Protein localization in the human eye and genetic screen of opticin.
The opticin (OPTC) gene encodes a protein that is a member of the small leucine-rich repeat protein (SLRP) family. OPTC is located on chromosome 1q31-q32 within an age-related macular degeneration (AMD) susceptibility locus. We have developed an affinity-purified N-terminal anti-opticin antibody and used it to examine opticin expression in human eye tissues. The antibody was also used for opticin protein localization in human eye sections. Immunoblots of human eye tissues detected a predominant band of approximately 62 kDa in size in iris, trabecular meshwork/ciliary body, retina, vitreous, and optic nerve. Immunohistochemical experiments revealed that opticin is specifically localized in human cornea, iris, ciliary body, vitreous, choroid and retina. Due to opticin's protein profile in the eye, we have also screened OPTC for mutations in individuals with primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG) or AMD. We identified four sequence variations, all of which were observed in normal controls except for the Arg229Cys change. Three amino acid substitutions (Ile182Thr, Arg229Cys and Arg325Trp) were in residues conserved in dog, mouse, pig and human. The Arg229Cys alteration was present in a homozygous state in one individual with neovascular AMD. Examination of the other AMD afflicted family members showed that the OPTC Arg229Cys variant did not segregate with the disorder within the family. The protein localization pattern of opticin and our preliminary screen of AMD patients suggest that a larger AMD patient screen may be warranted.


Cave-dwelling crabs of the genus Karstarma from lava tubes of the volcano 'Piton de la Fournaise', in Réunion Island, with description of a new species and redescription of Karstarma jacksoni (Balss, 1934) from Christmas Island (Decapoda, Brachyura, Sesarmidae).
Sesarmid crabs of the genus Karstarma Davie Ng, 2007 are reported for the first time in the Western Indian Ocean: they were discovered in the lava tubes of the volcano 'Piton de la Fournaise', Réunion Island. A new species, morphologically similar to Karstarma jacksoni (Balss, 1934) from Christmas Island, Eastern Indian Ocean, is recognized and described. A redescription of K. jacksoni is also provided. A second species is recognized, but being represented in the collection by a single juvenile, it cannot be identified to species level until more collections are made in the lava tubes. [Zoobank: http://zoobank.org/NomenclaturalActs/C70A95B2-D667-491D-BD35-5DF32E3FFB08].


Ligand Binding Constants to Lithium Hexamethyldisilazide Determined by Diffusion-Ordered NMR Spectroscopy.
We report the direct measurement of ligand-binding constants of organolithium complexes using a 1H NMR/diffusion-ordered NMR spectroscopy (DOSY) titration technique. Lithium hexamethyldisilazide complexes with ethereal and ester donor ligands (THF, diethyl ether, MTBE, THP, tert-butyl acetate) are characterized using 1H NMR and X-ray crystallography. Their aggregation and solvation states are confirmed using diffusion coefficient-formula weight correlation analysis, and the 1H NMR/DOSY titration technique is applied to obtain their binding constants. Our work suggests that steric hindrance of ethereal ligands plays an important role in the aggregation, solvation, and reactivity of these complexes. It is noteworthy that diffusion methodology is utilized to obtain binding constants.


Screening for functional sequence variations and mutations in ABCA1.
Mutations in the ATP-binding cassette 1 transporter gene (ABCA1) are responsible for the genetic HDL-deficiency syndromes, which are characterized by severely diminished plasma HDL-C levels and a predisposition to cardiovascular disease and splenomegaly. The ABCA1 gene contains 50 exons and codes for a 2261-amino acid long membrane protein that facilitates phospholipid and cholesterol transport. Several mutations have been identified so far as responsible either for Tangier disease or for reduced HDL levels. We have selectively looked for additional polymorphisms in functionally relevant regions of the gene in cohorts constituted of individuals with altered HDL levels as well as healthy blood donors and octogenarians, and screened for mutations in the complete coding region of selected individuals with extremely aberrant HDL levels. In the promoter region, which is important for regulation of gene expression, we have identified several polymorphisms including one VNTR polymorphism, located at a putative ZNF202 binding site, which displayed different binding of ZNF202 in an electromobility shift assay. Three novel SNPs were discovered in the promoter region (G1047C, C1152T and C1440T). The prevalence of exchange G1047C (G-395C) was found significantly increased in probands with low HDL compared to probands with high HDL. Exchanges C1152T (C-290T) and C1440T (C-7T) were significantly more frequent in the cohort with low HDL compared to healthy blood donors and octogenarians. In the C-terminal part of ABCA1, known to interact with other proteins, two novel sequence variations (F2163S and V2244I) have been found in one phenotype related to cardiovascular disease, but none in the aforementioned cohorts. In one individual with extremely high HDL levels, the V771M polymorphism was found in a homozygous state. In patients with HDL deficiency, three novel mutations have been identified (W590L, W840R and R1068C). To facilitate further research in ABCA1 sequence variations and expand our understanding of their effects, we are introducing a webpage archive (http://www.abca1-mutants.all.at) containing all sequence variations reported in ABCA1 so far. This webpage provides a more recent and detailed summary of sequence variations and mutations in ABCA1 than existing databases and should also be of interest for molecular diagnosis of ABCA1-related HDL deficiency.


Pharmacology of pain and analgesia.
Physiological events involved in nociception and pain perception are examined. Substance P could be a primary afferent transmitter of certain nociceptive information. Transmission of this information can be modulated within the spinal cord by intrinsic and descending mechanisms. The intrinsic mechanism involves inhibitory opiate effects within substantia gelatinosa. Centres for descending systems are located in medulla and periaqueductal gray matter. They are activated by exogenous narcotic agonists, and by regional connections. Descending inhibitory pathways are serotonergic and noradrenergic. GABA and glycine are also possibly involved in antinociception. Narcotics have been shown to produce analgesia when administered to the intrathecal or epidural spaces of humans. These routes are still experimental. The place of clinical modification of transmitter system is discussed, but no conclusions or recommendations can be made at this early stage.


BioAdvance Patient Support Program Survey: Positive Perception of Intravenous Infusions of Infliximab.
To understand the perception of intravenous infusions in patients receiving infliximab (Remicade) within the BioAdvance patient support program (PSP). Intravenous infusion of infliximab occurs at approximately 200 clinics across Canada and is managed via the BioAdvance PSP. Patients were invited to complete a 28-question survey on demographics, disease/treatment characteristics, health rating, lifestyle, employment, and perception of intravenous infusions and the BioAdvance program. Analyses were exploratory and descriptive; collected data were self-reported ordinal (Likert scale, unfavorable-to-favorable, 1-10). The Wilcoxon signed-rank test was used to assess statistical significance, and multinomial logistic regression identified predictors of a positive perception of intravenous infusions. 1,712 patients completed the survey. Most respondents had been treated with infliximab for >2 years (58%), had not been previously treated with a biologic (74%), and were receiving treatment for inflammatory bowel disease (76%). Sixty-two percent of patients were employed and most traveled for personal/work reasons (57%) and had a busy/active lifestyle (76%) while attending the BioAdvance clinics. Before treatment, participants rated their perceived favorability of intravenous infusions at 5/10 (median; interquartile range, 5-7); after multiple infusions, their rating increased significantly to 8 (7-9) (P<.001). Regression analysis identified four predictors of a positive infusion experience: French language, favorable ratings of health, accuracy of physician's description, and satisfaction with their BioAdvance coordinator. The vast majority of participants were likely to recommend the BioAdvance PSP. The survey results indicate that the majority of patients receiving infliximab have a positive infusion experience within the BioAdvance PSP.


Avascular necrosis of the femoral head: vascular hypotheses.
Vascular hypotheses provide compelling pathogenic mechanisms for the etiology of avascular necrosis of the femoral head (ANFH). A decrease in local blood flow of the femoral head has been postulated to be the cause of the disease. Several studies in human and animal models of ANFH have shown microvascular thrombosis. Endothelial cell damage could be followed by abnormal blood coagulation and thrombus formation with any resulting degeneration distal to the site of vascular occlusion. Other studies suggest that thrombophilia, particularly impaired fibrinolysis, plays a potential role in thrombus formation in ANFH. Reduction in shear stress due to decreased blood flow could lead to apoptosis of endothelial cells, which can ultimately contribute to plaque erosion and thrombus formation. Dysregulation of endothelial cell activating factors and stimulators of angiogenesis or repair processes could also affect the progression and outcome of ANFH. Likewise, regional endothelium dysfunction (RED), referred to as a potential defect in endothelial cells located in the feeding vessels of the femoral head itself, may also have a crucial role in the pathogenesis of ANFH. Molecular gene analysis of regional endothelial cells could also help to determine potential pathways important in the pathogenesis of ANFH.


Biomarkers of pediatric brain tumors.
Background and Need for Novel Biomarkers: Brain tumors are the leading cause of death by solid tumors in children. Although improvements have been made in their radiological detection and treatment, our capacity to promptly diagnose pediatric brain tumors in their early stages remains limited. This contrasts several other cancers where serum biomarkers such as cancer antigen (CA) 19-9 and CA 125 facilitate early diagnosis and treatment. The aim of this article is to review the latest literature and highlight biomarkers which may be of clinical use in the common types of primary pediatric brain tumor. A PubMed search was performed to identify studies reporting biomarkers in the bodily fluids of pediatric patients with brain tumors. Details regarding the sample type [serum, cerebrospinal fluid (CSF), or urine], biomarkers analyzed, methodology, tumor type, and statistical significance were recorded. A total of 12 manuscripts reporting 19 biomarkers in 367 patients vs. 397 controls were identified in the literature. Of the 19 biomarkers identified, 12 were isolated from CSF, 2 from serum, 3 from urine, and 2 from multiple bodily fluids. All but one study reported statistically significant differences in biomarker expression between patient and control groups. This review identifies a panel of novel biomarkers for pediatric brain tumors. It provides a platform for the further studies necessary to validate these biomarkers and, in addition, highlights several techniques through which new biomarkers can be discovered.


