Evaluation of Physicians' Compliance With Secondary Prevention Among Ischemic Stroke Patients: A Retrospective Study.
Stroke is a leading cause of disability and death worldwide. Globally, stroke affects 13.7 million individuals every year. Several studies have shown an increase in the rehospitalization rate among stroke patients caused by non-adherence to secondary prevention as recommended by the American Heart Association/American Stroke Association (AHA/ASA) guideline. The aim of this study was to evaluate physicians' compliance with secondary prevention of stroke upon patients' discharge. A retrospective chart review study was conducted at King Fahad Medical City. The primary outcome of this study was the number of patients discharged with the recommended medications for the secondary prevention of ischemic stroke (IS). The data were collected from the patient's medical record files and analyzed using the Statistical Package for the Social Sciences (SPSS). Of the 675 patients who were screened for eligibility, 507 were included and 168 were excluded. The mean age of the patients was 59.5 (± 15.6) years. Of the 507 patients, 181 (35.7%) had a history of previous stroke. Overall, 376 (74%) stroke patients were discharged with appropriate secondary prevention recommendation per AHA/ASA guideline. This study stresses the importance of compliance with the AHA/ASA guideline for secondary stroke prevention and highlights the role of pharmacists in the stroke unit in which it is necessary to ensure that all stroke patients are discharged with the recommended medications to reduce recurrent stroke.


Serotonergic and noradrenergic markers of post-traumatic stress disorder with and without major depression.
Some studies have suggested that disorders in the peripheral and central metabolism of serotonin (5-HT) and noradrenaline (NE) may play roles in the pathophysiology of post-traumatic stress disorder (PTSD). This study examines (1) the availability of plasma total tryptophan, the precursor of 5-HT, and tyrosine, the precursor of NE; and (2) the platelet 5-HT transporter and alpha 2-adrenoceptor (alpha 2-AR) binding sites in patients with PTSD and healthy volunteers. High-performance liquid chromatography (HPLC) was employed to measure plasma tryptophan and tyrosine as well as amino acids known to compete with the same cerebral transport system; that is, valine, leucine, phenylalanine, and isoleucine. The maximum number of binding sites (Bmax) and their affinity (Kd) for binding to [3H]-paroxetine and [3H]-rauwolscine, a selective alpha 2-AR antagonist, were determined. [3H]-paroxetine and [3H]-rauwolscine binding Kd values were significantly higher in patients with PTSD than in healthy volunteers. [3H]-rauwolscine binding Kd values were significantly higher in patients with PTSD and concurrent major depression (MD) than in PTSD patients without MD and healthy volunteers. Plasma tyrosine concentrations and the ratio of tyrosine/valine + leucine + isoleucine + phenylalanine + tryptophan were significantly higher in PTSD patients with MD than in those without MD and healthy volunteers. The results show that PTSD is accompanied by lower affinity of paroxetine binding sites and that PTSD with concurrent MD is accompanied by lower affinity of alpha 2-ARs and increased plasma tyrosine availability to the brain. The results suggest that (1) serotonergic mechanisms, such as defects in the 5-HT transporter system, may play a role in the pathophysiology of PTSD; and (2) that catecholaminergic mechanisms, such as increased precursor availability and lowered affinity of alpha 2-ARs, may play a role in the pathophysiology of PTSD with concurrent MD.


Shear modulus-temperature meltdown profiles of gelatin and pectin gels. A cascade theory description.
In this paper, a cascade theory approach to biopolymer gelation is developed to describe variation of the shear modulus with temperature for thermoreversible gels. The broadness of this 'melting transition' is seen to depend crucially on the enthalpy of cross-linking, while the critical gel melting temperature is determined by additional factors such as the entropy of cross-linking, the polymer concentration, the molecular weight, and the number of cross-linking sites. On using the model to fit experimental data for specific gelatin and pectin systems, it was found that the behaviour of gelatin (sharp melting transition and low melting temperature) is a consequence of the large negative enthalpy and entropy of cross-linking, while, in contrast, the broad melting transition and high melting point of the pectin system are consistent with much smaller negative values for these parameters.


