Sub-cellular localization specific SUMOylation in the heart.
Although the majority of SUMO substrates are localized in the nucleus, SUMOylation is not limited to nuclear proteins and can be also detected in extra-nuclear proteins. In this review, we will highlight and discuss how SUMOylation in different cellular compartments regulate biological processes. First, we will discuss the key role of SUMOylation of proteins in the extra-nuclear compartment in cardiomyocytes, which is overwhelmingly cardio-protective. On the other hand, SUMOylation of nuclear proteins is generally detrimental to the cardiac function mainly because of the trans-repressive nature of SUMOylation on many transcription factors. We will also discuss the potential role of SUMOylation in epigenetic regulation. In this review, we will propose a new concept that shuttling of SUMO proteases between the nuclear and extra-nuclear compartments without changing their enzymatic activity regulates the extent of SUMOylation in these compartments and determines the response and fate of cardiomyocytes after cardiac insults. Approaches focused specifically to inhibit this shuttling in cardiomyocytes will be necessary to understand the whole picture of SUMOylation and its pathophysiological consequences in the heart, especially after cardiac insults. This article is part of a Special Issue entitled: Genetic and epigenetic control of heart failure - edited by Jun Ren & Megan Yingmei Zhang.


"Because Even the Person Living With HIV/AIDS Might Need to Make Babies" - Perspectives on the Drivers of Feasibility and Acceptability of an Integrated Community Health Worker Model in Iringa, Tanzania.
Countries with health workforce shortages are increasingly turning to multipurpose community health workers (CHWs) to extend integrated services to the community-level. However, there may be tradeoffs with the number of tasks a CHW can effectively perform before quality and/or productivity decline. This qualitative study was conducted within an existing program in Iringa, Tanzania where HIV-focused CHWs working as volunteers received additional training on maternal, newborn, and child health (MNCH) promotion, thereby establishing a dual role CHW model. To evaluate the feasibility and acceptability of the combined HIV/MNCH CHW model, qualitative in-depth interviews (IDIs) with 36 CHWs, 21 supervisors, and 10 program managers were conducted following integration of HIV and MNCH responsibilities (n=67). Thematic analysis explored perspectives on task planning, prioritization and integration, workload, and the feasibility and acceptability of the dual role model. Interview data and field observations were also used to describe implementation differences between HIV and MNCH roles as a basis for further contextualizing the qualitative findings. Perspectives from a diverse set of stakeholders suggested provision of both HIV and MNCH health promotion by CHWs was feasible. Most CHWs attempted to balance HIV/MNCH responsibilities, although some prioritized MNCH tasks. An increased workload from MNCH did not appear to interfere with HIV responsibilities but drew time away from other income-generating activities on which volunteer CHWs rely. Satisfaction with the dual role model hinged on increased community respect, gaining new knowledge/skills, and improving community health, while the remuneration-level caused dissatisfaction, a complaint that could challenge sustainability. Conclusions: Despite extensive literature on integration, little research at the community level exists. This study demonstrated CHWs can feasibly balance HIV and MNCH roles, but not without some challenges related to the heavier workload. Further research is necessary to determine the quality of health promotion in both HIV and MNCH domains, and whether the dual role model can be maintained over time among these volunteers.


Postsecondary study and mental ill-health: a meta-synthesis of qualitative research exploring students' lived experiences.
The postsecondary educational experiences of students living with mental health issues are not well understood. Existing studies are generally qualitative, small and context-specific in nature, and individually have limited influence on policy and practice. To identify and synthesise the findings of qualitative studies exploring student views of studying while living with mental ill-health. A systematic search of six electronic databases including CINAHL, ERIC, PsycINFO and Medline up to March 2013 was conducted. Findings were extracted from included studies and combined using qualitative meta-synthesis to identify core processes. The search identified 16 studies from five countries, with a total of 231 participants. Meta-synthesis of the findings revealed three common core processes: (1) knowing oneself and managing one's mental illness, (2) negotiating the social space, and (3) doing the academic work required for successful postsecondary participation. Beyond the learning processes that underpin studying, these findings suggest knowing oneself and negotiating social spaces of educational settings are key processes for students living with mental ill-health seeking to survive and thrive in postsecondary education. With increased awareness of these processes, students and policy makers may conceive new ways to optimise student experiences of postsecondary study.


Use of coherent control methods through scattering biological tissue to achieve functional imaging.
We test whether coherent control methods based on ultrashort-pulse phase shaping can be applied when the laser light propagates through biological tissue. Our results demonstrate experimentally that the spectral-phase properties of shaped laser pulses optimized to achieve selective two-photon excitation survive as the laser pulses propagate through tissue. This observation is used to obtain functional images based on selective two-photon excitation of a pH-sensitive chromophore in a sample that is placed behind a slice of biological tissue. Our observation of coherent control through scattering tissue suggests possibilities in multiphoton-based imaging and photodynamic therapy.


Immune Modulation in Prostate Cancer Patients Treated with Androgen Receptor (AR)-Targeted Therapy.
Androgen deprivation therapy (ADT) is a cornerstone of treatment for prostate cancer and, in recent years, androgen receptor (AR)-targeted therapies (abiraterone and enzalutamide) have both been used for the treatment of castration-resistant prostate cancer (CRPC). In our study, we sought to investigate the association between ADT and immune disorders, considering a potential role of androgens in the immune modulation. We retrospectively evaluated CRPC patients treated with abiraterone/enzalutamide between July 2011 and December 2018. We assessed the risk of developing immune alterations and their impact on outcome. We included 844 CRPC patients receiving AR-directed therapies, of whom 36 (4.3%) had autoimmune diseases and 47 (5.6%) second tumors as comorbidities. Median age was 70 years [interquartile range (IQR) = 63-75)]. We showed higher significant incidence of autoimmune diseases during their hormone sensitive status (p = 0.021) and the presence of autoimmune comorbidities before starting treatment with abiraterone/enzalutamide was significantly associated with worse overall survival (OS) (10.1 vs. 13.7 months, HR = 1.59, 95% CI 1.03-2.27, p = 0.038). In a multivariate analysis, the presence of autoimmune disorders was an independent predictor of OS (HR = 1.65, 95% CI 1.05-2.60, p = 0.031). In conclusion, CRPC patients with autoimmune alterations before starting AR-directed therapies may have worse prognosis. Further prospective studies are warranted to assess the role of immune modulation in the management of prostate cancer patients.


[Diagnostic and treatment of necrotizing cervical fascitis. Clinical course after a Ludwig angina].
The Ludwig angina is an infection of the base of the mouth and submandibular region, frecuently after a dental extraction or a piece in bad state. When it surpassees the milohioid muscle it extends dissecting the superficial aponeurotic planes, and can evolve to a necrotisant fascitis. We present the case of a 67 years old man with a painful tumefaction of the mouth base and submandibular region. The CT reflected an heterogenous submaxilar lesion that extended by the deep cervical fascia introducing itself in the thorax. Under antibiotic treatment the pus was drained by cervicotomy, with daily cures during 3 weeks.


[Torus mandibularis. Apropos a case].
One case of mandibular torus is described. It was an hyperostosis of the lower jaw, of big size, condition scarcely presented, and characterized by its long course and slight local feeling of discomfort. Total removing of the mass is the indicated surgical treatment.


Projections from the ventral cochlear nucleus to the dorsal cochlear nucleus in rats.
Local circuit interactions between the dorsal and ventral divisions of the cochlear nucleus are known to influence the evoked responses of the resident neurons to sound. In the present study, we examined the projections of neurons in the ventral cochlear nucleus to the dorsal cochlear nucleus by using retrograde transport of biotinylated dextran amine injected into restricted but different regions of the dorsal cochlear nucleus. In all cases, we found retrogradely labeled granule, unipolar brush, and chestnut cells in the granule cell domain, and retrogradely labeled multipolar cells in the magnocellular core of the ventral cochlear nucleus. A small number of the labeled multipolar cells were found along the margins of the ventral cochlear nucleus, usually near the boundaries of the granule cell domain. Spherical bushy, globular bushy, and octopus cells were not labeled. Retrogradely-labeled auditory nerve fibers and the majority of labeled multipolar neurons formed a narrow sheet extending across the medial-to-lateral extent of the ventral cochlear nucleus whose dorsoventral position was topographically related to the injection site. Labeled multipolar cells within the core of the ventral cochlear nucleus could be divided into at least two distinct groups. Planar neurons were most numerous, their somata found within the associated band of labeled fibers, and their dendrites oriented within this band. This arrangement mimics the organization of isofrequency contours and implies that planar neurons respond best to a narrow range of frequencies. In contrast, radiate neurons were infrequent, found scattered throughout the ventral cochlear nucleus, and had long dendrites oriented perpendicular to the isofrequency contours. This dendritic orientation suggests that radiate neurons are sensitive to a broad range of frequencies. These structural differences between planar and radiate neurons suggest that they subserve separate functions in acoustic processing.


Salmonella infection of a penile prosthesis.
Patients with erectile dysfunction (ED) who have failed oral or intracavernosal erectogenic therapy may benefit from inflatable penile prosthesis (IPP) placement. Such individuals commonly include patients with diabetes mellitus or chronic renal insufficiency. Complications of IPP placement include erosion and infection. Most often, infection of IPPs involves skin flora that are hypothesized to be introduced at the time of device placement and persist as a biofilm, causing clinical infection as a result of failure of containment by host defense mechanisms. In this report, we describe a renal transplant patient with a Salmonella infection of an IPP following a diarrheal illness. To our knowledge, this organism has not been implicated in penile prosthesis infection. The clinical course of, and microbiological data pertinent to, this patient are summarized. Additionally, a limited literature review was undertaken and is here summarized. Retrospective review of medical record documentation. This patient was found to have a Salmonella infection of his IPP with ensuing device erosion. Following urgent device removal and culture-specific antibiotic therapy, he was discharged from the hospital at his baseline functional status and renal function. This is the first report of which we are aware in which Salmonella penile prosthesis infection is described. While this man's immunocompromised status may have made him more vulnerable to device infection, the literature is generally supportive of IPP placement in the transplant population when other modes of ED treatment have failed. Moreover, we postulate a hematogenous mechanism for device seeding in this patient.


