Excellent functional recovery after Kirschner-wire extension blocking technique for displaced closed bony mallet finger injuries; results of 36 cases.
Bony mallet finger injuries comprise 30% of all mallet injuries. Operative treatment of bony mallet fingers injuries still remains controversial. The aim of this study was to describe the k-wire extension blocking technique and the functional results using the PRWHE questionnaire. A single center retrospective observational cohort of 36 patients was defined between January 2010 and December 2015. Inclusion criteria for this study were acute fractures with 1) persistent displacement of more than 3 mm in extension splint, 2) palmar subluxation of the distal phalanx or 3) fracture fragments consisting of more than one third of the joint surface. According to the PRWHE questionnaire, excellent results were observed with a mean follow up period of 32 months of all patients. Two patients developed a clinically relevant superficial wound infection and one patient developed a nail deformity. In conclusion, the k-wire extension blocking technique is safe and results in excellent mid-term functional outcome.


High consumption of commercial food products among children less than 24 months of age and product promotion in Kathmandu Valley, Nepal.
Commercially produced complementary foods can help improve nutritional status of young children if they are appropriately fortified and of optimal nutrient composition. However, other commercially produced snack food products may be nutritionally detrimental, potentially increasing consumption of foods high in salt or sugar and displacing consumption of other more nutritious options. Helen Keller International, in collaboration with the Nepal government, implemented a study to assess mothers' utilization of commercial food products for child feeding and exposure to commercial promotions for these products. A cross-sectional survey was conducted among 309 mothers of children less than 24 months of age across 15 health facilities. Utilization of breastmilk substitutes was low, having been consumed by 6.2% of children 0-5 months of age and 7.5% of children 6-23 months of age. Approximately one-fourth (24.6%) of children 6-23 months age had consumed a commercially produced complementary food in the prior day. Twenty-eight percent of mothers reported observing a promotion for breastmilk substitutes, and 20.1% reported promotions for commercially produced complementary foods. Consumption of commercially produced snack food products was high at 74.1% of children 6-23 months. Promotions for these same commercially produced snack food products were highly prevalent in Kathmandu Valley, reported by 85.4% of mothers. In order to improve diets during the complementary feeding period, development of national standards for complementary food products is recommended. Nutritious snack options should be promoted for the complementary feeding period; consumption of commercially produced snack food products high in sugar and salt and low in nutrients should be discouraged.


Rheumatic and musculoskeletal features of Whipple disease: a report of 29 cases.
Whipple disease is a rare infection caused by Tropheryma whipplei. Although patients commonly complain of osteoarticular involvement, musculoskeletal manifestations have been poorly described. We report cases of Whipple disease with rheumatic symptoms and describe their clinical presentation, modes of diagnosis, and outcomes. This retrospective multicenter study included patients with Whipple disease diagnosed and referenced between 1977 and 2011 in 10 rheumatology centers in France and Italy. Twenty-nine patients were included. The median age was 55 years. The median time to diagnosis from first symptoms was 5 years. Polyarthritis was the most frequent presentation (20/29), and was most often chronic, intermittent (19/29), seronegative (22/23), and nonerosive (22/29). In all cases, the symptoms had led to incorrect diagnosis of inflammatory rheumatic disease and immunosuppressants, including biotherapy, were prescribed in most cases (24/29) without success. The diagnosis of Whipple disease was made by histological analysis, molecular biology tests, or both in 21%, 36%, and 43% of the cases, respectively. Duodenal biopsies were performed in most cases (86%). Synovial biopsies were performed in 18% of cases, but all contributed to diagnosis. The clinical outcomes after antibiotic therapy were good for all patients. Polyarthritis is the main feature observed in cases of Whipple disease; it is seronegative and associated with general and gastrointestinal symptoms. The molecular analysis of duodenal tissue and/or other tissues remains the method of choice to confirm the diagnosis. Reducing the time to diagnosis is important because severe late systemic and fatal forms of the disease may occur.


Acetic acid induces cell death: an in vitro study using normal rat gastric mucosal cell line and rat and human gastric cancer and mesothelioma cell lines.
We recently reported that topical application of acetic acid promptly caused tumor necrosis in a mouse model of gastric cancer. The aim of the present study was to examine whether acetic acid can directly induce cancer cell death. Rat gastric epithelial cell line (RGM-1), rat gastric carcinoma cell line (RGK-1), human gastric cancer cell line (KATO III), and human mesothelioma cell lines (ACC-MESO1 and MSTO-211H) were used. Acetic acid was added into the cell culture at different concentrations for different time periods. Cell death was analyzed by MTT assay, flow cytometry, and trypan blue exclusion test. Acetic acid promptly induced the cell death of RGM-1, RGK-1 cells, and KATO III cells in a concentration-dependent manner from 0.01% to 0.5%. Acetic acid at 0.5% for 1 min induced the cell death by 80%. RGK-1 cells were more sensitive to acetic acid than RGM-l cells. KATO III cells were more sensitive to acetic acid than RGK-1 cells. Acetic acid at 0.5% for 10 min induced almost complete cell death of ACC-MESO1 and MSTO-211H. Acetic acid is a powerful anticancer agent. Topical application of acetic acid may be a feasible approach for the treatments of gastric cancer and possibly other malignancies.


Determination of the relative ligand-binding strengths in heteroleptic Ir(III) complexes by ESI-Q-TOF tandem mass spectrometry.
An electrospray ionization quadrupole time-of-flight mass spectrometer has been utilized to investigate the relative ligand-binding strengths in a series of heteroleptic-charged iridium(III) complexes of the general formula [(C^N)(2) Ir(III) (S-tpy)](PF(6) ) by using variable collision energies. Collision-induced dissociation experiments were performed in order to study the stability of the Ir(III) complexes that are, for instance, suitable phosphors in light-emitting electrochemical cells. The ratio of signal intensities belonging to the fragment and the undissociated complex depends on the collision energy applied for the tandem mass spectra (MS/MS) analysis. By defining the threshold collision energy and the point of complete complex dissociation, it is possible to estimate the relative complex stabilities depending on the nature of the coordinated ligands [i.e. type of cyclometalating ligand (C^N), substituents on the S-shaped terpyridine (S-tpy)]. The collision energy values differed as a function of the coordination sphere of the Ir(III) centers.


[Regionalization in health: an instrument for jurisdictional planning].
This study carried out the regionalization of Sanitary Jurisdiction No. III seated in Cuautla, Morelos, consisting of 16 of a total of 33 municipalities in the state of Morelos. This regionalization was carried out through the delination of areas sharing similar socioeconomical and demographic characteristics (SED). Subsequently, the major health hazards and the intraregional distribution of human health resources (physicians and nurses) and infrastructure services (institutional health centers) were identified for each region. The aim of this work was to devise an instrument for a better understanding of and approach to health problems at a juridictional level and to pave the way for health planning that would be congruent with regional characteristics and needs. Health sector efforts would be directed towards the promotion of preventive health care with greater efficiency and equity. In order to regionalize the jurisdiction, 17 SED indicators were studied in each of the 16 municipalities. Analysis was performed using the Principal Components Method (MCP) and an epidemiologic score. As a result, the sanitary jurisdiction was divided into three regions: Region I, with the best SED conditions, Region II, with moderate SED conditions and Region III with the lowest SED conditions. The results of this study show that there is an inverse relationship between the intraregional distribution of health resources with respect to the delineated regions and the health resources with respect to the delineated regions and the health needs and problems found in each one. Region III showed the worst SED conditions and the highest incidence of disease. It proved to be the region which had the greatest lack of material and human health resources, the latter having the lowest technical training level in all of the jurisdiction. In contrast. Region I had the best SED conditions and the lowest incidence of disease. It also had the highest number of material and human health resources, the latter having a high level of preparation. This situation is opposite to the national health policies in regards to equity "...give more benefits to the more vulnerable groups..."


Estimation of group B streptococcus type III polysaccharide-specific antibody concentrations in human sera is antigen dependent.
The presence of immunoglobulin G (IgG) antibodies against group B streptococcus (GBS) type III polysaccharide (PS) has been correlated with protection against GBS disease. The GBS type III PS is structurally similar to the pneumococcal type 14 PS, differing only in the presence of sialic acid residues. Four different preparations of GBS type III PS were evaluated for their specificity in enzyme-linked immunosorbent assay (ELISA): free PS, free PS mixed with methylated human serum albumin (mHSA), PS conjugated to biotin and PS conjugated to human serum albumin. Three groups of human sera were used to evaluate these PS preparations: sera from recipients of a GBS PS vaccine, sera from women receiving a GBS type III PS-tetanus toxoid conjugate vaccine, and sera from nonimmunized healthy women of childbearing age. Estimated antibody concentrations were different depending on the PS preparation used. Using any of the four preparations, we were able to measure </=0.05 micrograms of IgG antibody to the GBS type III PS per ml. The specificity of the assay was determined by competitive inhibition with homologous and heterologous PS. The pneumococcal type 14 PS did not inhibit binding of antibody to the native GBS type III PS in sera from adults receiving the GBS PS vaccine or in sera from nonimmunized adults (except serum G9). The pneumococcal type 14 PS inhibited 50% in sera from recipients of GBS type III conjugate vaccine and in serum G9 when GBS type III PS conjugated to biotin or to HSA was used as antigen in ELISA. These data show that free GBS type III PS or PS mixed with mHSA is a sensitive and specific antigen for ELISA and that conjugation can alter the antigenic specificity of a PS.


Relative roles of collagenase and lysosomal cysteine-proteinases in bone resorption.
Both lysosomal cysteine-proteinases and collagenase appear to be necessary for the resorption of actively growing, immature woven bone, but their relative roles are not yet clearly elucidated. The present evidence indicates that, during bone resorption, the osteoclast first solubilizes the mineral by a secretion of acid and then removes the exposed demineralized collagen by the action of secreted lysosomal collagenolytic cysteine-proteinases. Collagenase in bone seems to be mainly a product of osteoblasts and related cells, not osteoclasts. Its role could be limited in the removal of any non-mineralized collagen layers which could be covering mineralized bone surfaces and which seem to prevent the activation of osteoclasts and thus their action; such a "shield" of unmineralized osteoid is well-established at the surface of actively growing woven bone, although not on the resorbing surfaces of mature lamellar bone. Moreover, some osteoblast-derived procollagenase is stored in the mineralized bone matrix from which it can be released by demineralization. It is therefore possible that it may also contribute to the degradation of demineralized bone collagen once it has been released and activated by lysosomal cysteine-proteinases under the osteoclast.


