Integrative review of breast cancer survivors' transition experience and transitional care: dialog with transition theory perspectives.
The health of breast cancer survivors (BCSs) is an essential concern worldwide. This review summarizes current knowledge and proposes a novel framework for understanding BCSs' transition experiences and adopting a more holistic view of transitional care to ensure a successful shift from patient-to-survivor. An integrative review was applied whereby we searched CINAHL, MEDLINE, PubMed, and ProQuest. Eleven qualitative and 16 experimental articles were extracted and evaluated. Constant comparison and matrix classification were used for data analysis, extraction, and synthesizing, which were circulated between the study findings and transitions theory. The breast cancer survivors' incorporated transition theory (BCSITT) encompasses the concepts of transition nature, conditions, intervention strategies, and patterns of response as developed from the data analysis. Facilitators and inhibitors of BCSs' transition experience in the personal, interpersonal, organizational, communal, societal dimensions as well as an empirical intervention of BCSs' transitional care from micro to macro levels are proposed. In conclusion, the BCSITT could provide comprehensive insights for understanding the phenomenon of BCSs' transition from primary treatment completion to self-management and serve as a holistic framework to guide clinical practice and research for BCSs' transitional care. Health care professionals need to assess the readiness of BCSs for transition and provide early interventions for enhancing BCSs' mastering of new skills to manage the challenges of transition. Incorporating stakeholders at each level and providing a comprehensive continuum of care may successfully assist BCSs' patient-to-survivor transition.


Delivery of FGF genes to wound repair cells enhances arteriogenesis and myogenesis in skeletal muscle.
Tissue repair is driven by migratory macrophages and fibroblasts that infiltrate injury sites and secrete growth factors. We now report the enhancement of skeletal muscle repair by targeting transgene delivery to these repair cells using matrix-immobilized gene vectors. Plasmid and adenovirus vectors immobilized in collagen-gelatin admixtures were delivered to excisional muscle wounds, and when encoding either fibroblast growth factor-2 (FGF2) or FGF6 transgenes, produced early angiogenic responses that subsequently remodeled into arteriogenesis. FGF2 gene delivery enhanced the number of CD31(+) endothelial cells present at treatment sites > 6-fold by day 14, and muscular arteriole density up to 11-fold by day 21 (P<0.0001). Muscle repair was also enhanced, as FGF gene-treated wounds filled with regenerating myotubes expressing the marker CD56 (an average 20-fold increase in CD56 expression versus controls, P<0.0001). These responses required transfection of a threshold level of repair cells, achievable only in injured muscles, and were transgene-driven, as neither platelet-derived growth factor-B (PDGFB) gene nor FGF2 protein delivery produced equivalent responses. In conclusion, using biomatrices to direct gene delivery to repair cells allows for relatively complex regenerative processes such as arteriogenesis and myogenesis, and therefore represents a promising approach to treating injured and ischemic muscle.


Repetitive tissue biopsy by venipuncture: enzyme activities in isolated leukocyte populations.
Despite the rapidly expanding clinical use of leukocyte biochemistry, there is a limited amount of data available on normal human leukocytes. Some of the problems associated with the clinical use of leukocytes are discussed briefly. Enzyme activities of alkaline and acid phosphatase, lysozyme, and beta-galactosidase are presented. Results are reproducible between normals when expressed per mg of leukocyte deoxyribonucleic acid (DNA). Much higher lymphocyte activties of lysozyme and alkaline phosphatase are noted than previously reported with cytochemical or intact cell systems. It has been demonstrated that leukocytes cannot be considered chemically homogenous but should be separated and considered as individual cell types.


Dislocations in nanostructured two-phase Fe30Ni20Mn20Al30.
In a previous study, the dislocations in Fe(30)Ni(20)Mn(25)Al(25) (at. %), which consist of 50 nm wide alternating b.c.c. and B2 phases, were shown to have a/2<111> Burgers vectors after room temperature deformation. The dislocations were found to glide in pairs on both {110} and {112} slip planes and were relatively widely separated in the b.c.c. phase, where the dislocations were uncoupled, and closely spaced in the B2 phase, where the dislocations were connected by an anti-phase boundary. In this article, we analyze the dislocations in the two ~5 nm-wide B2 phases in a related two-phase alloy Fe(30)Ni(20)Mn(20)Al(30), with compositions Fe-23Ni-21Mn-24Al and Fe-39Ni-12Mn-34Al, compressed to ~3% strain at a strain rate 5 × 10(-4) s(-1) at 873 K (the lowest temperature at which substantial plastic flow was observed). It is shown that slip occursby the glide of a<100> dislocations. A review of the literature suggests that the differences in the observed slip vector between these B2 phases could be due to the differences in composition, differences in deformation temperature, or possibly both.


How universal health care would influence decisions about work and retirement.
The current U.S. health care system distorts individual decisions about work and retirement. After a brief explanation of how the current health care system works, this article reviews those distortions and considers how individuals would respond to the implementation of a universal health care system. The author argues that the likely adverse impacts of an employer health insurance mandate on low-skilled workers could be more than offset by a well-designed system of government subsidies.


Effect of age and sex on gene expression-based radiation biodosimetry using mouse peripheral blood.
Blood-based gene expression profiles that can reconstruct radiation exposure are being developed as a practical approach to radiation biodosimetry. However, age and sex could potentially limit the accuracy of the approach. In this study, we determined the impact of age on the peripheral blood cell gene expression profile of female mice exposed to radiation and identified differences and similarities with a previously obtained transcriptomic signature of male mice. Young (2 months) and old (24 months) female mice were irradiated with 4 Gy X-rays, total RNA was isolated from blood 24hr later and subjected to whole genome microarray analysis. Dose reconstruction analyses using a gene signature trained on gene expression data from irradiated young male mice showed accurate reconstruction of 0 or 4 Gy doses with root mean square error of ± 0.75 Gy (R^2 = 0.90) in young female mice. Although dose reconstruction for irradiated old female mice was less accurate than young female mice, the deviation from the actual radiation dose was not statistically significant. Pathway analysis of differentially expressed genes revealed that after irradiation, apoptosis-related functions were overrepresented, whereas functions related to quantities of various immune cell subtypes were underrepresented, among differentially expressed genes from young female mice, but not older animals. Furthermore, young mice significantly upregulated genes involved in phagocytosis, a process that eliminates apoptotic cells and preserves tissue homeostasis. Both functions were also overrepresented in young, but not old, male mice following 4 Gy X-irradiation. Lastly, functions associated with neutrophil activation that is essential for killing invading pathogens and regulating the inflammatory response were predicted to be uniquely enriched in young but not old female mice. This work supports the concept that peripheral blood gene expression profiles can be identified in mice that accurately predict physical radiation dose exposure irrespective of age and sex.


[Psychosomatic aspects in orthopedic legal assessment].
Complaints in orthopaedics that are not sufficiently explainable can be caused (partly) by psychosomatic disorders. A manual psychosomatic disorders for legal assessment in orthopaedics will be supplied. Diagnoses essential for orthopaedics are classified by DSM-IV and ICD-10 in consideration of the current literature; evaluation was performed under legal assessment criterions. The most important complaints that are often poorly explainable results in musculoskeletal pain. Since a sensorial perception of pain is combined with emotions, emotions and psychic disorders can be perceived as pain. The most important diagnoses for assessing not sufficiently explainable complaints by somatic cause are "somatoform pain disorder", "somatization disorder", "undifferentiated somatoform disorder", "conversion disorder", "hypochondriasis", "body dysmorphic disorder", "maior depression", "dysthymic disorder", "posttraumatic stress disorder", and "adjustment disorder". The relevance of psychosomatic comorbidity in legal assessment is possible in all affairs of civil and social law. Private accident insurances exclude psychic and psychosomatic diseases from all insurance benefits. When composing legal assessments in orthopaedics, especially on pain, the knowledge of psychosomatic (co)morbidity is necessary for meeting the different causes of the complaints. Under awareness of possible psychosomatic disorders, additional psychosomatic legal assessments can be recommended and understood as well.


Patients with Obesity Have Better Long-Term Outcomes after Hospitalization for COPD Exacerbation.
Obesity has been shown to have a paradoxical benefit in a number of conditions, but the long-term effects in obesity after chronic obstructive pulmonary disease (COPD) exacerbation is still unclear. In this study, the effects of obesity on short- and long-term outcomes after a COPD exacerbation were evaluated. This was a secondary analysis of the Rapid Empiric Treatment with Oseltamivir Study (RETOS): a prospective, randomized, unblinded clinical trial. Patients were included in the study if they were hospitalized for acute exacerbation of COPD. Obesity was noted as patients with BMI >30. Clinical outcomes of time to clinical stability, length of stay, and mortality were compared. A total of 301 patients were included in the study, 122 (41%) patients were obese. There was no significant difference in the length of stay and time to clinical stability between patients with and without obesity. Mortality for patients with and without obesity was 3% and 3% at 30 days, 7% and 18% at six months, and 8% and 28% at one year, respectively. After adjusting with multivariable regression analysis, patients with obesity had a significant reduction in odds of dying at one year (adjusted odds ratio (aOR): 0.18; 95% CI: 0.06-0.58; p = .004) and at six months (aOR: 0.28; 95% CI: 0.09-0.89; p = .031). Our study showed that obesity was associated with reduced mortality at one year and six months after a COPD exacerbation. Although patients with obesity had higher rates of comorbidities, they had reduced mortality at one year after multivariable regression analysis.


A Case of Persistent Muscle Cramps in an American Football Player With Cystic Fibrosis.
Exercised-associated muscle cramp (EAMC) is a common occurrence in sports medicine. We highlight a 17-year-old male high-school football player with a history of cystic fibrosis and hyponatremic seizure, who presented for recurrent EAMC. After establishing an appropriate electrolyte replacement and hydration plan, he was able to complete his season with minimal symptoms. This case highlights the importance of hydration and nutrition planning when managing athletes with cystic fibrosis.