Contrasting patterns of polymorphism and selection in bacterial-sensing toll-like receptor 4 in two house mouse subspecies.
Detailed investigation of variation in genes involved in pathogen recognition is crucial for understanding co-evolutionary processes between parasites and their hosts. Triggering immediate innate response to invading microbes, Toll-like receptors (TLRs) belong presently among the best-studied receptors of vertebrate immunity. TLRs exhibit remarkable interspecific variation and also intraspecific polymorphism is well documented. In humans and laboratory mice, several studies have recently shown that single amino acid substitution may significantly alter receptor function. Unfortunately, data concerning polymorphism in free-living species are still surprisingly scarce. In this study, we analyzed the polymorphism of Toll-like receptor 4 (Tlr4) over the Palearctic range of house mouse (Mus musculus). Our results reveal contrasting evolutionary patterns between the two recently (0.5 million years ago) diverged house mouse subspecies: M. m. domesticus (Mmd) and M. m. musculus (Mmm). Comparison with cytochrome b indicates strong directional selection in Mmd Tlr4. Throughout the whole Mmd western Palaearctic region, a single variant of the ligand-binding region is spread, encoded mainly by one dominant haplotype (71% of Mmd). In contrast, Tlr4 in Mmm is much more polymorphic with several haplotypes at intermediate frequencies. Moreover, we also found clear signals of recombination between two principal haplogroups in Mmm, and we identified eight sites under positive selection in our dataset. Our results suggest that observed differences in Tlr4 diversity may be attributed to contrasting parasite-mediated selection acting in the two subspecies.


Acetylcholinesterase/butyrylcholinesterase inhibition activity of some new carbacylamidophosphate derivatives.
Eight newly synthesized carbacylamidophosphates with the general formula RC(O)NHP(O)Cl2 with R = pCl-C6H4 1a, pBr-C6H4 2a, C6H5 3a, and pMe-C6H4 4a and RC(O)NHP(O)(NC4H8O)2 R = pCl-C6H4 1b, pBr-C6H4 2b, C6H5 3b, pMe-C6H4 4b, were selected to compare the inhibition kinetic parameters, IC50, Ki, kp and KD, on human erythrocyte acetylcholinesterase (hAChE) and bovine serum butyrylcholinesterase (BuChE), Also, the in vivo inhibition potency of compound 2a, 2b and 3a, were studied. The data demonstrates that compound 2a and compound 2b are the potent sensitive as AChE and BuChE inhibitors respectively, and the inhibition of hAChE is about 10-fold greater than that of BuChE.


Isolation and characterization of coagulant extracted from Moringa oleifera seed by salt solution.
It is known that M. oleifera contains a natural coagulant in the seeds. In our previous research, the method using salt water to extract the active coagulation component from M. oleifera seeds was developed and compared with the conventional method using water. In this research, the active coagulation component was purified from a NaCl solution crude extract of Moringa oleifera seeds. The active component was isolated and purified from the crude extract through a sequence of steps that included salting-out by dialysis, removal of lipids and carbohydrates by homogenization with acetone, and anion exchange. Specific coagulation activity of the active material increased up to 34 times more than the crude extract after the ion exchange. The active component was not the same as that of water extract. The molecular weight was about 3000 Da. The Lowry method and the phenol-sulfuric acid method indicated that the active component was neither protein nor polysaccharide. The optimum pH of the purified active component for coagulation of turbidity was pH 8 and above. Different from the conventional water extracts, the active component can be used for waters with low turbidity without increase in the dissolved organic carbon concentration.


A picture of tuberculosis in young Portuguese people in the early 20th century: a multidisciplinary study of the skeletal and historical evidence.
The aim of this study was to examine the evidence, and consider the differential diagnosis, for tuberculosis (TB) in juvenile individuals from early 20th century documented skeletons. There are 66 male and female juvenile individuals in the Coimbra Identified Skeletal Collection (CISC) with an age at death ranging from 7-21 years. The individuals died between 1904-1936 in different areas of Coimbra, Portugal. Eighteen of these individuals died from TB affecting different parts of the body. Thirteen (72.2%) showed skeletal lesions that may be related to this infection. Of the 48 individuals with a non-tuberculous cause of death, only 2 (4.2%) had skeletal changes that could be attributed to TB. The distribution of skeletal manifestations caused by the types of TB under study, based on macroscopic and radiological findings, is described and discussed. In addition, the medical records from 6 tuberculous individuals who died in Coimbra University Hospital (CUH) were analysed, and the information, including their diet and access to treatment, is presented. This work, based on data arising before antibiotics became available for treatment, can contribute to the future diagnosis of TB in non-documented skeletal material, and will facilitate a more reliable diagnosis of TB in juvenile individuals.


Genetic and antigenic characterization of infectious bursal disease viruses isolated in Italy during the period 2002-2005.
During the period 2002-2005, 109 infectious bursal disease virus (IBDV) field strains were isolated from bird flocks located in various parts of Italy. Out of these strains, 91 were isolated from broilers, 12 from pullets, and six from backyard flocks. Forty-two IBDV strains were further investigated and characterized on the basis of the geographical origin, source, and clinical signs. Antigenic and genetic characterizations were carried out using a monoclonal antibody (MAb)-based antigen-capture (AC) enzyme-linked immunosorbent assay (ELISA) or a virus neutralization assay and a reverse transcription, amplification, and direct sequencing of a genome fragment encoding the VP2 variable domain. The viruses were compared with reference IBDV strains, F52/70 (classical, 1970), 89163 (typical very virulent [vv]IBDV, 1989), 91168 (antigenically modified vvIBDV, 1991) and 94432 (antigenically modified vvIBDV, 1994) among others. All 42 strains were genetically characterized, and the comparison of their nucleotide sequences revealed the presence of six clusters having 100% identity, named group 1, 2, 3, 4, 5, and 6. Twelve strains, representative of each molecular group and/or with interesting amino acid sequence, were also antigenically characterized. The antigenic characterization showed six strains--151573, 157185 (group 1), 192294 (group 2), 77882 (group 3), 217 (group 4), and 192304--with the profile typical of vvIBDV (lack of binding of MAbs 3 and 4). Two strains, 77165 and 204875 (group 6), were also related to vvIBDV but did not react with MAb 5. Three isolates exhibited a profile of cell culture-adapted viruses and classical strains but with some differences: strain 157776 reacted with all MAbs; strain 168026 with all MAbs except MAb 4, which weakly neutralized it; and strain 72293 with all MAbs except MAb 9, which is rather unusual. The last strain, 213622, showed a very uncommon antigenic profile with missing or reduced binding of MAbs 3, 4, 5, 6, 8, and 9. Genetic characterization revealed 37 strains identified as vvIBDV viruses divided in 26 isolates (including groups 1, 2, 3, and 4) with the four amino acids residues typical of vvIBDV (222A, 256I, 294I, 299S) and 11 isolates (including groups 5, 6, and 213622) with some other amino acid exchanges. Four isolates (72293, 168026, 196783, and 222220) presented an amino acid sequence closely related to attenuated classical viruses whereas the last isolate (157776) exhibited a rather different sequence with some mutations typical of vvIBDV and others for cell culture-adapted viruses. Results of the antigenic and genetic characterization revealed that the majority of viruses (n = 37) were related to vvIBDV strains but, among these, 11 strains presented antigenically and genetically modified characteristics and originated, in major part, from the area where viruses have been circulating for a long time. The remaining viruses (n = 5) were related but not identical to attenuated classical viruses and came from areas where vaccination with intermediate strains is applied.


Differential roles of individual domains in selection of secretion route of a Streptococcus parasanguinis serine-rich adhesin, Fap1.
Fimbria-associated protein 1 (Fap1) is a high-molecular-mass glycosylated surface adhesin required for fimbria biogenesis and biofilm formation in Streptococcus parasanguinis. The secretion of mature Fap1 is dependent on the presence of SecA2, a protein with some homology to, but with a different role from, SecA. The signals that direct the secretion of Fap1 to the SecA2-dependent secretion pathway rather than the SecA-dependent secretion pathway have not yet been identified. In this study, Fap1 variants containing different domains were expressed in both secA2 wild-type and mutant backgrounds and were tested for their ability to be secreted by the SecA- or SecA2-dependent pathway. The presence or absence of the cell wall anchor domain (residues 2531 to 2570) at the C terminus did not alter the selection of the Fap1 secretion route. The Fap1 signal peptide (residues 1 to 68) was sufficient to support the secretion of a heterologous protein via the SecA-dependent pathway, suggesting that the signal peptide was sufficient for recognition by the SecA-dependent pathway. The minimal sequences of Fap1 required for the SecA2-dependent pathway included the N-terminal signal peptide, nonrepetitive region I (residues 69 to 102), and part of nonrepetitive region II (residues 169 to 342). The two serine-rich repeat regions (residues 103 to 168 and 505 to 2530) were not required for Fap1 secretion. However, they were both involved in the specific inhibition of Fap1 secretion via the SecA-dependent pathway.


Computational Approach Towards Exploring Potential Anti-Chikungunya Activity of Selected Flavonoids.
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes chikungunya infection in humans. Despite the widespread distribution of CHIKV, no antiviral medication or vaccine is available against this virus. Therefore, it is crucial to find an effective compound to combat CHIKV. We aimed to predict the possible interactions between non-structural protein 3 (nsP) of CHIKV as one of the most important viral elements in CHIKV intracellular replication and 3 potential flavonoids using a computational approach. The 3-dimensional structure of nsP3 was retrieved from the Protein Data Bank, prepared and, using AutoDock Vina, docked with baicalin, naringenin and quercetagetin as ligands. The first-rated ligand with the strongest binding affinity towards the targeted protein was determined based on the minimum binding energy. Further analysis was conducted to identify both the active site of the protein that reacts with the tested ligands and all of the existing intermolecular bonds. Compared to the other ligands, baicalin was identified as the most potential inhibitor of viral activity by showing the best binding affinity (-9.8 kcal/mol). Baicalin can be considered a good candidate for further evaluation as a potentially efficient antiviral against CHIKV.