Metabolism and toxicological detection of the new designer drug 3',4'-methylenedioxy-alpha-pyrrolidinopropiophenone studied in urine using gas chromatography-mass spectrometry.
R,S-3',4'-Methylenedioxy-alpha-pyrrolidinopropiophenone (MDPPP) is a new designer drug with assumed amphetamine-like effects, which has appeared on the illicit drug market. The aim of this study was to identify the MDPPP metabolites using solid-phase extraction, ethylation or acetylation as well as to develop a toxicological detection procedure in urine using solid-phase extraction, trimethylsilylation and GC-MS. Analysis of urine samples of rats treated with MDPPP revealed that MDPPP was completely metabolized by demethylenation of the methylenedioxy group followed by partial 3'-methylation of the resulting catechol, oxidative desamination to the corresponding diketo compounds and/or hydroxylation of the pyrrolidine ring with subsequent dehydrogenation to the corresponding lactam. The hydroxy groups were found to be partly conjugated. Based on these data, MDPPP could be detected in urine via its metabolites by full-scan GC-MS using mass chromatography for screening and library search for identification by comparison of the spectra with reference spectra.


Marrow granulocyte reserves in black Americans. Hydrocortisone-induced granulocytosis in the "benign" neutropenia of the black.
The bone marrow granulocyte reserves of nine black patients with "benign" neutropenia were estimated by measuring the maximum neutrophil increment after the administration of hydrocortisone. Thirty control subjects, including 16 black and 14 white adults, were also studied. The mean neutrophil increment in the black patients with neutropenia was significantly less than that in the control subjects. The mean increment in the black control was also significantly less than that in the white control subjects. Four of the 16 black control subjects had neutrophil counts below 2,000/microliter; if these four are excluded from the analysis, the difference between the black and white control subjects is no longer significant. These data suggest that there is a subpopulation of healthy black adults with neutrophil counts below 2,000/microliter with reduced marrow granulocyte reserves as tested by corticosteroids. Bone marrow aspirates in four of the neutropenic patients showed normal cellularity and myeloid maturation suggesting that the lower increments are due to a difference in granulocyte release rather than to a difference in granulocyte production.


Euthanasia and other end-of-life decisions in the Netherlands in 1990, 1995, and 2001.
Empirical data on the rate of euthanasia, physician-assisted suicide, and other end-of-life decisions have greatly contributed to the debate about the role of such practices in modern health care. In the Netherlands, the continuing debate about whether and when physician-assisted dying is acceptable seems to be resulting in a gradual stabilisation of end-of-life practices. We replicated interview and death-certificate studies done in 1990 and 1995 to investigate whether end-of-life practices had altered between 1995 and 2001. Since 1995, the demand for physician-assisted death has not risen among patients and physicians, who seem to have become somewhat more reluctant in their attitude towards this practice.


[The significance of the characteristics of lubricating jellies in use during transurethral prostate resections with metallic sheaths (author's transl)].
If a metallic sheath is used during a transurethral resection of the prostate with high-frequency currents, the lubricating jelly has to exceed a prescribed conductivity, in order to prevent dangerous current-density spots within the urethra. Furthermore, the mechanical behaviour of the lubricating jelly and the mode of its application have to be considered carefully.


Proposal for a European COPD network.
Over the past few years, pulmonary rehabilitation programs have become more usual in Europe. Even COPD patients on LTOT no longer feel home-bound or grounded. Nevertheless, they experience anxiety when leaving their usual medical environment. The SEP would like to encourage COPD patients to travel by creating a European COPD network. The objectives of this network would be (1) to record all the pulmonary centers in Europe that are involved in pulmonary rehabilitation; (2) to know the availability of oxygen in the different European countries and pulmonary centers; (3) to record those of these centers that would agree to take under supervision COPD patients traveling in their respective area and to provide all technical and medical assistance; (4) to select the most suitable holiday resorts for COPD patients according to ambient temperature, altitude, hotel accommodation, pollution, and possibility for COPD patients to walk around and take excursions; (5) to include oxygen suppliers and medical equipment companies involved in the technical assistance of these COPD patients traveling with all their paraphernalia. Such a European network would enable COPD patients to travel securely, being sure to find medical and technical assistance in all of these "SEP-recommended" places (SEP Guide).


Effect of chronic nitrofurantoin on the rabbit urinary bladder.
Interstitial cystitis is a pathological condition whose symptoms mimic urinary tract infection and include urgency, frequency, and moderate to severe pain. Many more women than men are affected, with antibiotic therapy being the usual first treatment approach based on symptomology. Some clinicians believe that chronic antibiotic therapy may play an etiological role in interstitial cystitis; however neither clinical nor experimental data support their opinion. The implied pathogenesis of antibiotic injury is an alteration of the bladder mucosa and its protective mucin coating to allow urine-mediated damage to the bladder wall. The purpose of this study is to evaluate rabbit urinary bladder function and morphology during chronic nitrofurantoin administration. The results demonstrate that up to twelve months of chronic nitrofurantoin administration produce no changes in 1) bacterial adherence to the rabbit bladder mucosa, 2) specific antibacterial adherence activity of the bladder mucin, and 3) ultrastructure of the mucosa, submucosa, and muscularis.