Summation and quantity judgments of sequentially presented sets by capuchin monkeys (Cebus apella).
Capuchin monkeys (Cebus apella) were presented with two sets of food items, identical in food type but differing in number. Animals selected one set and were permitted to consume their choice. Set sizes ranged from 1 to 6 items. In experiment 1, each set was uncovered and recovered before a response was made, and the monkeys selected the larger set at high levels. Experiment 2 presented sets that had both visible and nonvisible food items in them at the time of the response, thus requiring the monkeys to sum the total amount of food that was available. The monkeys again selected the larger set with no decrement in performance. Overall, the data indicate that capuchins, like other more extensively studied primate species in this area of research, are responsive to quantitative differences between sets. Capuchins succeed in making these quantity judgments when sets are nonvisible at choice time and when summation of items must be performed, thus demonstrating coordination of quantification skills and memory. Capuchins also inhibit responses to visible food items when those items are only part of an overall smaller quantity of food compared with a completely nonvisible set.


A mass spectrometry-based proteomic analysis of Homer2-interacting proteins in the mouse brain.
In the brain, the Homer protein family modulates excitatory signal transduction and receptor plasticity through interactions with other proteins in dendritic spines. Homer proteins are implicated in a variety of psychiatric disorders such as schizophrenia and addiction. Since long Homers serve as scaffolding proteins, identifying their interacting partners is an important first step in understanding their biological function and could help to guide the design of new therapeutic strategies. The present study set out to document Homer2-interacting proteins in the mouse brain using a co-immunoprecipitation-based mass spectrometry approach where Homer2 knockout samples were used to filter out non-specific interactors. We found that in the mouse brain, Homer2 interacts with a limited subset of its previously reported interacting partners (3 out of 31). Importantly, we detected an additional 15 novel Homer2-interacting proteins, most of which are part of the N-methyl-D-aspartate receptor signaling pathway. These results corroborate the central role Homer2 plays in glutamatergic transmission and expand the network of proteins potentially contributing to the behavioral abnormalities associated with altered Homer2 expression. Long Homer proteins are scaffolding proteins that regulate signal transduction in neurons. Identifying their interacting partners is key to understanding their function. We used co-immunoprecipitation in combination with mass spectrometry to establish the first comprehensive list of Homer2-interacting partners in the mouse brain. The specificity of interactions was evaluated using Homer2 knockout brain tissue as a negative control. The set of proteins that we identified minimally overlaps with previously reported interacting partners of Homer2; however, we identified novel interactors that are part of a signaling cascade activated by glutamatergic transmission, which improves our mechanistic understanding of the role of Homer2 in behavior.


Recording brain activities in unshielded Earth's field with optically pumped atomic magnetometers.
Understanding the relationship between brain activity and specific mental function is important for medical diagnosis of brain symptoms, such as epilepsy. Magnetoencephalography (MEG), which uses an array of high-sensitivity magnetometers to record magnetic field signals generated from neural currents occurring naturally in the brain, is a noninvasive method for locating the brain activities. The MEG is normally performed in a magnetically shielded room. Here, we introduce an unshielded MEG system based on optically pumped atomic magnetometers. We build an atomic magnetic gradiometer, together with feedback methods, to reduce the environment magnetic field noise. We successfully observe the alpha rhythm signals related to closed eyes and clear auditory evoked field signals in unshielded Earth's field. Combined with improvements in the miniaturization of the atomic magnetometer, our method is promising to realize a practical wearable and movable unshielded MEG system and bring new insights into medical diagnosis of brain symptoms.


Characterization of in vitro 3D cultures.
Over the past decade, 3D culture models of human and animal cells have found their way into tissue differentiation, drug development, personalized medicine and tumour behaviour studies. Embryoid bodies (EBs) are in vitro 3D cultures established from murine pluripotential stem cells, whereas tumoroids are patient-derived in vitro 3D cultures. This thesis aims to describe a new implication of an embryoid body model and to characterize the patient-specific microenvironment of the parental tumour in relation to tumoroid growth rate. In this thesis, we described a high-throughput monitoring method, where EBs are used as a dynamic angiogenesis model. In this model, digital image analysis (DIA) is implemented on immunohistochemistry (IHC) stained sections of the cultures over time. Furthermore, we have investigated the correlation between the genetic profile and inflammatory microenvironment of parental tumours on the in vitro growth rate of tumoroids. The EBs were cultured in spinner flasks. The samples were collected at days 4, 6, 9, 14, 18 and 21, dehydrated and embedded in paraffin. The histological sections were IHC stained for the endothelial marker CD31 and digitally scanned. The virtual whole-image slides were digitally analysed by Visiopharm® software. Histological evaluation showed vascular-like structures over time. The quantitative DIA was plausible to monitor significant increase in the total area of the EBs and an increase in endothelial differentiation. The tumoroids were established from 32 colorectal adenocarcinomas. The in vitro growth rate of the tumoroids was followed by automated microscopy over an 11-day period. The parental tumours were analysed by next-generation sequencing for KRAS, TP53, PIK3CA, SMAD4, MAP2K1, BRAF, FGFR3 and FBXW7 status. The tumoroids established from KRAS-mutated parental tumours showed a significantly higher growth rate compared to their wild-type counterparts. The density of CD3+ T lymphocytes and CD68+ macrophages was calculated in the centre of the tumours and at the invasive margin of the tumours. The high density of CD3+ cells and the low density of CD68+ cells showed a significant correlation with a higher growth rate of the tumoroids. In conclusion, a novel approach for histological monitoring of endothelial differentiation is presented in the stem cell-derived EBs. Furthermore, the KRAS status and density of CD3+ T cells and macrophages in the parental tumour influence the growth rate of the tumoroids. Our results indicate that these parameters should be included when tumoroids are to be implemented in personalized medicine.


Cordycepin Enhances the Cytotoxicity of Human Natural Killer Cells against Cancerous Cells.
Cancer treatment with natural killer (NK) cell immunotherapy is promising. NK cells can recognize and kill cancer cells without sensitization, making them a potential cancer treatment alternative. To improve clinical efficacy and safety, more research is needed. Enhancing NK cell function improves therapeutic efficacy. Due to its potent apoptosis induction, Cordycepin, a bioactive compound from Cordyceps spp., inhibits cancer cell growth. Cordycepin has immunoregulatory properties, making it a promising candidate for combination therapy with NK cell-based immunotherapy. Cordycepin may enhance NK cell function and have clinical applications, but more research is needed. In this study, cordycepin treatment of NK-92 MI cells increased THP-1 and U-251 cell cytotoxicity. Cordycepin also significantly increased the mRNA expression of cytokine-encoding genes, including tumour necrosis factor (TNF), interferon gamma (IFNG), and interleukin 2 (IL2). NK-92 MI cells notably secreted more IFNG and granzyme B. Cordycepin also decreased CD27 and increased CD11b, CD16, and NKG2D in NK-92 MI cells, which improved its anti-cancer ability. In conclusion, cordycepin could enhance NK cell cytotoxicity against cancerous cells for the first time, supporting its use as an alternative immunoactivity agent against cancer cells. Further studies are needed to investigate its efficacy and safety in clinical settings.


Determinants of hospital length of stay for people with serious mental illness in England and implications for payment systems: a regression analysis.
Serious mental illness (SMI), which encompasses a set of chronic conditions such as schizophrenia, bipolar disorder and other psychoses, accounts for 3.4 m (7 %) total bed days in the English NHS. The introduction of prospective payment to reimburse hospitals makes an understanding of the key drivers of length of stay (LOS) imperative. Existing evidence, based on mainly small scale and cross-sectional studies, is mixed. Our study is the first to use large-scale national routine data to track English hospitals' LOS for patients with a main diagnosis of SMI over time to examine the patient and local area factors influencing LOS and quantify the provider level effects to draw out the implications for payment systems. We analysed variation in LOS for all SMI admissions to English hospitals from 2006 to 2010 using Hospital Episodes Statistics (HES). We considered patients with a LOS of up to 180 days and estimated Poisson regression models with hospital fixed effects, separately for admissions with one of three main diagnoses: schizophrenia; psychotic and schizoaffective disorder; and bipolar affective disorder. We analysed the independent contribution of potential determinants of LOS including clinical and socioeconomic characteristics of the patient, access to and quality of primary care, and local area characteristics. We examined the degree of unexplained variation in provider LOS. Most risk factors did not have a differential effect on LOS for different diagnostic sub-groups, however we did find some heterogeneity in the effects. Shorter LOS in the pooled model was associated with co-morbid substance or alcohol misuse (4 days), and personality disorder (8 days). Longer LOS was associated with older age (up to 19 days), black ethnicity (4 days), and formal detention (16 days). Gender was not a significant predictor. Patients who self-discharged had shorter LOS (20 days). No association was found between higher primary care quality and LOS. We found large differences between providers in unexplained variation in LOS. By identifying key determinants of LOS our results contribute to a better understanding of the implications of case-mix to ensure prospective payment systems reflect accurately the resource use within sub-groups of patients with SMI.


Inflammatory choroidal neovascular membrane after healed tuberculous choroidal granuloma.
Objective: To present a case of choroidal granuloma masquerading as intraocular tumor that healed on anti-tuberculous treatment but led to the development of inflammatory choroidal neovascular membrane (CNVM). Method: A 42-year-old female patient with past history of hysterectomy presented with diminution of vision in the right eye. Fundus examination in the right eye showed a yellowish white choroidal mass with associated bullous retinal detachment superotemporal to fovea. Left eye fundus was normal. Fundus flourescein angiography showed early and late hyperflourescence with late pooling in serous detachments. Complete systemic evaluation did not yield a clue to diagnosis. Positron emission tomography scan (PET scan) showed enlarged lymph nodes in cervical, mediastinal and peritoneal regions. Lymph node biopsy showed caseating granulomas. Results: The granuloma subsided and a scar formed 5 months after starting anti-tuberculous treatment with improvement in vision. Six months later, the vision deteriorated again with the development of a choroidal neovascular membrane (CNVM) at the margin of the scar. The CNVM resolved and all the signs of activity subsided after giving intravitreal antivascular endothelial growth factor (anti-VEGF) injections. Conclusions: Making a diagnosis of tuberculous granuloma in a case of choroidal mass lesion is a challenge. PET scan helps in identifying metabolically active lymph nodes appropriate for biopsy. Healed scars of tuberculous choroid lesions should be followed closely to detect the development of CNVM.


Water permeability in resting and stimulated crayfish nerve.
The hydraulic conductivity, L(p), was determined in single axons of the crayfish, Procambarus clarkii, by injecting a hypertonic sample between two drops of silicone oil and photographing the volume increase of the sample. The method has the advantage of minimizing errors due to hydrostatic pressure differences across the membrane. In resting axons an L(p) of 0.236 x 10(-8) cm/ sec per cm H(2)O was found and similar values were obtained with low external calcium concentration and when the nerve was continuously stimulated at 20-30 impulses/sec. Thus the experiments have failed to demonstrate any change of water permeability in cases in which the ionic conductance is known to change. Some possible implications of this are discussed.


