaminated rooms in the ICU. No significant difference was found between aHPP and HPV regarding their disinfection efficiency.


The microRNA expression signature of pancreatic ductal adenocarcinoma by RNA sequencing: anti-tumour functions of the microRNA-216 cluster.
We analysed the RNA sequence-based microRNA (miRNA) signature of pancreatic ductal adenocarcinoma (PDAC). Aberrantly expressed miRNAs were successfully identified in this signature. Using the PDAC signature, we focused on 4 clustered miRNAs, miR-216a-5p, miR-216a-3p, miR-216b-5p and miR-216b-3p on human chromosome 2p16.1. All members of the miR-216 cluster were significantly reduced in PDAC specimens. Ectopic expression of these miRNAs suppressed cancer cell aggressiveness, suggesting miR-216 cluster as anti-tumour miRNAs in PDAC cells. The impact of miR-216b-3p (passenger strand of pre-miR-216b) on cancer cells is still ambiguous. Forkhead box Q1 (FOXQ1) was directly regulated by miR-216b-3p and overexpression of FOXQ1 was confirmed in clinical specimens. High expression of FOXQ1 predicted a shorter survival of patients with PDAC by Kaplan-Meier analysis. Loss-of-function assays showed that cancer cell migration and invasion activities were significantly reduced by siFOXQ1 transfectants. We investigated pathways downstream from FOXQ1 by using genome-wide gene expression analysis. Identification of the miR-216-3p/FOXQ1-mediated network in PDAC should enhance understanding of PDAC aggressiveness at the molecular level.


[Brazilian geography congresses from 1909 to 1944].
This analysis of the Brazilian geography congresses sponsored by the Geography Society of Rio de Janeiro between 1909 and 1944 identifies commonalities as well as differences over the years. Given how these scientific events focused on both the state of the art within the field as well as on its overall development, such an analysis serves as a good thermometer for measuring the social, economic, and political changes underway in Brazil.


Single-cell RNA-sequencing of Nicotiana attenuata corolla cells reveals the biosynthetic pathway of a floral scent.
High-throughput single-cell RNA sequencing (scRNA-Seq) identifies distinct cell populations based on cell-to-cell heterogeneity in gene expression. By examining the distribution of the density of gene expression profiles, we can observe the metabolic features of each cell population. Here, we employ the scRNA-Seq technique to reveal the entire biosynthetic pathway of a flower volatile. The corolla of the wild tobacco Nicotiana attenuata emits a bouquet of scents that are composed mainly of benzylacetone (BA). Protoplasts from the N. attenuata corolla limbs and throat cups were isolated at three different time points, and the transcript levels of > 16 000 genes were analyzed in 3756 single cells. We performed unsupervised clustering analysis to determine which cell clusters were involved in BA biosynthesis. The biosynthetic pathway of BA was uncovered by analyzing gene co-expression in scRNA-Seq datasets and by silencing candidate genes in the corolla. In conclusion, the high-resolution spatiotemporal atlas of gene expression provided by scRNA-Seq reveals the molecular features underlying cell-type-specific metabolism in a plant.


Correlating Drug-Target Kinetics and In vivo Pharmacodynamics: Long Residence Time Inhibitors of the FabI Enoyl-ACP Reductase.
Drug-target kinetics enable time-dependent changes in target engagement to be quantified as a function of drug concentration. When coupled to drug pharmacokinetics (PK), drug-target kinetics can thus be used to predict in vivo pharmacodynamics (PD). Previously we described a mechanistic PK/PD model that successfully predicted the antibacterial activity of an LpxC inhibitor in a model of Pseudomonas aeruginosa infection. In the present work we demonstrate that the same approach can be used to predict the in vivo activity of an enoyl-ACP reductase (FabI) inhibitor in a model of methicillin-resistant Staphylococcus aureus (MRSA) infection. This is significant because the LpxC inhibitors are cidal, whereas the FabI inhibitors are static. In addition P. aeruginosa is a Gram-negative organism whereas MRSA is Gram-positive. Thus this study supports the general applicability of our modeling approach across antibacterial space.


Timing and type of surgical treatment of Clostridium difficile-associated disease: a practice management guideline from the Eastern Association for the Surgery of Trauma.
Clostridium difficile infection is the leading cause of nosocomial diarrhea in the United States; however, few patients will develop fulminant C. difficile-associated disease (CDAD), necessitating an urgent operative intervention. Mortality for patients who require operative intervention is very high, up to 80% in some series. Since there is no consensus in the literature regarding the best operative treatment for this disease, we sought to answer the following:PICO [population, intervention, comparison, and outcome] Question 1: In adult patients with CDAD, does early surgery compared with late surgery, as defined by the need for vasopressors, decrease mortality?PICO Question 2: In adult patients with CDAD, does total abdominal colectomy (TAC) compared with other types of surgical intervention decrease mortality? A subcommittee of the Practice Management Guideline Committee of the Eastern Association for the Surgery of Trauma conducted a systematic review and meta-analysis for the selected questions. RevMan software was used to generate forest plots. Grading of Recommendations, Assessment, Development and Evaluations methodology was used to rate the quality of the evidence, using GRADEpro software to create evidence tables. Reduction in mortality was significantly associated with early surgery, with a risk ratio (RR) of 0.5 (95% confidence interval [CI], 0.35-0.72). The quality of evidence was rated "moderate." Considering only the first procedure performed, mortality seemed to trend higher for TAC, with an RR of 1.11 (95% CI, 0.69-1.80). Considering only the actual procedure performed, the point estimate switched sides, showing a trend toward decreased mortality with TAC (RR, 0.86; 95% CI, 0.56-1.31). The quality of evidence was rated "very low." We strongly recommend that adult patients with CDAD undergo early surgery, before the development of shock and need for vasopressors. We conditionally recommend total or subtotal colectomy (vs. partial colectomy or other surgery) when the diagnosis of The Centers for Disease Control and Prevention is known.