Diminished androgen and estrogen receptors and aromatase levels in hypogonadal diabetic men: reversal with testosterone.
One-third of males with type 2 diabetes (T2DM) have hypogonadism, characterized by low total and free testosterone concentrations. We hypothesized that this condition is associated with a compensatory increase in the expression of androgen receptors (AR) and that testosterone replacement reverses these changes. We also measured estrogen receptor and aromatase expression. This is a randomized double-blind placebo-controlled trial. Thirty-two hypogonadal and 32 eugonadal men with T2DM were recruited. Hypogonadal men were randomized to receive intramuscular testosterone or saline every 2 weeks for 22 weeks. We measured AR, ERα and aromatase expression in peripheral blood mononuclear cells (MNC), adipose tissue and skeletal muscle in hypogonadal and eugonadal males with T2DM at baseline and after 22 weeks of treatment in those with hypogonadism. The mRNA expression of AR, ERα (ESR1) and aromatase in adipose tissue from hypogonadal men was significantly lower as compared to eugonadal men, and it increased significantly to levels comparable to those in eugonadal patients with T2DM following testosterone treatment. AR mRNA expression was also significantly lower in MNC from hypogonadal patients compared to eugonadal T2DM patients. Testosterone administration in hypogonadal patients also restored AR mRNA and nuclear extract protein levels from MNC to that in eugonadal patients. In the skeletal muscle, AR mRNA and protein expression are lower in men with hypogonadism. Testosterone treatment restored AR expression levels to that comparable to levels in eugonadal men. We conclude that, contrary to our hypothesis, the expression of AR, ERα and aromatase is significantly diminished in hypogonadal men as compared to eugonadal men with type 2 diabetes. Following testosterone replacement, there is a reversal of these deficits.


Neonatal status epilepticus II: Electroencephalographic aspects.
A prospective study of 15 newborns were identified with NSE. In 11 cases the findings were electrical only without clinical manifestations (ENSE), and the other four presented simultaneously clinical seizures and electrical discharges (ECNSE).


Polycystic Ovary Syndrome: An Under-recognized Cause of Abnormal Uterine Bleeding in Adolescents Admitted to a Children's Hospital.
To evaluate whether ovulatory dysfunction due to polycystic ovary syndrome (PCOS) is a common underlying etiology of abnormal uterine bleeding (AUB) in adolescents who require hospitalization and to explore etiology, treatment, and complications of AUB with severe anemia in adolescents. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: We identified female patients aged 8-20 years admitted to a children's hospital for treatment of AUB from January 2000 to December 2014. Our hospital protocol advises hormonal testing for PCOS and other disorders before treatment for AUB. We reviewed medical records and recorded laboratory evaluations, treatments, and final underlying diagnoses as well as recurrences of AUB and readmissions in the subsequent year. Of the 125 subjects, the mean age was 16.5 ± 2.9 years; mean hemoglobin level was 7.0 ± 1.8 g/dL; 54% were overweight/obese; and 41% sexually active. PCOS accounted for 33% of admissions; hypothalamic pituitary ovarian axis immaturity 31%; endometritis 13%; bleeding disorders 10%. Girls with PCOS were more likely to be overweight/obese (74% vs 46%; P < .01) and girls with hypothalamic pituitary ovarian axis immaturity had lower hemoglobin levels (6.4 g/dL vs 7.4 g/dL; P < .05), than girls with all other etiologies of AUB. Treating physicians failed to diagnose endometritis as the etiology for AUB in 4 of 8 girls with positive tests for sexually transmitted infection and no other etiology. PCOS was the most common underlying etiology in adolescents hospitalized with AUB. Screening for hyperandrogenemia is important for early diagnosis of PCOS to allow ongoing management and prevention of comorbidities. Endometritis was frequently underestimated as an etiology for AUB.


Elevated serum levels of advanced glycation end products and their monocyte receptors in patients with type 2 diabetes.
Animal experiments showed that interaction between advanced glycation end products (AGE) and their receptors (RAGE) play an important role in the pathogenesis of diabetic complications. Soluble RAGE (sRAGE) can function as a decoy for RAGE ligands. The present study aimed to examine the levels of AGEs, RAGE and sRAGE in patients with type 2 diabetes (T2D). RAGE gene expression was determined by real-time PCR in 50 patients with T2D (27 men, mean age 52 ± 7.7 years) and 50 age-matched controls without T2D. Serum AGEs and sRAGEs were assayed by enzyme-linked immunosorbent assay (ELISA). Serum level of AGEs was increased in patients with T2D (10.35 ± 2.27 μg/mL vs.7.69 ± 0.56 μg/mL, p <0.05). sRAGE was decreased in patients with T2D (573.6 ± 172.5 pg/mL vs. 603.4 ± 120.8 pg/mL p <0.01). RAGE gene expression was higher in T2D than in controls (p <0.01). There was an association between monocyte RAGE and serum levels of AGEs in both T2D patients (r = 0.29, p = 0.03) and controls (r = 0.31, p = 0.02). Serum AGEs correlated with homeostasis model assessment of insulin resistance (HOMA-IR) in both patients with T2D (r = 0.322, p = 0.004) and controls (r = 0.281, p = 0.003). Serum AGEs and monocyte RAGE expression are increased in patients with T2D, whereas serum sRAGE is decreased. Pharmacological intervention on serum AGEs and sRAGE may be a potential therapy for diabetes.


Recombinant Human Soluble Thrombomodulin Contributes to a Reduction In-Hospital Mortality of Acute Cholangitis with Disseminated Intravascular Coagulation: A Propensity Score Analyses of a Japanese Nationwide Database.
The anti-DIC biological agent, recombinant human soluble thrombomodulin (rhTM), is being used clinically for DIC treatment in Japan. Patients with acute cholangitis associated with DIC are severe and require improved treatment. In addition, although clinical efficacy of rhTM in patients with acute cholangitis and DIC is expected, its efficacy is controversial. Thus, it is useful to evaluate rhTM in patients with acute cholangitis with DIC. This study aimed to validate the hypothesis that rhTM use improves in-hospital mortality in patients with acute cholangitis with DIC. A propensity score-matching analysis using a nationwide administrative database, the Japanese Diagnosis Procedure Combination Inpatient Database from April 2012 to March 2018, was performed. This database includes administrative claims data for all inpatients discharged from more than 1,000 participating hospitals, covering 92% of all tertiary-care emergency hospitals in Japan. Eligible patients (n = 2,865) were categorized into the rhTM (n = 1,636) or control groups (n = 1,229). Propensity score-matching created a matched cohort of 910 pairs with and without rhTM. In-hospital mortality between the groups in the unmatched analysis showed no significant difference (rhTM vs. control; 10.8% vs. 12.2%; p = 0.227). However, in-hospital mortality between the groups in the propensity score-matched analysis showed a significant difference (rhTM vs. control; 9.5% vs. 12.9%; p = 0.021). These results demonstrated that the rhTM group had significantly lower in-hospital mortality for patients with acute cholangitis with DIC. We propose that rhTM should be used for the treatment of patients with acute cholangitis with DIC.


Cerebral spinal fluid positive pertussis encephalopathy in infants: Case reports.
Pertussis has re-emerged in both developed and developing countries and is an ongoing public health problem, even in countries with high rates of vaccination. Pertussis encephalopathy is a known complication of the disease, but the pathophysiology of this complication and the role of the pertussis bacteria have not been elucidated. We report three confirmed cases of pertussis infant younger than 3 months of age with neurological complications including lethargy, encephalopathy, and seizures. In each case, the cerebrospinal fluid was positive for Bordetella pertussis as determined by polymerase chain reaction. One patient did not survive and two were discharged with a normal neurological exam on follow-up. The cases emphasize the importance of analyzing cerebrospinal fluid in cases of pertussis-associated encephalopathy including polymerase chain reaction.


New experimental markers for early detection of high-risk prostate cancer: role of cell-cell adhesion and cell migration.
Today's treatment and diagnosis of prostate cancer still exhibit major limitations. The search for new and additional prognostic markers is therefore still an actual field of interest. Potential markers involved in numerous biological processes in the tumor cell have been investigated intensively. For therapeutic interventions it is important to distinguish between harmless and aggressive disease in an early stage. Therefore the subject of this review is limited to markers associated with those functional processes, which discriminate early stage aggressive, metastatic cancer from harmless disease. Important processes in this respect are: altered cell adhesion and cellular migration. E-cadherin, N-cadherin, beta-catenin, integrins, focal adhesion kinase, connexins and matrix metalloproteinases all appear promising biological markers associated with the early stage metastatic process in prostate cancer. Here we discuss their potential to become valid biological markers based on literature data. Thus far, none of these markers proved to be a valid individual marker by itself due to prostate cancer heterogeneity and transient expression. Analyzing a combination of the potential markers discussed in this review is expected to be a better approach toward discriminating high- from low-risk tumors in an early stage of prostate cancer.


Uninterrupted real-time cerebral stress level monitoring using wearable biosensors: A review.
Stress is the major unseen bug for the health of humans with the increasing workaholic era. Long periods of avoidance are the main precursor for chronic disorders that are quite tough to treat. As precaution is better than cure, stress detection and monitoring are vital. Although there are ways to measure stress clinically, there is still a constant need and demand for methods that measure stress personally and in an ex vitro manner for the convenience of the user. The concept of continuous stress monitoring has been introduced to tackle the issue of unseen stress accumulating in the body simultaneously with being user-friendly and reliable. Stress biosensors nowadays provide real-time, noninvasive, and continuous monitoring of stress. These biosensors are innovative anthropogenic creations that are a combination of biomarkers and indicators like heart rate variation, electrodermal activity, skin temperature, galvanic skin response, and electroencephalograph of stress in the body along with machine learning algorithms and techniques. The collaboration of biological markers, artificial intelligence techniques, and data science tools makes stress biosensors a hot topic for research. These attributes have made continuous stress detection a possibility with ease. The advancement in stress biosensing technologies has made a great impact on the lives of human beings so far. This article focuses on the comprehensive study of stress-indicating biomarkers and the techniques along with principles of the biosensors used for continuous stress detection. The precise overview of wearable stress monitoring systems is also sectioned to pave a pathway for possible future research studies.