Intestinal Spirochetosis and Chronic Diarrhea: A Case Report and Literature Review.
Spirochetosis is a rare condition characterized by the presence of spirochetes in the gastrointestinal tract. It is typically associated with immunodeficiency. We present a case of chronic watery diarrhea in a 48-year-old housewife who had a 12-week history of variable-volume bowel movements without blood or mucus, accompanied by a sense of urgency. Chronic diarrhea led to weight loss and fatigue, significantly impacting her quality of life. Despite the absence of known risk factors, a comprehensive clinical evaluation and exclusion of other potential causes prompted a rectosigmoid biopsy, which revealed distinctive histological findings of spirochetosis. This case underscores the significance of considering spirochetosis as a differential diagnosis in cases of chronic watery diarrhea, even in the absence of immunodeficiency. The utilization of rectosigmoid biopsy and careful histopathological examination played a pivotal role in establishing an accurate diagnosis.


MYOC gene mutations in Spanish patients with autosomal dominant primary open-angle glaucoma: a founder effect in southeast Spain.
Primary open angle glaucoma (POAG) is a genetically heterogeneous disease resulting in optic disc cupping and visual impairment. It can be inherited as either a complex or a monogenic trait. Autosomal dominant POAG is the most frequent type of monogenic glaucoma. In this study, we investigated the role of myocilin MYOC in Spanish patients with autosomal dominant POAG. We retrospectively analyzed the MYOC gene by PCR-DNA sequencing in five Southeast Spanish families and one Colombian family of Hispanic origin affected by autosomal dominant juvenile-onset open angle glaucoma (JOAG). We also analyzed two families with adult-onset POAG (AOAG). MYOC mutations D380A and P370L segregated with the disease in the five JOAG Spanish families and the Colombian family, respectively. Neither MYOC mutations nor cytochrome P4501B1 CYP1B1 mutations were detected in the AOAG families. The disease showed an insidious onset in D380A carriers, making early diagnosis difficult. A delay in diagnosis resulted in severe visual impairment. Topical medications were effective in controlling intraocular pressure (IOP) in D380A carriers, but 72.2% of them required surgery for long-term IOP control. Conversely, only 30% of AOAG patients required surgery. Mutation P370L was associated with a severe phenotype unresponsive to medical treatment. Analysis of the four MYOC-linked polymorphic microsatellite markers in the JOAG Spanish families revealed a common disease haplotype, indicating that the D380A mutation was inherited from the same founder. This is the first evidence of a founder effect for a MYOC mutation in Spanish JOAG patients. Analysis of the MYOC gene in Spanish patients with JOAG is useful to identify at-risk individuals thus help prevent visual impairment through early treatment.


Fatal cytomegalovirus pneumonia in patients with haematological malignancies: an autopsy-based case-control study.
Cytomegalovirus (CMV) pneumonia is a life-threatening infection in patients with haematological malignancies (HMs) or in haematopoietic stem cell transplant (HSCT) recipients. To assess the incidence and risk factors for developing fatal CMV pneumonia in these patients, a case-control study based on 999 autopsies was performed at The University of Texas M. D. Anderson Cancer Center, Houston, Texas (January 1990 to December 2004). Twenty-five cases (patients who died with CMV pneumonia) were matched with 34 controls (patients who died without CMV pneumonia) by type of HM or HSCT, year of autopsy, age and gender. The incidence of CMV pneumonia declined between January 1990 to June /1997 and July 1997 to December 2004 (CMV pneumonia rates were 22/620 and 3/379 autopsies, respectively; p 0.006). Logistic regression analysis identified complete remission and sustained lymphopenia as independent predictors of CMV pneumonia (all p <0.05). The incidence of fatal CMV pneumonia has decreased over the last 15 years, which might reflect earlier diagnosis or the use of pre-emptive therapy or more effective preventive strategies. Complete remission of an HM does not preclude the development of CMV pneumonia among patients with prolonged lymphopenia.


Sonographic markers of fetal aneuploidy--a review.
The most effective sonographic marker of trisomy 21 and other chromosomal defects is increased nuchal translucency (NT) thickness at 11-14 weeks. Extensive studies over the last decade have examined the methodology of measuring NT, the development of the necessary algorithms for calculating the individual patient risk for trisomy 21 by NT in combination with maternal age and with various maternal serum biochemical markers, and the performance of this test. Another promising marker for trisomy 21, both in the first and second trimesters, is absence of the fetal nasal bone. There is also an extensive literature on the association between chromosomal abnormalities and a wide range of second trimester ultrasound findings. However, there are very few reports that have prospectively examined the screening performance of second trimester markers. This article reviews the association between sonographically detectable fetal abnormalities and chromosomal defects, and examines the value of incorporating these defects in screening policies.


What role could community pharmacists in Malaysia play in diabetes self-management education and support? The views of individuals with type 2 diabetes.
This study explored the experiences and views of individuals with type 2 diabetes mellitus (T2D) on their diabetes self-management and potential roles for community pharmacists in diabetes self-management education and support (DSME/S) in Malaysia. A qualitative study, using semi-structured, face-to-face interviews, was conducted with patients with T2D attending a primary care health clinic in Kuala Lumpur, Malaysia. The interviews were audio-recorded, transcribed verbatim and analysed inductively. Fourteen participants with T2D were interviewed. Data were coded into five main themes: experience and perception of diabetes self-management, constraints of the current healthcare system, perception of the community pharmacist and community pharmacies, perceived roles for community pharmacists in diabetes care, and challenges in utilising community pharmacies to provide DSME/S. There were misconceptions about diabetes management that may be attributed to a lack of knowledge. Although participants described potential roles for community pharmacists in education, medication review and continuity of care, these roles were mostly non-clinically oriented. Participants were not confident about community pharmacists making recommendations and changes to the prescribed treatment regimens. While participants recognised the advantages of convenience of a community pharmacy-based diabetes care service, they raised concerns over the retail nature and the community pharmacy environment for providing such services. This study highlighted the need to improve the care provision for people with T2D. Participants with T2D identified potential, but limited roles for community pharmacists in diabetes care. Participants expressed concerns that need to be addressed if effective diabetes care is to be provided from community pharmacies in Malaysia.


The pancreas: Bandmaster of glucose homeostasis.
The pancreas is a centralized organ vital for whole body metabolic control. Recent advances in the field of metabolism have reinforced its importance for orchestrating endocrine hormone secretion in response to several nutrients including glucose, lipids and amino acids, in addition to hormones and inflammatory signals. Cell types within the pancreas, in particular the insulin-producing β cells, control nutrient breakdown and energy production and are essential to maintain not only efficient hormone secretion, but also cell integrity, survival, and the ability to sense and adapt to changing metabolic environments. The present review highlights recent research advances on how glucolipotoxicity, mitochondrial dysfunction, and systemic inflammation affects pancreatic metabolism, and how new technologies and more advanced research models are improving our ability to study this organ system. Taken together, careful characterization and understanding of the importance of nutrient metabolism within this important, yet complex organ, will help us to better understand pathologies intimately associated with the pancreas and possibly discover new and more effective therapeutic strategies.


The regulation of microRNA expression by DNA methylation in hepatocellular carcinoma.
Emerging evidence indicates that microRNAs (miRNAs) are often dysregulated and play a fundamental role in hepatocellular carcinoma (HCC). However, the mechanism underlying miRNA dysregulation is still elusive. In the present study, we adopted an integrated analysis strategy combining data from genome-wide methylated DNA immunoprecipitation chip and miRNA expression microarray to study the regulation of DNA methylation on miRNA expression in HCC. We first characterized 864 differentially methylated regions (DMRs) located in 236 miRNA regions between cancerous and normal hepatocytes in HCC. We observed that the occurrence of miRNA DNA hypomethylation was more common than its hypermethylation while miRNA DNA hypermethylation was usually found in CpG islands. Then through correlation analysis between miRNA methylation and expression data, we identified 10 dysregulated miRNAs under the potential regulation of DNA methylation in HCC. Five of them (miR-148a, miR-375, miR-195, miR-497 and miR-378) were in hypermethylation and down-regulation status, while another five (miR-106b, miR-25, miR-93, miR-23a and miR-27a) were in hypomethylation and up-regulation status in HCC. Bioinformatics analysis showed that miR-148a may form a negative feedback loop with its targets DNMT1 and DNMT3B and the expression of the miR-195/497 cluster may be affected not only by their hypermethylated promoter region but also by their hypermethylated transcription factors NEUROG2 and DDIT3. our preliminary data and bioinformatics analysis suggest that DNA methylation plays an important and complex role in the regulation of miRNA expression in HCC, which may provide insights into the pathogenesis of HCC and thus may be used for diagnosis and intervention.


Health and Economic Impact of a Tender-Based, Sex-Neutral Human Papillomavirus 16/18 Vaccination Program in the Netherlands.
Uptake of human papillomavirus (HPV) vaccine among girls in the Dutch immunization program has plateaued at around 60%. Vaccinating boys may be an appealing complementary strategy for the prevention of HPV-related diseases, especially since tender negotiations and reduced dosing schemes have driven down the cost of vaccination. We expanded a previously published Bayesian synthesis framework to account for all vaccine type-related cancers and herd immunity effects from vaccinating girls and boys. We evaluated the efficiency of vaccinating boys relative to increasing vaccine uptake among girls and assessed the cost-effectiveness of a sex-neutral program. Vaccinating 40% of boys along with 60% of girls yielded the same gain in life-years (LYs) as increasing the uptake in girls from 60% to 80%. The incremental cost-effectiveness ratio (ICER) of vaccinating boys was €9134/LY (95% credible interval [CrI], €7323/LY-€11231/LY) under 3% discounting. The ceiling vaccination costs at which the ICER remained below the per capita gross domestic product threshold was €240 (95% CrI, €200-€280) per vaccinated boy. If girls' uptake increased to 90%, the ceiling costs decreased to €70 (95% CrI, €40-€100) per vaccinated boy. Vaccinating boys along with girls is only modestly less efficient than increasing uptake among girls and highly likely to be cost-effective under current vaccine costs and uptake in the Netherlands.