Solid pseudopapillary tumor of the pancreas in children: 15-year experience at a single institution with assays using an immunohistochemical panel.
The aim of this study was to analyze the clinicopathological characteristics of solid pseudopapillary tumor (SPT) of the pancreas and to utilize an immunohistochemical panel to identify specific markers of the disease. Eleven patients diagnosed with and treated for SPT of the pancreas over the past 15 years were retrospectively analyzed. The 11 patients consisted of 8 females and 3 males, of mean age at operation of 13.5 years (range, 10 to 18 years). The most frequent presenting symptom was abdominal pain and/or mass. One patient was referred with hemoperitoneum due to traumatic tumor rupture. The lesions were located in the body, head and tail of the pancreas in four, four, and three patients, respectively. Mean tumor diameter was 7.9 cm (range, 2.5 to 15 cm). Surgical procedures included distal pancreatectomy with splenectomy in four patients, pylorus preserving pancreaticoduodenectomy in four, distal pancreatectomy in two, and subtotal pancreatectomy with splenectomy in one. Mean follow-up was 60.5 months (range, 15 to 126 months). All patients remain alive without tumor recurrence. Immunohistochemical staining showed that all tumors were positive for β-catenin, progesterone receptor (PR), vimentin, and CD99. However, all tumors were negative for E-cadherin and cytokeratin 7 expression. Patients with SPT of the pancreas have an excellent prognosis after surgical excision. Immunohistochemically, E-cadherin/β-catenin, PR, vimentin, and CD99 would help establish the diagnosis of SPT of the pancreas, although the results of immunohistochemical staining were found to have an indistinct complex immunoprofile.


Malignant melanoma arising in a seborrheic keratosis.
We report a case of malignant melanoma associated with seborrheic keratosis. This has been reported rarely in the literature, with disagreement regarding whether it is coincidental or whether malignant transformation occurs. Because seborrheic keratoses are common and association with malignant melanoma is very rare, we conclude that the association is coincidental. However, because of the association of other malignancies, a biopsy of any suspect or changing seborrheic keratosis is essential.


Cytotoxic effect of ergot alkaloids in Achnatherum inebrians infected by the Neotyphodium gansuense endophyte.
Ergonovine or ergonovinine was isolated from the aerial parts of endophyte (Neotyphodium gansuense) infected (E+) drunken horse grass (Achnatherum inebrians), neither of which existed in endophyte-free (E-) plants. Both of these ergot alkaloids had a cytotoxic effect on animal smooth muscle cells and increased cell growth inhibition with greater concentrations, in a significantly (P < 0.05) positive correlation. The median inhibitory concentrations (IC50) for ergonovine and ergonovinine were 71.95 and 72.75 μg/mL, respectively. These results indicate that endophytic ergot alkaloids may be the cause of drunken horse grass poisoning.


A microsurgical anterior cervical approach and the immediate impact of mechanical retractors: A case control study.
A microsurgical anterior cervical approach with discectomy and fusion (MACDF) is one of the most widely used procedures for treating radicular disorders. This approach is highly successful; however, it is not free from complications. These can be associated with soft tissue injuries. The recognition of the risks for these complications should be identified for timely prevention and safe treatment. Retrospective case control study. This study includes a retrospective case series of 37 patients, paying special attention to immediate complications related to the use of mechanical retraction of soft tissue (dysphagia, dysphonia, esophageal lesions and local hematoma); and a comparative analysis of the outcomes after changes in the retraction method. All selected cases had a positive neurological symptom response in relation to neuropathic pain. Dysphagia and dysphonia were found during the first 72 h in 94.1% of the cases in which automatic mechanical retraction was used for more than one hour during the surgical procedure. A radical change was noted in the reduction of the symptoms after the use of only manual protective blades without automatic mechanical retraction: 5.1% dysphagia and 0% dysphonia in the immediate post-operative period, P = 0.001. Soft tissue damage due to the use of automatic retractors in MACDF is not minor and leads to general discomfort in the patient in spite of good neurological results. These problems most often occur when automatic retractors are used continuously for more than 1 hour, as well as when they are used in multiple levels. Dysphagia, dysphonia and local pain decreased with the use of transient manual blades for retraction, and with intermittent release following minimally invasive principles.


Anomalies associated with pulmonary hypoplasia.
We reviewed the records of 756 consecutive newborns autopsied over a 10-yr period. Using published standards for normal lung weights, low lung weight for total body weight was determined to be a reasonable estimate of pulmonary hypoplasia. Seventy-seven infants with pulmonary hypoplasia were identified. Multiple congenital malformation syndromes were found in the majority of infants with pulmonary hypoplasia. These included major diaphragmatic anomalies, renal anomalies, chromosomal disorders, extralobar pulmonary sequestration, severe musculoskeletal disorders, and isolated right-sided cardiac lesions. Ten infants had no known associated anomalies. The various theories of pathogenesis of pulmonary hypoplasia are reviewed and the suggestion is made that the cause of pulmonary hypoplasia in newborns may well be multifactorial. Various theories of pathogenesis are discussed ranging from an actual lack of space for the lungs to grow, to the possible necessity for appropriate respiratory movement during intrauterine life, to the possibility, particularly in the case of Potter's syndrome, of a primary mesodermal defect affecting multiple organ systems.


[Pediatric problems of the children of immigrants in Spain].
The author, Consultant and Expert in Maternal and Child Health of the WHO in Africa and Europe, after a complete study of the Spanish demography, the country with the lower natality in all the world, arrives to the conclusion that Spain is the country with more possibilities for the immigration from Africa, Latino-America and Philippines. So, is absolutely necessary that Spanish paediatricians know the troubles and diseases of the children of these groups as a way for their integration.


Review: Endogenously Produced Volatiles for In Vitro Toxicity Testing Using Cell Lines.
Due to the ∼86,000 chemicals registered under the Toxic Substances Control Act and increasing ethical concerns regarding animal testing, it is not economically or technically feasible to screen every registered chemical for toxicity using animal-based toxicity assays. To address this challenge, regulatory agencies are investigating high-throughput screening in vitro methods to increase speed of toxicity testing, while reducing the overall cost. One approach for rapid toxicity testing currently being investigated is monitoring of volatile emissions produced by cell lines in culture. Such a metabolomics approach would measure gaseous emissions from a cell line and determine if such gaseous metabolites are altered upon exposure to a xenobiotic. Herein, we describe the history and rationale of monitoring endogenously produced volatiles for identification of pathologic conditions, as well as emerging applications in toxicity testing for such an approach.


Impact of stent type on incidence of major adverse cardiac events in large coronary arteries with tubular and diffuse lesions.
The aim of this study was to compare 3 year incidence of major adverse cardiac events (MACE) between bare metal stents (BMS) and drug-eluting stents (DES) in large coronary arteries with tubular and diffuse lesions. Seven hundred forty-five consecutive patients (894 lesions) who underwent percutaneous coronary intervention (PCI) on large coronary arteries (3.0, 3.5 and 4 mm) with tubular (10-20 mm length) or diffuse (>20 mm) lesions using BMS or DES at Ekbatan University Hospital, Hamadan, Iran between October 2009 and September 2012 were included. Patients were divided into six groups based on the diameter and length of the stents: 3.0*≤20 mm, 3.0*>20 mm, 3.5*≤20 mm, 3.5*>20 mm, 4.0*≤20 mm and 4.0*>20 mm. Follow-up visits were set at 1, 2, and 3 years after the procedure. Endpoints of the study were MACE including cardiac death, nonfatal MI (due to in-stent thrombosis) and target lesion revascularization (TLR). Cardiac death occurred in 12 patients (1.7%), (1.8% in BMS vs. 1.2% in DES). The incidence of MACE was significantly higher in 3-mm coronary arteries with diffuse lesions (>20 mm) in BMS group; however, there were no statistically significant difference in the incidence of MACE following PCI with BMS and DES in 3, 3.5 and 4 mm coronary arteries with tubular lesions (≤20 mm) and 3.5 and 4 mm coronary arteries with diffuse lesions. Since the incidence of MACEs did not differ significantly between BMS and DES in most sizes, we suggested that PCI with BMS for coronary arteries in the mentioned sizes can be safe and effective. Further randomized clinical trials focusing simultaneously on diameter and the length of stents are required to corroborate this finding.


Cadmium - a complex environmental problem. Part II. Cadmium in sludges used as fertilizer.
In intensively populated countries efficient sewage treatment is essential to protect river quality. An inevitable by-product is sewage sludge which has to be disposed of safely and economically. Utilisation of sludge as a fertilizer of agricultural land is the most economic disposal route for inland sewage-treatment works and also benefits farmers by providing a cheap manure. Much of the cadmium in wastewater is concentrated into sludge which consequently contains higher concentrations of cadmium than soil does. It is impracticable to reduce cadmium concentrations in sludge below certain levels. When sludge is used on farmland rates of application must be controlled so that cadmium concentrations in soil never reach levels that could significantly contaminate food crops. Cadmium is a principal factor limiting the use of sludge on land. Nevertheless, it is a local problem since agricultural land in general receives more cadmium from aerial deposition and phosphatic fertilizers. The significance of accumulations of cadmium in soil depends mainly on its availability for crop uptake. Investigations are described which have attempted to identify and to determine the availability of forms of cadmium in soil. There is considerable research interest in cadmium in soil solution which is likely to be directly available for crop uptake. Another area of interest is the apparent disappearance of cadmium from sludge-treated soil. Soil analysis often cannot fully account for the cadmium added in sludge. Apart from the effect of soil conditions, especially pH value, crop uptake varies according to the particular crop examined. Highest concentrations of cadmium occur in tobacco, lettuce, spinach and other leafy vegetables. Using crop uptake data from field trials it is possible to relate potential human dietary intake of cadmium, on which hazard depends, to soil concentrations of cadmium, which can be controlled by regulating applications of sludge. This provides an objective basis for limits for cadmium concentrations in soils receiving sludge. Transfer of cadmium via farm animals to meat and dairy products for human consumption is thought to be minimal, even allowing for some direct ingestion of sludge-treated soil by the animals. Evidence from these and other investigations suggests that a loading rate limit of 5 kg Cd/ha (equivalent to a soil concentration of about 3.5 mg Cd/kg) affords adequate protection to the foodchain where sludge is used on agricultural land. More research work is needed to provide a basis for predicting the long-term availability of cadmium introduced to the soil in sludge.