Role of radio-aerosol and perfusion lung imaging in early detection of chronic obstructive lung disease.
The efficacy of radio-aerosol and perfusion lung imaging in the early detection of chronic obstructive lung disease was evaluated in 38 subjects. The subjects included 5 non-smokers, 21 smokers with minimal or no respiratory symptoms and 12 patients with chronic obstructive lung disease. Each subject consented to a respiratory questionnaire, detailed physical examination, chest X-ray examinations, detailed pulmonary function tests and 99mTc-radio aerosol-inhalation lung imaging. Perfusion lung imaging with 99mTc-labelled macroaggregated albumin was performed in 22 subjects. A significant correlation (P less than 0.001) was observed between the degree of abnormalities on radio-aerosol imaging and pulmonary function tests (PFTs) including forced expiratory volume in 1 s, maximum mid-expiratory flow rate and mean transit time analysis. Abnormal radio-aerosol patterns and deranged PFTs were observed in 21 subjects each. Of 21 subjects with abnormal radioaerosol pattern 8 had normal PFTs. Of 21 subjects with abnormal PFTs 8 had normal aerosol images. Aerosol lung images and PFTs were abnormal more frequently than perfusion lung images. The results suggest that radio-aerosol lung imaging is as sensitive an indicator as PFTs for early detection of chronic obstructive lung disease and can be usefully combined with PFTs for early detection of alteration in pulmonary physiology in smokers.


Breast carcinoma diffusely metastatic to the spleen. A report of two cases presenting as idiopathic thrombocytopenic purpura.
Carcinoma metastatic to the spleen is found at autopsy in 6% to 13% of patients who die of cancer, yet clinical symptoms referable to splenic metastases are unusual. Two cases of breast carcinoma metastatic to the spleen discovered incidentally at therapeutic splenectomy for idiopathic thrombocytopenic purpura are described. On gross examination, the spleens were mildly enlarged with a homogeneous congested cut surface; rare 0.2-cm white nodules were present in one case. Microscopic examination revealed large, poorly cohesive cells that diffusely involved both the red and white pulp. Histochemical, immunohistochemical, and ultrastructural analyses confirmed the epithelial nature of the cellular infiltrate. These cases show that idiopathic thrombocytopenic purpura may herald the presence of diffuse splenic metastases when metastatic disease is not otherwise clinically suspected. The lack of a discrete tumor mass in the spleen in such cases may make the diagnosis of metastatic carcinoma a challenge both clinically and pathologically. Immunohistochemical and electron microscopic examinations are useful to establish the appropriate diagnosis in such cases.


Hydantoin analogs inhibit the fully assembled ClpXP protease without affecting the individual peptidase and chaperone domains.
Proteolysis mediated by ClpXP is a crucial cellular process linked to bacterial pathogenesis. The development of specific inhibitors has largely focused on ClpP. However, this focus was challenged by a recent finding showing that conformational control by ClpX leads to a rejection of ClpP binders. Thus, we here follow up on a hit molecule from a high throughput screen performed against the whole ClpXP complex and demonstrate that stable inhibition with high potency is possible. Further investigations revealed that the small molecule binds to ClpP without affecting its activity. Likewise, the molecule does not inhibit ClpX and retains the overall oligomeric state of ClpXP upon binding. Structure activity relationship studies confirmed structural constraints in all three parts of the molecule suggesting binding into a defined stereospecific pocket. Overall, the inhibition of ClpXP without affecting the individual components represents a novel mechanism with perspectives for further optimization for in situ applications.


Dynamics of normalization underlying masking in human visual cortex.
Stimulus visibility can be reduced by other stimuli that overlap the same region of visual space, a process known as masking. Here we studied the neural mechanisms of masking in humans using source-imaged steady state visual evoked potentials and frequency-domain analysis over a wide range of relative stimulus strengths of test and mask stimuli. Test and mask stimuli were tagged with distinct temporal frequencies and we quantified spectral response components associated with the individual stimuli (self terms) and responses due to interaction between stimuli (intermodulation terms). In early visual cortex, masking alters the self terms in a manner consistent with a reduction of input contrast. We also identify a novel signature of masking: a robust intermodulation term that peaks when the test and mask stimuli have equal contrast and disappears when they are widely different. We fit all of our data simultaneously with family of a divisive gain control models that differed only in their dynamics. Models with either very short or very long temporal integration constants for the gain pool performed worse than a model with an integration time of ∼30 ms. Finally, the absolute magnitudes of the response were controlled by the ratio of the stimulus contrasts, not their absolute values. This contrast-contrast invariance suggests that many neurons in early visual cortex code relative rather than absolute contrast. Together, these results provide a more complete description of masking within the normalization framework of contrast gain control and suggest that contrast normalization accomplishes multiple functional goals.


Membrane-bound steel factor maintains a high local concentration for mouse primordial germ cell motility, and defines the region of their migration.
Steel factor, the protein product of the Steel locus in the mouse, is a multifunctional signal for the primordial germ cell population. We have shown previously that its expression accompanies the germ cells during migration to the gonads, forming a "travelling niche" that controls their survival, motility, and proliferation. Here we show that these functions are distributed between the alternatively spliced membrane-bound and soluble forms of Steel factor. The germ cells normally migrate as individuals from E7.5 to E11.5, when they aggregate together in the embryonic gonads. Movie analysis of Steel-dickie mutant embryos, which make only the soluble form, at E7.5, showed that the germ cells fail to migrate normally, and undergo "premature aggregation" in the base of the allantois. Survival and directionality of movement is not affected. Addition of excess soluble Steel factor to Steel-dickie embryos rescued germ cell motility, and addition of Steel factor to germ cells in vitro showed that a fourfold higher dose was required to increase motility, compared to survival. These data show that soluble Steel factor is sufficient for germ cell survival, and suggest that the membrane-bound form provides a higher local concentration of Steel factor that controls the balance between germ cell motility and aggregation. This hypothesis was tested by addition of excess soluble Steel factor to slice cultures of E11.5 embryos, when migration usually ceases, and the germ cells aggregate. This reversed the aggregation process, and caused increased motility of the germ cells. We conclude that the two forms of Steel factor control different aspects of germ cell behavior, and that membrane-bound Steel factor controls germ cell motility within a "motility niche" that moves through the embryo with the germ cells. Escape from this niche causes cessation of motility and death by apoptosis of the ectopic germ cells.


Transforming growth factor alpha production and epidermal growth factor receptor expression in normal and oncogene transformed human mammary epithelial cells.
We have characterized the expression of transforming growth factor alpha (TGF alpha) and its receptor, the epidermal growth factor receptor (EGF-R), in normal and malignantly transformed human mammary epithelial cells. Human mammary epithelial cells were derived from a reduction mammoplasty (184), immortalized by benzo-a-pyrene (184A 1N4), and further transformed by the oncogenes simian virus 40 T (SV40 T), v-Ha-ras, and v-mos alone or in combination using retroviral vectors. 184 and 184A 1N4 cells require EGF for anchorage-dependent clonal growth. In mass culture, they secrete TGF alpha at high concentrations and exhibit an attenuated requirement for exogenous EGF/TGF alpha. SV40 T transformed cells have 4-fold increased EGF-R, have acquired the ability to clone in soft agar with EGF/TGF alpha supplementation, but are not tumorigenic. Cells transformed by v-mos or v-Ha-ras are weakly tumorigenic and capable of both anchorage dependent and independent growth in the absence of EGF/TGF alpha. Cells transformed by both SV40 T and v-Ha-ras are highly tumorigenic, are refractory to EGF/TGF alpha, and clone with high efficiency in soft agar. The expression of v-Ha-ras is associated with a loss of the high (but not low) affinity binding component of the EGF-R. Malignant transformation and loss of TGF alpha/EGF responsiveness did not correlate with an increase in TGF alpha production. Thus, TGF alpha production does not appear to be a tumor specific marker for human mammary epithelial cells. Differential growth responses to EGF/TGF alpha, rather than enhanced production of TGF alpha, may determine the transition from normal to malignant human breast epithelium.


Anaphylaxis from intraperitoneal infusion of cisplatin: a case report.
Anaphylactic reactions to platinum compounds and paclitaxel are well-recognized complications during their systemic administration. Although there have been reports describing anaphylaxis during intravesical instillation of chemotherapeutic agents, to the best of the authors' knowledge, no hypersensitivity reactions after intraperitoneal administration of chemotherapeutic drugs has been reported in the English literature. The authors report an unusual case of anaphylaxis occurring in a 33-year-old woman who has been treated with paclitaxel and cisplatin for ovarian cancer. She developed a hypersensitivity reaction during her ninth cycle of chemotherapy, immediately after institution of intraperitoneal infusion of cisplatin. It is important to be aware of the possibility of anaphylaxis during chemotherapy administration other than the systemic route so that appropriate premedication or effective treatment can be promptly instituted.


An industry picture of u.s. Science policy.
With regard to promoting the competitiveness of U.S. industry, federal science policy is performing unevenly. Federally supported basic research is not well aligned with industrial needs, although the National Science Foundation's Engineering Research Centers and similar programs are improving matters. Large-scale federal undertakings in science and technology, such as the Apollo program and now the Strategic Defense Initiative, actually tend to divert resources away from commercial research and development. Needed are federal and industrial leaders who will work together to serve the interests of both competitive industry and efficient government in the United States.


Community-Based Participatory Research-Speed Dating: An Innovative Model for Fostering Collaborations Between Community Leaders and Academic Researchers.
Developing meaningful community-based participatory relationships between researchers and the community can be challenging. The overall success of a community-based participatory relationship should be predicated on commitment and respect from empowered stakeholders. Prior to developing the technique discussed in this article, we hypothesized that the process of fostering relationships between researchers and the community was much like a social relationship: It has to develop organically and cannot be forced. To address this challenge, we developed a community-based participatory research-speed dating technique to foster relationships based on common interests, which we call CBPR-SD. This article describes the logistics of implementing CBPR-SD to foster scholarly collaborations. As part of a federally funded community-based research project, the speed dating technique was implemented for 10 researchers and 11 community leaders with a goal of developing scholarly collaborative groups who will submit applications for community-based research grants. In the end, four collaborative groups developed through CBPR-SD, three (75%) successfully submitted grant applications to fund pilot studies addressing obesity-related disparities in rural communities. Our preliminary findings suggest that CBPR-SD is a successful tool for promoting productive scholarly relationships between researchers and community leaders.