[The biological effects of combined exposure to low-dose irradiation and heavy metal ions].
It was shown that chronic 0.25 Gy irradiation of rats (0.01 Gy/day) at background of heavy metal penetration (Cu2+, 20 mg/l or Co2+, 5 mg/l) with drinking water had caused significant accumulation of the free-radical products proportional to exhausting antioxidant and oxidizing-reduction potential in various organs and tissues. Radiation was shown to be primary harmful factor for the brain, spleen, lungs, and blood plasma, whereas the liver and heart muscle were affected with chemicals at first. Under prolonged unfavourable influence the biochemical changes observed were sustainable and progressing that satisfied to transformation of protective-adaptive reactions into prepathology stage.


Single-Tube qPCR Detection and Quantitation of Hotspot Mutations Down to 0.01% Variant Allele Fraction.
Clinically and biologically, rare DNA sequence variants are significant and informative. However, existing common detection technologies are either complex and time-consuming in workflow, or restricted in the limit of detection (LoD), or do not allow for multiplexing. Blocker displacement amplification (BDA) method can stably and effectively detect and enrich multiple rare variants with LoD around 0.1% variant allele fraction (VAF). Nonetheless, the detailed mutation information has to be identified by additional sequencing technologies. Here, we present allele-specific BDA (As-BDA), a method combining BDA with allele-specific TaqMan (As-TaqMan) probes for effective variant enrichment and simultaneous single nucleotide variant or small insertions and deletions (INDELs) profiling. We demonstrated that As-BDA could detect mutations down to 0.01% VAF. Further, As-BDA could detect up to four mutations with low to 0.1% VAF per reaction using only 15 ng DNA input. The median error of As-BDA in VAF determination is approximately 9.1%. Comparison experiments using As-BDA and droplet digital PCR on peripheral blood mononuclear cell clinical samples showed 100% concordance for samples with mutations at ≥ 0.1% VAF. Hence, we have shown that As-BDA can achieve simultaneous enrichment and identification of multiple targeted mutations within the same reaction with high clinical sensitivity and specificity, thus helpful for clinical diagnosis.


A current reader's response to the article of 50 years ago by Karpman, B. (1949): "The principles and methods of objective psychotherapy".
The first aim is to describe the psychotherapy of 1949 in the light of today's psychotherapies. The old psychotherapy is suited to treating severely ill patients. It does not use free association, but rather is focused on current problems. It uses dreams, yet it also uses homework and bibliotherapy. The second aim is to critique the treatment. Consistent with its era. it does not make use of medications, and there is an absence of references to psychotherapy research, which was then just starting. The treatment relies over-heavily on the authority of the therapist. A third aim is to describe the changes in our field in the past 50 years and examine the predictions for the future. Although the treatment is called objective psychotherapy, it does not make use of the most up-to-date means of measuring accuracy of interpretations, such as the Core Conflictual Relationship Theme (CCRT) method and other methods like it.


A taxonomy of requests by patients (TORP): a new system for understanding clinical negotiation in office practice.
The goal of our investigation was to facilitate research on clinical negotiation between patients and physicians by developing a reliable and valid classification system for patients' requests in office practice. We developed the Taxonomy of Requests by Patients (TORP) using input from researchers, clinicians, and patient focus groups. To assess the system's reliability and validity, we applied TORP to audiotaped encounters between 139 patients and 6 northern California internists. Reliability was assessed with the kappa statistic as a measure of interrater agreement. Face validity was assessed through expert and patient judgment of the coding system. Content validity was examined by monitoring the incidence of unclassifiable requests. Construct validity was evaluated by examining the relationship between patient requests and patient health status; patient request fulfillment and patient satisfaction; and patient requests and physician perceptions of the visit. The 139 patients made 772 requests (619 requests for information and 153 requests for physician action). Average interrater agreement across a sample of 40 cases was 94% (kappa = 0.93; P <.001). Patients with better health status made fewer requests (r = -0.17; P = .048). Having more chronic diseases was associated with more requests for physician action (r = 0.32; P = .0002). Patients with more unfulfilled requests had lower visit satisfaction (r = -0.32; P <.001). More patient requests was also associated with physician reports of longer visit times (P = .016) and increased visit demands (P = .006). Our study provides evidence that TORP is a reliable and valid system for capturing and categorizing patients' requests in adult primary care. Further research is needed to confirm the system's validity, expand its applicability, and explore its usefulness as a tool for studying clinical negotiation.


What's in a manner of speaking? Children's sensitivity to partner-specific referential precedents.
Do young children form "referential pacts"? If a person has referred to an object with a certain term (e.g., the horse), will children expect this person to use this term in the future but allow others to use a different expression (e.g., the pony)? One hundred twenty-eight children between 3 and 5 years old co-operated with an experimenter (E1) to move toys to new locations on a shelf. E1 established referential terms for all toys in a warm-up game. Then, either the original partner, E1, or a new partner, E2, played a second game with the same toys. In this game, the experimenters referred to toys using either their original terms from the warm-up game or new terms. Children were slower to react to new terms than old, and this difference in reaction times was greater in the original partner condition (but only on the first trial). Children sometimes protested at the use of new terms, doing so regardless of their interlocutor's identity. We contrast these findings with those for adults and discuss their implications for the debate regarding the nature of referential pacts.