Characterization of placental transfer of polychlorinated dibenzo-p-dioxins, dibenzofurans and polychlorinated biphenyls in normal pregnancy.
Prenatal exposure to dioxins may result in many adverse health effects. However, the mechanisms by which dioxins are transferred from mother to fetus through the placenta are not well understood. The aim of this study was to investigate the differences in dioxin concentrations between maternal blood, the placenta, and cord blood in normal pregnant women, and to identify which individual congeners of these compounds are transferred from mother to fetus through the placenta. Samples were collected from 19 pregnant Japanese women. Specific congeners of seven polychlorinated dibenzo-p-dioxins (PCDDs), 10 polychlorinated dibenzofurans (PCDFs), and four non-ortho polychlorinated biphenyls (PCBs) were analyzed. The TEQ concentrations of PCDDs, PCDFs, and non-ortho PCBs were 8.03, 3.39, and 3.95 pg TEQ/g lipid, respectively, in the maternal blood; 8.78, 3.61, and 0.87 pg TEQ/g lipid in the placenta; and 4.33, 1.25, 1.08 pg TEQ/g lipid in the cord blood. Among specific congeners, 1,2,3,7,8-PentaCDD and 2,3,4,7,8-PentaCDF exhibited a placenta to maternal blood ratio greater than 1.0, while OctaCDD exhibited the greatest cord blood to placenta ratio. The cord blood to maternal blood ratio of total PCDDs was significantly higher than that of total PCDFs and total non-ortho PCBs. The dioxin concentration in cord blood was approximately half of the amount in maternal blood, despite congeners showing a high toxic equivalency factor accumulating in the placenta. PCDDs were transferred more readily than PCDFs and non-ortho PCBs from maternal blood to the fetus through the placenta.


[18F]-fluoro-ethyl-L-tyrosine PET: a valuable diagnostic tool in neuro-oncology, but not all that glitters is glioma.
To assess the sensitivity and specificity of [(18)F]-fluoro-ethyl-l-tyrosine ((18)F-FET) PET in brain tumors and various non-neoplastic neurologic diseases. We retrospectively evaluated (18)F-FET PET scans from 393 patients grouped into 6 disease categories according to histology (n = 299) or distinct MRI findings (n = 94) (low-grade/high-grade glial/nonglial brain tumors, inflammatory lesions, and other lesions). (18)F-FET PET was visually assessed as positive or negative. Maximum lesion-to-brain ratios (LBRs) were calculated and compared with MRI contrast enhancement (CE), which was graded visually on a 3-point scale (no/moderate/intense). Sensitivity and specificity for the detection of brain tumor were 87% and 68%, respectively. Significant differences in LBRs were detected between high-grade brain tumors (LBR, 2.04 ± 0.72) and low-grade brain tumors (LBR, 1.52 ± 0.70; P < .001), as well as among inflammatory (LBR, 1.66 ± 0.33; P = .056) and other brain lesions (LBR, 1.10 ± 0.37; P < .001). Gliomas (n = 236) showed (18)F-FET uptake in 80% of World Health Organization (WHO) grade I, 79% of grade II, 92% of grade III, and 100% of grade IV tumors. Low-grade oligodendrogliomas, WHO grade II, had significantly higher (18)F-FET uptakes than astrocytomas grades II and III (P = .018 and P = .015, respectively). (18)F-FET uptake showed a strong association with CE on MRI (P < .001) and was also positive in 52% of 157 nonglial brain tumors and nonneoplastic brain lesions. (18)F-FET PET has a high sensitivity for the detection of high-grade brain tumors. Its specificity, however, is limited by passive tracer influx through a disrupted blood-brain barrier and (18)F-FET uptake in nonneoplastic brain lesions. Gliomas show specific tracer uptake in the absence of CE on MRI, which most likely reflects biologically active tumor.


Multidimensional Approach Assessing the Role of Interleukin 1 Beta in Mesial Temporal Lobe Epilepsy.
We aimed to investigate the role of interleukin-1 beta (IL-1β) in the mechanisms underlying mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE+HS). We assessed a cohort of 194 patients with MTLE+HS and 199 healthy controls. Patients were divided into those with positive and negative antecedent febrile seizures (FS). We used a multidimensional approach, including (i) genetic association with single nucleotide polymorphisms (SNPs) in the IL1B gene; (ii) quantification of the IL1B transcript in the hippocampal tissue of patients with refractory seizures; and (iii) quantification of the IL-1β protein in the plasma. We found a genetic association signal for two SNPs, rs2708928 and rs3730364*C in the IL1B gene, regardless of the presence of FS (adjusted p = 9.62e-11 and 5.14e-07, respectively). We found no difference between IL1B transcript levels when comparing sclerotic hippocampal tissue from patients with MTLE+HS, without FS, and hippocampi from autopsy controls (p > 0.05). Nevertheless, we found increased IL-1β in the plasma of patients with MTLE+HS with FS compared with controls (p = 0.0195). Our results support the hypothesis of a genetic association between MTLE+HS and the IL1B gene.


Estimated microplastic stress and potential affiliated toxic elements on phytoplankton in a floodplain-lake system.
Hazards associated with microplastics (MPs) and the pollutants they absorb in freshwater lake ecosystems have become a hot research topic in academia. In this study, in order to investigate potential affiliated MP hazards, lake MP samples were collected from a typical subtropical freshwater lake system in China (Poyang Lake) during the dry season (here, you should show the specific months) to explore their potential toxic element (PTE) response (i.e., exposure to Cu, Pb, and Zn) respective to the ecological environment and resident phytoplankton. Results show that average MP abundance in surface water can reach up to 1800 items m-3, which higher in the Nanjishan Wetland National Nature Reserve (NWNNR) (1175 items m-3). Polyester (i.e., purified terephthalic acid [PTA]) and polyethylene (PE) were the main polymer types found in surface water, fiber was the main MP shape, and most of the MP particle sizes are greater than 100 μm. Moreover, phytoplankton biomass was significantly higher in the NWNNR compared to Poyang Lake's retention basin and water channel. It indicated that MP pollutant status of Poyang Lake is mild; however, the ecological risks that MPs pose should not be ignored. The significant positive correlation between MPs and PTEs indicated that PTE absorption and desorption by MPs may cause potential ecological stress. Although we anticipate no direct link between ecotoxicity and phytoplankton, MPs may have indirect effects on phytoplankton through their regulatory effects on PTE levels in water.


Callosal morphology in schizophrenia: what can shape tell us about function and illness?
Examination of the corpus callosum provides a window to cortical brain change in brain disorders. Combining volumetric with microstructural analysis allows a greater understanding of the biology underpinning change, and examining callosal structure alongside the structure of the cortical regions it interconnects may allow us to understand the true significance of callosal change in psychiatric disorders.


Isolation, molecular cloning, and characterization of a novel porcine lymphotoxin beta receptor gene.
The lymphotoxin beta receptor (LTβR) is a member of the tumor necrosis factor family of receptors (TNFR). It plays a role in regulating lymphoid organogenesis and homeostasis of the immune system. In the present study, the full coding region of a putative LTβR gene of Sus scrofa was amplified by reverse transcription-polymerase chain reaction (RT-PCR) and cloned for the first time (accession Nos. JX457347 and AFU74012). In addition, analysis of the tissue expression profile was carried out via RT-PCR. The full-length coding region of porcine LTβR had 1266 nucleotides (molecular weight, 45.61 kDa; pI, 5.71) and encoded 421 amino acids. Bioinformatic prediction indicates that LTβR belongs to the TNFR superfamily and contains a TNFR domain. The sequence homology analysis revealed that the amino acid sequences of S. scrofa LTβR had 82.9, 82.4, 81.3, 80.5, 78.7, 74.6, and 73.0% identity with those of Equus caballus, Canis lupus, Ailuropoda melanoleuca, Oryctolagus cuniculus, Bos taurus, Mus musculus, and Homo sapiens, respectively. The phylogenetic tree based on the amino acid sequences of LTβR from 8 species revealed that S. scrofa was more closely related to E. caballus, C. lupus, and A. melanoleuca. RT-PCR analysis showed that the porcine LTβR gene was differentially expressed (e.g., high, moderate, low, or nonexistent) in various tissues (e.g., prostate, pituitary, brainstem, and esophagus, respectively). This may be related to differences in the regulation of LTβR in the different tissues.


Sulfonamide resistance in Haemophilus influenzae mediated by acquisition of sul2 or a short insertion in chromosomal folP.
Determinants of sulfonamide resistance were investigated in clinical isolates of Haemophilus influenzae from the United Kingdom and Kenya. The mechanism of sulfonamide resistance in H. influenzae has not previously been reported. Eight isolates requiring at least 1,024 microg of sulfamethoxazole per ml for inhibition carried the sul2 gene, a common mediator of acquired sulfonamide resistance in enteric bacteria. In other isolates with similarly high levels of resistance, the chromosomal gene encoding dihydropteroate synthase, folP, was found to carry an insertion of 15 bp together with other missense mutations relative to folP of H. influenzae strain Rd RM118 (MIC, 8 microg/ml); the folP sequence was identical in all seven such isolates investigated, although they represented three different strains by restriction pattern analysis. The 15-bp insertion was absent in isolates inhibited by sulfamethoxazole at 2 to 64 microg/ml (although these exhibited considerable divergence in folP sequence) and in highly resistant isolates carrying sul2. Transformation with a 599-bp fragment of folP containing the insertion but no other differences conferred high-level resistance on a recipient strain, confirming the role of the insertion. Other amino acid substitutions in dihydropteroate synthase may modulate the level of sulfonamide inhibition in susceptible isolates and those with more moderate levels of resistance. The two mechanisms of resistance, mediated by sul2 and modified folP, were detected in isolates from both the United Kingdom and Kenya.