Physically Exfoliating 2D Materials: A Versatile Combination of Different Materials into a Layered Structure.
Improving the properties of the existing two-dimensional (2D) materials is a major concern for many researchers today. Synergistic coupling of single-phase 2D material species with secondary functional materials has resulted in 2D nanohybrids with significantly enhanced properties beyond the sum of their individual components. In particular, nanohybrids created by alternatingly integrating different material species in the confined 2D nanometer regime have the potential to meet the needs of a wide variety of applications, particularly the many important energy-related applications that are of interest. However, scaling up production of 2D nanohybrids is still challenging, which is a major barrier to their practical application. Delamination and exfoliation by physical means separate the weakly bound 2D nanosheets into kinetically stable single- or few-layers. Herein, we provide a concise overview of recent achievements in the physical exfoliation-based fabrication of 2D nanohybrids featuring controlled heterolayered structures. Several strategies to efficiently produce heterolayered 2D nanohybrids in large quantities are described, such as (i) coexfoliation of different 2D species, (ii) aqueous-phase synthesis, and (iii) gas-phase synthesis. The versatility of the 2D nanohybrids was also illustrated by remarkable research examples, especially in energy-related applications.


Convergence of electronic bands for high performance bulk thermoelectrics.
Thermoelectric generators, which directly convert heat into electricity, have long been relegated to use in space-based or other niche applications, but are now being actively considered for a variety of practical waste heat recovery systems-such as the conversion of car exhaust heat into electricity. Although these devices can be very reliable and compact, the thermoelectric materials themselves are relatively inefficient: to facilitate widespread application, it will be desirable to identify or develop materials that have an intensive thermoelectric materials figure of merit, zT, above 1.5 (ref. 1). Many different concepts have been used in the search for new materials with high thermoelectric efficiency, such as the use of nanostructuring to reduce phonon thermal conductivity, which has led to the investigation of a variety of complex material systems. In this vein, it is well known that a high valley degeneracy (typically ≤6 for known thermoelectrics) in the electronic bands is conducive to high zT, and this in turn has stimulated attempts to engineer such degeneracy by adopting low-dimensional nanostructures. Here we demonstrate that it is possible to direct the convergence of many valleys in a bulk material by tuning the doping and composition. By this route, we achieve a convergence of at least 12 valleys in doped PbTe(1-x)Se(x) alloys, leading to an extraordinary zT value of 1.8 at about 850 kelvin. Band engineering to converge the valence (or conduction) bands to achieve high valley degeneracy should be a general strategy in the search for and improvement of bulk thermoelectric materials, because it simultaneously leads to a high Seebeck coefficient and high electrical conductivity.


High-performance cation-exchange chromatography and pulsed amperometric detection for the separation, detection, and quantitation of N-alkylated imino sugars in biological samples.
The use of imino sugars for the potential treatment of lysosomal glycolipid storage diseases and hepatitis virus infections requires accurate, quantitative measurement of these compounds in biological samples. We demonstrate here the versatility of cation-exchange chromatography and pulsed amperometric detection of a range of compounds that differ in both isometric structure and N-alkyl chain length. Although column retention appears dependent upon residual charge on the imine function, successful isocratic separation can be achieved by secondary hydrophobic interactions. A series of N-alkylated deoxynojirimycin compounds containing C(1-10) alkyl chains are readily separated and detected by pulsed amperometry after cation suppression. Using experimentally derived response factors for imino sugars and measurement of peak areas we have developed a reliable method for quantitatively determining concentrations in solution. A rapid protocol for the removal of protein and contaminants in biological samples is described. This has allowed the successful measurement of imino sugars in animal tissues and will be useful for understanding the factors involved in compound bioavailability and in the design of novel therapeutics.


Interactions between amprenavir and the lopinavir-ritonavir combination in heavily pretreated patients infected with human immunodeficiency virus.
This pharmacokinetic study was designed to characterize interactions between amprenavir and the lopinavir-ritonavir combination in patients infected with human immunodeficiency virus in whom previous antiretroviral therapy had failed. Twenty-seven patients included in a randomized clinical trial (ANRS [National Agency for AIDS Research] Protocol 104) participated in this study. They were randomized to receive ritonavir at a dose of either 100 mg twice daily or 200 mg twice daily. For the first 2 weeks of therapy, they were randomly assigned to receive lopinavir (400 mg twice daily) and ritonavir (100 mg twice daily), amprenavir (600 mg twice daily) plus ritonavir (100 mg twice daily), lopinavir (400 mg twice daily) and ritonavir (100 mg twice daily) plus additional ritonavir (100 mg twice daily), or amprenavir (600 mg twice daily) plus ritonavir (200 mg twice daily). From week 3 onward, all patients received amprenavir plus lopinavir-ritonavir with or without an additional ritonavir dose (100 mg twice daily). The pharmacokinetics of the 3 drugs was studied in weeks 2 and 6 of therapy. Median amprenavir concentrations decreased by 54% (P =.004) when lopinavir was added to the amprenavir-ritonavir regimen. Lopinavir weakly displaced amprenavir from plasma proteins: The average unbound fraction of amprenavir was 0.089 in week 2 and 0.114 in week 6 (P =.03), but this did not fully account for the observed interaction. Increasing the ritonavir dose did not affect the amprenavir concentration. The relationship between lopinavir and ritonavir concentrations fitted a maximum effect (E(max)) model;the average concentration of ritonavir that yielded a lopinavir concentration of 8119 ng/mL (50% of E(max)) was 602 ng/mL (coefficient of variation, 22%). There was a significant relationship between the lopinavir inhibitory quotient and the virologic response in week 2 (P =.005). Lopinavir markedly decreases the amprenavir concentration during amprenavir and lopinavir-ritonavir combination therapy. The inhibitory quotients were more predictive of the short-term virologic response than was the level of drug exposure.


Docs try to own managed care.
Fed up with big for-profit HMOs, physicians across the nation are forming plans, sometimes with the help of state associations, as they try to own managed care. However, the sale of an HMO that services as a model for other doctors fuels industry doubt.


Baseline vestibular and auditory findings in a trial of post-concussive syndrome
Previous studies have reported high rates of auditory and vestibular-balance deficits immediately following head injury. This study uses a comprehensive battery of assessments to characterize auditory and vestibular function in 71 U.S. military service members with chronic symptoms following mild traumatic brain injury that did not resolve with traditional interventions. The majority of the study population reported hearing loss (70%) and recent vestibular symptoms (83%). Central auditory deficits were most prevalent, with 58% of participants failing the SCAN3:A screening test and 45% showing abnormal responses on auditory steady-state response testing presented at a suprathreshold intensity. Only 17% of the participants had abnormal hearing (⟩25 dB hearing loss) based on the pure-tone average. Objective vestibular testing supported significant deficits in this population, regardless of whether the participant self-reported active symptoms. Composite score on the Sensory Organization Test was lower than expected from normative data (mean 69.6 ±vestibular tests, vestibulo-ocular reflex, central auditory dysfunction, mild traumatic brain injury, post-concussive symptoms, hearing15.6). High abnormality rates were found in funduscopy torsion (58%), oculomotor assessments (49%), ocular and cervical vestibular evoked myogenic potentials (46% and 33%, respectively), and monothermal calorics (40%). It is recommended that a full peripheral and central auditory, oculomotor, and vestibular-balance evaluation be completed on military service members who have sustained head trauma.


The shared medical appointment: a proposed model of medical appointments.
Today's healthcare providers are struggling more than ever with providing high-quality care and while controlling the spiraling costs of healthcare. The demands of an aging population, combined with a shrinking pool of medical personnel, have brought challenges to the medical office where doctors are saddled with the need of improving access to medical care. Recruiting new partners, using physician assistants and nurse practitioners, and seeing more patients in a workday are some ways doctors are trying to meet these challenges. For the most part, that does not solve the problems afflicting most physicians and practices. This article will discuss the concept of the shared medical appointment and how it might be applied to most medical practices.


Anterograde transport blockade precedes deficits in retrograde transport in the visual projection of the DBA/2J mouse model of glaucoma.
Axonal transport deficits have been reported as an early pathology in several neurodegenerative disorders, including glaucoma. However, the progression and mechanisms of these deficits are poorly understood. Previous work suggests that anterograde transport is affected earlier and to a larger degree than retrograde transport, yet this has never been examined directly in vivo. Using combined anterograde and retrograde tract tracing methods, we examined the time-course of anterograde and retrograde transport deficits in the retinofugal projection in pre-glaucomatous (3 month-old) and glaucomatous (9-13 month old) DBA/2J mice. DBA/2J-Gpnmb (+) mice were used as a control strain and were shown to have similar retinal ganglion cell densities as C57BL/6J control mice-a strain commonly investigated in the field of vision research. Using cholera toxin-B injections into the eye and FluoroGold injections into the superior colliculus (SC), we were able to measure anterograde and retrograde transport in the primary visual projection. In DBA/2J, anterograde transport from the retina to SC was decreased by 69% in the 9-10 month-old age group, while retrograde transport was only reduced by 23% from levels seen in pre-glaucomatous mice. Despite this minor reduction, retrograde transport remained largely intact in these glaucomatous age groups until 13-months of age. These findings indicate that axonal transport deficits occur in semi-functional axons that are still connected to their brain targets. Structural persistence as determined by presence of estrogen-related receptor beta label in the superficial SC was maintained beyond time-points where reductions in retrograde transport occurred, also supporting that transport deficits may be due to physiological or functional abnormalities as opposed to overt structural loss.