Transplantation of porcine umbilical cord matrix cells into the rat brain.
Immune rejection of transplanted material is a potential complication of organ donation. In response to tissue transplantation, immune rejection has two components: a host defense directed against the grafted tissue and an immune response from the grafted tissue against the host (graft vs host disease). To treat immune rejection, transplant recipients are typically put on immunosuppression therapy. Complications may arise from immune suppression or from secondary effects of immunosuppression drugs. Our preliminary work indicated that stem cells may be xenotransplanted without immunosuppression therapy. Here, we investigated the survival of pig stem cells derived from umbilical cord mucous connective tissue (UCM) after transplantation into rats. Our data demonstrate that UCM cells survive at least 6 weeks without immune suppression of the host animals after transplantation into either the brain or the periphery. In the first experiment, UCM cells were transplanted into the rat brain and recovered in that tissue 2-6 weeks posttransplantation. At 4 weeks posttransplantation, the UCM cells engrafted into the brain along the injection tract. The cells were small and roughly spherical. The transplanted cells were positively immunostained using a pig-specific antibody for neuronal filament 70 (NF70). In contrast, 6 weeks posttransplantation, about 10% of the UCM cells that were recovered had migrated away from the injection site into the region just ventral to the corpus callosum; these cells also stained positively for NF70. In our second experiment, UCM cells that were engineered to constitutively express enhanced green fluorescent protein (eGFP) were transplanted. These cells were recovered 2-4 weeks after brain transplantation. Engrafted cells expressing eGFP and positively staining for NF70 were recovered. This finding indicates a potential for gene therapy. In the third experiment, to determine whether depositing the graft into the brain protected UCM cells from immune detection/clearance, UCM cells were injected into the tail vein and/or the semitendinosis muscle in a group of animals. UCM cells were recovered from the muscle or within the kidney 3 weeks posttransplantation. In control experiments, rat brains were injected with PKH 26-labeled UCM cells that had been lysed by repeated sonic disruption. One and 2 weeks following injection, no PKH 26-labeled neurons or glia were observed. Taken together, these data indicate that UCM cells can survive xenotransplantation and that a subset of the UCM cells respond to local signals to differentiate along a neural lineage.


An ELISA-based platform for rapid identification of structure-dependent nucleic acid-protein interactions detects novel DNA triplex interactors.
Unusual nucleic acid structures play vital roles as intermediates in many cellular processes and, in the case of peptide nucleic acid (PNA)-mediated triplexes, are leveraged as tools for therapeutic gene editing. However, due to their transient nature, an understanding of the factors that interact with and process dynamic nucleic acid structures remains limited. Here, we developed snapELISA (structure-specific nucleic acid-binding protein ELISA), a rapid high-throughput platform to interrogate and compare up to 2688 parallel nucleic acid structure-protein interactions in vitro. We applied this system to both triplex-forming oligonucleotide-induced DNA triplexes and DNA-bound PNA heterotriplexes to describe the identification of previously known and novel interactors for both structures. For PNA heterotriplex recognition analyses, snapELISA identified factors implicated in nucleotide excision repair (XPA, XPC), single-strand annealing repair (RAD52), and recombination intermediate structure binding (TOP3A, BLM, MUS81). We went on to validate selected factor localization to genome-targeted PNA structures within clinically relevant loci in human cells. Surprisingly, these results demonstrated XRCC5 localization to PNA triplex-forming sites in the genome, suggesting the presence of a double-strand break intermediate. These results describe a powerful comparative approach for identifying structure-specific nucleic acid interactions and expand our understanding of the mechanisms of triplex structure recognition and repair.


Thyroid imaging reporting and data system (TI-RADS) in the diagnostic value of thyroid nodules: a systematic review.
This review was to assess the overall diagnostic accuracy of thyroid imaging reporting and data system (TI-RADS) classification in the differentiated diagnosis of patients with thyroid nodules. The diagnostic accuracy of TI-RADS was identified by using data from PubMed, the Cochrane Library, and other databases, which was from Jan 1966 to Dec 2013. Meta-analysis methods were used to obtain pooled sensitivity, specificity, negative likelihood ratio, positive likelihood ratio, diagnostic odds ratio, and summary receiver operating characteristic curves. A total of five studies with 7,753 thyroid nodules enrolled met the inclusion criteria in this meta-analysis. TI-RADS had a pooled sensitivity of 0.75 (95 % confidence interval 0.72-0.78) and a pooled specificity of 0.69 (95 % confidence interval 0.68-0.70). The pooled diagnostic odds ratio was 24.28 (95 % confidence interval 14.25-41.38). The overall area under the curve was 0.9177, and the Q* index was 0.8304. The TI-RADS classification was the accurate diagnostic technique for differentiating thyroid nodules.