Color values and other meat quality characteristics of breast muscles collected from 3 broiler genetic lines slaughtered at 2 ages.
Broilers from the lines Ross 308, Ross 708, and Cobb 700 were slaughtered at 28 and 41 d of age at a commercial abattoir. After slaughter, the carcass, breast, and leg weights as well as the breast and leg yields were determined. Further investigations analyzed the color [lightness (L*), redness (a*), and yellowness (b*)], pH at 24 h postmortem, electrical conductivity (EC), drip loss, grill loss, and shear force values as well as the muscle fiber cross-sectional areas of the breast muscles. The 41-d-old broilers had higher carcass, breast, and leg weights than the 28-d-old birds. The breast yield values were higher and the leg yields were lower in the 41-d-old broilers. The fiber cross-sectional area values were also higher in the older birds. Within the younger birds the slaughter characteristics were approximately comparable among the lines. The EC, L*, grill loss, and shear force values increased but the drip loss and a* values decreased with the age of the broiler. The genetic lines differed within the 28-d-old broilers with regard to EC, grill loss, and shear force values and within the 41-d-old broilers with regard to the EC, L*, grill loss, and shear force values. The pH correlated negatively with the EC, L*, b*, drip loss, and shear force values. During storage, L* and b* values of the breast muscles increased and a* values decreased in all genetic lines, whereas the L* values were generally higher in the older broilers and the a* and b* results were generally higher in the breast muscles of the younger broilers. In conclusion, the carcass and meat quality characteristics of broilers changed with age with positive (carcass and breast muscle weight, drip loss) but also negative (L*, a*, grill loss) effects. The effect of the genetic line was rather low. Despite the age-related changes of meat quality parameter, the pH values remained unchanged, indicating muscle structural influences on the muscle-to-meat-transition with increasing age of the broiler.


Depression networks: a systematic review of the network paradigm causal assumptions.
The network paradigm for psychiatric disorder nosology was proposed based on the hypothesis that mental disorders are caused by networks of symptoms that are themselves causally related. Researchers have widely applied and integrated this paradigm to examine a variety of mental disorders, particularly depression. Existing studies generally focus on the correlation structure of symptoms, inferring causal relationships. Thus, presumption of causality may not be justified. The goal of this review was to examine the assumptions necessary for causal inference in network studies of depression. Specifically, we examined whether and how network studies address common violations of causal assumptions (i.e. no measurement error, exchangeability, and positivity). Of the 41 studies reviewed, five (12%) studies discussed sources of confounding unrelated to measurement error; none discussed positivity; and five conducted post-hoc analysis for measurement error. Depression network studies, in principle, are conducted under the assumption that symptom relationships are causal. Yet, in practice, studies seldomly discussed or adequately tested assumptions required to infer causality. Researchers continue to design studies that are unable to support the credibility of the network paradigm for the study of depression. There is a critical need to ensure scientific efforts cease to perpetuate problematic designs and findings to a potentially unsubstantiated paradigm.


Statistical optimization of medium components for extracellular protease production by an extreme haloarchaeon, Halobacterium sp. SP1(1).
Optimization of medium components for extracellular protease production by Halobacterium sp. SP1(1) using statistical approach. The significant factors influencing the protease production as screened by Plackett-Burman method were identified as soybean flour and FeCl(3). Response surface methodology such as central composite design was applied for further optimization studies. The concentrations of medium components for higher protease production as optimized using this approach were (g l(-1)): NaCl, 250; KCl, 2; MgSO(4), 10; tri-Na-citrate, 1.5; soybean flour, 10 and FeCl(3), 0.16. This statistical optimization approach led to production of 69.44 +/- 0.811 U ml(-1) of protease. Soybean flour and FeCl(3) were identified as important factors controlling the production of extracellular protease by Halobacterium sp. SP1(1). The statistical approach was found to be very effective in optimizing the medium components in manageable number of experimental runs with overall 3.9-fold increase in extracellular protease production. The present study is the first report on statistical optimization of medium components for production of haloarchaeal protease. The study also explored the possibility of using extracellular protease produced by Halobacterium sp. SP1(1) for various applications like antifouling coatings and fish sauce preparation using cheaper raw material.


Isolation of rice genes possibly involved in the photoperiodic control of flowering by a fluorescent differential display method.
To better understand the molecular mechanisms of the photoperiodic regulation of rice, a short-day plant, we isolated 27 cDNAs that were differentially expressed in the photoperiod-insensitive se5 mutant from approximately 8,400 independent mRNA species by the use of a fluorescent differential display (FDD). For this screening, we isolated mRNAs at five different time points during the night and compared their expression patterns between se5 and the wild type. Of 27 cDNAs isolated, 12 showed diurnal expression patterns often associated with genes involved in the determination of the flowering time. In se5, expression of nine cDNAs was increased. Five of these cDNAs were up-regulated under SD, suggesting that they may promote flowering under SD. They included genes encoding a cDNA containing a putative NAC domain, the fructose-bisphosphate aldolase, and a protease inhibitor. Expression of three cDNAs was decreased in se5 but not photoperiodically regulated. These cDNAs included a rice homolog of Arabidopsis GIGANTEA (GI), lir1, and a gene for myo-inositol 1-phosphate synthase, all of which were previously shown to be under the control of circadian clocks. The expression patterns of the rice homolog of GI, OsGI, were similar to those of the Arabidopsis GI, suggesting the conservation of some mechanisms for the photoperiodic regulation of flowering between these two species.


Biatrial connection of partial anomalous pulmonary venous return.
We describe an extremely rare case of partial anomalous pulmonary venous return in a 3-year-old boy with an abnormal connection between the right upper pulmonary vein and the right middle pulmonary vein, which created biatrial communication hemodynamically. Patch closure on the orifice of the right upper pulmonary vein was performed to avoid distortion or kinking of the right pulmonary veins and the connection.


Reversible and cachexia-associated feline skin fragility syndrome in three cats.
Feline skin fragility syndrome (FSFS) is an acquired disorder characterized by altered collagen production resulting in an extremely thin and fragile skin. FSFS is associated with diseases characterized by excessive steroidal hormones that can inhibit collagen synthesis. It is also described concomitantly with severe inflammatory, infectious or neoplastic conditions where the pathogenesis remains largely unknown. To describe three cases of FSFS in cats that become cachectic secondary to different causes without glucocorticoid involvement. To describe the histopathological features of connective tissue for both fragile skin and the skin after healing. All cats developed cachexia in less than two months (body condition score ranging from 1-1.5). Concomitant diseases were diagnosed in Case 1 (aspiration pneumonia due to mega-oesophagus) and Case 2 (feline immunodeficiency virus (FIV)). In Case 3, malnutrition was suspected as a primary cause. The main histological feature of fragile skin was an atrophic dermis with pale eosinophilic, thin and irregular collagen fibres with numerous red cores observed with Masson's stain. Elastic fibres were normal. Postrecovery histopathological findings at 11 (Case 1) and six months (Case 3) after diagnosis, indicated normalization of the collagen and of the whole skin as compared with controls. To the best of the authors' knowledge, this is the first report describing a reversible, nonsteroid-induced FSFS, associated with rapidly developing cachexia in cats.


Immunoglobulin-bearing lymphocytes: their demonstration in adult sheep and ontogeny in the sheep fetus.
A method for the preparation of lymphocytes from sheep blood is described. Lymphocytes from adult and fetal sheep have been examined by immunofluorescence for surface immunoglobulin (sIg) determinants. Young adults (1.5 years) had a mean of 23.2% sIg cells, older adults (8.75 years) a mean of 9.7% sIg cells. Pregnancy did not influence these values. The earliest lymphocytes with sIg in fetal lambs were demonstrable at 52 days (96 mm crown-rump length) and countable by 56 days (110 mm CRL) at 0.3% sIg. The percentage rose rapidly to 15.1% between 78 and 87 days, followed by a fall to 2.1% around 117 days with a second increase thereafter. The significance of this spontaneous appearance of fetal sIg cells is discussed.


Use of live and inactivated Salmonella enteritidis phage type 4 vaccines to immunise laying hens against experimental infection.
Four groups of Dekalb Delta commercial layer hens (8 hens per group) were reared individually in cages in an isolation unit. At the age of 8 weeks, groups 1 and 2 were vaccinated with 9R Salmonella gallinarum live (9R live) vaccine. At the age of 18 weeks, group 1 was re-vaccinated with 9R live S. enteritidis vaccine, while groups 2 and 3 were vaccinated with S. enteritidis bacterin. At the age of 22 weeks, groups 2 and 3 were re-vaccinated with S. enteritidis bacterin. Group 4 was not vaccinated and was kept as a control group. At 24, 27 and 30 weeks of age, the four groups were challenged using various concentrations of S. enteritidis phage type 4 and various routes of inoculation. Eggs, cloacal swabs and blood were collected weekly for bacteriological and serological examination. Isolation of the challenge organism from the eggshells and egg contents of the vaccinated groups was significantly lower than with the control group. There was no correlation between humoral antibodies and the shedding of the challenge organism in eggs or cloacal swabs. A combined vaccination programme of 9R live S. enteritidis vaccine and S. enteritidis bacterin provided better protection to laying hens than either vaccine administered alone. Vaccination should never be performed alone but in conjunction with other measures related to veterinary hygiene and good management.


[New aspects of endocrine regulation of calcium metabolism].
The maintenance of circulating calcium levels within the narrow physiological range requires the action of two hormones, the polypeptide hormone parathyroid hormone and the steroid hormone 1-alpha-25-dihydroxyvitamin D3. These two hormones act on bone, kidney and intestine to regulate calcium homeostasis. Disorders of mineral metabolism are frequently associated with abnormal regulation of the metabolism of parathyroid hormone or 1-alpha-25-dihydroxyvitamin.


Pentylenetetrazol-induced epileptiform activity affects basal synaptic transmission and short-term plasticity in monosynaptic connections.
Epileptic activity is generally induced in experimental models by local application of epileptogenic drugs, including pentylenetetrazol (PTZ), widely used on both vertebrate and invertebrate neurons. Despite the high prevalence of this neurological disorder and the extensive research on it, the cellular and molecular mechanisms underlying epileptogenesis still remain unclear. In this work, we examined PTZ-induced neuronal changes in Helix monosynaptic circuits formed in vitro, as a simpler experimental model to investigate the effects of epileptiform activity on both basal release and post-tetanic potentiation (PTP), a form of short-term plasticity. We observed a significant enhancement of basal synaptic strength, with kinetics resembling those of previously described use-dependent forms of plasticity, determined by changes in estimated quantal parameters, such as the readily releasable pool and the release probability. Moreover, these neurons exhibited a strong reduction in PTP expression and in its decay time constant, suggesting an impairment in the dynamic reorganization of synaptic vesicle pools following prolonged stimulation of synaptic transmission. In order to explain this imbalance, we determined whether epileptic activity is related to the phosphorylation level of synapsin, which is known to modulate synaptic plasticity. Using western blot and immunocytochemical staining we found a PTZ-dependent increase in synapsin phosphorylation at both PKA/CaMKI/IV and MAPK/Erk sites, both of which are important for modulating synaptic plasticity. Taken together, our findings suggest that prolonged epileptiform activity leads to an increase in the synapsin phosphorylation status, thereby contributing to an alteration of synaptic strength in both basal condition and tetanus-induced potentiation.