Intrathecal morphine in younger patients for postoperative pain following spinal fusion.
Intrathecal morphine in an average dose of 0.01 mg/kg was given to 33 patients between ages 11 and 16 years who had spinal arthrodesis for idiopathic scoliosis. The morphine was administered intrathecally as a 10 cc bolus at the conclusion of the arthrodesis, but before closure. The goal was to study safety in terms of respiratory depression and pain relief. Respirations occurred spontaneously in 30 of the 33 patients within 15 minutes of cessation of anesthesia. Respiratory depression occurred in five patients, four of whom had arterial blood pCO2 levels greater than 60 mm Hg. Thirty-one patients had relief of pain for 8 to greater than 40 hours, averaging 18 hours. Two patients had no noticeable pain relief. There appeared to be no relation between dose and pain relief in this limited dose range. We were unable to duplicate the long duration of pain relief reported elsewhere. We also were unable to decrease the side effects of respiratory depression and nausea to a level reported by others. It may be that the 10 cc bolus injected intrathecally circulates to the brain and ventricles faster than desired, or that factors relating to type of anesthesia or dose need to be considered. Low-dose intrathecal morphine does provide noticeable pain relief in younger patients undergoing spinal fusion. The side effects of nausea and respiratory depression can be managed safely with medication.


The SAM domain-containing protein 1 (SAMD1) acts as a repressive chromatin regulator at unmethylated CpG islands.
CpG islands (CGIs) are key regulatory DNA elements at most promoters, but how they influence the chromatin status and transcription remains elusive. Here, we identify and characterize SAMD1 (SAM domain-containing protein 1) as an unmethylated CGI-binding protein. SAMD1 has an atypical winged-helix domain that directly recognizes unmethylated CpG-containing DNA via simultaneous interactions with both the major and the minor groove. The SAM domain interacts with L3MBTL3, but it can also homopolymerize into a closed pentameric ring. At a genome-wide level, SAMD1 localizes to H3K4me3-decorated CGIs, where it acts as a repressor. SAMD1 tethers L3MBTL3 to chromatin and interacts with the KDM1A histone demethylase complex to modulate H3K4me2 and H3K4me3 levels at CGIs, thereby providing a mechanism for SAMD1-mediated transcriptional repression. The absence of SAMD1 impairs ES cell differentiation processes, leading to misregulation of key biological pathways. Together, our work establishes SAMD1 as a newly identified chromatin regulator acting at unmethylated CGIs.


Larger Error Signals in Major Depression are Associated with Better Avoidance Learning.
The medial prefrontal cortex (mPFC) is particularly reactive to signals of error, punishment, and conflict in the service of behavioral adaptation and it is consistently implicated in the etiology of major depressive disorder (MDD). This association makes conceptual sense, given that MDD has been associated with hyper-reactivity in neural systems associated with punishment processing. Yet in practice, depression-related variance in measures of mPFC functioning often fails to relate to performance. For example, neuroelectric reflections of mediofrontal error signals are often found to be larger in MDD, but a deficit in post-error performance suggests that these error signals are not being used to rapidly adapt behavior. Thus, it remains unknown if depression-related variance in error signals reflects a meaningful alteration in the use of error or punishment information. However, larger mediofrontal error signals have also been related to another behavioral tendency: increased accuracy in avoidance learning. The integrity of this error-avoidance system remains untested in MDD. In this study, EEG was recorded as 21 symptomatic, drug-free participants with current or past MDD and 24 control participants performed a probabilistic reinforcement learning task. Depressed participants had larger mid-frontal EEG responses to error feedback than controls. The direct relationship between error signal amplitudes and avoidance learning accuracy was replicated. Crucially, this relationship was stronger in depressed participants for high conflict "lose-lose" situations, demonstrating a selective alteration of avoidance learning. This investigation provided evidence that larger error signal amplitudes in depression are associated with increased avoidance learning, identifying a candidate mechanistic model for hypersensitivity to negative outcomes in depression.


[Clinico-electrocardiographic syndromes, assossiated with risk of sudden death].
Sudden death (SD) rate acquires threatening dimensions in industrialized countries. Upon the average SD rate is about 1 case of 1000 citizens. According to the SD patients autopsy results 85% had coronary heart disease, 10% had other cardiac pathology and 5% did not have any organic heart pathology. One of the SD causes in patients without organic cardiac pathology can be "channelpathy" - clinico-electrocardiographic syndromes, caused by disturbances of ion channel functions.


Life history of Neoseiulus californicus (McGregor, 1954) (Acari: Phytoseiidae) fed with castor bean (Ricinus communis L.) pollen in laboratory conditions.
The predatory mite, Neoseiulus californicus (McGregor, 1954) (Acari: Phytoseiidae) is one of the principal natural enemies of tetranychid mites in several countries, promoting efficient control of those mites in several food and ornamental crops. Pest attacks such as that of the spider mite, Tetranychus urticae Koch, 1836 (Acari: Tetranychidae), is one of the problems faced by farmers, especially in the greenhouse, due to the difficulty of its control with the use of chemicals because of the development of fast resistance making it hard to control it. The objective of this work was to study the life history of the predatory mite N. californicus as a contribution to its mass laboratory rearing, having castor bean plant [Ricinus communis L. (Euphorbiaceae)] pollen as food, for its subsequent use as a natural enemy of T. urticae on a cultivation of greenhouse rosebushes. The studies were carried out in the laboratory, at 25 ± 2°C of temperature, 70 ± 10% RH and a 14 hour photophase. The biological aspects and the fertility life table were appraised. Longevity of 32.9 days was verified for adult females and 40.4 days for males. The intrinsic rate of increase (rm) was 0.2 and the mean generation time (T) was 17.2 days. The population doubled every 4.1 days. The results obtained were similar to those in which the predatory mite N. californicus fed on T. urticae.


Liquisolid Tablets for Dissolution Enhancement of a Hypolipidemic Drug.
This investigation was aimed to improve the dissolution rate of the poorly soluble drug lovastatin, by formulating it as a liquisolid compact. Different liquisolid compacts were prepared using mathematical formulae to calculate the required quantities of powder and liquid ingredients to produce acceptably flowable and compressible admixture. Avicel PH 200, Cab-O-Sil, sodium starch glycolate and PEG 400 were employed as carrier, coating material, disintegrant and non-volatile liquid vehicle, respectively. The various drug to liquid and carrier to coating ratio were used to prepare liquisolid compacts. The formulated liquisolid tablets were evaluated for weight variation, hardness, drug content, friability and disintegration time. The in vitro release characteristics of the drug from tablets formulated by direct compression and liquisolid technique were compared in two different dissolution media. The tableting properties of the liquisolid compacts were within the acceptable limits and drug release rates were distinctly higher as compared to directly compressed tablets. The FTIR spectra showed no interaction between drug-excipient and disappearance of the characteristic absorption band of lovastatin in liquisolid formulations could be attributed to the formation of hydrogen bonding between the drug and liquid vehicle, which resulted in dissolution enhancement. Thus, the liquisolid technique was found to be a promising approach for improving the dissolution of a poorly soluble drug like lovastatin.


[An application of low-invasive access in ultrasound-guided surgery of liquid formation of the abdominal cavity and retroperitoneal space].
The article presents a low-invasive method in the intraoperative ultrasound-guided surgery. The method had several steps: an access (2-3 cm) was made to a liquid formation with the following aspiration of contents, a necrotic detritus was removed through the wound tract using simultaneous ultrasound examination of efficacy of emptying the cavity with drainage. This means allowed the performance of single-stage sanitization and drainage of cavity formations, which contained the liquid and dense necrotic tissues in the lumen. The method was effective, technically workable in any surgical hospital. At the same time, it was economically reasonable, because there wasn't need to buy an additional equipment. The application of the means considerably shortened a hospital stay and the lethality was reduced.


Tal6 From Trichoderma atroviride Is a LysM Effector Involved in Mycoparasitism and Plant Association.
LysM effectors play a relevant role during the plant colonization by successful phytopathogenic fungi, since they enable them to avoid either the triggering of plant defense mechanisms or their attack effects. Tal6, a LysM protein from Trichoderma atroviride, is capable of binding to complex chitin. However, until now its biological function is not completely known, particularly its participation in plant-Trichoderma interactions. We obtained T. atroviride Tal6 null mutant and Tal6 overexpressing strains and determined the role played by this protein during Trichoderma-plant interaction and mycoparasitism. LysM effector Tal6 from T. atroviride protects the hyphae from chitinases by binding to chitin of the fungal cell wall, increases the fungus mycoparasitic capacity, and modulates the activation of the plant defense system. These results show that beneficial fungi also employ LysM effectors to improve their association with plants.


[Can injuries cause by train crash be prevented? Experiences from the train crash in Jelling in 1995].
Among 69 persons involved in a train crash, 53 were injured. Twenty-two persons were admitted to hospital. No-one was killed. There was a significantly increased risk of getting hurt when facing forward in the moving train. The mechanism of injury for the majority was being thrown forward and thereby hitting parts of the seats in front. The iron frames of the seats became exposed as some parts of the seats were only loosely attached. Arrangements to reduce injuries in train crashes could be an improved maintenance of the seats and their frames and the use of safety belts.


Coronary Artery Disease Severity Is Associated With Abdominal Aortic Intima-Media Thickness in Patients With Non-ST-Segment Elevation Myocardial Infarction.
The aim of this study was to evaluate the relationship between aortic intima-media thickness (aIMT) and coronary artery disease (CAD) severity in patients with non-ST-segment elevation myocardial infarction (NSTEMI). SYNTAX score (SS) was calculated. Patients were categorized into 2 main groups according to the SS: patient with high risk (SS ≥ 13) and low risk (SS < 13). Common carotid artery IMT (cIMT), common femoral artery IMT, and aIMT were measured with a high-resolution ultrasound Doppler system. We had 147 (52.9%) patients in the high-risk group and 132 patients in the low-risk group. Both cIMT and aIMT were significantly increased, and left ventricular ejection fraction (LVEF) was significantly lower in the high-risk group; aIMT (odds ratio [OR]: 1.272, P < .001), cIMT (OR: 1.239, P = .009), and LVEF (OR: 0.931, P = .002) were determined as independent predictors for the high-risk group. When the cutoff value was accepted as 1.25 mm for the aIMT, patients with high SS identification had 74.1% sensitivity and 89.4% specificity (area under the curve: 0.764, P < .001). In conclusion, aIMT detected by abdominal B-mode ultrasonography is closely associated with CAD severity in patients with NSTEMI.