Human Papillomavirus: Oral Lesions and Vaccination.
Human papillomavirus (HPV) is associated with benign and malignant lesions in various locations, such as the skin and oral and genital mucosa [...].


[Mothers experience in participating in the care of their hospitalised children].
The purpose of this study was to describe the experience, the meaning and importance to them, of mothers participating in the care process of their child, as well as to identify interventions in which mothers were involved. A qualitative approach was employed for this study, which was theoretically based on Symbolic Interactions and the Grounded Theory reference methodology. A semi-structured interview and observation were chosen as data collection techniques. The study included 18 mothers with hospitalised children. They were selected based on inclusion criteria: mothers with children hospitalised 5 or more days, and with a willingness to participate. The number of participants was defined using the criterion of data saturation. The data was analysed using the program Nvivo8. Mothers understood the participation as an obligation and an aid to nurses. They also considered it as a contribution to the personal care of their children, for their well-being and for continuity of the parental role. The care in which the mothers were involved were those of family care, already developed in the home. They developed other forms of care, which were delegated by nurses without negotiation. The confusion of roles and the non-distribution of power caused anxiety in mothers when confronted with new forms of care. The mothers considered their participation in their child's care as very important, but this involvement was characterised by a continuation of the care provided at home. They developed other forms of care but were not fully involved.


Sperm motility within the mammalian epididymis: species variation and correlation with free calcium levels in epididymal plasma.
The region within the epididymis where spontaneous sperm motility first appeared and the extent of later motility within that organ, as shown by microscopic observation of undiluted samples, varied with the species. In the rat, mouse, and hamster, little sperm motility was present. In other species, spontaneously motile sperm were obtained from the caput (rabbit) and corpus (bull and man) regions of the epididymis. Samples from the cauda region of the epididymis were found to contain many motile sperm in the rabbit, bull, and especially man, where most of the sperm were intensely motile. There was a correlation between the amount of free calcium surrounding the sperm within the cauda epididymidis of a given species and the level of sperm motility therein. An inverse relationship was also found between the free calcium concentration in the cauda epididymal plasma of a species and the later inducibility of motility in diluted sperm from that species by calcium ion.


Imatinib resistance in a novel translocation der(17)t(1;17)(q25;p13) with loss of TP53 but without BCR/ABL kinase domain mutation in chronic myelogenous leukemia.
We describe here two novel translocations, t(7;14)(p22;q13) and der(17)t(1;17)(q25;p13), in a 41-year-old man with an accelerated phase (AP) of chronic myelogenous leukemia (CML). Chromosome analysis initially showed 46,XY,t(7;14)(p13;q22),t(9;22)(q34;q11.2)[20]. In 3 years, the karyotype evolved to 45,X,-Y,der(7)t(7;14)(p13;q22),t(9;22)(q34;q11.2),-14,der(17)t(1;17)(q25;p13),+der(22)t(9;22)[20], accompanied with a resistance to imatinib mesylate. The TP53 was deleted from the der(17)t(1;17)(q25;p13), but there was no mutation of TP53 in the remaining allele. Mutations in the BCR/ABL kinase domain could not be detected as well. Morphologically, dysplastic changes including pseudo-Pelger-Huët anomaly appeared in the bone marrow cells. These findings suggest that the t(7;14)(p22;q13) translocation had a crucial role in the progression to CML-AP, and that the resistance to imatinib may be due to the additional cytogenetic abnormalities, including der(17)t(1;17)(q25;p13), but not to BCR/ABL mutations.


Diverse type I and type II methanotrophs cultivated from an Indian freshwater wetland habitat.
Wetlands are the main natural sources of methane emissions, which make up a significant portion of greenhouse gas emissions. Such wetland patches serve as rich habitats for aerobic methanotrophs. Limited knowledge of methanotrophs from tropical wetlands widens the scope of study from these habitats. In the present study, a freshwater wetland in a tropical region in India was sampled and serially diluted to obtain methanotrophs in culture. This was followed by the isolation of methanotrophs on agarose-containing plates, incubated under methane: air atmosphere. Methanotrophs are difficult to cultivate, and very few cultures of methanotrophs are available from tropical wetlands. Our current study reports the cultivation of a diverse community of methanotrophs from six genera, namely, Methylomonas, Methylococcus, Methylomagnum, Methylocucumis (type I methanotrophs) along with Methylocystis, Methylosinus (type II methanotrophs). A high abundance of methanotrophs (106-1010 methanotrophs/g fresh weight) was observed in the samples. A Methylococcus strain could represent a putative novel species that was also isolated. Cultures of Methylomagnum and Methylocucumis, two newly described type I methanotrophs exclusively found in rice fields, were obtained. A large number of Methylomonas koyamae strains were cultured. Our study is pioneering in the documentation of culturable methanotrophs from a typical tropical wetland patch. The isolated methanotrophs can act as models for studying methanotroph-based methane mitigation from wetland habitats and can be used for various mitigation and valorization applications.