[Protective effects of biphenyl dimethyl dicarboxylate on damage in isolated rat hepatocytes induced by carbon tetrachloride and D-galactosamine].
The protective effect of DDB on chemically induced damages was studied in primary culture of rat hepatocytes. The experimental results showed that DDB (200 ug/10(6) cells) efficiently protected the hepatocytes against carbon tetrachloride (10 mM) and D-galactosamine (1 mM) induced damages. Membrane lipid peroxidation (malondialdehyde, MDA) formation and Glutamic Pyruvic Transaminase (GPT) released from the hepatocytes were markedly decreased. The damage of the cell surfaces of the hepatocytes were also reduced as seen under a scanning electron microscope (SEM). Pretreatment with DDB (300 mg/kg) orally could ameliorate the reduction of liver glycogen and blood glucose caused by injection of D-gal (800 mg/kg i. p) in mice. When normal rats received 300 mg/kg of DDB once daily for 10 days, free ribosomal protein and RNA in the liver increased significantly. These results indicated that DDB is of beneficial effects on damaged and normal hepatocytes.


Creatine kinase.
Creatine kinase is present in significant concentrations in skeletal muscle and cardiac muscle and to a lesser extent in gastrointestinal tract and brain tissue. The enzyme has been purified from a variety of tissues and an examination of its kinetic and physical properties reveal that the enzyme consists of two subunits and can exist as three isoenzymes containing essential cysteine residues. These properties are important in understanding its stability, the assay conditions, and the techniques used to identify the different isoenzymes. The relationship between the properties and the determination of the enzyme in biological fluids will be a main thrust of the review. Creatine kinase activity in serum rises rapidly in conditions such as acute myocardial infarction and trauma to skeletal muscle. However, the interpretation of such increases is dependent upon a sound knowledge of the factors which influence both the total and isoenzyme activities. The nature of these factors will be discussed in detail.


Tactile representation of the head and shoulders assessed by fMRI in the nonhuman primate.
In nonhuman primates, tactile representation at the cortical level has mostly been studied using single-cell recordings targeted to specific cortical areas. In this study, we explored the representation of tactile information delivered to the face or the shoulders at the whole brain level, using functional magnetic resonance imaging (fMRI) in the nonhuman primate. We used air puffs delivered to the center of the face, the periphery of the face, or the shoulders. These stimulations elicited activations in numerous cortical areas, encompassing the primary and secondary somatosensory areas, prefrontal and premotor areas, and parietal, temporal, and cingulate areas as well as low-level visual cortex. Importantly, a specific parieto-temporo-prefrontal network responded to the three stimulations but presented a marked preference for air puffs directed to the center of the face. This network corresponds to areas that are also involved in near-space representation, as well as in the multisensory integration of information at the interface between this near space and the skin of the face, and is probably involved in the construction of a peripersonal space representation around the head.


Silybin-mediated inhibition of Notch signaling exerts antitumor activity in human hepatocellular carcinoma cells.
Hepatocellular carcinoma (HCC) is a global health burden that is associated with limited treatment options and poor patient prognoses. Silybin (SIL), an antioxidant derived from the milk thistle plant (Silybum marianum), has been reported to exert hepatoprotective and antitumorigenic effects both in vitro and in vivo. While SIL has been shown to have potent antitumor activity against various types of cancer, including HCC, the molecular mechanisms underlying the effects of SIL remain largely unknown. The Notch signaling pathway plays crucial roles in tumorigenesis and immune development. In the present study, we assessed the antitumor activity of SIL in human HCC HepG2 cells in vitro and in vivo and explored the roles of the Notch pathway and of the apoptosis-related signaling pathway on the activity of SIL. SIL treatment resulted in a dose- and time-dependent inhibition of HCC cell viability. Additionally, SIL exhibited strong antitumor activity, as evidenced not only by reductions in tumor cell adhesion, migration, intracellular glutathione (GSH) levels and total antioxidant capability (T-AOC) but also by increases in the apoptotic index, caspase3 activity, and reactive oxygen species (ROS). Furthermore, SIL treatment decreased the expression of the Notch1 intracellular domain (NICD), RBP-Jκ, and Hes1 proteins, upregulated the apoptosis pathway-related protein Bax, and downregulated Bcl2, survivin, and cyclin D1. Notch1 siRNA (in vitro) or DAPT (a known Notch1 inhibitor, in vivo) further enhanced the antitumor activity of SIL, and recombinant Jagged1 protein (a known Notch ligand in vitro) attenuated the antitumor activity of SIL. Taken together, these data indicate that SIL is a potent inhibitor of HCC cell growth that targets the Notch signaling pathway and suggest that the inhibition of Notch signaling may be a novel therapeutic intervention for HCC.


Range of refractive independence and mechanism of action of a corneal shape-changing hydrogel inlay: results and theory.
To demonstrate the independence of visual performance over a range of preoperative refraction and age in presbyopes implanted with a corneal shape-changing inlay (Raindrop Near Vision Inlay). Two multispecialty clinics, Monterrey and Tijuana, Mexico. Prospective case series. The nondominant eyes of patients were implanted with the hydrogel corneal inlay beneath a femtosecond flap, centered on the pupil. Clinical outcomes included uncorrected near, intermediate, and distance visual acuity (UNVA, UIVA, and UDVA) and patient-assessed task performance in good light and dim light. Statistical analyses assessed the dependencies on preoperative age (45 to 60 years) and preoperative manifest refraction spherical equivalent (MRSE) (-0.5 to +1.5 diopters [D]). Using the inlay effect derived from wavefront measurements, an eye model was created through which letter charts were simulated. The study evaluated eyes of 188 patients. Postoperative UNVA, UIVA, and task performance at these distances in good light was independent of age and preoperative MRSE (P > .05). Postoperative UDVA was weakly dependent on preoperative MRSE, but distance task performance in good light was not (P > .05). In the treated eye, the mean postoperative UNVA was 20/25, UIVA was 20/25, and UDVA was 20/32. The clinical outcomes are explained by consideration of zones within the pupil generating good near, intermediate, and distance image quality. This was confirmed by visual acuity simulations. The continuous center-near power profile induced by the corneal shape-changing inlay provides good visual acuity and performance from distance through near over a 2.0 D range of preoperative refraction and presbyopic age. Drs. Steinert, Schwiegerling, Barragán-Garza, and Chayet are consultants to Revision Optics, Inc. Drs. Lang and Holliday and Mr. Roy are employees of Revision Optics, Inc. Drs. Steinert, Schwiegerling, Barragán-Garza, and Chayet have no financial or proprietary interest in any material or method mentioned.


Dietary fibre intake is associated with reduced risk of lung cancer: a Japan public health centre-based prospective study (JPHC).
Several epidemiological studies have been conducted to draw consistent conclusions regarding the effect of dietary fibre on lung diseases and lung cancer. However, the effect of dietary fibre on the incidence of lung cancer remains unclear in an Asian population. We investigated the association between the intake of total dietary fibre and dietary fibre from different food sources and lung cancer incidence in a Japan public health centre-based prospective study (JPHC). A total of 73 405 participants (33 012 men and 40 393 women) aged 45-74 years were eligible for our study. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). During a median follow-up of 18.0 years, 1546 (1042 men and 504 women) newly diagnosed cases of lung cancer were ascertained. In the multivariable models, total dietary fibre intake was inversely associated with lung cancer risk in men, the HRs Q5 vs Q1 (95% CI) were 0.77 (0.62 to 0.94), P-trend = 0.020. Dietary fibre intake from vegetables was protectively associated with lung cancer risk in men [HR Q5 vs Q1 (95% CI): 0.80 (0.64 to 0.99), P-trend = 0.053]. However, no such association was observed in women. In men, a high intake of total dietary fibre may have preventive benefits for lung cancer incidence: dietary fibre intake from vegetables was associated with a lower incidence of lung cancer. However, similar associations did not appear in women. Further investigations are required to confirm the association between dietary fibre and lung cancer risk in women.


Immunometabolism in systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is an autoimmune disease mediated by pathogenic autoantibodies directed against nucleoprotein complexes. Beyond the activation of autoreactive B cells, this process involves dysregulation in many other types of immune cells, including CD4+ T cells, dendritic cells, macrophages and neutrophils. Metabolic substrate utilization and integration of cues from energy sensors are critical checkpoints of effector functions in the immune system, with common as well as cell-specific programmes. Patients with SLE and lupus-prone mice present with activated metabolism of CD4+ T cells, and the use of metabolic inhibitors to normalize these features is associated with therapeutic effects. Far less is known about the metabolic requirements of B cells and myeloid cells in SLE. This article reviews current knowledge of the alterations in metabolism of immune cells in patients with SLE and mouse models of lupus in the context of what is known about the metabolic regulation of these cells during normal immune responses. How these alterations might contribute to lupus pathogenesis and how they can be targeted therapeutically are also discussed.


Cycad Palm Toxicosis in 14 Dogs from Texas.
The goal of this study is to report clinical information, diagnostic findings, and treatment modalities; assess variables that may help distinguish survivors from nonsurvivors; and review the outcome of cycad palm toxicosis in dogs. Fourteen client-owned dogs with confirmed cycad palm ingestion were identified by reviewing the medical record database at Gulf Coast Veterinary Specialists. Information on signalment, time of ingestion to presentation, clinical signs, physical examination findings, initial and peak/nadir laboratory abnormalities, radiographic and ultrasonographic findings, treatment modalities, liver histopathology, and clinical outcome was retrieved. Of the 14 dogs, nine (64%) died as a direct result of cycad palm intoxication, and three survivors had persistently elevated liver enzymes, signifying residual liver damage. Despite decontamination, patients continued to display evidence of illness, indicating rapid absorption of toxins. When evaluating initial and peak/nadir laboratory values, nadir serum albumin levels and nadir platelet counts were significantly lower in nonsurvivors compared to survivors (1.25 g/dL [0.4-2.1 g/dL] versus 2.6 g/dL [1.7-3.4 g/dL] and 21 × 103 [0-64 × 103] versus 62 × 103 [6-144 × 103], respectively). In this cohort of dogs, the case fatality rate was higher than previously reported. Nadir serum albumin levels and nadir platelet counts may help distinguish potential survivors from nonsurvivors.