Ampullary cancer: an overview.
Ampullary cancers are rare, accounting for only 0.2% of gastrointestinal cancers and approximately 7% of all periampullary cancers. They arise from the ampullary complex, distal to the confluence of the common bile and pancreatic duct (Fig. 1). In contrast to other periampullary malignancies, true ampullary cancers present earlier in their disease course with symptoms that result from biliary obstruction. It is often difficult to distinguish primary ampullary cancers from other periampullary cancers preoperatively. In early stages, ampullary cancers are surgically treated, similar to pancreatic cancers, and typically with a pancreatico-duodenoectomy (or Whipple procedure). Because of their earlier presentation, resection rates for all patients are much higher than other periampullary carcinomas. Moreover, their prognosis tends to be better than those with other periampullary- and pancreatic-originating cancers. In patients with true ampullary cancer, there is very limited data to guide physicians on the choice of therapy, largely because of the rarity of the disease and the paucity of related research. Herein, we provide an overview of the biology, histology, current therapeutic strategies, and potential future therapies for carcinomas arising from the ampulla of Vater.


Low incidence of microsatellite instability in gastric cancers and its association with the clinicopathological characteristics: a comparative study.
Gastric cancer is a complex heterogeneous disease with different molecular subtypes that have clinical implications. It is characterized by high mortality rates and limited effective therapies. Microsatellite instability (MSI) has been recognized as a subgroup with a good prognosis based on TCGA and ACRG categorizations. Besides its prognostic and predictive value, gastric cancers with high MSI exhibit different clinical behaviors. The prevalence of high MSI has been assessed in gastric cancer worldwide, especially in East Asia, but there is a lack of such information in the Middle East. Therefore, this study aimed to investigate the incidence and status of MSI in Iranian gastric cancer patients using 53 samples collected from 2015 to 2020 at Taleghani Hospital Medical Center. DNA from tumoral and normal tissues were extracted and assessed through multiplex-PCR based on five mononucleotide repeats panel. Clinicopathological variables, including age, sex, Lauren classification, lymph node involvement, TNM stage, differentiation, localization, and tumor size, were also analyzed. With 2 males and 2 females, high microsatellite instability represented a small subgroup of almost 7.5% of the samples with a median age of 60.5 years. High microsatellite instability phenotypes were significantly associated with patients aged 68 years and older (p‑value of 0.0015) and lower lymph node involvement (p‑value of 0.0004). Microsatellite instability was also more frequent in females, with distal gastric location, bigger tumor size, and in the intestinal type of gastric cancer rather than the diffuse type.


Practice makes imperfect: stronger implicit interference with practice in individuals at high risk of developing Alzheimer's disease.
Early screening to determine patient risk of developing Alzheimer's will allow better interventions and planning but necessitates accessible methods such as behavioral biomarkers. Previously, we showed that cognitively healthy older individuals whose cerebrospinal fluid amyloid / tau ratio indicates high risk of cognitive decline experienced implicit interference during a high-effort task, signaling early changes in attention. To further investigate attention's effect on implicit interference, we analyzed two experiments completed sequentially by the same high- and low-risk individuals. We hypothesized that if attention modulates interference, practice would affect the influence of implicit distractors. Indeed, while both groups experienced a strong practice effect, the association between practice and interference effects diverged between groups: stronger practice effects correlated with more implicit interference in high-risk participants, but less interference in low-risk individuals. Furthermore, low-risk individuals showed a positive correlation between implicit interference and EEG low-range alpha event-related desynchronization when switching from high- to low-load tasks. These results demonstrate how attention impacts implicit interference and highlight early differences in cognition between high- and low-risk individuals.


Recent trends in human salmonellosis in England and Wales: the epidemiology of prevalent serotypes other than Salmonella typhimurium.
In the period 1960-70 meat and poultry products caused over 70% of successfully investigated outbreaks of human salmonellosis. The number of human incidents of salmonellosis declined from 1960 to 1966, but then more than doubled between 1966 and 1971. This increase was mainly due to a threefold increase of incidents of salmonella serotypes other than Salmonella typhimurium. The serotypes which increased most and contributed significantly to this trend were S. enteritidis, S. panama, S. stanley, S. virchow, S. agona, S. 4,12:d:- and S. indiana.Strong evidence exists that these serotypes have a path of infection from animal feedingstuffs to the pig and poultry animal reservoirs to pork and poultry foods to man. Cattle appear to be a less important source than pigs and poultry and this may be because the nature and content of their feed is different.The importance of the control of the pig and poultry reservoirs of salmonella infections is stressed and a significant role of animal feedingstuffs in the maintenance of these reservoirs strongly suggested.


Curcumin Inhibits the Tumorigenesis of Breast Cancer by Blocking Tafazzin/Yes-Associated Protein Axis.
This study was aimed to explore the anti-tumor effect of curcumin on breast cancer (BC) and the underlying mechanism involving Tafazzin (TAZ)/Yes-associated protein (YAP) axis. Different concentrations of curcumin (0, 10, 20 and 30 μM) were used to treat BC cells (MCF-7 and MDA-MB-231 cells). The viability, colony formation, apoptosis, migration, and invasion of BC cells were detected by MTT, colony formation, flow cytometry, wound-healing and transwell assay, respectively. The protein expression of TAZ and YAP (effectors of Hippo signaling pathway) was detected by Western blot. MDA-MB-231 cells were injected into mice to verify the anti-tumor effect of curcumin in vivo. Curcumin (20 and 30 μM) inhibited the proliferation, migration and invasion, and promoted the apoptosis of MCF-7 and MDA-MB-231 cells. Curcumin decreased the protein expression of TAZ and YAP in MCF-7 and MDA-MB-231 cells. Overexpression of YAP reversed the anti-tumor effect of curcumin on MDA-MB-231 cells. In addition, curcumin (100, 200 and 300 mg/kg/d) inhibited the growth of tumor xenografts in mice, and down-regulated the protein expression of TAZ and YAP in tumor xenografts. However, curcumin at a concentration of 300 mg/kg/d slowed the increasing of body weight in mice. Curcumin inhibited the tumorigenesis of BC by blocking TAZ/YAP axis.


On the choice of a sparse prior.
An emerging paradigm analyses in what respect the properties of the nervous system reflect properties of natural scenes. It is hypothesized that neurons form sparse representations of natural stimuli: each neuron should respond strongly to some stimuli while being inactive upon presentation of most others. For a given network, sparse representations need fewest spikes, and thus the nervous system can consume the least energy. To obtain optimally sparse responses the receptive fields of simulated neurons are optimized. Algorithmically this is identical to searching for basis functions that allow coding for the stimuli with sparse coefficients. The problem is identical to maximizing the log likelihood of a generative model with prior knowledge of natural images. It is found that the resulting simulated neurons share most properties of simple cells found in primary visual cortex. Thus, forming optimally sparse representations is a very compact approach to describing simple cell properties. Many ways of defining sparse responses exist and it is widely believed that the particular choice of the sparse prior of the generative model does not significantly influence the estimated basis functions. Here we examine this assumption more closely. We include the constraint of unit variance of neuronal activity, used in most studies, into the objective functions. We then analyze learning on a database of natural (cat-cam) visual stimuli. We show that the effective objective functions are largely dominated by the constraint, and are therefore very similar. The resulting receptive fields show some similarities but also qualitative differences. Even for coefficient values for which the objective functions are dissimilar, the distributions of coefficients are similar and do not match the priors of the assumed generative model. In conclusion, the specific choice of the sparse prior is relevant, as is the choice of additional constraints, such as normalization of variance.


Direct, indirect and pleiotropic effects of candidate genes on internalizing disorder psychopathology.
Twin studies of internalizing disorders suggest that their high co-morbidity is partially explained by shared genetic risk. Few studies have investigated pleiotropic effects of well-validated candidate genes across phenotypes. Subjects were 928 Caucasian patients who presented to an out-patient clinic specializing in the assessment and treatment of anxiety and mood disorders. We constructed latent dimensional phenotypes across the internalizing spectrum (neuroticism, extraversion, depression, generalized anxiety, panic/agoraphobia, social phobia, post-traumatic stress, and obsessions-compulsions) by combining diagnostic criteria with other clinical indicators. We selected multiple variants in four evidence-based candidate genes (SLC6A4, COMT, GAD1, RGS2) with previously reported effects on several of these phenotypes. We conducted genetic association testing of their direct and indirect effects as well as gene × stress interactions (G × E). We detected 19 nominally significant main effect associations for the 10 polymorphisms tested among the eight phenotypes (24%). These were generally phenotype non-specific, showing pleiotropic effects across multiple domains. The majority of observed sharing was between depression, panic disorder, and post-traumatic stress disorder. Some of these were best explained by mediational models in which genes increase liability for disorders indirectly via their effects on temperament. Limited G × E effects were detected between variants in SLC6A4 and both panic/agoraphobia and post-traumatic stress. Examining just a few candidate genes for their potential roles in internalizing phenotypes, we found moderate support for the shared effects of several polymorphisms. These findings highlight the richness and complexity by which genes potentially contribute to psychopathology via pleiotropy, moderation by stress, and mediation by temperament.