Outcome of surgery for failed endoscopic extraction of common bile duct stones in elderly patients.
Endoscopic sphincterotomy (ES) is the treatment of choice for common bile duct stones in elderly patients. For those in whom endoscopic clearance of the common bile duct fails the treatment options include stenting, dissolution therapy and lithotripsy. Surgery is often avoided because of the reported high morbidity and mortality in elderly patients. We have reviewed the outcome of patients referred for surgery after failed endoscopic clearance of common bile duct stones. Over a 3-year period, 100 patients with common bile duct stones were referred specifically for endoscopic clearance of the common bile duct (median age 69 years, range 19-97 years). In seven patients duct clearance was possible without ES and in five patients ES was considered inappropriate. ES was attempted in 88 patients and was successful in 75 (85%). Of the 13 patients failing ES or stone removal, surgery was performed in nine and four were stented. Of patients having successful ES (n = 75), ten were referred for surgery because of incomplete duct clearance. Surgery was performed to obtain duct clearance in 19 patients (eight male, 11 female, median age 77 years, range 47-90 years). Of the 19, eight had previously undergone a cholecystectomy (42%) and 17 of the 19 had biliary tract drainage preoperatively (90%). The procedures performed consisted of choledocholithotomy in all plus cholecystectomy (11), choledochoduodenostomy (7) and choledochojejunostomy (7). There were no deaths and only one major complication. The median total inpatient stay was 26 days (range 14-75 days) and the median postoperative stay was 12 days (range 7-50 days). We would conclude that open surgery can be performed safely and effectively in elderly patients with retained bile duct stones.


Circulating Non-coding RNAs in Renal Cell Carcinoma-Pathogenesis and Potential Implications as Clinical Biomarkers.
Liquid biopsy-the determination of circulating cells, proteins, DNA or RNA from biofluids through a "less invasive" approach-has emerged as a novel approach in all cancer entities. Circulating non-(protein) coding RNAs including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and YRNAs can be passively released by tissue or cell damage or actively secreted as cell-free circulating RNAs, bound to lipoproteins or carried by exosomes. In renal cell carcinoma (RCC), a growing body of evidence suggests circulating non-coding RNAs (ncRNAs) such as miRNAs, lncRNAs, and YRNAs as promising and easily accessible blood-based biomarkers for the early diagnosis of RCC as well as for the prediction of prognosis and treatment response. In addition, circulating ncRNAs could also play a role in RCC pathogenesis and progression. This review gives an overview over the current study landscape of circulating ncRNAs and their involvement in RCC pathogenesis as well as their potential utility as future biomarkers in RCC diagnosis and treatment.


Sectors of liguleless-1 tissue interrupt an inductive signal during maize leaf development.
The ligule and auricles separate the blade and sheath of normal maize leaves and are absent in liguleless-1 (lg1) mutant leaves. We induced chromosome breakage using X-rays to create plants genetically mosaic for lg1. In genetically mosaic leaves, when an lg1 mutant sector interrupts the normal ligule, the ligule is often displaced basipetally on the marginal side of the sector. Therefore, lg1 mutant sectors not only fail to induce ligule and auricle, but are also disrupting some form of intercellular communication that is necessary for the normally coordinated development of the ligular region. Our data are consistent with a model in which an inductive signal originates near the midvein, cannot traverse the lg1 mutant sector, and reinitiates in the wild-type tissue across the sector toward the leaf margin. The lg1 gene product, therefore, appears to be required for the transmission of this signal and could be involved with reception.


Effect of TEPC-183 plasmacytoma on resistance of passively or actively immunized BALB/c mice to infection with Streptococcus pneumoniae.
This study focuses on the effect of TEPC-183 (tetramethylpentadecane)-induced plasmacytoma on resistance of mice to infection with Streptococcus pneumoniae type III. Vaccination of normal or of TEPC-183-bearing mice with either a polyvalent pneumococcal vaccine (Pnu-Imune) or purified polysaccharide type III protects both against challenge with live S. pneumoniae. However, a 38-fold increase in susceptibility of the tumor-bearing mice over that of controls was observed. Immunized splenectomized mice were ten times more susceptible to infection than were immunized normal mice. However, this increased susceptibility of splenectomized mice could be overcome by passively administered antibody. In passive protection experiments, antisera obtained from normal and TEPC-183-bearing or from cyclophosphamide-treated mice were almost equally protective. A 6-fold increase of antibody (133 ng of antibody), however, was required to protect TEPC-183-bearing mice against challenge with 500 organisms, as compared with the 22 ng of antibody required to protect normal mice, indicative of defective host defense mechanisms in addition to the lower production of antibody in the TEPC-183-bearing mice. In contrast, mice bearing an equal tumor load of Sarcoma 37 behaved similarly to normal mice, showing that the increased susceptibility to infection was due to TEPC-183, a particularly immunosuppressive tumor.


Magnetic resonance in isolated noncompaction of the ventricular myocardium.
Non-compaction of the ventricular myocardium (LCVM) is a rare disorder of myocardial morphogenesis usually diagnosed in paediatric age. The diagnosis was echocardiographically made on the basis of a reported spongeous/compacted ratio >2 in one or more segments of the left ventricle during the diastolic period. We aimed to test the diagnostic accuracy of cardiovascular magnetic resonance (CMR) imaging in distinguishing pathological left ventricular non-compaction. We collected a consecutive series of 8 patients, 5 males and 3 females, with a mean age of 14.9 years with non-compaction of left ventricular myocardium. All patients were admitted in our divisions of cardiology. In all cases the diagnosis was performed by echocardiography. The diagnosis was obtained when the spongeous/compacted ratio was >2 in one or more segments of left ventricle, evaluated in systolic and diastolic period. In the end we completed the diagnosis by scanning with a Signa HD 1.5 T (GE, Milwaukee, USA) the same 8 patients affected by non compaction of ventricular myocardium. In all patients cardiac-gated T1 and T2 black-blood FSE images in short axis and in four-chamber horizontal long axis were obtained. Breath hold cine MR sequences (FIESTA) were performed, covering the whole left ventricle in short-axis plane and in four-chamber view. A segmented inversion-recovery fast gradient echo sequence (IR-FGE) was performed in the short-axis plane of the LV and in four-chamber-view after Gadolinium injection in 8 patients affected by non compaction of left ventricle. At the end of examination the spongeous/compacted ratio >2 was calculated in all involved segments of the left ventricle in diastole. In all cases we demonstrated by echocardiography an involvement of the ventricular apex. In 3 cases the structural alterations involved also lateral wall of left ventricle. Magnetic resonance evaluation showed that involvement demonstrated by the echocardiogram was the same: ventricular apex involved in every patient, lateral wall in 3 and all segments in 2. However the spongeous/compacted ratio was >>2 in all patients, with a mean value of 3,1. Although our data refer to a small population of patients and need further confirmation, they suggest that it seems reasonable increase the cut-off for spongeous/compacted ratio from a value of 2 to 2.5 for non-compaction diagnosis when high-resolution magnetic resonance is used.


Quantitative sensory testing in measurement of neuropathic pain phenomena and other sensory abnormalities.
Neuropathic pain disorders are usually characterized by spontaneous ongoing or intermittent symptoms, stimulus-evoked positive sensory phenomena, and negative sensory phenomena. Spontaneous individual subject specific phenomena are identified in the neurologic history and are quantifiable by means of self-reported neuropathic pain symptoms tools such as scales, inventories, and questionnaires. Negative and positive sensory phenomena are assessed by the neurologic bedside examination and quantitative sensory testing (QST), which refers to psychophysical tests of sensory perception during the administration of stimuli with predetermined physical properties and following specific protocols. QST is able to capture and quantify stimulus-evoked negative and positive sensory phenomena, and as such should become standard if not a critical tool in neuropathic pain research and practice. Although the advent of anatomic and functional imaging modalities is revolutionizing our understanding of the mechanisms of neuropathic pain, only by anchoring such test results to individual subjects' own perceptions via QST can they provide meaningful information about neuropathic pain, which is based on perceptual experience. To yield useful results, QST requires a cooperative subject and carefully standardized methods, including standardization of the stimulus parameters as well as the testing environment, instructions, and evaluation methods. This manuscript provides a concise review of fundamental concepts necessary for understanding the role of QST in the process of eliciting information about sensory abnormalities associated with neuropathic pain and the place of that information in analysis of pain mechanisms. Together with the companion manuscript, this review provides definitions that should help further the use of QST as a diagnostic tool as well.


RECK-Mediated β1-Integrin Regulation by TGF-β1 Is Critical for Wound Contraction in Mice.
Fibroblasts are critical for wound contraction; a pivotal step in wound healing. They produce and modify the extracellular matrix (ECM) required for the proper tissue remodeling. Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is a key regulator of ECM homeostasis and turnover. However, its role in wound contraction is presently unknown. Here we describe that Transforming growth factor type β1 (TGF-β1), one of the main pro-fibrotic wound-healing promoting factors, decreases RECK expression in fibroblasts through the Smad and JNK dependent pathways. This TGF-β1 dependent downregulation of RECK occurs with the concomitant increase of β1-integrin, which is required for fibroblasts adhesion and wound contraction through the activation of focal adhesion kinase (FAK). Loss and gain RECK expression experiments performed in different types of fibroblasts indicate that RECK downregulation mediates TGF-β1 dependent β1-integrin expression. Also, reduced levels of RECK potentiate TGF-β1 effects over fibroblasts FAK-dependent contraction, without affecting its cognate signaling. The above results were confirmed on fibroblasts derived from the Reck+/- mice compared to wild type-derived fibroblasts. We observed that Reck+/- mice heal dermal wounds more efficiently than wild type mice. Our results reveal a critical role for RECK in skin wound contraction as a key mediator in the axis: TGF-β1-RECK-β1-integrin.