The control of cardiovascular shunts in the fetal and perinatal period.
The fetal circulation has two major vascular shunts, the ductus arteriosus and the ductus venosus. The ductus arteriosus connects the pulmonary artery with the descending portion of the aortic arch, hence shunting most of the right ventricular output away from the unexpanded lungs. The ductus venosus connects instead the portal sinus with the inferior vena cava and allows well-oxygenated umbilical vein blood to bypass the liver and reach the central circulation rapidly. Both blood vessels cease their function after birth and undergo permanent closure. It is now well established that prenatal patency of the ductus arteriosus is an active state sustained by a prostaglandin. A similar mechanism has been recently recognized in the fetal ductus venosus. Evidence is presented indicating that prostaglandin E2 and prostaglandin I2 are natural relaxants, respectively, for the ductus arteriosus and the ductus venosus. In addition, both vascular shunts share the dependence on an endogenous cytochrome P-450 mechanism to develop their contractile tone. This mechanism may be important in the normal process of shunt closure at birth. While broadening the knowledge of fetal cardiovascular homeostasis, advances in this field have important implications for the prevention and management of certain pathological conditions affecting the newborn.


The Comparison of Levetiracetam and Piracetam Effectiveness on Breath-Holding Spells in Children: A Randomized Controlled Clinical Trial.
We aimed to compare the effectiveness of Levetiracetam and Piracetam on the severity and frequency of spells in children with severe breath-holding spells (BHS), i.e. bening, paroxysmal, and nonepileptic events that are common in early childhood. This study is a randomized controlled clinical trial in 71 children from 6 months to 6 years of age with BHS. They were randomly assigned to the two study groups (Levetiracetam and Piracetam group). The frequency and severity of BHS and the response to treatment were recorded on monthly visits during our 3 months follow-up. There was a significant decline in the average number of frequency of spells before and after 3 months of treatment in each group in this study. Levetiracetam had significant effects on the average incidence of the loss of consciousness and seizure-like movements in our study, while Piracetam had no significant effect on the loss of consciousness. Our result showed better response in the Levetiracetam group (88.9% partial or complete response after treatment) compared with the Piracetam group (77.1% partial or complete response after treatment); however, it was not significant. It seems that Levetiracetam had better effect than Piracetam in some aspects in the treatment of BHS. Both Piracetam and Levetiracetam are safe and had significant effects on the frequency of BHS in our study, however, levetiracetam showed superior effects on the severity of BHS.


Induced dipole in vanadium-doped zinc oxide nanosheets and its effects on photoelectrochemical water splitting.
Appropriate control of energy band bending at the interface between semiconductors and electrolytes are closely related to performance of photoelectrochemical (PEC) water splitting. Dipoles formed near the surface of semiconductors induces energy band bending at the interface. Energy band bending control has been demonstrated by employing charged molecules and piezoelectric materials. However, chemical and piezoelectric approaches have demerit of chemical instability and inducement of instantaneous dipole, respectively. To overcome these problems, we adopted the ferroelectric material for PEC water splitting, where spontaneous dipoles in the material can be oriented by applying external electric field. In this work, we hydrothermally synthesized vanadium (V)-doped ferroelectric ZnO nanosheets and employed to systematically investigate the dipole effect on performance of V-doped ZnO PEC for water oxidation. Consequently, positively polarized V-doped ZnO photoanode exhibits 125% enhanced water splitting efficiency compared to negatively polarized ones due to favorable band bending for carrier transport from semiconductor to water.


Management of bleeding complications in redo cardiac operations.
Bleeding remains a complication of certain complex surgical procedures, particularly those cardiac operations associated with long bypass times and profound hypothermia. Clinical and novel experimental strategies to reduce bleeding and the need for blood and blood-product transfusions are the focus of this review. Preoperative assessment of the patient will identify drug-induced, acquired, or inherited coagulation defects that may contribute to this problem. The main attention is directed to the perioperative period, and broad areas discussed include the preoperative use of erythropoietin to increase red blood cell mass, autologous donation either preoperatively or before bypass, autotransfusion/hemofiltration, and acceptance of relative anemia both during the operation and into the postoperative period. A further, often overlooked, management strategy in treating major coagulopathies is the consideration of the cost and half-lives of the coagulation factors in individual blood components. Prevention of bleeding has become possible both by manipulation of the control of coagulation and inflammatory processes and by the introduction of pharmacologic agents such as aprotinin. Aprotinin is widely used and has proven efficacy in the management of excess bleeding. It is a serine protease inhibitor and has several possible mechanisms of action, including inhibition of the plasma enzyme systems activated by contact with the foreign surface of the bypass circuit and preservation of platelet function. Safety issues include the possibility of hypersensitivity and anaphylactic reaction on a second exposure. Concerns that aprotinin may induce a prothrombotic or coagulant state have no basis in theory or any good evidence in the current literature. A recent study specifically sought to identify the presence of disseminated microvascular platelet-fibrin thrombi present at autopsy in patients who had received aprotinin therapy. The study concluded that diffuse platelet-fibrin thrombi were not a direct complication of aprotinin therapy. Finally, modern molecular biology has led to the recent development of an inhibitor for factor IXa that competitively replaced IXa in the intrinsic complex and blocked the conversion of factor X to factor Xa. This compound is under investigation in animal studies. These have so far shown efficacy in reducing blood loss after bypass in comparison with standard heparin anticoagulation.


Ethanol-induced oxygen radical formation and lipid peroxidation in rat brain: effect of chronic alcohol consumption.
The effect of chronic and in vitro ethanol exposure on brain oxygen radical formation and lipid peroxidation was analyzed. Ethanol induces a dose-dependent increase in lipid peroxidation in brain homogenates. The peroxidative effects of alcohol seem to be related to both cytochrome P450 and the ethanol-inducible form of cytochrome P450 (CYP2E1), because preincubation with metyrapone (an inhibitor of cytochrome P450) or with an antibody against CYP2E1 abolished the ethanol-increased lipid peroxidation. Using the formation of dichlorofluorescein, we also demonstrated that both in vitro and chronic alcohol exposure significantly enhanced the formation of oxygen radical species in synaptosomes. Chronic alcohol treatment also leads to an induction of cytochrome P450 (230%), NADPH cytochrome c reductase (180%), NADPH oxidation (184%), and CYP2E1 in brain microsomes. In addition, this treatment produced a decrease in the GSH/GSSG ratio in brain and significantly enhanced the levels of superoxide dismutase and catalase activities. This mechanism could be involved in the toxic effects of ethanol on brain and membrane alterations occurring after chronic ethanol intake.


Effects of amphetamine-CNS depressant combinations and of other CNS stimulants in four-choice drug discriminations.
Three pigeons were trained to discriminate among 5 mg/kg pentobarbital, 2 mg/kg amphetamine, a combination of these two drugs at these doses, and saline using a four-choice procedure (amphetamine-pentobarbital group). Three other pigeons were trained to discriminate among 5 mg/kg morphine, 2 mg/kg methamphetamine, a combination of these two drugs at these doses, and saline (methamphetamine-morphine group). After 10 to 13 months of training, the pigeons averaged more than 90% of their responses on the appropriate key during training sessions. In subsequent testing, dose-response curves were determined for the individual drugs, for a wide range of dose combinations of the training drugs, and for two drugs to which the pigeons had not been exposed previously (pseudoephedrine and nicotine). After low test doses of the training drugs, pigeons responded on the saline key. As the dose increased, responding on the key associated with that drug during training sessions increased. When training drugs were combined at doses that were not discriminable when given alone, responding occurred on the saline key. When a discriminable dose of one training drug was combined with a nondiscriminable dose of the other training drug, responding occurred on the key associated with the discriminable dose. When both drugs were given at discriminable doses, responding almost always occurred on the drug-combination key. The response-rate decreasing effects of pentobarbital and amphetamine were mutually antagonized when the drugs were combined, but the rate-decreasing effects of morphine and methamphetamine were not. After low doses of pseudoephedrine and nicotine, pigeons in both groups responded on the saline key. After higher doses of pseudoephedrine and nicotine, responding in the amphetamine-pentobarbital group occurred primarily on the amphetamine key. In the methamphetamine-morphine group, higher doses of pseudoephedrine and especially nicotine engendered more responding on the combination key than had occurred in the other group. The four-choice procedure can reveal subtle effects in the discrimination of individual drugs and drug combinations that are not apparent with procedures offering fewer response alternatives.


[The awareness and attitude of population of Kazakhstan to inoculation against human papilloma virus].
The vaccines against human papilloma virus are a potential tool for prevention of cervix cancer and particular other types of cancer. The high inclusion of target group in applied vaccination program is economically effective and successful activity depending in many instances on reliable knowledge and positive attitude of population to inoculation. The cross-sectional study was carried out using previously developed anonymous questionnaires for various groups of population in four pilot regions of Kazakhstan where national ministry of health proposes for inoculation of girls aged 9-13 years two vaccines against human papilloma virus (four- and two-valence) The data base was organized using software Microsoft Access. The materials were integrated and processed using variation statistics techniques in software IBM SPSS Statistics 19 and applying Student criterion and calculating correlation dependences. Out of all respondents, 66% were aware about existence of human papilloma virus/ the main portion of parents 'female adolescents learned about vaccination against human papilloma virus from Internet and medical workers. The most significant factor preventing implementation of vaccination and the proper perception by respondents was absence of confidence in safety of vaccine. About 54% of parents of female adolescents and 75% of teachers consider vaccine as unsafe. And only 72% of medical workers consider vaccine as safe. Despite known effectiveness of vaccination against human papilloma virus, number of problems exist related to implementation of program. The level of awareness and understanding of different groups of population concerning the role of vaccination in development of oncologic pathology and possibility of prevention of cancer at the expense of vaccination. The intersectoral relationships are to be developed between medicine and education system. The significance of information activities of medical control organs and organizations is to be enhanced.