Stratification and loading of fecal indicator bacteria (FIB) in a tidally muted urban salt marsh.
Stratification and loading of fecal indicator bacteria (FIB) were assessed in the main tidal channel of the Ballona Wetlands, an urban salt marsh receiving muted tidal flows, to (1) determine FIB concentration versus loading within the water column at differing tidal flows, (2) identify associations of FIB with other water quality parameters, and (3) compare wetland FIB concentrations to the adjacent estuary. Sampling was conducted four times during spring-tide events; samples were analyzed for FIB and turbidity (NTU) four times over a tidal cycle at pre-allocated depths, depending on the water level. Additional water quality parameters measured included temperature, salinity, oxygen, and pH. Loadings were calculated by integrating the stratified FIB concentrations with water column cross-sectional volumes corresponding to each depth. Enterococci and Escherichia coli were stratified both by concentration and loading, although these variables portrayed different patterns over a tidal cycle. Greatest concentrations occurred in surface to mid-strata levels, during flood tides when contaminated water flowed in from the estuary, and during ebb flows when sediments were suspended. Loading was greatest during flood flows and diminished during low tide periods. FIB concentrations within the estuary often were significantly greater than those within the wetland tide channel, supporting previous studies that the wetlands act as a sink for FIB. For public health water quality monitoring, these results indicate that more accurate estimates of FIB concentrations would be obtained by sampling a number of points within a water column rather than relying only on single surface samples.


Late-life brain volume: a life-course approach. The AGES-Reykjavik study.
The "fetal-origins-of-adult-disease" hypothesis proposes that an unfavorable intrauterine environment, estimated from small birth size, may induce permanent changes in fetal organs, including the brain. These changes in combination with effects of (cardiovascular) exposures during adult life may condition the later risk of brain atrophy. We investigated the combined effect of small birth size and mid-life cardiovascular risk on late-life brain volumes. Archived birth records of weight and height were abstracted for 1348 participants of the age, gene/environment susceptibility-Reykjavik study (RS; 2002-2006) population-based cohort, who participated in the original cohort of the RS (baseline 1967). Mid-life cardiovascular risk factors (CVRF) were collected in the RS. As a part of the late-life age, gene/environment susceptibility-RS examination, a brain magnetic resonance imaging was acquired and from it, volumes of total brain, gray matter, white matter, and white matter lesions were estimated. Adjusting for intracranial volume, demographics, and education showed small birth size (low ponderal index [PI]) and increased mid-life cardiovascular risk had an additive effect on having smaller late-life brain volumes. Compared with the reference group (high PI/absence of mid-life CVRF), participants with lower PI/presence of mid-life CVRF (body mass index >25 kg/m(2), hypertension, diabetes, "ever smokers") had smaller total brain volume later in life; B (95% confidence interval) were -10.9 mL (-21.0 to -0.9), -10.9 mL (-20.4 to -1.4), -20.9 mL (-46.9 to 5.2), and -10.8 mL (-19.3 to -2.2), respectively. These results suggest that exposure to an unfavorable intrauterine environment contributes to the trajectory toward smaller brain volume, adding to the atrophy that may be associated with mid-life cardiovascular risk.


Discussing randomised clinical trials of cancer therapy: evaluation of a Cancer Research UK training programme.
To evaluate a training intervention aimed at improving healthcare professionals' communication with cancer patients about randomised clinical trials. Before and after evaluation of training programme. Members of the National Cancer Research Network, Scottish Trials Network, and the Welsh Cancer Trials Network. 101 healthcare professionals (33 clinicians and 68 research nurses). Four modules delivered by a trained facilitator using videotapes and interactive exercises to cover general issues about discussing randomised clinical trials with patients, problems specific to adjuvant trials, trials with palliation as the goal, and trials where patients had a strong preference for one treatment arm. Before and after the intervention, participants were videotaped discussing a trial with an actor portraying a patient. These consultations were assessed for presence of information required by good clinical practice guidelines. The actor patients gave an assessment after each interview. Participants reported their self confidence about key aspects of trial discussion. Analysis of the videotaped consultations showed that, after intervention, significantly more participants displayed key communication behaviours such as explaining randomisation (69 v 81, odds ratio 2.33, P = 0.033), checking patients' understanding (11 v 31, odds ratio 3.22, P = 0.002), and discussing standard treatment (73 v 88, odds ratio 4.75, P = 0.005) and side effects (69 v 85, odds ratio 3.29, P = 0.006). Participants' self confidence increased significantly (P < 0.001) across all areas. Actor patients' ratings of participants' communication showed significant improvements for 12/15 key items. This intensive 8 hour intervention significantly improved participants' confidence and competence when communicating about randomised clinical trials.


[Mother Kangaroo Method: an investigation about the domestic practice].
This is a descriptive study, within uantitative approach, aiming at acquiring knowledge regarding the domestic practice of Mother Kangaroo Method. Data were collected from a survey for the parents of prematures hospitalized in a University Hospital in São Luís, Maranhão State, from May to August, 2005. According to the findings, 100% of the families received training and guidance in the hospital and only in 53.3% of the cases the mothers were guided. The benefits of the education works developed by the team were confirmed by domestic practice with 93.3% of the mothers performing the kangaroo position correctly, where 86.7% of the babies were slightly dressed, 86.7% of the mothers were breast feeding technically in a correct manner and 86.7% without any other items being used. 46.7% of the mothers stay 5 to 8 hours/day with their babies in this position and 66.7% identified house tasks as the principal obstacle of the practice. Regarding neonatal walk-in unit follow-up 63.3% of the mothers identified the lack of financial recourses to pay for transportation as the main difficulty factor. The data obtained show that the support from the family network and the health team seem to be the best way to guarantee the extension of domestic care.


Identification and targeting of novel CDK9 complexes in acute myeloid leukemia.
Aberrant activation of mTOR signaling in acute myeloid leukemia (AML) results in a survival advantage that promotes the malignant phenotype. To improve our understanding of factors that contribute to mammalian target of rapamycin (mTOR) signaling activation and identify novel therapeutic targets, we searched for unique interactors of mTOR complexes through proteomics analyses. We identify cyclin dependent kinase 9 (CDK9) as a novel binding partner of the mTOR complex scaffold protein, mLST8. Our studies demonstrate that CDK9 is present in distinct mTOR-like (CTOR) complexes in the cytoplasm and nucleus. In the nucleus, CDK9 binds to RAPTOR and mLST8, forming CTORC1, to promote transcription of genes important for leukemogenesis. In the cytoplasm, CDK9 binds to RICTOR, SIN1, and mLST8, forming CTORC2, and controls messenger RNA (mRNA) translation through phosphorylation of LARP1 and rpS6. Pharmacological targeting of CTORC complexes results in suppression of growth of primitive human AML progenitors in vitro and elicits strong antileukemic responses in AML xenografts in vivo.


Discrimination and streaming of speech sounds based on differences in interaural and spectral cues.
Differences in spatial cues, including interaural time differences (ITDs), interaural level differences (ILDs) and spectral cues, can lead to stream segregation of alternating noise bursts. It is unknown how effective such cues are for streaming sounds with realistic spectro-temporal variations. In particular, it is not known whether the high-frequency spectral cues associated with elevation remain sufficiently robust under such conditions. To answer these questions, sequences of consonant-vowel tokens were generated and filtered by non-individualized head-related transfer functions to simulate the cues associated with different positions in the horizontal and median planes. A discrimination task showed that listeners could discriminate changes in interaural cues both when the stimulus remained constant and when it varied between presentations. However, discrimination of changes in spectral cues was much poorer in the presence of stimulus variability. A streaming task, based on the detection of repeated syllables in the presence of interfering syllables, revealed that listeners can use both interaural and spectral cues to segregate alternating syllable sequences, despite the large spectro-temporal differences between stimuli. However, only the full complement of spatial cues (ILDs, ITDs, and spectral cues) resulted in obligatory streaming in a task that encouraged listeners to integrate the tokens into a single stream.


Race/Ethnicity, Perceived Skin Color, and the Likelihood of Adult Arrest.
Research has long-documented racial/ethnic disparities in criminal justice outcomes. However, despite race/ethnicity being a multidimensional social construct, prior research largely relies on self-identification measures, thereby disregarding research on skin tone stratification within-racial/ethnic groups. The current study extends beyond this by examining the relationship between race/ethnicity and arrest employing both self-identified race/ethnicity and perceived skin color. Using data from the National Longitudinal Study of Adolescent to Adult Health, we explore the main and intersecting effects of self-identified race/ethnicity and perceived skin color on experiencing an arrest in adulthood between- and within-self-identified Whites, Blacks, Latinos, Native Americans, and Asians. We use structural disadvantage as a framework for exploring how social structural factors as well as antisocial behavior mediate the relationship between race/ethnicity/color and arrest. Results suggest that focusing on the racial/ethnic disparities alone masks differences in arrest by color and that the effect of color varies by race/ethnicity. Results also suggest that measures indicative of disadvantage, but not offending, partially explain these associations.


Ranking low, feeling high: How hierarchical position and experienced power promote prosocial behavior in response to procedural justice.
Research shows that power can lead to prosocial behavior by facilitating the behavioral expression of dispositional prosocial motivation. However, it is not clear how power may facilitate responses to contextual factors that promote prosocial motivation. Integrating fairness heuristic theory and the situated focus theory of power, we argue that in particular, organization members in lower (vs. higher) hierarchical positions who simultaneously experience a high (vs. low) sense of power respond with prosocial behavior to 1 important antecedent of prosocial motivation, that is, the enactment of procedural justice. The results from a multisource survey among employees and their leaders from various organizations (Study 1) and an experiment using a public goods dilemma (Study 2) support this prediction. Three subsequent experiments (Studies 3-5) show that this effect is mediated by perceptions of authority trustworthiness. Taken together, this research (a) helps resolve the debate regarding whether power promotes or undermines prosocial behavior, (b) demonstrates that hierarchical position and the sense of power can have very different effects on processes that are vital to the functioning of an organization, and (c) helps solve ambiguity regarding the roles of hierarchical position and power in fairness heuristic theory. (PsycINFO Database Record


Effect of teniposide (VM-26) on the cell survival, micronuclei-induction and lactate dehydrogenase activity on V79 cells.
The genotoxic effect of 0, 1, 5, 10, 25, 50 and 100 nM teniposide (VM-26) treatment was studied on cultured V79 cells. Treatment of V79 cells with different concentrations of teniposide resulted in a concentration-dependent decline in the cell survival and growth kinetics. VM-26 treatment also caused alteration in the cell proliferation kinetics as evidenced by the increase in the frequency of mononucleate cells, with a consequent decline in the frequency of binucleate cells in a concentration-dependent manner at all the post-treatment time periods. Exposure of V79 cells to different concentrations of VM-26 resulted in a concentration related elevation in the frequency of micronucleated binucleate (MN) cells. The frequency of MN was significantly higher in VM-26 treated cells than that of non-drug treated cells at all the post-treatment time periods. A peak frequency of MN was observed at 16 h post-treatment that declined thereafter. The release of lactate dehydrogenase increased with the increase in drug concentration and a maximum LDH release was observed at 0.5 h post-treatment after exposure to 10-100 nM VM-26. While a peak value was observed at 1 and 2 h for 5 and 1 nM VM-26, respectively. The biological response was evaluated by determining the relationship between micronuclei and cell survival. The cell survival declined with increasing MN frequency, resulting in a close but an inverse relationship between the cell survival and micronuclei-induction. The dose effect relationships for micronuclei induction, LDH release and biological response was linear quadratic.