[Cardiovascular and metabolic impact of glucocorticoid substitution therapy in patients with Addison's disease].
Recent studies conducted in patients with Addison's disease (AD) highlighted that this disease, even after treatment, is a significant cause of morbi-mortality. This study aims to determine the cardiovascular and metabolic deleterious impact of long-course glucocorticoid substitution therapy. We conducted a retrospective study of 28 patients with treated Addison's disease evolving for more than 15 years. The average age of patients was 58, 53 years, with a female predominance (65%). The average follow-up period was 17, 87 years. Initial dose of hydrocortisone was 32, 5 mg/day (20.52 mg/m2) and 27, 9 mg/day (16,41mg/m2) at the time of the study. The prevalence of the metabolic syndrome (MS) in patients with AM was 35.71% after a period of treatment longer than 15 years. At the end of the follow-up period, 28.57% of patients were obese; 25% of patients had developed AH (arterial hypertension) and type 2 diabetes. The prevalence of dyslipidemia went from 3.57% to 42.85%. Only one patient had myocardial infarction at 25-year follow-up. Factors favoring the onset of MS in our study were history of disease and weight loss at the moment of diagnosis. Adjustment of substitution therapy is a challenge in patients with Addison's disease due to morbi-mortality associated with overdose. A regular follow-up and a personalized therapeutic approach are necessary to improve patients' prognosis.


Backward masking: evidence of reduced subcortical amygdala engagement in autism.
Recent data suggest that subthreshold presentation of emotional information is relayed to the amygdala along subcortical pathways. We examined the effect of backward masked neutral and anxious faces on the social decisions of a group of high functioning children with autism ages 7-13 years and matched controls. Participants were asked to select the friendliest of two faces, one of which was associated with the subthreshold (33 ms) presentation of an anxious face (A/N) and the other a subthreshold neutral face (N/N). Neutral paired faces were selected more often than A/N paired faces by both groups. However, children with autism selected significantly fewer N/N stimuli and more A/N stimuli than controls. These results suggest that the social choices of children with autism were influenced less by emotional information presented subconsciously and suggest a subcortical contribution to the social/emotional processing deficits observed in autism.


Adaptive evolution of hepcidin genes in antarctic notothenioid fishes.
Hepcidin is a small bioactive peptide with dual roles as an antimicrobial peptide and as the principal hormonal regulator of iron homeostasis in human and mouse. Hepcidin homologs of very similar structures are found in lower vertebrates, all comprise approximately 20-25 amino acids with 8 highly conserved cysteines forming 4 intramolecular disulfide bonds, giving hepcidin a hairpin structure. Hepcidins are particularly diverse in teleost fishes, which may be related to the diversity of aquatic environments with varying degree of pathogen challenge, oxygenation, and iron concentration, factors known to alter hepcidin expression in mammals. We characterized the diversity of hepcidin genes of the Antarctic notothenioid fishes that are endemic to the world's coldest and most oxygen-rich marine water. Notothenioid fishes have at least 4 hepcidin variants, in 2 distinctive structural types. Type I hepcidins comprise 3 distinct variants that are homologs of the widespread 8-cysteine hepcidins. Type II is a novel 4-cysteine variant and therefore only 2 possible disulfide bonds, highly expressed in hematopoietic tissues. Analyses of d(N)/d(S) substitution rate ratios and likelihood ratio test under site-specific models detected significant signal of positive Darwinian selection on the mature hepcidin-coding sequence, suggesting adaptive evolution of notothenioid hepcidins. Genomic polymerase chain reaction and Southern hybridization showed that the novel type II hepcidin occurs exclusively in lineages of the Antarctic notothenioid radiation but not in the basal non-Antarctic taxa, and lineage-specific positive selection was detected on the branch leading to the type II hepcidin clade under branch-site models, suggesting adaptive evolution of the reduced cysteine variant in response to the polar environment. We also isolated a structurally distinct 4-cysteine (4cys) hepcidin from an Antarctic eelpout that is unrelated to the notothenioids but inhabits the same freezing water. Neighbor-Joining (NJ) analyses of teleost hepcidins showed that the eelpout 4cys variant arose independently from the notothenioid version, which lends support to adaptive evolution of reduced cysteine hepcidin variants on cold selection. The NJ tree also showed taxonomic-specific expansions of hepcidin variants, indicating that duplication and diversification of hepcidin genes play important roles in evolutionary response to diverse ecological conditions.


Sirtuin 1 and endothelial glycocalyx.
Sirtuin1 deficiency or reduced activity comprises one of the hallmarks of diseases as diverse as chronic cardiovascular, renal, and metabolic, some malignancies, and infections, as well as aging-associated diseases. In a mouse model of endothelium-limited defect in sirtuin 1 deacetylase activity, we found a dramatic reduction in the volume of endothelial glycocalyx. This was associated with the surge in the levels of one of key scaffolding heparan sulfate proteoglycans of endothelial glycocalyx, syndecan-4, and specifically, its extracellular domain (ectodomain). We found that the defect in endothelial sirtuin 1 deacetylase activity is associated with (a) elevated basal and stimulated levels of superoxide generation (via the FoxO1 over-acetylation mechanism) and (b) increased nuclear translocation of NF-kB (via p65 over-acetylation mechanism). These findings laid the foundation for the proposed novel function of sirtuin 1, namely, the maintenance of endothelial glycocalyx, particularly manifest in conditions associated with sirtuin 1 depletion. In the forthcoming review, we summarize the emerging conceptual framework of the enhanced glycocalyx degradation in the states of defective endothelial sirtuin 1 function, thus explaining a broad footprint of the syndrome of endothelial dysfunction, from impaired flow-induced nitric oxide production, deterrent leukocytes infiltration, increased endothelial permeability, coagulation, and pro-inflammatory changes to development of microvascular rarefaction and progression of an underlying disease.