Culture negative endocarditis: a diagnostic and therapeutic challenge!
Infective endocarditis remains a diagnostic and therapeutic challenge. The authors report an older male who presented with a lower extremities rash and signs of cardiac failure. Echocardiography showed vegetations attached to the bio-prosthetic aortic valve, however, with negative blood cultures. Further investigation revealed positive Bartonella serologies. The patient was diagnosed with Bartonella endocarditis affecting the prosthetic valve and started on appropriate antibiotics. Valvular surgery was refused by patient secondary to age and medical co-morbidities. The patient presented 10 days later with intracerebral haemorrhage and progression of the endocarditis as demonstrated on echocardiogram. Valve replacement was contraindicated at this occasion due to the intracerebral bleed. The patient had poor prognosis and a decision to withdraw care was made by the family. The authors demonstrate a case of complicated infective endocarditis caused by Bartonella species leading to multisystem involvement. This case highlights the need for urgent valve replacement in the setting of Bartonella endocarditis.


Susceptibility of Broiler Chickens to Coccidiosis When Fed Subclinical Doses of Deoxynivalenol and Fumonisins-Special Emphasis on the Immunological Response and the Mycotoxin Interaction.
Deoxynivalenol (DON) and fumonisins (FB) are the most frequently encountered mycotoxins produced by Fusarium species in livestock diets. The effect of subclinical doses of mycotoxins in chickens is largely unknown, and in particular the susceptibility of birds to pathogenic challenge when fed these fungal metabolites. Therefore, the present study reports the effects of DON and FB on chickens challenged with Eimeria spp, responsible for coccidiosis. Broilers were fed diets from hatch to day 20, containing no mycotoxins, 1.5 mg DON/kg, 20 mg FB/kg, or both toxins (12 pens/diet; 7 birds/pen). At day 14, six pens of birds per diet (half of the birds) were challenged with a 25×-recommended dose of coccidial vaccine, and all birds (challenged and unchallenged) were sampled 6 days later. As expected, performance of birds was strongly affected by the coccidial challenge. Ingestion of mycotoxins did not further affect the growth but repartitioned the rate of reduction (between the fraction due to the change in maintenance and feed efficiency), and reduced apparent nitrogen digestibility. Intestinal lesions and number of oocysts in the jejunal mucosa and feces of challenged birds were more frequent and intense in the birds fed mycotoxins than in birds fed control feed. The upregulation of cytokines (interleukin (IL) IL-1β, IL-6, IL-8 and IL-10) following coccidial infection was higher in the jejunum of birds fed mycotoxins. Further, the higher intestinal immune response was associated with a higher percentage of T lymphocytes CD4⁺CD25⁺, also called Tregs, observed in the cecal tonsils of challenged birds fed mycotoxins. Interestingly, the increase in FB biomarker of exposure (sphinganine/sphingosine ratio in serum and liver) suggested a higher absorption and bioavailability of FB in challenged birds. The interaction of DON and FB was very dependent on the endpoint assessed, with three endpoints reporting antagonism, nine additivity, and two synergism. In conclusion, subclinical doses of DON and FB showed little effects in unchallenged chickens, but seem to result in metabolic and immunologic disturbances that amplify the severity of coccidiosis.


Studies on the role of interleukin-12 in acute murine toxoplasmosis.
Interleukin-12 (IL-12) is important in the regulation of resistance to Toxoplasma gondii in mice with severe combined immunodeficiency (SCID). The protective ability of IL-12 in SCID mice appears to be through its activity on natural killer (NK) cells to induce production of interferon-gamma (IFN-gamma). In this study we assessed the role of IL-12 in the acute stage of toxoplasmosis in immunocompetent mice. Administration of IL-12 to BALB/c mice infected with the virulent C56 strain of T. gondii remarkably delayed time to death. The protective activity of IL-12 was abrogated by administration of monoclonal antibodies to IFN-gamma or tumour necrosis factor-alpha (TNF-alpha), and by depletion of NK cells using an antisera against asialoGM1. Whereas BALB/c mice infected with the ME49 strain of T. gondii survived infection, administration of anti-IL-12 to infected mice resulted in 100% mortality accompanied by decreased serum levels of IFN-gamma. Furthermore, this treatment significantly reversed the suppression of spleen cell proliferation to concanavalin A (Con A), which is associated with the acute stage of infection, and resulted in decreased ex vivo production of IFN-gamma, IL-2, IL-4 and IL-10 in response to Con A. Our results indicate an important role for IL-12 in mediating resistance to T. gondii during acute infection in immunocompetent mice, that NK cells are required for this protective activity, and that IL-12 is involved in the immunosuppression which accompanies this infection.


Factors Affecting Anemia in Pregnancy Women in Ibeju-Lekki, Lagos State, Nigeria.
Anemia progresses due to low red blood cells counts or hemoglobin. The World Health Organization (WHO) has suggested the condition to be a serious global public health problem that affects pregnant women worldwide. Anemic pregnant women may suffer post-partum hemorrhage, pre-term delivery, seizures, and severe cases of anemia that potentially lead to cardiac failure or death. However, it is pertinent for pregnant women and health service providers to have the adequate knowledge about the factors associated with anemia in pregnancy. Thus, this study assessed the factors associated with anemia in pregnancy women attending primary healthcare (PHC) centers in Ibeju-Lekki Local government area, Lagos state. This study employed descriptive cross-sectional design using multi-stage sampling method to recruit 295 pregnant women into the study. Data were collected using a semi-structured, self-administered questionnaire. The recruited participants (56.6%) were majorly in their third trimester, of which their mean age was 28.7 ± 5.9 years. About 80.7% of the participants were married, having a mean knowledge score of 6.6 ± 3.2. More than half of respondents (56.3%) were anemic and had a poor knowledge (50.5%) of anemia in pregnancy. The mean hemoglobin concentration within the population was 11.06 ± 0.73 g/dl with a range of 8.3 to 12.0. There was no significant association between the respondents' knowledge of anemia in pregnancy and anemic status (X2 = 0.549; P = .45). However, this study observed a significant association between dietary diversity score and anemic status (X2 = 8.66; P = .01) and the trimester status of respondents' first antenatal visit (X2 = 9.603; P = .008). The study concluded that anemia in pregnancy was associated with maternal factors such as their first antenatal visit and the dietary diversity score. Due to this, proper education of pregnant women on anemia by health workers during antenatal clinics or visits should be prioritize to improve their anemia status.


Novel recombinant DNA vaccine candidates for human respiratory syncytial virus: Preclinical evaluation of immunogenicity and protection efficiency.
The development of safe and potent vaccines for human respiratory syncytial virus (HRSV) is still a challenge for researchers worldwide. DNA-based immunization is currently a promising approach that has been used to generate human vaccines for different age groups. In this study, novel HRSV DNA vaccine candidates were generated and preclinically tested in BALB/c mice. Three different versions of the codon-optimized HRSV fusion (F) gene were individually cloned into the pPOE vector. The new recombinant vectors either express full-length (pPOE-F), secretory (pPOE-TF), or M282-90 linked (pPOE-FM2) forms of the F protein. Distinctive expression of the F protein was identified in HEp-2 cells transfected with the different recombinant vectors using ELISA and immunofluorescence. Mice immunization verified the potential for recombinant vectors to elicit significant levels of neutralizing antibodies and CD8+ T-cell lymphocytes. pPOE-TF showed higher levels of gene expression in cell culture and better induction of the humoral and cellular immune responses. Following virus challenge, mice that had been immunized with the recombinant vectors were able to control virus replication and displayed lower inflammation compared with mice immunized with empty pPOE vector or formalin-inactivated HRSV vaccine. Moreover, pulmonary cytokine profiles of mice immunized with the 3 recombinant vectors were similar to those of the mock infected group. In conclusion, recombinant pPOE vectors are promising HRSV vaccine candidates in terms of their safety, immunogenicity and protective efficiency. These data encourage further evaluation in phase I clinical trials.


Community control of cardiovascular diseases. The pro and cons.
The need for an effective control of cardiovascular diseases is evident. Possibilities to achieve this both in the curative and the preventive field are restricted mainly due to the insufficient knowledge of their etiopathogenesis. Although the cause is not known, the discovery to risk factors provides a sound evidence for prevention. Attempts to reverse elevated risk factor levels are all directed towards a more healthy way of life. Group oriented prevention is one of the most frequently applied approaches to test the hypothesis of preventability. While it offers many advantages, the delayed timing of the intervention and the restricted coverage limits the possibility of inference from its results. The community approach implies acting on the whole population by changing their behaviour towards a more healthy way of life. Apart from the beneficial "side effects" on other chronic diseases, their outcome in the pilot areas may be inferred to the total population. The final proof of any scientific evidence from the public health point of view is, after all, its applicability and effectiveness in real life situation.


Eteplirsen in the treatment of Duchenne muscular dystrophy.
Duchenne muscular dystrophy is a fatal neuromuscular disorder affecting around one in 3,500-5,000 male births that is characterized by progressive muscular deterioration. It is inherited in an X-linked recessive fashion and is caused by loss-of-function mutations in the DMD gene coding for dystrophin, a cytoskeletal protein that stabilizes the plasma membrane of muscle fibers. In September 2016, the US Food and Drug Administration granted accelerated approval for eteplirsen (or Exondys 51), a drug that acts to promote dystrophin production by restoring the translational reading frame of DMD through specific skipping of exon 51 in defective gene variants. Eteplirsen is applicable for approximately 14% of patients with DMD mutations. This article extensively reviews and discusses the available information on eteplirsen to date, focusing on pharmacological, efficacy, safety, and tolerability data from preclinical and clinical trials. Issues faced by eteplirsen, particularly those relating to its efficacy, will be identified. Finally, the place of eteplirsen and exon skipping as a general therapeutic strategy in Duchenne muscular dystrophy treatment will be discussed.


Appetite, the enteroendocrine system, gastrointestinal disease and obesity.
The enteroendocrine system is located in the gastrointestinal (GI) tract, and makes up the largest endocrine system in the human body. Despite that, its roles and functions remain incompletely understood. Gut regulatory peptides are the main products of enteroendocrine cells, and play an integral role in the digestion and absorption of nutrients through their effect on intestinal secretions and gut motility. Several peptides, such as cholecystokinin, polypeptide YY and glucagon-like peptide-1, have traditionally been reported to suppress appetite following food intake, so-called satiety hormones. In this review, we propose that, in the healthy individual, this system to regulate appetite does not play a dominant role in normal food intake regulation, and that there is insufficient evidence to wholly link postprandial endogenous gut peptides with appetite-related behaviours. Instead, or additionally, top-down, hedonic drive and neurocognitive factors may have more of an impact on food intake. In GI disease however, supraphysiological levels of these hormones may have more of an impact on appetite regulation as well as contributing to other unpleasant abdominal symptoms, potentially as part of an innate response to injury. Further work is required to better understand the mechanisms involved in appetite control and unlock the therapeutic potential offered by the enteroendocrine system in GI disease and obesity.