Safety and Feasibility of High-Pressure/High-Dose Pressurized Intraperitoneal Aerosol Chemotherapy (HP/HD-PIPAC) for Primary and Metastatic Peritoneal Surface Malignancies.
The aim of this study was to evaluate the feasibility and perioperative safety of high-pressure/high-dose pressurized intraperitoneal aerosol chemotherapy (HP/HD-PIPAC) to manage peritoneal surface malignancies (PSM). Retrospective analysis of a prospective database of about 130 consecutive patients scheduled for HP/HD-PIPACs for PSM. Doxorubicin plus cisplatin (PIPAC-C/D) or oxaliplatin (PIPAC-Ox) were nebulized into a constant capnoperitoneum of 20 mmHg at doses of 6, 30, or 120 mg/m2 of body surface area (BSA). Outcome criteria were perioperative complications (Clavien-Dindo). The median age of patients was 62 years (range 9-82), and the primary tumor site was of colorectal (CRC), upper gastrointestinal tract (UGI), unknown primary (CUP), malignant epithelioid mesothelioma of the peritoneum (MPM), hepato-pancreatic-biliary tract (HPB), and other origin in 30 (23.1%), 27 (20.8%), 16 (12.3%), 16 (12.3%), 6 (4.6%), and 35 (26.9%) patients, respectively. Abdominal access failed for a first, second, third, and fourth or more HP/HD-PIPAC in 12/130 (9.2%), 4/64 (6.3%), 6/40 (15.0%), and 2/33 (6.1%) patients. A total of 243 procedures were performed in 118 patients. No intraoperative complications related to increased capnoperitoneal pressure occurred, but an intraoperative bleeding complication was observed in 1/243 (0.4%) patients. The overall rate of postoperative procedure-related complications was 19.3% (47/243), while 15.3% (37/243), 1.6% (6/243), 1.6% (1/243), 0.4% (1/243), and 0.4% (1/243) were Grade I, II, III, IV, and V complications, respectively. Perioperative complications of HP/HD-PIPAC are comparable with standard pressure/dose PIPAC treatment protocols. Prospective studies are warranted to examine potential improvement in therapy outcomes.


Preimplantation Genetic Diagnosis (PGD) for Monogenic Disorders: the Value of Concurrent Aneuploidy Screening.
Pre-implantation genetic diagnosis (PGD) has changed the landscape of clinical genetics by helping families reduce the transmission of monogenic disorders. However, given the high prevalence of embryonic aneuploidy, particularly in patients of advanced reproductive age, unaffected embryos remain at high risk of implantation failure or pregnancy loss due to aneuploidy. 24-chromosome aneuploidy screening has become widely utilized in routine in vitro fertilization (IVF) to pre-select embryos with greater pregnancy potential, but concurrent 24-chromosome aneuploidy screening has not become standard practice in embryos biopsied for PGD. We performed a retrospective cohort study of patients who underwent PGD with or without 24-chromosome aneuploidy screening to explore the value of concurrent screening. Among the PGD + aneuploidy-screened group (n = 355 blastocysts), only 25.6 % of embryos were both Single Gene Disorder (SGD)-negative (or carriers) and euploid; thus the majority of embryos were ineligible for transfer due to the high prevalence of aneuploidy. Despite a young mean age (32.4 ± 5.9y), 49.9 % of Blastocysts were aneuploid. The majority of patients (53.2 %) had ≥1 blastocyst that was Single Gene Disorder (SGD)-unaffected but aneuploid; without screening, these unaffected but aneuploid embryos would likely have been transferred resulting in implantation failure, pregnancy loss, or a pregnancy affected by chromosomal aneuploidy. Despite the transfer of nearly half the number of embryos in the aneuploidy-screened group (1.1 ± 0.3 vs. 1.9 ± 0.6, p < 0.0001), the implantation rate was higher (75 % vs. 53.3 %) and miscarriage rate lower (20 % vs. 40 %) (although not statistically significant). 24-chromosome aneuploidy screening when performed concurrently with PGD provides valuable information for embryo selection, and notably improves single embryo transfer rates.