A Cell-Free Biosensor for Detecting Quorum Sensing Molecules in P. aeruginosa-Infected Respiratory Samples.
Synthetic biology designed cell-free biosensors are a promising new tool for the detection of clinically relevant biomarkers in infectious diseases. Here, we report that a modular DNA-encoded biosensor in cell-free protein expression systems can be used to measure a bacterial biomarker of Pseudomonas aeruginosa infection from human sputum samples. By optimizing the cell-free system and sample extraction, we demonstrate that the quorum sensing molecule 3-oxo-C12-HSL in sputum samples from cystic fibrosis lungs can be quantitatively measured at nanomolar levels using our cell-free biosensor system, and is comparable to LC-MS measurements of the same samples. This study further illustrates the potential of modular cell-free biosensors as rapid, low-cost detection assays that can inform clinical practice.


The role of MCM proteins in the cell cycle control of genome duplication.
The regulatory mechanism which ensures that eukaryotic chromosomes replicate precisely once per cell cycle is a basic and essential cellular property of eukaryotes. This fundamental aspect of DNA replication is still poorly understood, but recent advances encourage the view that we may soon have a clearer picture of how this regulation is achieved. This review will discuss in particular the role of proteins in the minichromosome maintenance (MCM) family, which may hold the key to understanding how DNA is replicated once, and only once, per cell cycle.


SCelVis: exploratory single cell data analysis on the desktop and in the cloud.
Single cell omics technologies present unique opportunities for biomedical and life sciences from lab to clinic, but the high dimensional nature of such data poses challenges for computational analysis and interpretation. Furthermore, FAIR data management as well as data privacy and security become crucial when working with clinical data, especially in cross-institutional and translational settings. Existing solutions are either bound to the desktop of one researcher or come with dependencies on vendor-specific technology for cloud storage or user authentication. To facilitate analysis and interpretation of single-cell data by users without bioinformatics expertise, we present SCelVis, a flexible, interactive and user-friendly app for web-based visualization of pre-processed single-cell data. Users can survey multiple interactive visualizations of their single cell expression data and cell annotation, define cell groups by filtering or manual selection and perform differential gene expression, and download raw or processed data for further offline analysis. SCelVis can be run both on the desktop and cloud systems, accepts input from local and various remote sources using standard and open protocols, and allows for hosting data in the cloud and locally. We test and validate our visualization using publicly available scRNA-seq data. SCelVis is implemented in Python using Dash by Plotly. It is available as a standalone application as a Python package, via Conda/Bioconda and as a Docker image. All components are available as open source under the permissive MIT license and are based on open standards and interfaces, enabling further development and integration with third party pipelines and analysis components. The GitHub repository is https://github.com/bihealth/scelvis.


Improving a patient appointment call center at Mayo Clinic.
Contact centers for patient and referring physician are important to large medical-centers such as the Mayo Clinic's Central Appointment Office (CAO). The aim of this case study is to report the process and results of a major process improvement effort, designed to simultaneously improve service quality and efficiency. Discrete-event simulation and optimization are used and linked to significant service improvements. The process improvement efforts led to about a 70 percent improvement in patient service performance as measured by average answering-speed (ASA) and average abandonment rate (AAR). This was achieved without adding additional staff, despite call volume increasing by 12 percent. Evaluating process improvement projects is difficult owing to the "phased" implementation of changes. Thus, there is no true control against which to compare. Additionally, the results are based on a single case study. Evaluation of process improvement projects is difficult due to the "phased" implementation of changes. Thus, there is no true control to compare against. Contact center data and operations research methods, such as discrete-event simulation and optimization, can be integrated with change management, which results in significant process improvements in medical call-centers. Structured quantitative modeling of contact centers can be an important extension to traditional quality and process improvement techniques.


Pathology of lymph nodes from patients with breast implants: a histologic and spectroscopic evaluation.
There are only a few published reports describing the pathology of regional lymph nodes from patients with silicone breast implants. Systematic analytical chemical verification of foreign material has not previously been reported. In this study, biopsies of regional lymph nodes from 96 patients with breast implants were studied using conventional histology as well as laser-Raman microprobe spectroscopy and Fourier transform infrared microspectroscopy. Lymph nodes from 12 patients without implants served as negative controls. Foamy macrophages, ranging from rare scattered cells to confluent sheets, were observed in sections of lymph nodes from 91 patients with implants and only rare foamy macrophages were observed in sections from 4 patients without implants. Refractile material consistent with silicone was observed in sections from 86 patients with implants and in no sections from patients without implants. Fragments of foreign material consistent with polyurethane were observed in sections from 16 patients with implants and in no sections from patients without implants. Using spectroscopy, the presence of silicone was confirmed in 71 patients with implants, and the presence of polyurethane was confirmed in 2 patients with implants. Spectroscopy was negative for silicone and polyurethane in all patients without implants. In summary, regional lymph nodes from patients with breast implants often have histologic evidence of silicone migration. Characteristic histologic findings include foamy macrophages and refractile droplets of clear material. Polygonal fragments of polyurethane were observed in lymph nodes from a number of patients. This finding has not been previously reported. The presence of silicone and polyurethane was confirmed using confocal laser-Raman microprobe and Fourier transform infrared microspectroscopy. Other than two prior case reports, this is the first confirmatory evidence of silicone migration to lymph nodes in patients with breast implants and this is the first confirmatory report of polyurethane migration to lymph nodes.