Effects of long duration centrifugation on head movements and a psychomotor task.
Previous investigations suggest strong similarities between aftereffects of an 1.5-hour 3 gx centrifuge run (Sickness Induced by Centrifugation; SIC) and the Space Adaptation Syndrome (SAS). Head movements proved to be especially nauseogenic in both cases. Until recently, during SIC experimentation, the performance of head movements was not adequately operationalized, which hampered a statistical evaluation. For this purpose, a test was designed by which head movements in four directions (left, right, up, and down) were provoked and registered, once before and once after a 1-h 3 g centrifuge run. Subjects had to execute these head movements in order to perform well on a psychomotor task. The results indicate that the test described is sensitive in discriminating between subjects who are seriously affected after a long duration centrifugation and those who are not. Because differences in performance were found only on those parts of the task in which head movements were involved, objective evidence is obtained in favour of a vestibular cause in the etiology of SIC.


Game Addiction Scale for Adolescents-Psychometric Analyses of Gaming Behavior, Gender Differences and ADHD.
Internet gaming disorder (IGD) was recently added in the Diagnostic and Statistical Manual of Mental Disorder as a "condition for further studies." There is no consensus regarding which rating scales should be used but many scholars suggest the GASA (Game Addiction Scale for Adolescents) and a ranking of the criteria, "the core approach" to avoid over-diagnosing of disordered gaming. Male gender and ADHD are commonly listed as risk factors for disordered gaming but little is known about sex differences in gaming and gender specific health correlates. The present study aims to evaluate the core approach and the specific indicators of gaming behavior in GASA from a multifactorial perspective and explore the gender differences in a clinical setting, focusing on ADHD. Children and adolescents aged 8-18 years (n = 144) from Child and adolescent psychiatry (CAP) in Skane were assessed with the GASA. Psychometric analyses including confirmatory factor analyses (CFA) and structural equation modeling (SEM) were used to identify well-defined constructs and gender differences. Refined factor scores for single constructs were the outcome of alignment, a procedure for assessing measurement equivalence across gender. New model-based gaming behavior variables were used for descriptive statistics and ANOVA testing of gender differences. The results confirm that the core approach two-factor model is valid for the CAP sample, as well as a theory based psycho-social model for gaming behavior with over consumption and negative social and emotional consequences. Our findings suggest that negative consequences of over consumption take a social direction for boys and an emotional direction for girls. Also, ADHD was significantly associated with over consumption of video games and the negative consequences thereof for girls. Guided by psychometric analyses, the GASA could be strengthened by advancing the questionnaire design and by adding complementary items in order to illuminate the complexity of gaming behavior. Our findings suggest that additional research on potential gender related discrepancies of disordered gaming is needed.


Energy and protein metabolism during recovery from malnutrition due to nonneoplastic gastrointestinal disease.
The magnitude of metabolic adaptation to malnutrition is still debated and few studies have investigated the phase of recovery from malnutrition. The aim of the present work was to determine whether refeeding was associated with adaptive changes in 1) energy expenditure, 2) maximal capacity for oxidizing lipids, and 3) whole-body protein turnover. Eleven malnourished patients with nonneoplastic gastrointestinal diseases were studied by using indirect calorimetry and L-[1-13C]leucine infusion while being infused with lipid-rich total parenteral nutrition (TPN). The same study was performed before initiation of TPN and after a mean gain of 6.5 kg body wt. In absolute values, resting energy expenditure (REE) increased after refeeding (4.05 +/- 0.85 compared with 4.60 +/- 1.05 MJ/d). Change in REE adjusted for fat-free mass (FFM) correlated significantly with change in body weight (r = 0.850, P = 0.01) and change in body fat (r = 0.798, P = 0.01) but not with change in FFM (r = -0.06, NS). Lipid oxidation decreased significantly after body weight gain (0.93 +/- 0.28 compared with 0.50 +/- 0.37 mg.kg-1.min-1). When expressed per kg FFM, protein turnover and breakdown increased significantly during body weight gain. Moreover, the change in protein turnover correlated with the rate of change in FFM, suggesting that FFM accretion requires increased interorgan exchange of amino acids. Our data suggest that in patients similar to those studied here and during recovery from malnutrition, the degree of change in adjusted REE during refeeding is correlated with change in fat mass and not with change in FFM, and that there is a decrease in oxidation of infused lipids. These mechanisms may contribute to body fat repletion and regulation during weight gain.


Management of different types of gastric varices with band ligation: a 3-year experience.
Gastric varices (GVs) occur with an incidence of 20% in patients with portal hypertension. The aim of this study was to evaluate the efficacy of endoscopic band ligation (BL) as an option in the management of small-to-moderate nonbleeding GVs in cirrhotic patients. A total of 50 patients (GOV2; n=6, IGV1; n=34, IGV2; n=10) with nonbleeding small-to-moderate-sized GVs without local risk signs of bleeding, such as large size, red-colored elevated areas or red wales, and systemic factors of bleeding risk such as an international normalized ratio of at least 2 and a platelet count of 80 000/µl or less were subjected to endoscopic BL. The patients were followed up every 2 weeks for 1 month and then every 1.5 months for 6 months. The primary outcome was GV eradication, detection of complications such as postprocedural bleeding ulceration and mortality. The mean number of BL sessions was 2.2±0.8; post-BL ulceration occurred in two (4%) patients (n=2 in IGV1, P=0.61), bleeding occurred in one (2%) patient (n=1 in IGV1, P=0.79), and epigastric pain occurred in six (12%, n=4 in GOV2, n=2 in IGV1) patients. There was no mortality reported among patients treated with BL. Endoscopic BL resulted in better outcome and a lower incidence of complications when used to treat small-to-medium-sized nonbleeding GVs. Further, early eradication can save effort and cost, thus avoiding the future risk of treatment of large or risky GVs with sclerotherapy.


Treatment decision-making: student choices of autonomy versus paternalism.
The purpose of this study was to evaluate dental students' use of the Hippocratic Principle versus a patient-autonomy approach to ethical decision-making. A questionnaire composed of three independent case situations was distributed to 113 junior dental students. The survey instrument allowed subjects to prioritize their choices of action from a series of alternative responses and to identify factors that influence their choice of action. A majority of responses appear to reflect a decision-making process based on patient-autonomy principles. Patient rights are important for this population, and their choice of action and the factors influencing these choices consistently emphasized autonomy.


Antibody response to the circumsporozoite protein of Plasmodium vivax in naturally infected humans.
The circumsporozoite (CS) protein of Plasmodium vivax consists of a central repeat region flanked by highly conserved non-repeat regions. Serum samples from 33 individuals with naturally acquired infections of P. vivax were tested for antibodies to four antigens representing the vivax CS protein. Three recombinant proteins containing different overlapping sequences in the non-repeat regions and either the entire central repeat region (vivax-1 and vivax-2) or two of the repeat sequences (vivax-3) were used as antigens in an enzyme-linked immunosorbent assay (ELISA). Antibodies to two other proteins, one (NS1(81)V20) containing the entire predominant repeat region (GDRAA/DGQPA) and the other (Pvk247) containing the variant repeat sequence (ANGAGNQPG) that was recently reported from Thailand were also measured by ELISA. Immunoglobulin G antibodies to the antigen representing the predominant repeat were present in 15% of the patients on the first day of treatment (day 0) and in 24% of the patients two weeks later (post-treatment). Six and 12% of the patients had IgG antibodies to the antigen containing the variant repeat on day 0 and post-treatment, respectively. A larger proportion of the sera had antibodies to the three antigens containing the non-repeat sequences; on the first day of treatment and two weeks later, 79 and 97% of the patients, respectively, had antibodies to vivax-1, vivax-2, and vivax-3. In this sample of Peruvians naturally infected with P. vivax, the most prevalent antibody responses were targeted to epitopes in the non-repeat region of the CS protein rather than to epitopes in the repeat region.(ABSTRACT TRUNCATED AT 250 WORDS)


Allergen-specific IgE in the tear fluid of Chinese patients with common allergic conjunctivitis in autumn and winter.
In this study, we determined the positive rates of allergen-specific immunoglobulin E (IgE) in the tear fluid of Chinese patients with common allergic conjunctivitis (AC) in autumn and winter, compared systemic and ocular allergen tests, and explored the correlation between the numbers and categories of allergens and clinical AC features. This cross-sectional study recruited 44 patients with AC (86 eyes). Specific IgEs for allergens common in China (house dust mite, cat/dog dander, mugwort/ragweed pollen, cottonwood/willow/elm pollen, milk, egg whites, soybeans) were measured in collected tears using kits for allergen-specific IgE antibodies. AC signs and symptoms were graded according to severity. Specific IgE in tears was positive in 87.2% of eyes. House dust mite was the most common allergen (86.0%), followed by cat (24.4%) and dog (7.0%) dander; tree and grass pollen accounted for only 4.7% and 2.3%, respectively. Food allergens were not detected. The positive rates of the systemic allergen tests were lower than in tear fluid tests in both eyes, especially for house dust mites (P = 0.000). In patients with more allergens, itching was more severe (P = 0.035), while conjunctival hyperemia was milder (P = 0.002). In autumn and winter, the most common AC allergen in Chinese patients was house dust mites. Compared with systemic allergen tests, measuring specific IgE in tears may be a non-invasive method to diagnose and evaluate AC severity, which may be more suitable to reflect the local conditions of ocular surface inflammation due to its high positive rate and convenience.


Mesenchymal Stem Cell Exosomes Induce Proliferation and Migration of Normal and Chronic Wound Fibroblasts, and Enhance Angiogenesis In Vitro.
Although chronic wounds are common and continue to be a major cause of morbidity and mortality, treatments for these conditions are lacking and often ineffective. A large body of evidence exists demonstrating the therapeutic potential of mesenchymal stem cells (MSCs) for repair and regeneration of damaged tissue, including acceleration of cutaneous wound healing. However, the exact mechanisms of wound healing mediated by MSCs are unclear. In this study, we examined the role of MSC exosomes in wound healing. We found that MSC exosomes ranged from 30 to 100-nm in diameter and internalization of MSC exosomes resulted in a dose-dependent enhancement of proliferation and migration of fibroblasts derived from normal donors and chronic wound patients. Uptake of MSC exosomes by human umbilical vein endothelial cells also resulted in dose-dependent increases of tube formation by endothelial cells. MSC exosomes were found to activate several signaling pathways important in wound healing (Akt, ERK, and STAT3) and induce the expression of a number of growth factors [hepatocyte growth factor (HGF), insulin-like growth factor-1 (IGF1), nerve growth factor (NGF), and stromal-derived growth factor-1 (SDF1)]. These findings represent a promising opportunity to gain insight into how MSCs may mediate wound healing.