Polychaetes as environmental indicators revisited.
The utilization of polychaetes in descriptive ecology is reviewed in the light of recent research especially concerning the biota hard bottom environments. Polychaetes, often linked in the past to the concept of opportunistic species able to proliferate after an increase in organic matter, have played an important role especially with regard to impacted soft-bottom habitats. Increased knowledge of the group, suggests that not only opportunistic species can be utilised as indicators, so that these organisms can be disengaged from the old concept of opportunistic taxa. Moreover, recent researches conducted on this group allowed demonstrating as surrogacy is not always applicable. Among polychaetes inhabiting hard bottom environment, the analysis of family Syllidae appears particularly promising. Studied conducted in our laboratory demonstrated as syllid species decrease in abundance or completely disappear under varying sources of negative impact. The distribution of species also appeared indicative in underlying effects of marine protected areas (MPA) functioning, or in describing different climatic areas within biogeographical sectors. It is obvious that good results can only be obtained on the basis of good taxonomic resolution. We suggested that, in monitoring studies, operational time could be optimized not only by working at a higher-level on the whole invertebrate data set, but by also selecting a particularly indicative group and working at fine level.


The ICER review is in: hope amidst uncertainty.
DISCLOSURES: No funding contributed to the writing of this commentary. Smith Begolka, Butler, and Guadalupe are salaried employees of the National Eczema Association, which has received grants and sponsorship awards from a variety of industry partners, including AbbVie, Eli Lilly, Incyte, LEO Pharma, Pfizer, Regeneron, and Sanofi. Smith Begolka has received grant funding from Pfizer and advisory board honoraria from Pfizer and Incyte. Butler and Guadalupe have received advisory board honoraria from Incyte.


Electrical properties of the cellular transepithelial pathway in Necturus gallbladder: III. Ionic permeability of the basolateral cell membrane.
The ionic permeability of the basolateral membrane of Necturus gallbladder epithelium was studied with intracellular microelectrode techniques. After removal of most of the subepithelial tissue (to reduce unstirred layer thickness), impalements were performed from the serosal side, and ionic substitutions were made in the serosal solution while a microelectrode was kept in a cell. Thus, it was possible to obtain continuous (and reversible) records of transepithelial and cell membrane potentials and to measure intermittently the transepithelial resistance and the ratio of cell membrane resistances. From these data and the mean value of the equivalent resistance of the cell membranes in parallel (obtained from cable analysis in a different group of tissues), absolute cell membrane and shunt resistances and equivalent electromotive forces (emfs) were calculated. From the changes of basolateral membrane emf (Eb) produced by the substitutions, the conductance (G) and permeability (P) of the membrane for K, Cl and Na were estimated. Potassium-for-sodium substitutions produced large reductions of both cell membrane potentials, of Eb, and of the resistance of the basolateral membrane (Rb), indicating high GK and PK. Chloride substitution with isethionate or sulfate resulted in smaller changes of cell membrane potentials and Eb and in no significant change of Rb, indicating small but measurable values of GCl and PCl. Sodium substitutions with N-methyl-D-glucamine (NMDG) resulted in cell potential changes entirely attributable to the biionic potential produced in the shunt pathway (PNa greater than PNMDG), and in no significant changes of Rb or Eb, indicating that GNa and PNa are undetectable. The question of the mechanism of Cl transport across the basolateral membrane was addressed by comparing the mean rate of transepithelial Cl transport : formula, see text: and the predicted passive Cl flux across the basolateral membrane (from the membrane Cl conductance, potential, and Cl equilibrium potential). The conclusion is that only a very small fraction of the Cl flux across the basolateral membrane can be electrodiffusional. Since the paracellular Cl conductance is also too low to account for : formula, see text:, these results suggest the presence of a neutral mechanism of Cl extrusion from the cells. This could be a NaCl pump, a downhill KCl transport mechanism, or a Cl-HCO3 exchange mechanism.