Dynamics of among-individual behavioral variation over adult lifespan in a wild insect.
Investigating patterns of among and within-individual trait variation in populations is essential to understanding how selection shapes phenotypes. Behavior is often the most flexible aspect of the phenotype, and to understand how it is affected by selection, we need to examine how consistent individuals are. However, it is not well understood whether among-individual differences tend to remain consistent over lifetimes, or whether the behavior of individuals relative to one another varies over time. We examined the dynamics of 4 behavioral traits (tendency to leave a refuge, shyness, activity, and exploration) in a wild population of field crickets (Gryllus campestris). We tagged individuals and then temporarily removed them from their natural environment and tested them under laboratory conditions. All 4 traits showed among-individual variance in mean levels of expression across the adult lifespan, but no significant differences in how rapidly expression changed with age. For all traits, among-individual variance increased as individuals got older. Our findings reveal seldom examined changes in variance components over the adult lifetime of wild individuals. Such changes will have important implications for the relationship between behavioral traits, life-histories, and fitness and the consequences of selection on wild individuals.


Accuracy and efficiency of novice nurse practitioners using personal digital assistants.
To determine if using personal digital assistants (PDAs) increased accuracy and efficiency of clinical decisions made by novice nurse practitioners (NPs). Experimental with a repeated measures design. The study sample included 40 novice NPs. Data were collected from December 2003 to March 2004 following a stratified random assignment of the subjects to a textbook or PDA group. Participants identified appropriate laboratory value assessments, diagnosis, and medication decisions using the assigned resources when given two randomly administered clinical scenarios. Accuracy was determined by the correct response score to each clinical question. The completion of the scenario was timed by the investigator. Length of time necessary to answer each part of the scenario determined efficiency. Data analysis included mixed design repeated measures analysis of variance. There was a significant interaction and difference in accuracy in the laboratory analysis section of the case scenarios (F(1,38) = 21.256, p ≤ .001) in the PDA group when compared with the textbook group. There were no differences in accuracy by section. In three of six efficiency variables measured, the PDA users were significantly more efficient. In both laboratory values and one of the treatment sections, the PDA users were more efficient in determining an answer to the clinical questions. Accuracy of PDA users was equal to textbook users. The findings lend support to benefits for novice practitioners using PDAs when evaluating clinical situations, both in accessing certain correct information and doing this in a timely manner.


Crucial enzymes in the hydroxylated triacylglycerol-ricinoleate biosynthesis pathway of castor bean.
Castor bean (Ricinus communis L.) is an important oilseed crop for the rich hydroxylated triacylglycerol (TAG)-ricinoleate which is a raw material with wide applications in industry. Hydroxylated TAG synthesis occurs through complicated pathways among multiple subcellular organelles. Some crucial enzymes have been identified in previous studies. After analyzing the available castor tissue-specific transcriptome sequencing data and comparing the classic pathways in other plants, a possible de novo biosynthesis pathway for the hydroxylated TAG has been revealed. In this study, some other crucial enzymes were ascertained and their expression levels were characterized and pinpointed into the pathways in castor. Several key enzymes were analyzed in terms of structure, biofunction prediction and similarity of expression pattern mechanisms, aiming to give an insight on the better understandings of the molecular knowledge for this oil-rich plant and the crucial enzyme performances in the hydroxylated triacylglycerol-ricinoleate biosynthesis pathways.


Cellular mechanisms underlying prostaglandin-induced transient cAMP signals near the plasma membrane of HEK-293 cells.
We have previously used cyclic nucleotide-gated (CNG) channels as sensors to measure cAMP signals in human embryonic kidney (HEK)-293 cells. We found that prostaglandin E(1) (PGE(1)) triggered transient increases in cAMP concentration near the plasma membrane, whereas total cAMP levels rose to a steady plateau over the same time course. In addition, we presented evidence that the decline in the near-membrane cAMP levels was due primarily to a PGE(1)-induced stimulation of phosphodiesterase (PDE) activity, and that the differences between near-membrane and total cAMP levels were largely due to diffusional barriers and differential PDE activity. Here, we examine the mechanisms regulating transient, near-membrane cAMP signals. We observed that 5-min stimulation of HEK-293 cells with prostaglandins triggered a two- to threefold increase in PDE4 activity. Extracellular application of H89 (a PKA inhibitor) inhibited stimulation of PDE4 activity. Similarly, when we used CNG channels to monitor cAMP signals we found that both extracellular and intracellular (via the whole-cell patch pipette) application of H89, or the highly selective PKA inhibitor, PKI, prevented the decline in prostaglandin-induced responses. Following pretreatment with rolipram (a PDE4 inhibitor), H89 had little or no effect on near-membrane or total cAMP levels. Furthermore, disrupting the subcellular localization of PKA with the A-kinase anchoring protein (AKAP) disruptor Ht31 prevented the decline in the transient response. Based on these data we developed a plausible kinetic model that describes prostaglandin-induced cAMP signals. This model has allowed us to quantitatively demonstrate the importance of PKA-mediated stimulation of PDE4 activity in shaping near-membrane cAMP signals.


Forecasting roles of combinatorial chemistry in the age of genomically derived drug discovery targets.
Genomics has caused an explosion in the number of potential therapeutic targets with varying degrees of validated pathophysiology. Among the first applications of combinatorial chemistry in genomics-driven drug discovery is the search for surrogate ligands or substrates. In the event that no surrogate is found for molecular assays, more exotic functional screens in whole cells or model organisms are used. Protein-protein interaction mapping by yeast and mammalian two-hybrid systems dominates empirical functional genomics, and this will lead to a bias for screening projects targeting this type of interaction. Drug discovery for protein-protein interactions has a poor track record, and this will challenge prevailing views on the design of combinatorial libraries. Genomics based on structural homology will yield many putative kinases, receptors, enzymes, transporter proteins, ion channels and GPCRs. Most of these projects will require new surrogate agonists, ligands or substrates, and then pharmaceutically useful agonists or antagonists will need to be found. Again, combinatorial chemistry might be essential to these studies. Given the need to screen hundreds of targets at great risk of irrelevance to pathophysiology, combined with the challenge of finding surrogate or natural ligands for these new targets, there is an urgent need for efficiency. Different groups are addressing these concerns by developing biologically-driven combinatorial libraries in order to achieve a higher density of bioactivity. Early efforts in this regard will be described.