Intravascular papillary endothelial hyperplasia of the lung.
Intravascular papillary endothelial hyperplasia (IPEH) is a benign vascular endothelial proliferation, which is usually confined to the lumen of preexisting vessels or vascular malformation. IPEH usually presents as a single lesion, and it rarely involves the lung. We describe a rare case of intrapulmonary IPEH presented by multiple variably sized, well-defined nodules occurring in a 52-year-old woman.


Beyond money and survival: the meaning of paid work among older women.
This article explores the meaning and experiences of paid work for older women. Taped, in-person interviews were conducted with 53 ethnically and economically diverse women, 55 to 84 years old. The interview guide contained open-ended questions regarding the meaning of work, reasons for working, and the centrality of work to personal identity. Participants discussed the following topics: independence from men; lost dreams and regrets related to paid work and educational opportunities; being responded to as mother by co-workers and supervisors; and working above and beyond the call of duty.


Identification of Cellular Pathogenicity Markers for SIL1 Mutations Linked to Marinesco-Sjögren Syndrome.
Background and objective: Recessive mutations in the SIL1 gene cause Marinesco-Sjögren syndrome (MSS), a rare neuropediatric disorder. MSS-patients typically present with congenital cataracts, intellectual disability, cerebellar ataxia and progressive vacuolar myopathy. However, atypical clinical presentations associated with SIL1 mutations have been described over the last years; compound heterozygosity of SIL1 missense mutations even resulted in a phenotype not fulfilling the clinical diagnostic criteria of MSS. Thus, a read-out system to evaluate reliably the pathogenicity of amino acid changes in SIL1 is needed. Here, we aim to provide suitable cellular biomarkers enabling the robust evaluation of pathogenicity of SIL1 mutations. Methods: Five SIL1 variants including one polymorphism (p.K132Q), three known pathogenic mutations (p.V231_I232del, p.G312R, and p.L457P) and one ambiguous missense variant (p.R92W) were studied along with the wild-type proteins in Hek293 in vitro models by cell biological assays, immunoprecipitation, immunoblotting, and immunofluorescence as well as electron microscopy. Moreover, the SIL1-interactomes were interrogated by tandem-affinity-purification and subsequent mass spectrometry. Results: Our combined studies confirmed the pathogenicity of p.V231_I232del, p.G312R, and p.L457P by showing instability of the proteins as well as tendency to form aggregates. This observation is in line with altered structure of the ER-Golgi system and vacuole formation upon expression of these pathogenic SIL1-mutants as well as the presence of oxidative or ER-stress. Reduced cellular fitness along with abnormal mitochondrial architecture could also be observed. Notably, both the polymorphic p.K132Q and the ambiguous p.R92W variants did not elicit such alterations. Study of the SIL1-interactome identified POC1A as a novel binding partner of wild-type SIL1; the interaction is disrupted upon the presence of pathogenic mutants but not influenced by the presence of benign variants. Disrupted SIL1-POC1A interaction is associated with centrosome disintegration. Conclusions: We developed a combination of cellular outcome measures to evaluate the pathogenicity of SIL1 variants in suitable in vitro models and demonstrated that the p. R92W missense variant is a polymorphism rather than a pathogenic mutation leading to MSS.


The formation of the mesoderm in urodelean amphibians : I. Induction by the endoderm.
The blastula [stage 8+ to 8/9 (Harrison)] ofAmbystoma mexicanum was subdivided into four successive animal-vegetative zones and the relative amounts of cellular material present in the successive zones were determined. The developmental capacities of the isolates I, II, III, IV, and I.II and III.IV as well as of the various recombinates of three of the four and of all four zones were studied, and their quantitative composition at the end of the culture period was determined. To this end the embryos were allowed to develop for only 5 to 6 days, during which period the primary organization and initial differentiation was accomplished, but without the appearance of marked changes in the volumes of the different components, which would have occurred upon extensive decomposition of intracellular yolk and subsequent cytoplasmic growth during a longer period of development.Comparing the differentiation of the recombinates with that of the corresponding isolates - in particular the recombinate I.II.IV with the isolates I, II and IV - it was concluded that the mesoderm arises as a result of an interaction between the pigmented, ectodermal and the unpigmented, endodermal "halves" of the egg, which initially [before stage 7 (Harrison)] constitute the only two components of the egg. A comparison of the quantitative composition of the recombinates with that of the corresponding isolates yielded strong arguments in favour of the statement thatthe mesoderm develops exclusively from the ectodermal "half" of the egg under the influence of an inductive action from the part of the endodermal "half". This statement was further corroborated by arguments collected from the literature.Whereas neither the endoderm nor the ectoderm alone are initially able to differentiate beyond a certain point - so-called atypical ectodermal and endodermal differentiation respectively - their interaction product, the mesoderm, apparently contains the information needed for differentiation into the characteristic mesodermal structures. Influences emanating from the differentiating mesoderm then enable both the ectoderm and the endoderm to proceed further on their path of differentiation.The role of the blastocoelic cavity - a cavity with a negative morphogenetic function - in thespatial interaction between the two primary components of the egg was elucidated. In the light of the conclusions mentioned above the centrifugation experiments ofPASTEELS (1953, 1954) were reinterpreted, whileSCHULTZE'S "Umkehrexperiment" byPENNERS andSCHLEIP (1928),PENNERS (1929) andPASTEELS (1938, 1939) andCURTIS' cortical grafting experiments (1960, 1962) were briefly discussed. The hypothesis was then advanced that the inductive interactions taking place in the early embryo preferentially spread through the most superficial layer of the egg, where the cells are tightly connected with each other. Finally, thetemporal aspects of mesoderm induction were discussed in relation to observations collected from the literature.Some parallels were indicated between the morphogenetic events taking place in early amphibian development, and recent biochemical observations on RNA and protein synthesis before the onset of gastrulation.Finally a general picture was drawn of the development of the amphibian egg on the basis of the principle of a stepwise increase in multiplicity by means of inductive interactions.


A technique for securing transperitoneal tubes.
A simple technique for securing transperitoneal tubes is described. We believe this technique results in a tube fixation that is less traumatic to the surrounding skin, is difficult to remove accidentally and is easier to replace.


[A comparison between stereotaxic operation and conservative therapy for thalamic hemorrhage].
The subjects studied in this report included 17 surgical cases which underwent evacuation of hematoma by means of BRW CT stereotaxic system approximately 14 days after its onset, and 11 non-operated cases. The average age was 65.5 years for the operated and 68.7 years for the non-operated groups. The neurological grades on admission were Grade III or above (slight or mild disturbance of consciousness). The evaluation of the cases was made according to (1) laterality of the hematoma on the left or right, (2) neurological grading, (3) maximum anterio-posterior, lateral diameters, and maximum depth of the hematoma, (4) CT classification (Kanaya, 1981) and ADL (5 grades) at 4.5 months after onset. No correlation was found between ADL and the laterality of the lesion in both groups. As for neurological grading I and ADL on admission, 6/8 cases in the operated and 3/8 in the nonoperated groups recovered to ADL grade 2 or above and 2 bed-ridden cases were included in the latter group. In regard to the extent of the hematoma, the mean ADL was 1.83 in the operated group. While 2.75 in the non-operated group where the hematoma was 25 mm or less in its maximum anterio-posterior diameter. On CT, there existed a significant difference in ADL at IIb and 4/5 of the operated and 1/4 of the non-operated groups appeared to be ADL 2 or above. Assessment of the activities (mental change, willingness) as well as the muscle strength was performed within 3 days after surgery in operated group and 88.2% and 35.3% improvements were observed, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


[Selectins as adhesion molecules and potential therapeutic target].
Selectins belong to the family of adhesion molecules that recognize sugars as ligands through their Carbohydrate Recognition Domain (CRD). There are three types of selectin: the L-selectin (CD62L), which is constitutively expressed by most leukocyte populations, the P-selectin (CD62P) is found on activated platelets and endothelial cells, and the E-selectin (CD62E) expressed by activated endothelial cells. These three molecules exhibit high homology in their structures. Selectin-ligand interactions are among the most studied protein-glycan interactions in biology. The selectins and theirs ligands are involved in regulating inflammatory and immunological events that occur at the interface of the bloodstream and vessel walls. Their molecular partners are surface glycoconjugates harboring groups of the sialyl-Lewis antigens. This review presents an inventory of our current knowledge on the structures and functions of selectins and their ligands. We also provide an update on their involvement in pathophysiological processes, especially during inflammation and tumor development.


Diprophylline inhibits non-small cell lung cancer A549 cell proliferation and migration, and promotes apoptosis, by downregulating PI3K signaling pathway.
Diprophylline (DPL) is identified as a methylxanthine (MX) derivative. A number of MX derivatives are reported to have anti-tumor effects. However, it is not clear whether DPL has a therapeutic effect on non-small cell lung cancer (NSCLC). The aim of the present study was to investigate the effects of DPL on NSCLC and to elucidate the potential underlying mechanism. A Cell Counting Kit-8 assay was used to evaluate the potential effect of DPL on A549 cell proliferation. Transwell invasion and migration assays were performed to assess the effect of DPL on A549 cell migration and invasion. Furthermore, the percentage of apoptotic cells was detected by flow cytometric analysis, and proteins associated with apoptosis, including apoptosis regulator Bcl-2, apoptosis regulator BAX and active caspase-3, were examined by western blotting. Finally, the expression levels of molecules relevant to phosphoinositide 3-kinase (PI3K) signaling were detected by western blot analysis. The present study demonstrated that DPL may significantly inhibit A549 cell proliferation, migration and invasion. Furthermore, treatment with DPL may significantly induce A549 cell apoptosis. Finally, the protein expression levels associated with the PI3K signaling pathway were significantly inhibited in A549 cells following treatment with DPL. In conclusion, DPL may inhibit the proliferation and migration of NSCLC by inactivating the PI3K signaling pathway, and DPL is a promising novel therapeutic drug for NSCLC.