SNHG15 promotes chemoresistance and glycolysis in colorectal cancer.
Long noncoding RNAs (lncRNAs) play an important role in tumor progression. Small nucleolar RNA host gene 15 (SNHG15) is a lncRNA that has been confirmed to play an oncogenic role in multiple cancer types. However, its role in glycolysis and chemoresistance in colorectal cancer (CRC) is unclear. The expression of SNHG15 in CRC was analyzed using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases by bioinformatics methods. Cell Counting Kit-8 (CCK-8) and colony formation assays were used to evaluate cell viability. Cell sensitivity to 5-fluorouracil (5-FU) was detected by CCK-8. Glucose absorption and lactate production were used to evaluate the impact of SNHG15 on glycolysis. RNA-seq, real-time fluorescence quantitative reverse transcription PCR (RT-qPCR) and Western blotting (WB) were used to reveal the potential molecular mechanism of SNHG15 in CRC. SNHG15 was upregulated in CRC tissues compared with paired noncancerous tissues. Ectopic SNHG15 expression increased proliferation, 5-FU chemoresistance, and glycolysis in CRC cells. In contrast, SNHG15 knockdown inhibited CRC proliferation, 5-FU chemoresistance and glycolysis. Multiple pathways, including apoptosis and glycolysis, were potentially regulated by SNHG15 based on RNA-seq and pathway enrichment analyses. RT-qPCR and WB experiments confirmed that SNHG15 promoted the expression of TYMS, BCL2, GLUT1 and PKM2 in CRC cells. In conclusion, SNHG15 promotes 5-FU chemoresistance and glycolysis in CRC by potentially regulating the expression of TYMS, BCL2, GLUT1 and PKM2 and appears to be a new target for cancer therapy.


Multicenter Analysis of Patient Reported Outcomes Following Artificial Urinary Sphincter Placement for Male Stress Urinary Incontinence.
Patient centered data are lacking regarding functional and quality of life improvements after artificial urinary sphincter placement. We analyzed the degree of benefit from artificial urinary sphincter placement using ISI (Incontinence Symptom Index), a validated patient reported outcome measure assessing the severity and bother of urinary incontinence, and IIQ-7 (Incontinence Impact Questionnaire-7), a validated patient reported outcome measure assessing the impact and emotional distress of urinary incontinence. We performed a retrospective review at 4 centers participating in TURNS (Trauma and Urologic Reconstruction Network of Surgeons). Data were available on 51 and 45 patients who underwent artificial urinary sphincter placement, and had preoperative and postoperative ISI and IIQ-7 data, respectively. Mean age was 64.8 years. Median time from surgery to followup questionnaires was 8.5 months. On ISI the median preoperative severity and bother scores were 24 (IQR 20-28.5) and 6 (IQR 4-7), and the median postoperative severity and bother scores were 10 (IQR 4.5-17) and 1 (IQR 0-3), respectively. Improvement on each ISI item was statistically significant. On IIQ-7 the median preoperative impact and distress scores were 9 (IQR 6-13) and 4 (IQR 2-6), and the median postoperative impact and distress scores were 3 (IQR 0-7) and 0 (IQR 0-3), respectively. Improvement on each IIQ-7 item was statistically significant. Artificial urinary sphincter implantation significantly reduces the severity and bother of stress urinary incontinence symptoms. Longer followup and development are needed of a patient reported outcome measure targeting male stress urinary incontinence.


PPARδ prevents radiation-induced proinflammatory responses in microglia via transrepression of NF-κB and inhibition of the PKCα/MEK1/2/ERK1/2/AP-1 pathway.
Partial or whole-brain irradiation is often required to treat both primary and metastatic brain cancer. Radiation-induced normal tissue injury, including progressive cognitive impairment, however, can significantly affect the well-being of the approximately 200,000 patients who receive these treatments each year in the United States. Although the exact mechanisms underlying radiation-induced late effects remain unclear, oxidative stress and inflammation are thought to play a critical role. Microglia are key mediators of neuroinflammation. Peroxisomal proliferator-activated receptor (PPAR) δ has been shown to be a potent regulator of anti-inflammatory responses. Thus, we hypothesized that PPARδ activation would modulate the radiation-induced inflammatory response in microglia. Incubating BV-2 murine microglial cells with the PPARδ agonist L-165041 prevented the radiation-induced increase in: (i) intracellular reactive oxygen species generation, (ii) Cox-2 and MCP-1 expression, and (iii) IL-1β and TNF-α message levels. This occurred, in part, through PPARδ-mediated modulation of stress-activated kinases and proinflammatory transcription factors. PPARδ inhibited NF-κB via transrepression by physically interacting with the p65 subunit and prevented activation of the PKCα/MEK1/2/ERK1/2/AP-1 pathway by inhibiting the radiation-induced increase in intracellular reactive oxygen species generation. These data support the hypothesis that PPARδ activation can modulate radiation-induced oxidative stress and inflammatory responses in microglia.