Contesting asthma medication: patients' view of alternatives.
There are few studies pertaining to asthma patients' views on complementary and alternative medicine (CAM). The driving question behind the study is why some asthma patients choose noncompliance to conventional western medicine and resort to other modalities, often deemed as being 'alternative,' 'complementary,' or 'integrated.' Does the patients' emancipation movement lead to greater awareness of the benefits of alternative medicine? Does the patients' identity as asthma sufferers play a role in their decision? Case studies based on semistructured interviews were conducted between June 2009 and January 2010 with 19 asthma patients in The Netherlands who have chosen complementary and alternative medicine (CAM). Patients were contacted through online forum of Dutch asthma patients' organization Astma Fonds. We have discovered that on the whole patients in the present study were well informed about risks and benefits of both prescribed and alternative medicines. We have argued that noncompliance to medical regime by some asthma patients can be explained by the rationality of their choice based on evidence of clinical trials of commonly assigned asthma medication as well as partial and anecdotal evidence of the benefits of CAM therapies. It is the patients themselves who, by invoking the same evidence-based dominant paradigm choose to address the conflict between protagonists of 'conventional,' western medicine and other modalities. The author argues that asthma patients' noncompliance with (Western) medical regime and choice for alternative medical treatment of asthma is a matter of rational choice informed by evidence-based awareness. This evidence-based rationality particularly refers here to the patients' awareness of the rather controversial results of clinical trials of commonly used asthma medicines, particularly those containing elements of budesonide (Pulmicort), an anti-inflammatory corticosteroid, and formoterol (Oxis, Foradil), a rapid-acting and long-lasting beta(2)-agonist (bronchodilator).


Promotion of smoking cessation in developing countries: a framework for urgent public health interventions.
The rapid rise in smoking in many developing countries will have devastating consequences; by 2030 the developing world is expected to have 7 million deaths annually from tobacco use. Many smokers express a desire to quit, but they often fail because they are addicted to tobacco. Although a number of cessation aids are now available in the developed world, their applicability and affordability in developing countries is less clear. Successful interventions will require many stakeholder groups to take action at the local, national, and international levels. We discuss smoking cessation as a means of reducing disease burden, examine factors that may limit the promotion of smoking cessation in developing countries, and propose a framework for public health action. This framework should comprise intervention with healthcare professionals, strengthening national commitment, development of a model for developing countries, changing the social acceptability of smoking, strengthening community participation, integration of smoking cessation with other healthcare services, specifying the role of healthcare professionals, development of guidelines, mobilisation of the business community, provision of financial incentives, establishing population specific smoking cessation services, increased collaboration between countries, and development of international initiatives.


Child sexual abuse, harmful alcohol use and age as determinants of sexual risk behaviours among freshmen in a Nigerian university.
In Nigeria, freshmen constitute a risk group of adolescents and young adults capable of engaging in unsafe sexual practices. This study documents the associated factors to sexual risk behaviours practices of University of Ibadan, Nigeria freshmen. Eight hundred and forty one (841), freshmen who attended a routine orientation program were asked to respond to a questionnaire. Results showed that 30.8% were sexually active and 47% did not use condom in their last sexual episode. Associated with sexual risk behaviours include: being a male freshman increasing age; lower tendency for violence; increase sexual compulsivity; alcohol abuse; history of rape and a history of Child Sexual Abuse (CSA). Three variables: alcohol abuse; history of CSA and increasing age remained significant in a multiple regression analysis. The paper presents the first evidence of vulnerability of freshmen to sexual risk practices in a Nigerian University.


Short-term effects of psychiatric symptoms and interpersonal stressors on criminal violence--a case-crossover study.
The aim of the study was to analyse the triggering or acute risk effect of psychiatric symptoms and interpersonal stressors on criminal violence. One hundred and thirty three violent offenders were recruited from a forensic psychiatric evaluation (FPE) unit and a national prison evaluation unit in Sweden during 2002-2003, and were interviewed about trigger exposures. A case-crossover design was used eliminating long-term within individual confounding. Suicidal ideation or parasuicide within 24 h before the violent event conferred a ninefold risk increase. In contrast, violent ideation did not trigger criminal violence. Hallucinations yielded a fourfold risk increase, whereas paranoid thoughts were associated with a small and statistically non-significant risk increase. Acute conflicts with others and being denied psychiatric care within 24 h before violence also increased the risk of acting violently. Some tested psychiatric symptoms and stressors triggered criminal violence, whereas others did not. The case-crossover design may be particularly useful for the study of triggers of violence.