Fatigue effects on the coordinative pattern during cycling: kinetics and kinematics evaluation.
The aim of the present study was to analyze the net joint moment distribution, joint forces and kinematics during cycling to exhaustion. Right pedal forces and lower limb kinematics of ten cyclists were measured throughout a fatigue cycling test at 100% of PO(MAX). The absolute net joint moments, resultant force and kinematics were calculated for the hip, knee and ankle joint through inverse dynamics. The contribution of each joint to the total net joint moments was computed. Decreased pedaling cadence was observed followed by a decreased ankle moment contribution to the total joint moments in the end of the test. The total absolute joint moment, and the hip and knee moments has also increased with fatigue. Resultant force was increased, while kinematics has changed in the end of the test for hip, knee and ankle joints. Reduced ankle contribution to the total absolute joint moment combined with higher ankle force and changes in kinematics has indicated a different mechanical function for this joint. Kinetics and kinematics changes observed at hip and knee joint was expected due to their function as power sources. Kinematics changes would be explained as an attempt to overcome decreased contractile properties of muscles during fatigue.


The occurrence of hyponatremia and its importance as a prognostic factor in a cross-section of cancer patients.
Hyponatremia is prognostic of higher mortality in some cancers but has not been well studied in others. We used a longitudinal design to determine the incidence and prognostic importance of euvolemic and hypervolemic hyponatremia in patients following diagnosis with lymphoma, breast (BC), colorectal (CRC), small cell lung (SCLC), or non-small cell lung cancer (NSCLC). Medical record and tumor registry data from two large integrated delivery networks were combined for patients diagnosed with lymphoma, BC, CRC, or lung cancers (2002-2010) who had ≥1 administration of radiation/chemotherapy within 6 months of diagnosis and no evidence of hypovolemic hyponatremia. Hyponatremia incidence was measured per 1000 person-years (PY). Cox proportional hazard models assessed the prognostic value of hyponatremia as a time-varying covariate on overall survival (OS) and progression-free survival (PFS). Hyponatremia incidence (%, rate) was 76 % each, 1193 and 2311 per 1000 PY, among NSCLC and SCLC patients, respectively; 37 %, 169 in BC; 64 %, 637 in CRC, and 60 %, 395 in lymphoma. Hyponatremia was negatively associated with OS in BC (HR 3.7; P = <.01), CRC (HR 2.4; P < .01), lung cancer (HR 2.4; P < .01), and lymphoma (HR 4.5; P < .01). Hyponatremia was marginally associated with shorter PFS (HR 1.3, P = .07) across cancer types. The incidence of hyponatremia is higher than previously reported in lung cancer, is high in lymphoma, BC, and CRC and is a negative prognostic indicator for survival. Hyponatremia incidence in malignancy may be underestimated. The effects of hyponatremia correction on survival in cancer patients require further study.


[Specific and non-specific defense mechanisms against infection].
Defense mechanisms against bacterial, viral or parasitic infections require the cooperation of effector cells (mainly polymorphonuclear and mononuclear phagocytes) and mediators such as antibodies, complement and lymphokines. Antibodies and some complement components promote the endocytosis of microorganisms whereas lymphokines activate phagocytic cells. Once endocytosed, microorganisms are killed either by oxidative reactions consequent to the respiratory burst, or by the particular conditions and factors that they encounter in phagolysosomes. Intact microorganisms or their degradation products handled by mononuclear phagocytes represent immunogenic moieties which can trigger immunocompetent lymphocytes and induce specific immune responses. Phagocytic cells may have characteristic intrinsic deficiencies that are responsible for prolonged or recurrent infections.


Histological evaluation of a biomimetic material in bone regeneration after one year from graft.
The use of substitute materials is one of the solutions used in periodontology for the reconstruction of intrabony defects. Advances in scientific research gave rise to a new generation of biomaterials of synthetic origin stoichiometrically unstable and therefore really absorbable. Our research is directed precisely towards a biomaterial synthesis, Engipore® (Finceramica, Faenza, Italy) which is a bone substitute of the latest hydroxyapatite-based generation, that possesses chemical and morphological properties similar to those of natural bone in the treatment of infrabony periodontal defects. Aim of this study was to evaluate the efficacy of Engipore® in the treatment of intrabony periodontal defects. The study was conducted on 100 parodontopatics patients, which had gingival pockets of at least infrabonies 8/10 mm. The histological evaluation was performed with samples after one year from the graft. The histological samples collected after one year showed an abundant new bone formation, with mature lamellar bone tissue surrounding the residual particles of Engipore® that appear completely osteointegrated. The surrounding connective tissue shows no signs of inflammation. The results obtained in our research demonstrated that, after a proper selection of patients and lesions, and applying an adequate surgical technique, this type of biomaterial in the treatment of periodontal defects acts in an optimal manner as a filler inducing the formation of new bone as evidenced by histological examinations.


Children's understanding of area concepts: development, curriculum and educational achievement.
As one part of a series of studies undertaken to investigate the contribution of developmental attributes of learners to school learning, a representative sample of forty-two students (age from 5 years and 3 months to 13 years and 1 month) was randomly selected from a total student population of 142 students at a small private primary school in northern Australia. Those children's understandings of area concepts taught during the primary school years were assessed by their performance in two testing situations. The first consisted of a written classroom test of ability to solve area problems with items drawn directly from school texts, school examinations and other relevant curriculum documents. The second, which focused more directly on each child's cognitive development, was an individual interview for each child in which four "area" tasks such as the Meadows and Farmhouse Experiment taken from Chapter 11 of The Child's Conception of Geometry (Piaget, Inhelder and Szeminska, 1960, pp. 261-301) were administered. Analysis using the Rasch Partial Credit Model provided a finely detailed quantitative description of the developmental and learning progressions revealed in the data. It is evident that the school mathematics curriculum does not satisfactorily match the learner's developmental sequence at some key points. Moreover, the children's ability to conserve area on the Piagetian tasks, rather than other learner characteristics, such as age and school grade seems to be a precursor for complete success on the mathematical test of area. The discussion focuses on the assessment of developmental (and other) characteristics of school-aged learners and suggests how curriculum and school organization might better capitalize on such information in the design and sequencing of learning experiences for school children. Some features unique to the Rasch family of measurement models are held to have special significance in elucidating the development/attainment nexus.


Identification of a dup(5)(p15.3) by multicolor banding.
A 7-year-old female was referred to the Genetics Clinic because of developmental delay and attentional difficulty. The patient was adopted and there was a nonspecific prenatal history of drug and alcohol abuse. The patient had clinical signs that were not compatible with typical fetal alcohol syndrome (FAS), although there was a history of alcohol exposure in utero, neurodevelopmental difficulties with learning and behavioral problems, and mild dysmorphisms. Cytogenetic analysis revealed an unbalanced female karyotype with a dup(5) containing additional chromosome 5 material at band 5p15.3. The dup(5) showed normal copy number of the cri-du-chat region on 5p15.2 using locus-specific probes D5S721 and D5S23. Multicolor banding of chromosome 5 (MetaSystems) using partial chromosome paint (pcp) probes showed a duplication of band 5p15.3. The karyotype of the patient was therefore interpreted as follows: 46,XX,add(5)mat.ish dup(5)(p15.3)(wcp5 +, D5S271 +, D5S23 +, C84C11/T3 + +, pcp5p15.3 + +). The patient's biological mother and maternal half-brother were found to carry the identical chromosome duplication. The clinical phenotype of the biological mother is complicated by a difficult lifestyle but there were apparent learning and behavioral difficulties at school. The half-brother is nondysmorphic and presents with learning problems and attention deficit disorder (ADD). His physical examination was normal. To the best of our knowledge, this is the first report of a limited duplication of 5p15.3. The clinical significance of the dup(5)(p15.3) is still uncertain but may be the basis for learning and attention difficulties.


Mitochondrial Quality Control: the Role in Cardiac Injury.
The heart is a highly energy-dependent organ, and most of its energy is provided by mitochondrial oxidative phosphorylation. Therefore, maintaining a well-functioning mitochondrial population is of paramount importance for cardiac homeostasis, since damaged mitochondria produce less adenosine triphosphate (ATP) and generate higher amounts of reactive oxygen species (ROS). Mitochondrial dysfunction is associated with the development of many diseases, including cardiovascular disorders. In this article, we review the role of mitochondria as key determinants of acute myocardial ischemic/reperfusion injury (IRI) and also diabetic cardiomyopathy. The structure and function of mitochondria are regulated by the mitochondrial quality control (MQC) system. Mitochondrial quality control mechanisms involve a series of adaptive responses that preserve mitochondrial structure and function as well as ensure cardiomyocyte survival and cardiac function after injury. This review summarizes the basic mechanisms of MQC, including mitochondrial dynamics (fusion and fission), mitophagy and mitochondrial biogenesis. Mitochondrial dynamics are mainly controlled by the level of fission and fusion proteins and also by their post-translational modifications. In addition, this review aims to provide a contemporary view of the importance of miRNA molecules in the regulation of mitochondrial dynamics at the post-transcriptional level. Thus, miRNAs play an important role not only in the pathogenesis and prognosis of cardiac diseases, but can also be an important therapeutic target.


Epidermal growth factor increases c-myc mRNA without eliciting phosphoinositide turnover, protein kinase C activation, or calcium ion mobilization in Swiss 3T3 fibroblasts.
Incubation of quiescent cultures of Swiss 3T3 cells with epidermal growth factor (EGF) caused an increase in c-myc mRNA. Under these conditions, EGF did not induce phosphoinositide turnover, formation of diacylglycerol, formation of inositol tris-, bis-, and monophosphates, protein kinase C activation, or Ca2+ mobilization. Although it has been reported that both protein kinase C and Ca2+ may be responsible for the platelet-derived growth factor- and fibroblast growth factor-induced increases in c-myc mRNA in Swiss 3T3 cells (Kaibuchi, K., Tsuda, T., Kikuchi, A., Tanimoto, T., Yamashita, T., & Takai, Y. (1986) J. Biol. Chem. 261, 1187-1192), these results indicate that neither protein kinase C nor Ca2+ is involved in the EGF-induced increase in c-myc mRNA, and that an unidentified system may be involved in this reaction.