Absorption and utilization of polyglutamyl forms of folate in man.
Some three-quarters of folate compounds in a normal mixed diet have a chain of seven glutamic acid residues (polyglutamates). The extent to which these forms of folate are absorbed and utilized by man is of considerable nutritional importance. These studies indicate that the polyglutamate forms were absorbed and utilized to about one-third of the extent of simpler (monoglutamate) forms, as judged by the serum folate levels after oral equimolar doses, by the amount incorporated into red cells in long-term studies, by the amount excreted into the urine, and by their capacity to initiate haematological responses in patients with folate-deficient megaloblastic anaemias.


Promoting recovery in an evolving policy context: what do we know and what do we need to know about recovery support services?
As both a concept and a movement, "recovery" is increasingly guiding substance use disorder (SUD) services and policy. One sign of this change is the emergence of recovery support services that attempt to help addicted individuals using a comprehensive continuing care model. This paper reviews the policy environment surrounding recovery support services, the needs to which they should respond, and the status of current recovery support models. We conclude that recovery support services (RSS) should be further assessed for effectiveness and cost-effectiveness, that greater efforts must be made to develop the RSS delivery workforce, and that RSS should capitalize on ongoing efforts to create a comprehensive, integrated and patient-centered health care system. As the SUD treatment system undergoes its most important transformation in at least 40years, recovery research and the lived experience of recovery from addiction should be central to reform.


Background fluorescence estimation and vesicle segmentation in live cell imaging with conditional random fields.
Image analysis applied to fluorescence live cell microscopy has become a key tool in molecular biology since it enables to characterize biological processes in space and time at the subcellular level. In fluorescence microscopy imaging, the moving tagged structures of interest, such as vesicles, appear as bright spots over a static or nonstatic background. In this paper, we consider the problem of vesicle segmentation and time-varying background estimation at the cellular scale. The main idea is to formulate the joint segmentation-estimation problem in the general conditional random field framework. Furthermore, segmentation of vesicles and background estimation are alternatively performed by energy minimization using a min cut-max flow algorithm. The proposed approach relies on a detection measure computed from intensity contrasts between neighboring blocks in fluorescence microscopy images. This approach permits analysis of either 2D + time or 3D + time data. We demonstrate the performance of the so-called C-CRAFT through an experimental comparison with the state-of-the-art methods in fluorescence video-microscopy. We also use this method to characterize the spatial and temporal distribution of Rab6 transport carriers at the cell periphery for two different specific adhesion geometries.


A systematic review of the evidence supporting post-operative antithrombotic use following cardiopulmonary bypass in children with CHD.
To determine the optimal antithrombotic agent choice, timing of initiation, dosing and duration of therapy for paediatric patients undergoing cardiac surgery with cardiopulmonary bypass. We used PubMed and EMBASE to systematically review the existing literature of clinical trials involving antithrombotics following cardiac surgery from 2000 to 2020 in children 0-18 years. Studies were assessed by two reviewers to ensure they met eligibility criteria. We identified 10 studies in 1929 children across three medications classes: vitamin K antagonists, cyclooxygenase inhibitors and indirect thrombin inhibitors. Four studies were retrospective, five were prospective observational cohorts (one of which used historical controls) and one was a prospective, randomised, placebo-controlled, double-blind trial. All included were single-centre studies. Eight studies used surrogate biomarkers and two used clinical endpoints as the primary endpoint. There was substantive variability in response to antithrombotics in the immediate post-operative period. Studies of warfarin and aspirin showed that laboratory monitoring levels were frequently out of therapeutic range (variably defined), and findings were mixed on the association of these derangements with bleeding or thrombotic events. Heparin was found to be safe at low doses, but breakthrough thromboembolic events were common. There are few paediatric prospective randomised clinical trials evaluating antithrombotic therapeutics post-cardiac surgery; most studies have been observational and seldom employed clinical endpoints. Standardised, validated endpoints and pragmatic trial designs may allow investigators to determine the optimal drug, timing of initiation, dosing and duration to improve outcomes by limiting post-operative morbidity and mortality related to bleeding or thrombotic events.


Using convolutional neural networks to estimate time-of-flight from PET detector waveforms.
Although there have been impressive strides in detector development for time-of-flight positron emission tomography, most detectors still make use of simple signal processing methods to extract the time-of-flight information from the detector signals. In most cases, the timing pick-off for each waveform is computed using leading edge discrimination or constant fraction discrimination, as these were historically easily implemented with analog pulse processing electronics. However, now with the availability of fast waveform digitizers, there is opportunity to make use of more of the timing information contained in the coincident detector waveforms with advanced signal processing techniques. Here we describe the application of deep convolutional neural networks (CNNs), a type of machine learning, to estimate time-of-flight directly from the pair of digitized detector waveforms for a coincident event. One of the key features of this approach is the simplicity in obtaining ground-truth-labeled data needed to train the CNN: the true time-of-flight is determined from the difference in path length between the positron emission and each of the coincident detectors, which can be easily controlled experimentally. The experimental setup used here made use of two photomultiplier tube-based scintillation detectors, and a point source, stepped in 5 mm increments over a 15 cm range between the two detectors. The detector waveforms were digitized at 10 GS s-1 using a bench-top oscilloscope. The results shown here demonstrate that CNN-based time-of-flight estimation improves timing resolution by 20% compared to leading edge discrimination (231 ps versus 185 ps), and 23% compared to constant fraction discrimination (242 ps versus 185 ps). By comparing several different CNN architectures, we also showed that CNN depth (number of convolutional and fully connected layers) had the largest impact on timing resolution, while the exact network parameters, such as convolutional filter size and number of feature maps, had only a minor influence.


Inhibition of initiation of DNA synthesis by aminoglycoside antibiotics.
In a dnaCts mutant of E. coli, the reinitiation of DNA synthesis, which occurred by the shift of the culture from a restrictive temperature to a permissive temperature, was markedly prevented by habakacin, dibekacin, kanamycin, and gentamicin. On the contrary, chloramphenicol did not inhibit the reinitiation synthesis for 30 min. In a parallel experiment, leucine uptake into protein was profoundly blocked by chloramphenicol, but only slightly by habekacin. Habekacin did not significantly affect DNA elongation of the cells at a restrictive temperature. We propose that inhibition of initiation of replication by aminoglycoside antibiotics is related to their lethality.


Identification and functional characterization of FGLamide-related allatostatin receptor in Rhodnius prolixus.
FGLamide-related ASTs (FGLa/ASTs) are a family of brain/gut peptides with numerous physiological roles, including inhibition of juvenile hormone (JH) biosynthesis by the corpora allata and inhibition of visceral muscle contraction. FGLa/ASTs mediate their effects by binding to a rhodopsin-like G-protein coupled receptor that is evolutionarily related to the vertebrate galanin receptor. Here we determine the cDNA sequence encoding FGLa/AST receptor (FGLa/AST-R) from the Chagas disease vector, Rhodnius prolixus (Rhopr-FGLa/AST-R), determine its spatial expression pattern using quantitative PCR and functionally characterize the receptor using a heterologous assay. Our expression analysis indicates that Rhopr-FGLa/AST-R is highly expressed in the central nervous system. The receptor is also expressed in various peripheral tissues including the dorsal vessel, midgut, hindgut and reproductive tissues of both males and females, suggesting a role in processes associated with feeding and reproduction. The possible involvement of Rhopr-FGLa/ASTs in the inhibition of JH biosynthesis is also implicated due to presence of the receptor transcript in the R. prolixus corpora cardiaca/corpora allata complex. The functional assay showed that various Rhopr-FGLa/ASTs activate the receptor, with EC50 values for the response in the nanomolar range. Moreover, Rhopr-FGLa/AST-R can couple with Gq alpha subunits and cause an increase in intracellular calcium concentration. Lastly, we tested various FGLa/AST analogs in our heterologous assay. These compounds also activated the receptor and thus have the potential to serve as insect growth regulators and aid in pest control.


X-ray Absorption Spectroscopic Investigation of Sulfur Sites in Coal: Organic Sulfur Identification.
High-resolution x-ray absorption spectroscopy was used to probe the chemical and structural environments of sulfur in coal. Measurement of the sulfur Kedge spectra down to 2472.0 electron volts under nonvacuum conditions was made possible in an all-helium path, and a Stern-Heald type ion chamber was used for fluorescence detection. For a number of selected sulfur-containing minerals and organic model compounds, results show that near-edge spectral features are diagnostic for sulfur in specific organic moieties such as thiols, disulfides, and various heterocyclics, as well as in mineral sulfide and sulfate phases. The spectrum of a model system containing 35 percent iron pyrite and 65 percent benzothiophene was found to match the observed spectral features of a bituminous coal from the eastern United States.


Crystal structure of troponin C in complex with troponin I fragment at 2.3-A resolution.
Troponin (Tn), the complex of three subunits (TnC, TnI, and TnT), plays a key role in Ca2+-dependent regulation of muscle contraction. To elucidate the interactions between the Tn subunits and the conformation of TnC in the Tn complex, we have determined the crystal structure of TnC (two Ca2+ bound state) in complex with the N-terminal fragment of TnI (TnI1-47). The structure was solved by the single isomorphous replacement method in combination with multiple wavelength anomalous dispersion data. The refinement converged to a crystallographic R factor of 22.2% (Rfree = 32.6%). The central, connecting alpha-helix observed in the structure of uncomplexed TnC (TnCfree) is unwound at the center (residues Ala-87, Lys-88, Gly-89, Lys-90, and Ser-91) and bent by 90 degrees. As a result, TnC in the complex has a compact globular shape with direct interactions between the N- and C-terminal lobes, in contrast to the elongated dumb-bell shaped molecule of uncomplexed TnC. The 31-residue long TnI1-47 alpha-helix stretches on the surface of TnC and stabilizes its compact conformation by multiple contacts with both TnC lobes. The amphiphilic C-end of the TnI1-47 alpha-helix is bound in the hydrophobic pocket of the TnC C-lobe through 38 van der Waals interactions. The results indicate the major difference between Ca2+ receptors integrated with the other proteins (TnC in Tn) and isolated in the cytosol (calmodulin). The TnC/TnI1-47 structure implies a mechanism of how Tn regulates the muscle contraction and suggests a unique alpha-helical regulatory TnI segment, which binds to the N-lobe of TnC in its Ca2+ bound conformation.