BRCA1 and BRCA2 mutations in the ovarian cancer population across race and ethnicity: special reference to Asia.
To evaluate the prevalence and spectrum of BRCA mutations among ovarian carcinoma patients of different races and ethnicity with special reference to Asia. A systematic review of the literature was undertaken to evaluate the prevalence of BRCA mutations among people belonging to different races. The electronic search strategy was developed specifically for the different databases concerned and via cross-referencing. The frequency of BRCA1 and BRCA2 mutations ranged from 1.1 to 39.7 and from 0 to 13.9, respectively. BRCA1 mutations are more common among ovarian cancer cases than BRCA2 mutations, although the ratio of BRCA1 to BRCA2 varies between populations. The Swedish and Indian populations showed 12 and 7 times as many BRCA1 as BRCA2 mutations, respectively, whilst in a study from Iceland the ratio was 0.5:1. These wide-ranging estimates of the mutation prevalence suggest genetic heterogeneity between different populations. The ability to identify BRCA1/2 mutations was found to be successful in the clinical management of ovarian cancer. Given the implications for clinical care and for advances in cancer prevention, identifying racial difference in genetic or lifestyle factors, which may modify the cancer risk due to BRCA1/2 mutations, is a high priority for future research.


Mizolastine in primary acquired cold urticaria.
Treatment of primary acquired cold urticaria (CU) is quite difficult because of variable clinical effectiveness and side effects of classic antihistamines. The objective of the study was to assess the efficacy and safety of mizolastine, an antihistaminic with antiallergic properties, versus placebo in primary acquired CU. This study was a phase II, multicenter, randomized, double-blind, crossover, placebo-controlled study of mizolastine (10 mg, once daily) versus placebo in 28 patients with primary acquired CU. Efficacy was measured by the cold-stimulation time test, the wheal response, and pruritus intensity after an ice-cube test. Mizolastine delayed the cold-induced wheal reaction, reduced wheal response at 3 and 10 minutes, and reduced pruritus intensity. Statistically significant differences were observed versus placebo for the cold-stimulation time test, wheal response at 3 and 10 minutes, and pruritus intensity (P =.006,.015,.009, and.005, respectively). No clinically relevant adverse events were reported. Mizolastine (10 mg, once daily) was shown to be superior to placebo for both delaying and reducing the cold-induced wheal reaction without significant adverse events. Results suggest that mizolastine may be effective in the treatment of CU.


Genetics, lighting environment, and heritable responses to lighting environment affect male color morph expression in bluefin killifish, Lucania goodei.
Determining the degree to which variation in traits is controlled by genetics and/or environment is fundamental to understanding adaptation. In this study, we examine the genetic and environmental influences on color pattern expression in male bluefin killifish, Lucania goodei. This is a compelling system because both male color patterns and vision physiology are correlated with basic properties of the environment. Across populations, males with blue anal fins are more abundant in waters with low transmission of UV and blue wavelengths. Here, we present results from two paternal half-sib breeding experiments (one in the laboratory, one in the greenhouse) in which offspring were raised under light treatments that mimicked natural variation in the spectral composition of light. In both experiments, we found that red-versus-yellow expression is controlled by an autosomal locus of large effect where yellow (Y) is dominant over red (y). There was little blue expression in the laboratory. In the greenhouse, we found higher expression of blue anal fin morphs when males were raised in tea-stained water (low transmission UV/blue) than when raised in clear water (high transmission UV/blue). We also found genetic effects of sires and an interaction between sire and lighting environment (i.e. heritable plasticity). These results show that a relatively simple, environmentally dependent, epistatic interaction can produce a large amount of variation in male color patterns that presumably function in sexual selection.


Do mothers accurately identify their child's overweight/obesity status during early childhood? Evidence from a nationally representative cohort study.
Maternal recognition of overweight/obesity during early childhood is a key determinant in achieving healthy weight status in children. The aim of this study is to 1) investigate maternal perceptions of their child weight, focusing on whether or not mothers accurately identify if their child is overweight or obese at three years old and five years old; 2) identify the factors influencing maternal misperceptions regarding their child's weight at three years old and five years old, 3) ascertain if a failure to recognize overweight/obesity at three years old is associated with the likelihood of doing so at five years old. Using two waves of the longitudinal Growing Up in Ireland study data regarding child, maternal, and household characteristics as well as healthcare access and utilization variables were obtained for mothers when their children are three and five years old respectively. Multivariate logistic analysis was used to examine the factors associated with mothers inaccurately perceiving their child to be of normal weight status when the child is in fact either clinically overweight or obese. In wave 2, 22% of mothers failed to accurately identify their child to be overweight or obese. This inaccuracy decreased to 18% in wave 3. A failure of mothers to identify their child's overweight/obesity was more likely to occur if the child was a girl (OR: 1.25) (OR: 1.37), had a higher birth weight (OR:1.00), if the mother was obese (OR: 1.50), (OR: 1.72) or working (OR:1.25) (OR:1.16) in wave 2 and wave 3, respectively. Other factors affecting the odds of misperceiving child's weight include gestation age, income and urban living. These findings suggest that mothers of overweight or obese three and five year olds show poor awareness of their child's weight status. Both child and mother characteristics play a role in influencing this awareness. Mothers unable to accurately identify their child's overweight or obesity status at three years old are likely to do again when the child is five years old. This study highlights the need for increased support to help improve mothers' understanding of healthy body size in preschool aged children.


Immunosenescence: potential causes and strategies for reversal.
Age-related deterioration in immune function has been recognized in many species. In humans the clinical manifestation of such immune dysfunction is age-related increases in the susceptibility to certain infections and in the incidence of some autoimmune disease and certain cancers. Laboratory investigations reveal age-related changes in the peripheral T cell pool, in the predominant phenotype, cytokine production profiles, signalling function and in replicative ability following stimulus with antigen, mitogens or anti-CD3 antibody. These changes in the properties of peripheral T cells are thought to be causally linked to an age-associated involution in the thymus. Our analysis reveals that thymic involution is due to a change in the thymic microenvironment linked to a reduction in the level of available interleukin 7. Treatment with interleukin 7 leads to a reversal of thymic atrophy with increased thymopoiesis. This provides the potential to reverse the immune dysfunction seen in the peripheral T cell pool by replacing old cells with new output generated in the thymus. Problems to overcome in order for such an experimental therapy to be successful require careful analysis in order to provide an optimal strategy to ensure that new T cell emigrants from the thymus have a broad range of specificities and are able to enter the peripheral T cell pool.