A predictable but life-threatening complication of hydroxyurea in a patient with sickle cell anaemia: an experience learned from a Jehovah's Witness.
It is well known that hydroxyurea can cause pancytopaenia secondary to bone marrow suppression, which is reversible with short-term discontinuation of the therapy. However, it is important to note that bone marrow suppressive effects caused by hydroxyurea could be easily potentiated in patients with sickle cell anaemia complicated by chronic kidney disease (CKD). We present a case of a Jehovah's Witness with sickle cell anaemia, who developed severe bone marrow suppression due to the combined effects of hydroxyurea and CKD, resulting in a prolonged recovery period after discontinuation of hydroxyurea.


[Somatomedins (author's transl)].
Research on somatomedins (insulin-like growth factors) has progressed greatly over the past few years. In the present review we summarize, in addition to our own results, some recent findings concerning the structure of these factors, their carrier protein, their biosynthesis and hormonal regulation. We also stress the interest of specific assays for their use in clinical investigation.


Screening for circulating immune complexes in blood donors as an effective method of further HBsAg carriers detection.
The loss of counterimmunoelectrophoretic (CIEP) HBsAg reactivity resulting from circulating immune complexes (CIC) formation, observed earlier, prompted us to evaluation the CIC screening in blood donors as an aid in HBsAg detecting. CIC were examined by means of a simple screening modification of the Pegikem test. Among 2.150 normal blood donors there were 21 (0.98%) CIC carriers found, in 13 (61.90%) of them HBsAg was then proved by means of a third generation test. In this population, CIC presence indicated twice as many HBsAg carriers as the CIEP. HBsAg is evidently a very important source of CIC in normal population. The CIC presence is supposed to be a good indicator of HBsAg as well. Therefore, before being accepted as blood donors, CIC carriers should be tested by sensitive test for HBsAg presence.


Injuries sustained by colorectal surgeons performing colonoscopy.
Repetitive tasks in the workplace are one cause of injury. This study aimed to identify injuries specific to physicians routinely performing colonoscopy, and to identify prevention strategies. A survey was sent to all 2,173 worldwide members of the American Society for Colon and Rectal Surgery to investigate injuries or disabilities that resulted from performing colonoscopy and the methods used to prevent and alleviate symptoms related to the procedure. The response rate was 28%. Of the respondents, 96% performed colonoscopy. At least one injury or pain believed to result from performing colonoscopy was reported by 39% of the respondents. The most frequently reported injuries were to hands and fingers (n = 257), neck (n = 65), and back (n = 52). The methods adopted to alleviate injury included changing the height of the stretcher or video monitor, changing from a standing to a sitting position, minimizing torque on the colonoscope, having an assistant perform the torque maneuver, and resting or taking time off from colonoscopy. Two respondents also created devices to make the instrument more ergonomic. The number of colorectal surgeons encountering injury from colonoscopy highlights the need for preventive strategies. The study results suggest that it may be necessary to improve the design of colonoscopes to make them more ergonomic. Appropriate positioning of the endoscopist, patient, and monitors may diminish some of the injuries encountered.


First fetal case of the 8q24.3 contiguous genes syndrome.
Molecular cytogenetics, particularly array-CGH, opened the way to the « genotype first approach » and for the discovery of new micro rearrangement syndromes. This was the case for the 8q24.3 microdeletion syndrome. Here, we describe the phenotype of a fetus with a 8q24.3 deletion. This rare condition has to be considered as a contiguous genes syndrome because its phenotype is generated by the SCRIB and PUF60 adjacent gene endophenotypes. The fetus presented atrioventricular septal defect and hypoplastic aortic arch, facial dysmorphism, microretrognathia, dysmorphic ears, clinodactyly of the 5th digit on both hands, mild rocker bottom feet and abnormal third sacral vertebra. This fetus is the first case where the endophenotype produced by SCRIB gene is absent. This case is compared with the previous published cases.


[Surgical methods for the treatment of breast phyllodes tumors--a report of 319 cases].
Breast phyllodes tumors (FT) belong the fibroapitelial group of breast tumors arising in terminal ductulo-lobular unit (TDLU). Their incidence do not exceed 1% of all breast tumors. Biologicaly they can be divided into benign, borderline and malignant group. Incomplete tumor excision can be the reason for local reccurence. Malignant form of FT metastazise hematogenous most often in the lung. There is no uniform surgical opinion about the treatment FT. We analyzed histopathology features of 319 FT of the breast surgicaly removed on Departement of surgery Institut of oncology and radiology of Serbia between 1.1.1985.-31.12.1994. Retrospective study of surgical treatment 84 patients with FT of the breast (69 benign, 4 borderline and 11 malignant) and 5 year follow up after surgery we analysed. local reccurence after surgery was found in 17 (20,2 %) patients(14 benign , 2 borderline and 1 malignant FT), pulmonary metastases in 6 (7,1%) patients with malignant FT. DFI was 21,3 months for local reccurences and 25,1 months for pulmonary metastases. DFS for al forms of FT was 71 % (p =0,7104) in 5-year follow up. According to biological behavior we propose wide excision for benign and borderline forms and simple mastectomy for malignant FT, and voluminous benign and borderline forms. Axillary disection is not necessary because lymphatic spread of malignant FT is unfrequent.


3D printed microfluidic mixer for point-of-care diagnosis of anemia.
3D printing has been an emerging fabrication tool in prototyping and manufacturing. We demonstrated a 3D microfluidic simulation guided computer design and 3D printer prototyping for quick turnaround development of microfluidic 3D mixers, which allows fast self-mixing of reagents with blood through capillary force. Combined with smartphone, the point-of-care diagnosis of anemia from finger-prick blood has been successfully implemented and showed consistent results with clinical measurements. Capable of 3D fabrication flexibility and smartphone compatibility, this work presents a novel diagnostic strategy for advancing personalized medicine and mobile healthcare.


Mechanically robust nanocomposites from screen-printable polymer/graphene nanosheet pastes.
Innovative methods for producing graphene-based polymer nanocomposites with excellent mechanical robustness have become a focus for their practical utilization, existing solutions suffer from drawbacks such as limited laboratory-scale fabrication, affordability, and inadequate processability. To address these issues, we proposed a screen printing approach utilizing formulated graphene-modified water-based printable pastes to achieve inexpensive and scalable manufacturing of graphene-reinforced polymer nanocomposites. Leveraging this simple and versatile manufacturing process, mass production, as well as personalized-patterned bulk materials, can be efficiently produced using easily obtainable substrates. The surface-tailored graphene (PEI-rGO) can improve the dispersion quality and strengthen the interfacial bonding with a waterborne polyurethane (WPU) matrix, yielding an optimized enhancement effect and enhancing the tensile strength and Young's modulus about 9.46 and 19.8 times higher than those of the pure WPU, respectively. In particular, their utility as an anti-wear modifier through direct printing on textile and wear-reduction performance were investigated. Our study establishes screen printing as a general strategy to achieve facile fabrication of polymer nanocomposites at an industrial-scale in an economically viable manner, which can to a great extent bridge the gap between scientific research and real-world applications.


Passive delivery of protein drugs through transdermal route.
Skin is the largest external organ in the human body but its use for therapeutic purposes has been minimal. Stratum corneum residing on the uppermost layer of the skin provides a tough barrier to transport the drugs across the skin. Very small group of drugs sharing Lipinski properties, i.e. drugs having molecular weight not larger than 500 Da, having high lipophilicity and optimum polarity are fortunate enough to be used on skin therapeutics. But, at a time where modern therapeutics is slowly shifting from use of small molecular drugs towards the use of macromolecular therapeutic agents such as peptides, proteins and nucleotides in origin, skin therapeutics need to be evolved accordingly to cater the delivery of these agents. Physical technologies like iontophoresis, laser ablation, micro-needles and ultrasound, etc. have been introduced to enhance skin permeability. But their success is limited due to their complex working mechanisms and involvement of certain irreversible skin damage in some or other way. This review therefore explores the delivery strategies for transport of mainly peptide and protein drugs that do not involve any injuries (non-invasive) to the skin termed as passive delivery techniques. Chemical enhancers, nanocarriers, certain biological peptides and miscellaneous approaches like prodrugs are also thoroughly reviewed for their applications in protein delivery.


Electromyographic activity and applied load during shoulder rehabilitation exercises using elastic resistance.
Muscle activity (measured by electromyography) and applied load were measured during seven shoulder rehabilitation exercises done with an elastic resistance device. Nineteen men with no shoulder abnormalities performed seven exercises: external and internal rotation, forward punch, shoulder shrug, and seated rowing with a narrow, middle, and wide grip. Qualitative video (60 Hz) was synchronized with the electromyography data from eight muscles (2000 Hz). Fine-wire intramuscular electrodes were inserted into the supraspinatus and subscapularis muscles, and surface electrodes were placed over the anterior deltoid, infraspinatus, pectoralis major, latissimus dorsi, serratus anterior, and trapezius muscles. Ten trials per subject were analyzed for average and peak amplitude, and the results were expressed as a percentage of maximum voluntary contractions. The peak loads for all exercises ranged from 21 to 54 N. The muscle activity patterns suggest that these shoulder rehabilitation exercises incorporating elastic resistance, controlled movements, and low initial loading effectively target the rotator cuff and supporting musculature and are appropriate for postinjury and postoperative patients.


Stathmin 1/2-triggered microtubule loss mediates Golgi fragmentation in mutant SOD1 motor neurons.
Pathological Golgi fragmentation represents a constant pre-clinical feature of many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) but its molecular mechanisms remain hitherto unclear. Here, we show that the severe Golgi fragmentation in transgenic mutant SOD1(G85R) and SOD1(G93A) mouse motor neurons is associated with defective polymerization of Golgi-derived microtubules, loss of the COPI coat subunit β-COP, cytoplasmic dispersion of the Golgi tether GM130, strong accumulation of the ER-Golgi v-SNAREs GS15 and GS28 as well as tubular/vesicular Golgi fragmentation. Data mining, transcriptomic and protein analyses demonstrate that both SOD1 mutants cause early presymptomatic and rapidly progressive up-regulation of the microtubule-destabilizing proteins Stathmins 1 and 2. Remarkably, mutant SOD1-triggered Golgi fragmentation and Golgi SNARE accumulation are recapitulated by Stathmin 1/2 overexpression but completely rescued by Stathmin 1/2 knockdown or the microtubule-stabilizing drug Taxol. We conclude that Stathmin-triggered microtubule destabilization mediates Golgi fragmentation in mutant SOD1-linked ALS and potentially also in related motor neuron diseases.