Use of periosteal membrane as a barrier membrane for the treatment of buccal Grade II furcation defects in lower molars: a novel technique.
To use the periosteum as a barrier in treatment of buccal Grade II furcation defects of lower molars. This technique was performed on 12 patients with bilateral buccal Grade II furcation defects of lower molars. On a random basis, one furcation defect of each pair was selected for the control group and other for the experimental group. Debridement was done in the defect area in both groups. In the control group, after debridement, mucoperiosteal flap was sutured back. In the experimental group, after reflection of the mucoperiosteal flap, a portion of the periosteum along with a layer of connective tissue (periosteal membrane) was incised and mobilized in the defect area for defect coverage as a barrier, and then the periosteal membrane and mucoperiosteal flap were fixed with suture, respectively. Horizontal dimension of the furcation defect was the primary outcome measure. Gingival index, probing attachment level (PAL), and vertical dimension of furcation defect were the secondary outcome measures. Clinical parameters were registered at baseline and at 6 months. Every clinical parameter was improved by surgery. Significant gain in PAL as well as horizontal and vertical dimensions of the furcation defects was found. This periosteum displacement technique is effective for the treatment of buccal Grade II furcation defects of lower molars.


STAMP: components of observable behaviour that indicate potential for patient violence in emergency departments.
This paper is the report of a study to explicate the components of observable behaviour that indicate a potential for violence in patients, their family and friends when presenting at an emergency department. Violence towards nurses is a contemporary, multifaceted problem for the healthcare workforce globally. International literature identifies emergency departments as having high levels of violence. A mixed method case study design was adopted, and data were collected by means of 290 hours of participant observation, 16 semi-structured interviews and 13 informal field interviews over a 5-month period in 2005. Thematic analysis of textual data was undertaken using NVivo2. Frequency counts were developed from the numerical data. Five distinctive elements of observable behaviour indicating potential for violence in patients, their families and friends were identified. These elements can be conceptualized as a potential nursing violence assessment framework and described through the acronym STAMP: Staring and eye contact, Tone and volume of voice, Anxiety, Mumbling and Pacing. Staring and eye contact, Tone and volume of voice, Anxiety, Mumbling and Pacing provides a useful, practical nursing violence assessment framework to assist nurses to quickly identify patients, families and friends who have a potential for violence.


Is a genome a codeword of an error-correcting code?
Since a genome is a discrete sequence, the elements of which belong to a set of four letters, the question as to whether or not there is an error-correcting code underlying DNA sequences is unavoidable. The most common approach to answering this question is to propose a methodology to verify the existence of such a code. However, none of the methodologies proposed so far, although quite clever, has achieved that goal. In a recent work, we showed that DNA sequences can be identified as codewords in a class of cyclic error-correcting codes known as Hamming codes. In this paper, we show that a complete intron-exon gene, and even a plasmid genome, can be identified as a Hamming code codeword as well. Although this does not constitute a definitive proof that there is an error-correcting code underlying DNA sequences, it is the first evidence in this direction.


Physiological identification of morphologically distinct afferent classes innervating the cristae ampullares of the squirrel monkey.
1. Semicircular-canal afferents in the squirrel monkey were characterized by their resting discharge, discharge regularity, sensitivity to galvanic currents delivered to the ear (beta *), the gain (g2Hz), and phase lead (phi 2Hz) of their response to 2-Hz sinusoidal head rotations, and their antidromic conduction velocity. Discharge regularity was measured by a normalized coefficient of variation (CV*); the higher the CV*, the more irregular the discharge. g2Hz and phi 2Hz were expressed relative to angular head velocity. 2. These physiological measures were used in an attempt to discern the discharge properties of the three morphological classes of afferents innervating the crista. Presumed bouton (B) fibers were identified as slowly conducting afferents. Presumed calyx (C) fibers were recognized by their irregular discharge and low rotational gains. The remaining fibers were considered to be dimorphic (D) units. Single letters (B, C, and D) are used to emphasize that the classification is based on circumstantial evidence and may be wrong for individual fibers. Of the 125 identified fibers, 13 (10%) were B units, 36 (29%) were C units, and 76 (61%) were D units. 3. B units were regularly discharging D units ranged from regularly to irregularly discharging. C units were the most irregularly discharging afferents encountered. The mean resting discharge for the entire sample was 74 spikes/s. Resting rates were similar for regularly discharging B and D units and higher than those for irregularly discharging C and D units. 4. Except for their lower conduction velocities, the discharge properties of B units are indistinguishable from those of regularly discharging D units. Many of the discharge properties of B and D units vary with discharge regularity. There is a strong, positive relation when beta *, g2Hz, or phi 2Hz is plotted against CV*. For beta * or phi 2Hz, C units conform to the relation for B and D units. In contrast, values of g2Hz for C units are three to four times lower than predicted from the relation for the other two classes. 5. Internal (axon) diameters (dp) of peripheral vestibular-nerve fibers were estimated from central antidromic conduction velocities. Thick fibers (dp > or = 49 microns) were irregularly discharging, mostly C units. Medium-sized fibers (dp = 1.5-4 microns) included regular, intermediate, and irregular D units, as well as C units. Thin fibers (dp < or = 1.5 microns) were defined as B units.(ABSTRACT TRUNCATED AT 400 WORDS)


Different populations of DNA polymerase alpha in HeLa cells.
Three different populations of HeLa DNA polymerase alpha have been distinguished using a novel preparation of chromatin isolated using an isotonic salt concentration, which contains intact DNA. One synthesizes DNA in vitro at 85% of the rate in vivo, is found only in S-phase nuclei tightly associated with the nucleoskeleton and requires unbroken DNA in the form of chromatin as a template: we assume this is the authentic S-phase activity. On incubation at 37 degrees C, this activity dissociates from the nucleoskeleton to give a soluble activity that prefers broken templates. This soluble activity is in turn heterogeneous, containing active complexes of about 0 X 75 X 10(6) and 3 X 10(6) Mr. The third activity is also soluble and released by lysing cells at any stage of the cell cycle. It, too, prefers broken templates. The authentic activity is obscured by the soluble ones if broken templates are provided.


Tear osmolarity in ocular graft-versus-host disease.
The aim of this study was to evaluate tear osmolarity in patients with chronic graft-versus-host disease (cGVHD) with ocular involvement. In this observational cross-sectional study of 56 patients with ocular cGVHD referred to the tertiary-care Ocular Immunology and Uveitis Service at the San Raffaele Scientific Institute, Milan, from May 2010 to November 2013, we evaluated the following clinical parameters: Ocular Surface Disease Index (OSDI) symptoms questionnaire, tear osmolarity, Schirmer test, tear film break-up time (TBUT), corneal and conjunctival staining. All patients developed systemic GVHD after undergoing allogeneic hematologic stem cell transplantation. Mean osmolarity was 314.0 ± 22.1 mOsm/L, mean OSDI score was 26.4 ± 21.2, mean TBUT was 6.50 ± 4.75 seconds, and mean Schirmer test value was 3.8 ± 3.3 mm. Tear osmolarity significantly inversely correlated with TBUT (r = 0.681; P < 0.001). Statistically significant inverse correlation was present with the Schirmer test (r = 0.203; P < 0.001), and positive correlation with the OSDI score (r = 0.188; P < 0.001), but both with low correlation strength. Osmolarity was statistically different in the subgroups according to the Oxford corneal staining scale (P = 0.0006) and to the van Bijsterveld conjunctival staining score (P = 0.006). Tear osmolarity increased in patients with ocular cGVHD, significantly correlated with TBUT and, to a lesser extent, with the Schirmer test value and OSDI. These results emphasize the role of aqueous-deficient and evaporative dry eye disease in patients with cGVHD after undergoing allogeneic hematologic stem cell transplantation. Tear osmolarity may be considered a useful test in diagnostic assessment of dry eye disease associated with cGVHD.


Organ trafficking and transplant tourism: the role of global professional ethical standards-the 2008 Declaration of Istanbul.
By 2005, human organ trafficking, commercialization, and transplant tourism had become a prominent and pervasive influence on transplantation therapy. The most common source of organs was impoverished people in India, Pakistan, Egypt, and the Philippines, deceased organ donors in Colombia, and executed prisoners in China. In response, in May 2008, The Transplantation Society and the International Society of Nephrology developed the Declaration of Istanbul on Organ Trafficking and Transplant Tourism consisting of a preamble, a set of principles, and a series of proposals. Promulgation of the Declaration of Istanbul and the formation of the Declaration of Istanbul Custodian Group to promote and uphold its principles have demonstrated that concerted, strategic, collaborative, and persistent actions by professionals can deliver tangible changes. Over the past 5 years, the Declaration of Istanbul Custodian Group organized and encouraged cooperation among professional bodies and relevant international, regional, and national governmental organizations, which has produced significant progress in combating organ trafficking and transplant tourism around the world. At a fifth anniversary meeting in Qatar in April 2013, the DICG took note of this progress and set forth in a Communiqué a number of specific activities and resolved to further engage groups from many sectors in working toward the Declaration's objectives.