Fluorescence tomography characterization for sub-surface imaging with protoporphyrin IX.
Optical imaging of fluorescent objects embedded in a tissue simulating medium was characterized using non-contact based approaches to fluorescence remittance imaging (FRI) and sub-surface fluorescence diffuse optical tomography (FDOT). Using Protoporphyrin IX as a fluorescent agent, experiments were performed on tissue phantoms comprised of typical in-vivo tumor to normal tissue contrast ratios, ranging from 3.5:1 up to 10:1. It was found that tomographic imaging was able to recover interior inclusions with high contrast relative to the background; however, simple planar fluorescence imaging provided a superior contrast to noise ratio. Overall, FRI performed optimally when the object was located on or close to the surface and, perhaps most importantly, FDOT was able to recover specific depth information about the location of embedded regions. The results indicate that an optimal system for localizing embedded fluorescent regions should combine fluorescence reflectance imaging for high sensitivity and sub-surface tomography for depth detection, thereby allowing more accurate localization in all three directions within the tissue.


Common problems in hospitalized older adults.
Hospitalized older adults are vulnerable to many conditions that can cause functional decline. According to Inouye, Bogardus, Baker, Leo-Summers, and Cooney (2000), 34% to 50% of hospitalized older adults experience poor health outcomes, which can prolong their hospital stay, increase their risk for institutionalization, and increase hospital costs and mortality rates. The objectives of this article are to present national models that have been successful, identify hospitals in Connecticut that are using the models, and to discuss and compare interventions and protocols within Connecticut hospitals. A survey was designed to gather data from 32 hospitals in Connecticut. Twenty-four hospital professionals responded (response rate = 75%), and the majority was found to be creative and eager to share ideas to improve the quality of care.


Malaria prevalence, risk factors and spatial distribution in a hilly forest area of Bangladesh.
Malaria is a major public health concern in Bangladesh and it is highly endemic in the Chittagong Hill Tracts where prevalence was 11.7% in 2007. One sub-district, Rajasthali, had a prevalence of 36%. Several interventions were introduced in early 2007 to control malaria. This study was undertaken to evaluate the impacts of these intensive early stage interventions on malaria in Bangladesh. This prevalence study assesses whether or not high malaria prevalence remains, and if so, which areas and individuals remain at high risk of infection. A 2-stage cluster sampling technique was used to sample 1,400 of 5,322 (26.3%) households in Rajasthali, and screened using a rapid diagnostic test (Falci-vax). Overall malaria prevalence was 11.5%. The proportions of Plasmodium falciparum, Plasmodium vivax and infection with both species were 93.2%, 1.9% and 5.0%, respectively. Univariate, multivariate logistic regression, and spatial cluster analyses were performed separately. Sex, age, number of bed nets, forest cover, altitude and household density were potential risk factors. A statistically significant malaria cluster was identified. Significant differences among risk factors were observed between cluster and non-cluster areas. Malaria has significantly decreased within 2 years after onset of intervention program. Both aspects of the physical and social environment, as well as demographic characteristics are associated with spatial heterogeneity of risk. The ability to identify and locate these areas provides a strategy for targeting interventions during initial stages of intervention programs. However, in high risk clusters of transmission, even extensive coverage by current programs leaves transmission ongoing at reduced levels. This indicates the need for continued development of new strategies for identification and treatment as well as improved understanding of the patterns and determinants of parasitaemia.


Urinary ATP Synthase Subunit β Is a Novel Biomarker of Renal Mitochondrial Dysfunction in Acute Kidney Injury.
Although the importance of mitochondrial dysfunction in acute kidney injury (AKI) has been documented, noninvasive early biomarkers of mitochondrial damage are needed. We examined urinary ATP synthase subunit β (ATPSβ) as a biomarker of renal mitochondrial dysfunction during AKI. Mice underwent sham surgery or varying degrees (5, 10, or 15 min ischemia) of ischemia/reperfusion (I/R)-induced AKI. Serum creatinine, BUN, and neutrophil gelatinase-associated lipocalin were elevated only in the 15 min I/R group at 24 h. Immunoblot analysis of urinary ATPSβ revealed two bands (full length ∼52 kDa and cleaved ∼25 kDa), both confirmed as ATPSβ by LC-MS/MS, that increased at 24 h in 10- and 15-min I/R groups. These changes were associated with mitochondrial dysfunction evidenced by reduced renal cortical expression of mitochondrial proteins, ATPSβ and COX1, proximal tubular oxygen consumption, and ATP. Furthermore, in the 15-min I/R group, urinary ATPSβ was elevated until 72 h before returning to baseline 144 h after reperfusion with recovery of renal function. Evaluation of urinary ATPSβ in a nonalcoholic steatohepatitis model of liver injury only revealed cleaved ATPSβ, suggesting specificity of full-length ATPSβ for renal injury. Immunoblot analyses of patient urine samples collected 36 h after cardiac surgery revealed increased urinary ATPSβ levels in patients with postcardiac surgery-induced AKI. LC-MS/MS urinalysis in human subjects with AKI confirmed increased ATPSβ. These translational studies provide evidence that ATPSβ may be a novel and sensitive urinary biomarker of renal mitochondrial dysfunction and could serve as valuable tool for the testing of potential therapies for AKI and chemical-induced nephrotoxicity.