Death-stricken survivor mother: the lived experience of near miss mothers.
A Near Miss Mother (NMM) who survives life-threatening conditions, experiences intense physical, emotional, and psychological consequences following the maternal near-miss (MNM) events. The aim of this study was therefore to explore indepth understanding meaning of NMM everyday lived experiences on the social and cultural background of Iran. This qualitative study utilized a hermeneutic phenomenology procedure. The study was conducted in hospitals affiliated with the Educational, Research and Treatment Centerwhich usually handle the NMMs. The sampling was purposeful with a maximum variation of eleven NMMs. Datawere collected using unstructured face-to-face interviews, and thetranscribed data were analyzed using Diekelmann, Allen, and Tanner's seven-stage thematic analysis approach. "Death-stricken survivor mother" was the central emerged theme, and three extracted sub-themes included: "Distorted psyche on a journey to death", "physical destruction due to an ominous event ", and the "vicissitudinous life after reviving ". These sub-themes, in turn, involved 12 sub-themes that emerged from 38 common meanings and 1200 codes. Findings demonstrate that the living conditions of NMMs are mixed in all aspects of the MNM event. They need a supportive program that includes additional follow-up visits, psychological support from the time of hospitalization until long-time after discharge, alleviation of social, sexual, and financial worries to return them to the normal life, as well as psychosocial rehabilitation to increase their life quality. Furthermore, post-discharge care in NMMs should be done actively and directly at their homes.


The School Garden: A Social and Emotional Place.
School gardens are part of many schools. Especially in primary schools, but also in secondary schools, they are used as a learning space and experience space for the pupils. Their importance for the development of cognitive and emotional-affective abilities of pupils is empirically well proven. It is also empirically well proven that exposure to nature has an influence on the prosocial behavior of children and adults. However, there is a lack of studies investigating the effect of the stay in the school garden on the social behavior of pupils in secondary class. To investigate whether a school garden is a good environment for social learning, a self-report study and standardized observations with sixth-grade pupils were carried out. Thus, the socially competent behavior of the pupils (communication and cooperation) and their emotions could be analyzed. In order to provide emotional access to the scientific content of biology lessons and to strengthen social learning, each pupil was responsible for their own plant and the group bed over a period of 10 weeks. The design of the lessons followed the principles of basic needs-competence, autonomy, and relatedness-of the Self Determination Theory. The observations were made during a 90-min class, in the school garden as well in the classroom. The 31 girls and 22 boys, aged 11-12 years, changed weekly between the garden and the classroom. Over 150 observations were made in the school garden (82) and in the classroom (68). In summary, pupils showed more socially competent behavior in school garden lessons than in classroom lessons. The school garden lessons, designed according to the basic needs, seem to create favorable incentives for social learning. Due to frequent social interactions, it can be assumed that learning activities in school gardens can promote emotional and social competence.


Subgroup identities as a key to cooperation within large social groups.
We experimentally investigated the effect of superordinate (i.e. British) versus subordinate (i.e. English) identity salience on willingness to contribute to a resource shared at the superordinate level (the British coast). Contrary to what would be expected from straightforward application of self-categorization theory, two studies demonstrated that willingness to contribute to this shared resource was higher when subordinate (rather than superordinate) identity was activated. To explain this effect, we suggest that subordinate identities sometimes provide a more meaningful basis for self-definition and, when this is the case, activating subordinate level of identity might lay the foundation for enhanced cooperation within higher-order identities. Indeed, consistent with this argument, Study 2 showed that increased meaningfulness and coherence of the self-concept mediated the effect of subordinate identity salience on contributions to the shared (superordinate) resource. The results are discussed with respect to the role of meaning in determining categorization effects.


Historical trauma in American Indian/Native Alaska communities: a multilevel framework for exploring impacts on individuals, families, and communities.
Over multiple generations, American Indian communities have endured a succession of traumatic events that have enduring consequences for community members. This article presents a multilevel framework for exploring the impact of historically traumatic events on individuals, families, and communities. The critical connection between historically traumatic events and contemporary stressors is also discussed at length.


Genomic analysis of the rare British Lop pig and identification of distinctive genomic markers.
Concentration of production on a few commercial pig breeds has led to the marginalization of many native, numerically small breeds, increasing their risk of endangerment. In the UK, one such rare breed is the British Lop, a lop-eared breed, of similar origin to the Welsh breed. The objective of the present study was to address the genomic status of the British Lop and its relationship with other breeds and identify a small set of genomic markers that uniquely characterize and distinguish British Lop animals. Results have shown that the British Lop is a relatively distinct population with reduced genomic diversity and effective size consistent with its status as a rare breed. Furthermore, we demonstrated the genetic closeness of the British Lop to phenotypically similar breeds such as Landrace and Welsh as well Large White, Middle White and Pietrain. Finally, a set of 75 Single Nucleotide Polymorphisms distributed across multiple chromosomes were identified and validated as markers that can consistently distinguish British Lops from other closely related breeds. Results may inform breeding and management strategies aiming to enhance diversity as well as the development of a breed purity test.


Structural Connectivity Enriched Functional Brain Network using Simplex Regression with GraphNet.
The connectivity analysis is a powerful technique for investigating a hard-wired brain architecture as well as flexible, functional dynamics tied to human cognition. Recent multi-modal connectivity studies had the challenge of combining functional and structural connectivity information into one integrated network. In this paper, we proposed a simplex regression model with graph-constrained Elastic Net (GraphNet) to estimate functional networks enriched by structural connectivity in a biologically meaningful way with a low model complexity. Our model constructed the functional networks using sparse simplex regression framework and enriched structural connectivity information based on GraphNet constraint. We applied our model on the real neuroimaging datasets to show its ability for predicting a clinical score. Our results demonstrated that integrating multi-modal features could detect more sensitive and subtle brain biomarkers than using a single modality.


A hypothesis of osmotic endothelial injury. A pathogenetic mechanism in central pontine myelinolysis.
Central pontine myelinolysis (CPM) is a demyelinative disorder of unknown origin. Recent clinical and experimental studies have indicated an association of CPM with a rise in the serum sodium level. I propose that the rapid rise in the serum sodium level causes an osmotic injury to the endothelium resulting in the release of myelinotoxic factors and/or the production of vasogenic edema. The latter factors may lead to demyelination. The patient at risk, viz, a chronically ill, alcoholic, cirrhotic person, may be the one least able to generate protective cerebral mechanisms against the osmotic stress. The location of lesions may be explained by a suitable anatomic arrangement consisting of an extensive admixture of gray and white matter; thus, myelinotoxic factors derived from the richly vascular gray are able to interact with adjacent bundles of myelin-containing white matter.


Fatty acid esterification in the yolk sac membrane of the avian embryo.
The transfer of lipid from the yolk to the avian embryo is mediated by the yolk sac membrane (YSM). Some, but not all, of the published morphological evidence supports the view that the lipid undergoes a cycle of hydrolysis and re-esterification during translocation across the YSM. The present study aims to test this view by investigating the capacity of the YSM to perform esterification of free fatty acids to form acyl-lipids. YSM pieces (area vasculosa), obtained from the chicken embryo at day 10 of development, were incubated in vitro in medium containing [14C]-palmitic acid. Radioactivity was rapidly incorporated into the tissue lipid indicating a high capacity for esterification. The incorporation was linear with time during the 1-h incubation. Approximately 84% of the incorporated label was recovered in triacylglycerol, 12% was incorporated into phospholipid and less than 1% was detected in cholesteryl ester. [14C]-palmitic acid was incorporated primarily at the sn-1/3 positions in the triacylglycerol molecule and at the sn-1 position of phospholipid. The incorporation of label into tissue pieces obtained from the non-vascularized peripheral region of the YSM (area vitellina) was much more limited than that observed for the area vasculosa. The results support the hypothesis that yolk lipid is hydrolyzed and re-esterified during transfer across the YSM.


A 1H-NMR study of human interleukin-1 beta. Sequence-specific assignment of aromatic residues using site-directed mutant proteins.
Complete identification of spin systems in the aromatic region of recombinant human interleukin-1 beta has been achieved using two-dimensional homonuclear Hartmann-Hahn spectroscopy. In addition, sequence-specific assignments for the four tyrosine residues have been carried out with the help of a series of mutant proteins, obtained by site-directed mutagenesis of the cloned gene. It is shown that, for the mutant proteins investigated, either none or only local structural changes occur. The use of NMR spectroscopy to determine the structural identity of site-directed mutant proteins with respect to the wild-type protein is discussed.


Highly photosensitive Sb/Er/Ge-codoped silica fiber for writing fiber Bragg gratings with strong high-temperature sustainability.
A highly photosensitive Sb/Er/Ge-codoped silica fiber for fabricating fiber Bragg gratings (FBGs) with strong high-temperature sustainability is presented. The photosensitivity and the high-temperature sustainability of FBGs created in this fiber are examined and compared with those produced in a Sn-doped silica fiber. The results show that the Sb/Er/Ge fiber has a much higher level of photosensitivity than the Sn-doped silica fiber and that the FBGs have a similar high-temperature sustainability of 800 degrees C. The strong fluorescence properties observed from this fiber are also examined.