The effect of progestins on prolactin receptor gene transcription in human breast cancer cells.
The sex steroid hormone progesterone modulates the developmental and lactogenic activity of prolactin in the mammary gland. Regulation of the level of prolactin receptor (PRLR) provides one possible mechanism by which this may occur, prompting this investigation of the molecular mechanisms involved in progestin regulation of prolactin receptor levels. Treatment of T-47D and MCF-7 human breast cancer cells with 10 nM of the synthetic progestin ORG 2058 for 24 hr resulted in an increase in all four PRLR mRNA transcripts detected. The effect of ORG 2058 was shown in T-47D cells to be time- and concentration-dependent and resulted in an approximate two-fold increase in PRLR mRNA after 24 hr of treatment with 10 nM or 100 nM ORG 2058. Nuclear run-on assays indicated that ORG 2058 increased the rate of T-47D PRLR gene transcription at all times between 1 hr and 28 hr of treatment. The protein synthesis inhibitors cycloheximide and puromycin abrogated the induction of PRLR gene transcription at 1 hr and 2 hr, which demonstrated that on-going protein synthesis was required for the ORG 2058 effect and suggested that progestins may exert some transcriptional effects via the induction of an intermediary protein. These experiments demonstrated that progestin induced a transcriptionally based increase in PRLR gene expression and provided a mechanism by which progesterone may modulate the mitogenic activity of prolactin during mammary gland development.


Identifying rice stress on a regional scale from multi-temporal satellite images using a Bayesian method.
Crops are prone to various types of stress, such as caused by heavy metals, drought and pest/disease, during their life cycle. Heavy metal stress in crops poses a serious threat to crop quality and human health. However, differentiating between heavy metal and non-heavy metal stress presents a great challenge, since responses to environmental stress in crops are complex and uncertain, with different stressors possibly triggering similar canopy reflectance responses. This study aims to infer the occurrence probability of heavy metal stress (i.e., Cd stress) on a regional scale by integrating satellite-derived vegetation index and spatio-temporal characteristics of different stressors with a Bayesian method. The study area is located in the Hunan Province, China. Seven scenes of Sentinel-2 satellite images from 2016 to 2017 were collected, as well as Cd concentrations in the soil. First, the probability of rice being stressed was screened using the normalized difference red-edge index (NDRE) at all the growth stages of rice. Further, the stressed rice was used as input, along with the coefficients of spatio-temporal variation (CSTV) derived from NDRE, for a Bayesian method to infer rice exposed to Cd pollution. The results demonstrated that NDRE was a sensitive indicator for assessing stress levels in rice crops. The CSTV with a threshold of 2.7 successfully detected rice under Cd as well as abrupt stress on a regional scale. A high map accuracy for Cd induced stress in rice was achieved with an accuracy of 81.57%. This study suggests that vegetation index obtained from satellite images can assist in capturing crop stress, and that the used Bayesian method can be very useful for distinguishing a specific stressor in crops by incorporating temporal-spatial characteristic of different stressors in crops into satellite-derived vegetation index.


[Clinical significance of the relation of primary or secondary hepatic ducts and their surrounding vessels].
It is necessary that surgeons, who perform the operation on the primary and secondary hepatic ducts, should be familiar with the topography of these ducts and their surrounding vessels. A total of 22 "frame-specimens" of cadaveric liver (FSL) were built by the authors, from which the length of left and right hepatic ducts (LHD, RHD), right anterior lobe duct (RAD), the distance from the confluence of RAD and right posterior lobe duct (CAP) to the visceral surface of the liver, and the projection point of CAP on the diaphragmatic surface of Liver were all directly measured. The relationship between these proximal hepatic ducts and their surrounding vessels was also observed. Based on this study the authors proposed a new approach to incision of the whole length of LHD, RHD and RAD. The stenotic opening of right posterior lobe duct (RPD) can be exposed through the lumen of RHD. In 18.2% of 22 FSLs, the right posterior lobe artery was found in the lateral angle formed by RAD and RPD. To prevent the damage of this artery, which may cause intrahepatic hematoma, and its rupture into biliary tract, the cholongiotomy incision at the stenotic opening of RPD should be made within the lateral-superior quadrant of it close to the horizontal level.


Macaques immunized with HLA-DR are protected from challenge with simian immunodeficiency virus.
Macaques immunized with uninfected human cells have been shown to be protected from challenge with simian immunodeficiency virus (SIV) propagated in human cells. To identify the potential antigens involved in this protection, macaques were immunized with uninfected human cells, sucrose density gradient-purified culture fluid from uninfected human cells (mock virus), beta-2 microglobulin (beta 2M), immunoaffinity-purified HLA class I and class II proteins from these human cells, and adjuvant. Although all macaques immunized with beta 2M and HLA class I developed high antibody titers to beta 2M, these animals were not protected from a subsequent challenge with infectious SIV grown in human cells. In contrast, the macaques immunized with class II protein (HLA-DR) and mock virus developed antibodies to class II protein and were protected from the intravenous infectious virus challenge. The class II protein- and mock virus-immunized animals which were protected from challenge were given boosters of the appropriate antigen and challenged with the same SIV propagated in macaque cells. All animals became infected, indicating that the protection seen with human class II protein did not extend to protection from infection with SIV containing macaque class II proteins. Since the virus released from SIV-infected macaque cells would contain macaque class II proteins, our results suggest that the initial SIV infected was completely prevented. In addition, the lack of protection from challenge with SIV propagated in macaque cells provided strong evidence that the protection was due to an immune response to the cellular proteins and not to epitopes cross-reactive between class II proteins and the viral proteins, since the identical virus proteins were present in both challenge stocks. These results are the first demonstration that immunization with a purified cellular protein can protect from virus infection.


Peritransplant VLA-4 blockade inhibits endogenous memory CD8 T cell infiltration into high-risk cardiac allografts and CTLA-4Ig resistant rejection.
Recipient endogenous memory CD8 T cells expressing reactivity to donor class I MHC infiltrate MHC-mismatched cardiac allografts within 24 hours after reperfusion and express effector functions mediating graft injury. The current study tested the efficacy of Very Late Antigen-4 (VLA-4) blockade to inhibit endogenous memory CD8 T cell infiltration into cardiac allografts and attenuate early posttransplant inflammation. Peritransplant anti-VLA-4 mAb given to C57BL6 (H-2b ) recipients of AJ (H-2a ) heart allografts completely inhibited endogenous memory CD4 and CD8 T cell infiltration with significant decrease in macrophage, but not neutrophil, infiltration into allografts subjected to either minimal or prolonged cold ischemic storage (CIS) prior to transplant, reduced intra-allograft IFN-γ-induced gene expression and prolonged survival of allografts subjected to prolonged CIS in CTLA-4Ig treated recipients. Anti-VLA-4 mAb also inhibited priming of donor-specific T cells producing IFN-γ until at least day 7 posttransplant. Peritransplant anti-VLA plus anti-CD154 mAb treatment similarly prolonged survival of allografts subjected to minimal or increased CIS prior to transplant. Overall, these data indicate that peritransplant anti-VLA-4 mAb inhibits early infiltration memory CD8 T cell infiltration into allografts with a marked reduction in early graft inflammation suggesting an effective strategy to attenuate negative effects of heterologous alloimmunity in recipients of higher risk grafts.


Integration of thought and action continued: Scale errors and categorization in toddlers.
To further explore the effect of weighted arms on toddler's performance in problem solving (Arterberry et al., 2018, Infancy, 23(2), 173), the present study explored scale errors and categorization, two instances where infants appear to show more advanced knowledge than toddlers. Experiment 1 (N = 67) used a novel task for inducing scale errors among 24- to 29-month-olds. Results replicated rates of scale errors found in previous research that used different tasks. Experiment 2 used sequential touching (N = 31) and sorting measures (N = 23) to test categorization in 24-month-old children. In both measures, children showed categorization at the basic level when there was high contrast between the exemplars, but not at a basic level with low contrast or a subordinate level. In Experiments 1 and 2, half the participants were tested while wearing weighted wristbands. Weighting the arms did not affect error rates, in contrast to previous research showing that weights improved performance in search tasks. The findings are discussed in light of children's difficulty in integrating perception, cognition, and action.


The psychosocial impact of oral conditions during transition to secondary education.
Transition to secondary education is a significant life event. Little is known about the impact of oro-facial conditions during this time and how concerns may contribute as a risk factor to negative adaptation. The aim of the study was to explore experiences of young people with oro-facial conditions as they undergo the transition to secondary education. Qualitative interview and diary study. Participants were children aged 11-12 years with a range of clinical conditions who attended a dental hospital. Participants completed a two-week diary during the transition and were interviewed about the diary and their experiences. The interviews were audio-taped and transcribed verbatim. Seventeen participants returned the diary and were interviewed; they described both changes in school environment and social interactions. A key finding was the concerns about aspects of themselves that children developed during this time. For some young people these concerns were about their oro-facial condition. No links between gender, severity of condition and experiences of school were apparent. Transition to secondary education affected young people to varying degrees. Timely treatment for those concerned about the condition of their teeth may improve the likelihood of positive adaptation.


A neural signature of phonological access: distinguishing the effects of word frequency from familiarity and length in overt picture naming.
Cognitive models of word production correlate the word frequency effect (i.e., the fact that words which appear with less frequency take longer to produce) with an increased processing cost to activate the whole-word (lexical) phonological representation. We performed functional magnetic resonance imaging (fMRI) while subjects produced overt naming responses to photographs of animals and manipulable objects that had high name agreement but were of varying frequency, with the purpose of identifying neural structures participating specifically in activating whole-word phonological representations, as opposed to activating lexical semantic representations or articulatory-motor routines. Blood oxygen level-dependent responses were analyzed using a parametric approach based on the frequency with which each word produced appears in the language. Parallel analyses were performed for concept familiarity and word length, which provided indices of semantic and articulatory loads. These analyses permitted us to identify regions related to word frequency alone, and therefore, likely to be related specifically to activation of phonological word forms. We hypothesized that the increased processing cost of producing lower-frequency words would correlate with activation of the left posterior inferotemporal (IT) cortex, the left posterior superior temporal gyrus (pSTG), and the left inferior frontal gyrus (IFG). Scan-time response latencies demonstrated the expected word frequency effect. Analysis of the fMRI data revealed that activity in the pSTG was modulated by frequency but not word length or concept familiarity. In contrast, parts of IT and IFG demonstrated conjoint frequency and familiarity effects, and parts of both primary motor regions demonstrated conjoint effects of frequency and word length. The results are consistent with a model of word production in which lexical-semantic and lexical-phonological information are accessed by overlapping neural systems within posterior and anterior language-related cortices, with pSTG specifically involved in accessing lexical phonology.