Molecular genotyping and quantitation assay for rotavirus surveillance.
Rotavirus genotyping is useful for surveillance purposes especially in areas where rotavirus vaccination has been or will be implemented. RT-PCR based molecular methods have been applied widely, but quantitative assays targeting a broad spectrum of genotypes have not been developed. Three real time RT-PCR panels were designed to identify G1, G2, G9, G12 (panel GI), G3, G4, G8, G10 (panel GII), and P[4], P[6], P[8], P[10], P[11] (panel P), respectively. An assay targeting NSP3 was included in both G panels as an internal control. The cognate assays were also formulated as one RT-PCR-Luminex panel for simultaneous detection of all the genotypes listed above plus P[9]. The assays were evaluated with various rotavirus isolates and 89 clinical samples from Virginia, Bangladesh and Tanzania, and exhibited 95% (81/85) sensitivity compared with the conventional RT-PCR-Gel-electrophoresis method, and 100% concordance with sequencing. Real time assays identified a significantly higher rate of mixed genotypes in Bangladeshi samples than the conventional gel-electrophoresis-based RT-PCR assay (32.5% versus 12.5%, P<0.05). In these mixed infections, the relative abundance of the rotavirus types could be estimated by Cq values. These typing assays detect and discriminate a broad range of G/P types circulating in different geographic regions with high sensitivity and specificity and can be used for rotavirus surveillance.


Billroth-I anastomosis in distal subtotal gastrectomy for non-early gastric adenocarcinoma.
Billroth-I (B-I) anastomosis is known as a simple and physiological reconstruction method after distal subtotal gastrectomy for early gastric cancer. Yet its role and oncological validity in non-early gastric adenocarcinoma (NEGA) remain unclear. Patients with NEGA without distant metastases operated between May 2004 and December 2020 were included. Surgical and oncologic outcomes of distal subtotal gastrectomy were studied in patients with B-I and Billroth II (B-II) anastomoses. Propensity score matching (PSM) was used to adjust for age, gender, tumor size, location, resection type, pT and pN stages. A total number of 332 patients underwent distal subtotal gastrectomy for NEGA followed by B-I and B-II anastomoses in 165 (49.7%) and 167 (50.3%) cases, respectively. B-I was applied in patients with smaller tumor size, less advanced pT stage and tumor location in the gastric antrum. The former was also associated with lower proportion of multiorgan resections and shorter operative time. After PSM, these differences became statistically non-significant, except operative time. Postoperative outcomes were similar before and after PSM. Greater lymph node yield was observed in patients with B-I anastomosis. The incidence of recurrence, specifically local recurrence was lower in patients with B-I anastomosis. However, this association was not statistically significant in the multivariable model. Median overall survival was 38 months, without significant differences between the groups. The use of B-I anastomosis after distal subtotal gastrectomy for NEGA is associated with satisfactory surgical and oncologic outcomes. B-I anastomosis should be considered as a valid reconstruction method in these patients.


Detection and structural characterization of glutathione-trapped reactive metabolites using liquid chromatography-high-resolution mass spectrometry and mass defect filtering.
The present study was designed to apply the mass defect filter (MDF) approach to the screening and identification of reactive metabolites using high-resolution mass spectrometry. Glutathione (GSH)-trapped reactive metabolites of acetaminophen, diclofenac, carbamazepine, clozapine, p-cresol, 4-ethylphenol, and 3-methylindole in human liver microsomes (HLM) were analyzed by HPLC coupled with Orbitrap or Fourier transform ion cyclotron resonance mass spectrometry. Through the selective removal of all ions that fall outside of the GSH adduct MDF template windows, the processed full scan MS chromatograms displayed GSH adducts as major components with no or a few interference peaks. The accurate mass LC-MS data sets were also utilized for the elimination of false positive peaks, detection of stable oxidative metabolites with other MDF templates, and determination of metabolite molecular formulas. Compared to the neutral loss scan by a triple quadrupole instrument, the MDF approach was more sensitive and selective in screening for GSH-trapped reactive metabolites in HLM and rat bile and far more effective in detecting GSH adducts that do not afford the neutral loss of 129 Da as a significant fragmentation pathway. The GSH adduct screening capability of the MDF approach, together with the utility of accurate mass MS/MS information in structural elucidation, makes high-resolution LC-MS a useful tool for analyzing reactive metabolites.


Endovascular Treatment of Isolated Chronic Abdominal Aortic Dissection.
Isolated acute abdominal aortic dissection is a relatively rare event. Its natural history is not fully understood and its optimal treatment is not established. Open surgery represents the most described treatment but endovascular intervention has had increasing application. Isolated chronic abdominal aortic dissection is even less described in the literature. We describe three patients with isolated chronic abdominal aortic dissection who underwent endovascular treatment in our institution. Mean age at presentation was 82 years. Indication for surgical intervention was aneurismal degeneration. Mean aortic diameter at presentation was 46.7 mm. There was no perioperative mortality or reinterventions. Mean follow-up was 5.3 years (2-12 years). Late reintervention was needed in one patient, eight years after initial surgery, due to type 1 endoleak. According to our experience, endovascular intervention represents an effective and durable treatment option in isolated chronic abdominal aortic dissection. However, long-term follow-up is mandatory. Furthermore, larger studies are still needed to understand this disease and its adequate treatment.


Humoral immune responses to XMMCO-791-RTA immunotoxin in colorectal cancer patients.
Monoclonal antibody 791 (XMMCO-791) recognizes a colorectal tumour-associated antigen. Antibody 791-ricin A chain immunotoxin (XMMCO-791-RTA) inhibits growth of human tumour xenografts and it is therefore being evaluated for the treatment of colorectal cancer. One of the problems with therapy with mouse monoclonal antibodies is they stimulate humoral responses in patients. However antigens linked to ricin are cytotoxic for B cells and therefore XMMCO-791-RTA may not be immunogenic. The humoral antibody response to murine monoclonal antibody XMMCO-791 (IgG2b) conjugated to the plant toxin, ricin A chain (RTA), was measured in colorectal cancer patients in a phase I clinical trial. All patients produced strong responses to the XMMCO-791 immunoglobulin and to RTA. The predominant response to the antibody was against the idiotypic determinant although anti-subclass and anti-mouse antibodies were also detected. A component of the anti-idiotypic immunoglobulin response in the colorectal cancer patients was directed against the combining site of XMMCO-791. These antibodies inhibited in-vitro binding of XMMCO-791 to target 791 cells and so may be inhibitors of repeated immunotoxin therapy. Immunotoxins do not abrogate the immune response to mouse immunoglobulin in vivo but instead are highly immunogenic.


Speech perception and language criteria for paediatric cochlear implant candidature.
Existing criteria for cochlear implantation of children with impaired hearing aim to select children who will eventually achieve better speech perception scores with an implant than with a hearing aid. It is difficult to predict the eventual outcomes with hearing aid and implant because speech perception scores typically increase with age, and because the distribution of scores for implant and hearing aid users overlap considerably at all ages. This paper shows how speech perception scores can be combined with spoken language measures to arrive at an objective criterion for implant selection. The method also allows estimation of the likely increase in speech perception score within a few months of implantation and estimation of the probability that the child will perform better with the implant than the hearing aid. The criteria were based on data from 135 evaluations of 50 children using cochlear implants with monosyllabic words, open-set sentences, the Clinical Evaluation of Language Fundamentals, and the Peabody Picture Vocabulary Test. Data from 114 evaluations of 43 children using hearing aids were used to illustrate the sensitivity of the criteria.


Racial Differences in Treatment Approaches and Mortality Following Arterial Trauma.
We sought to evaluate the impact of race on treatment approaches and mortality following arterial trauma. The National Trauma Data Bank (version 7.2, American College of Surgeons) was queried from 2002 to 2012 to identify patients aged 18 to 65 years with arterial trauma. The association between race (white, black, and Hispanic) and mortality following arterial injury was assessed, stratified by penetrating or blunt injury. Temporal trends in the use of open and endovascular procedures were evaluated across the racial groups. Multivariable regression models adjusting for patient demographics, injury severity, hospital characteristics, insurance status, and type of intervention performed were used to evaluate potential contributors to the association of race with mortality. The study cohort consisted of 58 626 patients (52% white, 31% black, and 17% Hispanic). A majority (57%) of patients had penetrating injuries, with black and Hispanic patients being more likely to sustain penetrating injuries (80% and 65%, respectively) compared to white patients (41%, P < .001). Overall, black patients had higher mortality for penetrating injuries (16.8% vs 13.0% vs 7.8%, P < .001) when compared to Hispanic and white patients, correspondingly. Over the study period, there was increasing use of endovascular and decreasing open surgical procedures for treatment of arterial trauma. This finding was similar across all groups studied. In multivariable analysis, black race was found to be associated with higher mortality compared to white for both penetrating (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.33-1.75, P < .001) and blunt (OR 1.27 95%CI 1.09-1.47, P = .002) arterial trauma. Even after adjusting for potential confounders, minority patients had increased odds of mortality following arterial trauma compared to their white counterparts. Further studies are needed to understand and to eliminate these observed disparities in outcome.


Area deprivation, screen time and consumption of food and drink high in fat salt and sugar (HFSS) in young people: results from a cross-sectional study in the UK.
To investigate associations between deprivation in young people and consumption of foods high in fat, salt and sugar (HFSS), screen time exposure and health knowledge. An online cross-sectional survey with people aged 11-19 years in the UK, where participants reported consumption behaviours across 13 HFSS and two non-HFSS groups; screen time for commercial television and streaming services; and knowledge of health conditions and their links to obesity. UK PARTICIPANTS: A total of 3348 young people aged 11-19 years across the UK. The study assessed the consumption behaviours, commercial screen time exposure and the health knowledge of 3348 people aged 11-19 years. Multivariate binary regression analysis, controlling for age and gender, was performed. Deprivation level was associated with increases in consumption of six of the HFSS products including energy drinks (OR: 2.943, p<0.001) and sugary drinks (OR: 1.938, p<0.001) and a reduction in consumption in the two non-HFSS products included in the study, fruit (OR: 0.668, p=0.004) and vegetables (OR: 0.306, p<0.001). Deprivation was associated with high weekly screen time of both television (OR: 2.477, p<0.001) and streaming (OR: 1.679, p=0.001). Health knowledge was also associated with deprivation. There was lower awareness of the association of obesity and cancer (OR: 0.697, p=0.003), type 2 diabetes (OR: 0.64, p=0.004) and heart disease (OR: 0.519, p<0.001) in the most deprived. Young people from the more deprived areas of the UK were more likely to consume a range of HFSS products, report increased exposure to HFSS advertising and have a poorer awareness of health conditions associated with overweight and obesity. The findings suggest that population-level measures addressing childhood obesity should account for consumption patterns among different groups of children and young people and the factors that may influence these.


Effectiveness of Removal of Hard Tissue Debris from the Mesial Root Canal System of Mandibular Molars using Different Supplementary Irrigation Protocols: An Original Study.
An instrumented and endodontically treated tooth may sometimes impede disinfection by trapping hard tissue as well as the other canal contents at the isthmus level of the canal. Thus, the current in vitro study was piloted to assess the competence of two irrigating systems. Twenty mandibular with two mesial canals convergent into a single foramen and joined by an isthmus of the human permanent teeth were compared for the two irrigation systems of continuous and intermittent ultrasonic (US) motions of the irrigation. The teeth were prepared by a single rotary system and were imaged using the "Scanning electronic microscopy-SCM". The parameters were compared before and after the irrigation of the canal with the intended US systems for the removal of hard tissue debris. The appropriate statistical tools were used to find the significance, the value of which was kept at P < 0.05. Significant percentage reduction of the hard tissue debris was achieved after the application of the supplemental irrigation protocols (P < 0.05). However between the groups, there was no significant difference. Comparable removal of the hard tissue debris was obtained in both the irrigation systems. Though not significant, the GentleWave performed better than the Irrisafe.


Physiological and anatomical characteristics of primary vestibular afferent neurons in the bullfrog.
Intracellular recordings were made in the VIIIth nerve of the bullfrog (Rana catesbiana) to measure the membrane characteristics and obtain records of spontaneous and evoked spike activity of primary semicircular canal afferents. Physiological stimulation of the canals was achieved by rotating the preparation on a servomotor driven turntable with the animals' head centered in the rotational axis. The responses of each neuron to sinusoidal rotations at frequencies of 0.05Hz, 0.5Hz and for impulsive accelerations of 400 deg/sec2 were obtained. Membrane characteristics measured included the cell resting and action potential amplitude, and spike-activation threshold for applied currents. Physiologically characterized neurons were injected with horseradish peroxidase by applying pneumatic pressure and/or iontophoretic currents to the micropipettes containing 5% HRP in 1 M KCI. Following survival times of 12--48 h, the VIIIth nerve and attached vestibular end organ was removed for histochemical processing using a diaminobenzidine procedure to visualize the HRP reaction product. Light microscopy was used to discern the anatomical features of the neurons and to trace their peripheral dendritic trajectories from the ganglion to their termination(s) in the crista. Our studies have revealed that the bullfrog's primary vestibular afferents are characterized by a broad range of soma and axon diameters which correspond to an equally broad range of spontaneous and evoked activity characteristics. The largest neurons had more irregular spontaneous firing rates and consistently exhibited the greatest gain and smallest phase shifts with respect to head acceleration. These neurons consistently terminated at or near the central region of the crista. On the other hand, the smallest neurons were characterized by having the most regular spontaneous discharge patterns, the lowest gains, and greatest phase shifts with respect to head acceleration. Our findings are thus consistent with the view that the anatomical features of the primary vestibular neurons are important in determining the neuron's physiological characteristics. In terms of response dynamics our observations indicate that the receptors in the frog's crista ampullaris are heterogeneous and differentially sensitive to a wide range of stimulus frequencies.


Comparative pharmacokinetics of acteoside from total glycoside extracted from leaves of Rehmannia and Dihuangye total glycoside capsule in normal and diabetic nephropathy rats.
Rehmannia glutinosa Libosch (RG), is officially listed in the Chinese Pharmacopoeia and is widely used in China. In this paper, a sensitive and rapid ultra-performance liquid chromatography-mass spectrometry method including multiple-reaction monitoring mode was developed and applied to study the pharmacokinetic effect of acteoside from total glycoside extracted from the leaves of Rehmannia (TLR) and Dihuangye total glycoside capsule (DTG) in normal and diabetic nephropathy rats. The diabetic nephropathy rat model was induced by intraperitoneal injection of a small dose of streptozotocin and high-fat diet and plus 5% glucose drinking water. Samples of plasma of rats were obtained at different times after rats were administered TLR (7.2 g/kg) and DTG (360 mg/kg). After deproteinization by acetonitrile, the concentrations of acteoside in rats at different time points were detected by UPLC-TQ-MS method and pharmacokinetics parameters were calculated using DAS 3.2.8 software. A good linearity of acteoside was shown in the range of 8.51-3404.8 ng/m L (r2 = 0.9987). The mean extraction recovery of analyte was in the range of 63.55-79.49%, and the intra- and inter-day RSD values were <8.8%. Compared with the normal group, the maximum plasma concentration, AUC0-t , AUC0-∞ and apparent plasma clearance corresponding dose in model group rats decreased significantly. After rats were administered TLR and DTG, the acteoside reached the maximum plasma concentration at about 15 min. The method proved to be simple, rapid and specific, and to be suitable for the determination of acteoside in plasma of diabetic nephropathy rats and pharmacokinetic study.


MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification.
Efficient analysis of very large amounts of raw data for peptide identification and protein quantification is a principal challenge in mass spectrometry (MS)-based proteomics. Here we describe MaxQuant, an integrated suite of algorithms specifically developed for high-resolution, quantitative MS data. Using correlation analysis and graph theory, MaxQuant detects peaks, isotope clusters and stable amino acid isotope-labeled (SILAC) peptide pairs as three-dimensional objects in m/z, elution time and signal intensity space. By integrating multiple mass measurements and correcting for linear and nonlinear mass offsets, we achieve mass accuracy in the p.p.b. range, a sixfold increase over standard techniques. We increase the proportion of identified fragmentation spectra to 73% for SILAC peptide pairs via unambiguous assignment of isotope and missed-cleavage state and individual mass precision. MaxQuant automatically quantifies several hundred thousand peptides per SILAC-proteome experiment and allows statistically robust identification and quantification of >4,000 proteins in mammalian cell lysates.


"Let's Get This Party Started!": An Analysis of Health Risk Behavior on MTV Reality Television Shows.
Past research has examined portrayals of risk behavior in various media, including television, advertising, and film. To address an underexplored area, this study analyzed drinking, smoking, and sexual activities in MTV reality programming popular among adolescent viewers from 2004 to 2011. Cast members' demographic attributes were also examined in relation to their risk behaviors. Results demonstrated that drinking and casual sexual behaviors were pervasive among cast members. Smoking and more intense sexual behaviors were also present, but to a smaller degree. Men and young adult cast members were more likely to engage in risk behaviors than women and teenage cast members. Also, ethnic/racial minority characters were shown drinking more often than were White cast members. Interpretations of these findings are discussed based in social cognitive theory and the concept of super peers. Implications for future research are provided.


Anterior Segment Characteristics of Fuchs Uveitis Syndrome.
To evaluate the differences in the biometric parameters of the anterior segment in Fuchs' uveitis syndrome (FUS). 30 eyes of 15 consecutive patients with unilateral FUS were examined. Anterior segment parameters were measured by rotating Scheimpflug imaging camera. Central endothelial cell count was measured by noncontact specular microscopy. The central cornea was thinner (p < 0.001), the iridocorneal angle was significantly larger (p < 0.010), anterior chamber depth was deeper in the eyes with FUS (p < 0.006). The iris bowing was different between the affected eye and the healthy eye. The mean endothelial cell density of eyes with FUS was significantly lower than control eyes (p < 0.001). Scheimpflug imaging method is a useful tool to analyze the anterior segment parameters in FUS. Endothelial cell loss, as well as decreased percentage of endothelial hexagonal cells, is obtained by noncontact specular microscopy in patients with FUS.


Magnitude of late effects of breast cancer treatments on shoulder function: a systematic review.
Late effects of treatment for breast cancer on shoulder function have been documented by a number of investigators; however, many studies include only prevalence data. When comparisons are provided that assess differences between treatment groups, only P-values without magnitudes of effect are often reported. The purpose of this systematic review was to identify literature that could be used to examine the magnitude of late effects of breast cancer treatments on shoulder function with a particular focus on axillary lymph node dissection (ALND) and on radiotherapy. A comprehensive search of online databases was performed for research papers published between 1980 and 2008 that provided comparison data between treatment groups, between the affected and unaffected side of individuals, or between pre-operative and subsequent assessments 12 months or more after diagnosis of breast cancer. Papers that met inclusion criteria were reviewed using a methodological checklist. Standardized effect sizes were computed for continuous data; odds ratios and 95% confidence intervals were computed for dichotomous data if not already available. Twenty-two papers met the inclusion criteria. With a few exceptions, most analyses showed excess shoulder morbidity with breast cancer treatment, ALND, or radiotherapy. Although effect sizes varied, moderate to large effects predominated across the different outcomes. There is sufficient evidence of late effects of ALND or radiotherapy post-breast cancer to warrant careful attention to shoulder function across time in individuals who have had breast cancer. Implications for future shoulder dysfunction are discussed.


Overview of Single-Molecule Speckle (SiMS) Microscopy and Its Electroporation-Based Version with Efficient Labeling and Improved Spatiotemporal Resolution.
Live-cell single-molecule imaging was introduced more than a decade ago, and has provided critical information on remodeling of the actin cytoskeleton, the motion of plasma membrane proteins, and dynamics of molecular motor proteins. Actin remodeling has been the best target for this approach because actin and its associated proteins stop diffusing when assembled, allowing visualization of single-molecules of fluorescently-labeled proteins in a state specific manner. The approach based on this simple principle is called Single-Molecule Speckle (SiMS) microscopy. For instance, spatiotemporal regulation of actin polymerization and lifetime distribution of actin filaments can be monitored directly by tracking actin SiMS. In combination with fluorescently labeled probes of various actin regulators, SiMS microscopy has contributed to clarifying the processes underlying recycling, motion and remodeling of the live-cell actin network. Recently, we introduced an electroporation-based method called eSiMS microscopy, with high efficiency, easiness and improved spatiotemporal precision. In this review, we describe the application of live-cell single-molecule imaging to cellular actin dynamics and discuss the advantages of eSiMS microscopy over previous SiMS microscopy.


Capability of Scottish emergency departments to provide physician-based prehospital critical care teams: a national survey.
The aim of this study was to establish the current capabilities of emergency departments in Scotland to provide a prehospital medical team at the request of the ambulance service. A prospective telephone survey of all major emergency departments in Scotland was conducted, requesting information on their ability to provide a prehospital team, the configuration of the team and the equipment, transport, training and governance arrangements for this service. All 25 major emergency departments in Scotland responded to the survey (100% response). Eighteen departments (72%) were able to provide a prehospital team, with 15 (60%) able to provide a team 24 h/day. Team composition was variable and only one-third of teams were able to deploy within 15 min. In total, 50% of departments able to respond had received no requests in the preceding 12 months and only two departments had each received more than 50 requests. Less than half of the departments checked prehospital equipment on a weekly or a more frequent basis and only three departments provided ongoing training in prehospital care. The majority of emergency departments in Scotland are able to provide a prehospital team on the request of the ambulance service. There is high variability in the composition and seniority of the team, with less ability to provide a team out of hours. With two notable exceptions, the overall activation of these prehospital teams is infrequent, and there are significant improvements required with regard to the clinical governance surrounding the provision of these teams.


SULFATE PARTICULATES: SIZE DISTRIBUTION IN PITTSBURGH AIR.
Sulfate particles with diameters of less than 1.7 microns contribute approximately 40 percent by weight to total sulfate particulate in Pittsburgh air. The irritant nature of these particles and their small size and associated long atmospheric residence time, as well as the short half-life of sulfur dioxide in the atmosphere, suggest that particulate sulfate may be abetter indicator of atmospheric pollution than sulfur dioxide.


Circulating blood levels of IL-6, IFN-γ, and IL-10 as potential diagnostic biomarkers in gastric cancer: a controlled study.
Gastric adenocarcinoma is the third most common cause of cancer-associated death worldwide. Helicobacter pylori infection activates a signaling cascade that induces production of cytokines and chemokines involved in the chronic inflammatory response that drives carcinogenesis. We evaluated circulating cytokines and chemokines as potential diagnostic biomarkers for gastric cancer. We included 201 healthy controls and 162 patients with distal gastric cancer who underwent primary surgical resection between 2009 and 2012 in Mexico City. The clinical and pathological data of patients were recorded by questionnaire, and the cancer subtype was classified as intestinal or diffuse. Pathological staging of cancer was based on the tumor-node-metastasis staging system of the International Union Against Cancer. Concentrations of IL-1β, IL-6, TNF-α, IL-10, and MCP-1 in serum were measured using multiplex analyte profiling technology and concentrations of IL-8, IFN-γ, and TGF-β in plasma were measured using enzyme-linked immunosorbent assay. Levels of IL-1β, IL-6, IFN-γ, and IL-10 were significantly higher and that of MCP-1 was lower in gastric cancer patients compared with controls. No differences in IL-8 or TNF-α levels were observed between gastric cancer and controls. IFN-γ and IL-10 were significantly higher in both intestinal and diffuse gastric cancer, whereas IL-1β and IL-6 were higher and TGF-β lower only in intestinal gastric cancer; MCP-1 was lower only in diffuse gastric cancer. IFN-γ and IL-10 levels were significantly higher in early (I/II) and late stage (III/IV) gastric cancer; IL-1β and IL-8 were higher and MCP-1 was lower only in late stage (IV) patients. Receiver-operating characteristic analysis showed that for diagnosis of GC, IL-6 had high specificity (0.97) and low sensitivity (0.39), IL-10 had moderate specificity (0.82) and low sensitivity (0.48), and IL-1β and IFN-γ showed low specificity (0.43 and 0.53, respectively) and moderate sensitivity (0.76 and 0.71, respectively). Increased levels of IL-6, IFN-γ, and IL-10 might be useful as diagnostic biomarkers for GC; however, this needs to be confirmed with larger number of patients and with control groups other than blood donors, properly age paired. IL-1β, IL-6, MCP-1, and TGF-β differentiate intestinal from diffuse GC. IFN-γ and IL-10 might be useful for diagnosis of early stage GC, and IL-1β, IL-8, and MCP-1 for late stages of the disease.


The assessment and measurement of adult life stress: Basic premises, operational principles, and design requirements.
Life stress is a central factor in the onset and course of a wide range of medical and psychiatric conditions. Determining the precise etiological and pathological consequences of stress, though, has been hindered by weaknesses in prevailing definitional and measurement practices. The purpose of the current paper is to evaluate the primary strategies for defining and measuring major and minor acute life events, chronic stressors, and daily hassles as informed by 3 basic scientific premises. The first premise concerns the manner in which stress is conceptualized and operationally defined, and specifically we assert that stress measures must not conflate the stress exposure with the stress response. The second premise concerns how stress exposures are measured, and we provide guidelines for optimizing standardized and sensitive indicators of life stress. The third premise addresses the consequences of variations in the procedures for life event measurement with regard to the validity of the research designs employed. We show that life stress measures are susceptible to several sources of bias, and if these potential sources of bias are not controlled in the design of the research, spurious findings may result. Our goal is to provide a useful guide for researchers who consider life stress to be an important factor in their theoretical models of disease, wish to incorporate measures of life stress in their research, and seek to avoid the common pitfalls of past measurement practices. (PsycINFO Database Record


Fibrinogen adsorption by PS latex particles coated with various amounts of a PEO/PPO/PEO triblock copolymer.
Polystyrene (PS) latex particles of different sizes were adsorption coated with the polymeric surfactant Pluronic F108 (PEO129-PPO56-PEO129). The commercial surfactant was found to have a bimodal molecular weight distribution. However, the maximum surface concentrations resulting from adsorption of either the purified high molecular weight component or the composite were identical. An increase in the copolymer surface concentration on 252-nm particles was found to decrease their fibrinogen uptake exponentially. At maximum copolymer surface concentration, the fibrinogen uptake was two orders of magnitude lower than that of bare particles (down from 3.3 mg/m2 to 0.03 mg/m2). This surface protection was equally effective whether the adsorption involved the bimodal polymer surfactant or the purified high molecular weight fraction. The PEO tail mobility was investigated with electron paramagnetic resonance (EPR), and found to increase with an increase in polymer surface concentration. The comparatively slow motion of the PEO chains at low surface concentration indicated that not only the PPO block, but also the PEO blocks interacted hydrophobically with the PS surface. When the copolymer surface concentration was increased, the PEO tails were gradually being released, acquiring higher mobility as the surface became covered by the more strongly binding PPO blocks. Results obtained with F108 coated particles of different sizes showed that particle size had a significant effect on the fibrinogen uptake, with larger particles showing larger fibrinogen uptakes.


The use of vascular access audit and infections in home hemodialysis.
Vascular access-related infection is an important adverse event in home hemodialysis (HHD). We hypothesize that errors in self-cannulation or manipulation of dialysis vascular access are associated with increased incidence of access-related infection. We conducted a retrospective cohort study of all prevalent HHD patients at the University Health Network. All vascular access-related infections were recorded from 2006 to 2013. Errors in dialysis access were ascertained by nurse-administered vascular access checklist. Ninety-two patients had completed at least one vascular access audit. Median HHD vintage was 2.3 (0.9-5.0) years in patients with appropriate vascular access technique and 5.8 (1.5-9.4) years in patients with erroneous vascular access technique. The overall rate of infection between patients with and without appropriate vascular access technique was similar (0.27 and 0.28 infections per year, P = 0.166). Among patients who were identified with errors in dialysis access manipulation, patients with five or more errors were associated with higher rate of access-related infection (mean of 0.47 vs. 0.16 infection per patient-year, P < 0.001). The use of vascular access audit is a feasible strategy, which can identify errors in vascular access technique. Patients with a longer median HHD vintage are associated with higher risk of inappropriate vascular access technique. Patients with multiple errors in vascular access technique are associated with a higher risk of dialysis access-related infection. Prospective evaluation of the impact of vascular access audit on adverse vascular access events is warranted.


Psychometric Properties of the Parental Bonding Instrument in a Sample of Canadian Children.
The parental bonding instrument (PBI) is a self-report questionnaire that was initially designed to retrospectively assess perceived parenting style during childhood in adult respondents. Recent studies have used the PBI to assess current perception of parenting in children. However, few studies have evaluated the psychometric properties of the PBI in children. This study examined the factor structure and reliability of the PBI in a sample of Canadian children aged 7-18 years (n = 257). Confirmatory factor analyses (CFA) were conducted separately for the mother and father form of the PBI and composite reliability was used to determine internal consistency of the PBI. A four-factor model (care, overprotection, autonomy, indifference) showed the best fit to the data. The PBI exhibited good internal consistency but poor convergent validity. Configural invariance was not found for the PBI between two age groups (7-12 and 13-18 years), however these findings should be interpreted with caution due to the small sample size in each age group. This study suggests the PBI may be a valid and reliable self-report measure of parental bonding in children but further research is needed.


Low-power laser in osteoarthritis of the cervical spine.
Patients with symptomatic osteoarthritis of the cervical spine were treated with very low-power modulated laser (LPL). Two applications were performed at an interval of 20 days. Changes in pain and ultrasound thickness of the soft connective tissue layer above the right and the left superior trapezium were studied. No worsening of pain was observed. Pain improved after the first application of LPL in 9 out of 14 patients, but the difference was not significant. Pain improvement remained stable between the first assessment and the second assessment, which was performed after 20 days. In comparison with the first application, at the second application the number of patients with improved pain after LPL increased to 12 out of 14 (p < 0.01). An appreciable difference in the thickness of the subcutaneous soft tissue layer overlying the two superior trapezia was demonstrated in all patients at the first examination. Comparison of the measurements before and after the application of LPL showed significant differences.


Fermentation kinetics of Zymomonas mobilis near zero growth rate.
The fermentation kinetics Zymomonas mobilis were studied near zero growth rate in fed-batch cultures and continuous cultures with complete cell recycle. The results show the ethanol enhances that specific substrate conversion rate under these conditions. The maximum achievable ethanol concentration in continuous cultures with cell recycle (66 g/L) was significantly lower than in fed-batch cultures (100 g/L). The results indicate that growth-rate-independent metabolism is not instantaneous and can lag behind steadily increasing ethanol concentrations in fed-batch fermentations. A model is proposed to account for this slow adaptation.


Streptococcal throat infections: still a complex clinical problem.
Acute pharyngotonsillitis is an inflammatory syndrome of the pharynx caused by both viral and bacterial infections. Most cases are of viral etiology and occur as part of common cold and influenzal syndromes. The most important of the bacterial infections is due to beta-streptococci. It is important to differentiate streptococcal from viral pharyngotonsillitis because of the response of streptococcal infection to antibiotic therapy and the ineffectiveness of antibiotic therapy in viral infections. Streptococcal pharyngotonsillitis may also be complicated by acute rheumatic fever and acute glomerulonephritis. Streptococcal pharyngotonsillitis still constitutes many problems in regard to diagnosis and treatment mainly because there is not sufficient knowledge concerning the pathogenetic events in these infections. In this review article different aspects on microbiological and clinical diagnosis of streptococcal pharyngotonsillitis, streptococcal carriers and antibiotic treatment are presented.


Seroepidemiological Studies on Japanese Encephalitis: A Systematic Review.
Japanese encephalitis (JE) is one of the major mosquito-borne infectious diseases in the Western Pacific region, accounting for 20%-30% of mortality cases. The JE virus (JEV) seroprevalence fluctuations indicate that continuous research is important for prevention and control activities. By mapping JEV seroprevalence by age stratification, the population profile for immunity and susceptibility can be identified to aid in vaccination program planning. Thus, this study aimed to determine the trend of age-specific JEV seroprevalence. We conducted a systematic review of all studies conducted on JEV seroprevalence between 2010 and 2019. The two search engines used were PubMed and Web of Science. Eligible criteria were set, and articles were screened according to the Preferred Reporting Items for Systematic Reviews and Meta- Analyses guidelines. Three investigators cross-checked all articles assigned. Data were extracted into an Excel sheet, and results were tabulated in tables and graphs accordingly. Four studies from four countries (Taiwan, Sri Lanka, South Korea, and India) met the eligibility criteria. The papers showed an increasing trend of JEV seropositivity in all countries as their populations reach older age cohorts. Nonetheless, there were slight downtrend notches seen among young adults in Taiwan and India before increasing after reaching more mature ages. South Korea has the highest seroprevalence rate (97.8%-98.3%) among the compared countries. This is most likely because it was the earliest to introduce the JEV vaccine in 1967, which was later made mandatory in the early 1980s, while India has the lowest seroprevalence rate (12.9%-18.1%). Among the old vaccination-naïve population, seropositivity is commonly derived from natural infection. Decreases in reported JE cases are mainly due to immunization. As JEV is expected to remain in nature and the zoonotic chains, the risk of infection will persist. Hence, it is important to apply JEV vaccination protocols in national immunization programs, prioritizing young children.


Pregnancy may favour the development of severe autoimmune central diabetes insipidus in women with vasopressin cell antibodies: description of two cases.
Recently, an increased incidence of central diabetes insipidus (CDI) in pregnancy, and less frequently in the post partum period, has been reported, most probably favoured by some conditions occurring in pregnancy. This study was aimed at investigating the influence of pregnancy on a pre-existing potential/subclinical hypothalamic autoimmunity. We studied the longitudinal behaviour of arginine-vasopressin cell antibodies (AVPcAbs) and post-pituitary function in two young women with a positive history of autoimmune disease and presence of AVPcAbs, but without clinical CDI, and who became pregnant 5 and 7 months after our first observation. The behaviour of post-pituitary function and AVPcAbs (by immunofluorescence) was evaluated at baseline, during pregnancy and for 2 years after delivery. AVPcAbs, present at low/middle titres at baseline in both patients, showed a titre increase during pregnancy in one patient and after delivery in the other patient, with development of clinically overt CDI. Therapy with 1-deamino-8-d-arginine vasopressin (DDAVP) caused a prompt clinical remission. After a first unsuccessful attempt of withdrawal, the therapy was definitively stopped at the 6th and the 7th month of post partum period respectively, when AVPcAbs disappeared, accompanied by post-pituitary function recovery, persisting until the end of the follow-up. The determination of AVPcAbs is advisable in patients with autoimmune diseases planning their pregnancy, because they could be considered good predictive markers of gestational or post partum autoimmune CDI. The monitoring of AVPcAb titres and post-pituitary function during pregnancy in these patients may allow for an early diagnosis and an early replacement therapy, which could induce the disappearance of these antibodies with consequent complete remission of CDI.


[Late catatonic syndrom symptomatic of a degenerative encephalopathy (author's transl)].
The authors have observed the evolution of a late catatonic syndrome in a 50 years old woman, without psychological background. They have observed a progressive mental (intellectual) deterioration which have had for a long time a partial and paradoxical aspect, while on the thymic and affective stade an atypical melancolic picture evolved toward a schizophrenic syndrome with catatonic traits which finally came to a stade of marasmus and death after three and a half years of illness. A psychological examination performed at mid course confirmed the mental deterioration without intellectual disorganisation (Wechler) while the Rorschach indicated schizophrenia. The neuro-radiological explorations, repeated several times, have demonstrated the existence of a diffuse cerebral atrophy on the white substance and yet more on the cortex, and it was possible to follow the aggravation of this atrophy. Repeated biological tests were less informative: albumine in the CSF was 0.15 to 0.63 g % and an isolated increase of alpha1-globulines in the CSF was observed at the electrophoresis 4 months before the exitus. Histological examination of cortical biopsies and of the white substance indicates a degenerative encephalopathy with spongiosis and cortical atrophy. Because of the limited value of the histopathological examination, one cannot suggest a systematic interpretation of the catatonic symptoms.


Structure-biological function relationship extended to mitotic arrest-deficient 2-like protein Mad2 native and mutants-new opportunity for genetic disorder control.
Overexpression of mitotic arrest-deficient proteins Mad1 and Mad2, two components of spindle assembly checkpoint, is a risk factor for chromosomal instability (CIN) and a trigger of many genetic disorders. Mad2 transition from inactive open (O-Mad2) to active closed (C-Mad2) conformations or Mad2 binding to specific partners (cell-division cycle protein 20 (Cdc20) or Mad1) were targets of previous pharmacogenomics studies. Here, Mad2 binding to Cdc20 and the interconversion rate from open to closed Mad2 were predicted and the molecular features with a critical contribution to these processes were determined by extending the quantitative structure-activity relationship (QSAR) method to large-size proteins such as Mad2. QSAR models were built based on available published data on 23 Mad2 mutants inducing CIN-related functional changes. The most relevant descriptors identified for predicting Mad2 native and mutants action mechanism and their involvement in genetic disorders are the steric (van der Waals area and solvent accessible area and their subdivided) and energetic van der Waals energy descriptors. The reliability of our QSAR models is indicated by significant values of statistical coefficients: Cross-validated correlation q2 (0.53-0.65) and fitted correlation r2 (0.82-0.90). Moreover, based on established QSAR equations, we rationally design and analyze nine de novo Mad2 mutants as possible promoters of CIN.


Cellular Identification and In Silico Characterization of Protein Phosphatase 2C (PP2C) of Cryptosporidium parvum.
Cryptosporidium parvum is an Apicomplexa parasite that causes watery diarrhea (cryptosporidiosis), especially in children and immunocompromised adults (the latter in a very severe form). No effective treatment exists against infection by this parasite. Phosphatases participate in the regulation of various cellular functions and are thus considered potential therapeutic targets in many diseases. The aim of the present study was to indirectly identify and in silico characterize a protein phosphatase 2C of C. parvum. Western blot and indirect immunofluorescence microscopy were performed with a polyclonal antibody against Leishmania major PP2C. Possible cross-reactivity with LmPP2C was assessed by in silico sequence homology to analyze phylogenetic relationships between distinct C. parvum PP2Cs. In addition, another bioinformatics approach was used to predict the possible relationship and function of C. parvum PP2C in the regulation of several cellular processes. Western blotting showed a protein of approximately 72 kDa. With immunofluorescence, PP2C was localized in the nucleus of oocysts (with some additional labeling in the cytoplasm) and at the apical region of sporozoites. By aligning C. parvum PP2C with known ortholog sequences and carrying out PPI analysis, a determination could be made of the degree of conservation of these enzymes, their possible relationship, and their function in the regulation of several cellular processes associated with a likely nuclear location. Microscopic localization by immunofluorescence identified CpPP2C at the nucleus in oocysts and at the apical end of the sporozoite body. Hence, this enzyme could be associated with proteins that have an important role in the regulation of transcription and other processes orchestrated by MAPK kinases, according to in silico analysis.


The active movement scale: an evaluative tool for infants with obstetrical brachial plexus palsy.
Newborns with peripheral nerve lesions involving the upper extremity are difficult to evaluate. The reliability of the Active Movement Scale (AMS), a tool for assessing motor function in infants with obstetrical brachial plexus palsy (OBPP), was examined in 2 complementary studies. Part A was an interrater reliability study in which 63 infants younger than 1 year with OBPP were independently evaluated by 2 physical therapists using the AMS. The scores were compared for reliability and controlled for chance agreement by using kappa statistics. Overall kappa analysis of the 15 tested movements showed a moderate strength of score agreement (kappa = 0.51). Quadratic-weighted kappa (kappa(quad)) statistics showed that 8 of the 15 movements tested were in the highest strength of agreement category (kappa(quad) = 0.81-1.00). Five movements showed substantial agreement (kappa(quad) = 0.61-0.80), and 2 movements had moderate agreement (kappa(quad) = 0.41- 0.60). The overall kappa(quad) was 0.89. Part B was a variability study designed to examine the dispersion of scores when infants with OBPP were evaluated with the AMS by multiple raters. Ten pediatric physical therapists with varying degrees of experience using the scale attended a 1(1/2)-hour instructional workshop on administration of the tool for infants with OBPP. A chain-block study design was used to obtain 30 assessments of 10 infants by 10 raters. A 2-way analysis of variance indicated that the variability of scores due to rater factors was low compared with the variability due to patient factors and that variation in scores due to rater experience was minimal. The results of part A indicate that the AMS is a reliable tool for the assessment of infants with OBPP when raters familiar with the scale are compared. The results of part B suggest that, with minimal training, raters with a range of experience using the AMS are able to reliably evaluate infants with upper-extremity paralysis.