[Parapharyngeal space-occupying lesions. Differential diagnosis based on case examples].
Parapharyngeal tumors account for only 0.8% of all head and neck tumors which often presents the problem of preoperative diagnosis. Up to 80% of parapharyngeal tumors are benign. Starting November 1995 to March 2001, 16 patients with parapharyngeal tumors and 1 retropharyngeal abscess were treated. The median age was 54 years. Only 2 patients demonstrated peripheral nerve lesions preoperatively. 17 tumors and the retropharyngeal abscess were excised via transcervical approach, with an extension by parotidectomy and temporary mandibular split in 1 case. Histological entities were pleomorphic adenomas in 5 cases, a ganglioneurinoma, neurinoma of the vagal nerve and metastasis of a squamous cell carcinoma in 2 patients each, furthermore neuroblastoma, extramedullary plasmocytoma, T-cell lymphoma, and hemangioma in 1 patient each. We demonstrate the differential diagnosis of parapharyngeal tumors as well as their diagnostic and therapeutic management. The tumors should be excised by a transcervical approach to protect cervical vessels and nerves, which is limited by a transoral approach.


Streptomyces plicatus as a model biocontrol agent.
Three hundred and seventy two isolates belonging to the genus Streptomyces were isolated and screened for chitinase production. Streptomyces plicatus was found to be the best producer. The highest chitinase production were incubated for 3 d at 30 degrees C on buffered culture medium (pH 8.0) containing chitin plus sucrose and calcium nitrate as carbon and nitrogen sources. S. plicatus chitinase had a highly significant inhibitory effect on spore germination, germ tube elongation and radial growth of Fusarium oxysporum f.sp. lycopersici, Altrernaria alternata and Verticillium albo-atrum, the causal organisms of Fusarium wilt, stem canker and Verticillium wilt diseases of tomato. Application of S. plicatus to the root system of tomato plants before transplantation markedly protected tomato plants against the tested phytopathogenic fungi in vivo.


A geological history of reflecting optics.
Optical reflectors in animals are diverse and ancient. The first image-forming eye appeared around 543 million years ago. This introduced vision as a selection pressure in the evolution of animals, and consequently the evolution of adapted optical devices. The earliest known optical reflectors--diffraction gratings--are 515 Myr old. The subsequent fossil record preserves multilayer reflectors, including liquid crystals and mirrors, 'white' and 'blue' scattering structures, antireflective surfaces and the very latest addition to optical physics--photonic crystals. The aim of this article is to reveal the diversity of reflecting optics in nature, introducing the first appearance of some reflector types as they appear in the fossil record as it stands (which includes many new records) and backdating others in geological time through evolutionary analyses. This article also reveals the commercial potential for these optical devices, in terms of lessons from their nano-level designs and the possible emulation of their engineering processes--molecular self-assembly.


Electronic Dynamics of a Molecular System Coupled to a Plasmonic Nanoparticle Combining the Polarizable Continuum Model and Many-Body Perturbation Theory.
The efficiency of plasmonic metallic nanoparticles in harvesting and concentrating light energy in their proximity triggers a wealth of important and intriguing phenomena. For example, spectroscopies are able to reach single-molecule and intramolecule sensitivities, and important chemical reactions can be effectively photocatalyzed. For the real-time description of the coupled dynamics of a molecule's electronic system and of a plasmonic nanoparticle, a methodology has been recently proposed (J. Phys. Chem. C. 120, 2016, 28774-28781) which combines the classical description of the nanoparticle as a polarizable continuum medium with a quantum-mechanical description of the molecule treated at the time-dependent configuration interaction (TDCI) level. In this work, we extend this methodology by describing the molecule using many-body perturbation theory: the molecule's excitation energies, transition dipoles, and potentials computed at the GW/Bethe-Salpeter equation (BSE) level. This allows us to overcome current limitations of TDCI in terms of achievable accuracy without compromising on the accessible molecular sizes. We illustrate the developed scheme by characterizing the coupled nanoparticle/molecule dynamics of two prototype molecules, LiCN and p-nitroaniline.


Symbiogenesis as a driving force of evolution: The legacy of Boris Kozo-Polyansky.
We analyze evolutionary views of Boris Kozo-Polyansky (1890-1957) who was the first who formulated the symbiotic theory of evolution as a concept in his book, Symbiogenesis: A New Principle of Evolution (1924). Later, starting from 1967, Lynn Margulis independently formulated and further developed the concept of symbiogenesis. Although the ideas on the symbiotic origin of chloroplasts and mitochondria appeared earlier, the book of Kozo-Polyansky presented symbiogenesis as the main factor of complexification in the course of evolution, not only in relation to the origin of eukaryotic cell. Kozo-Polyansky incorporated the ideas of symbiogenesis into a broader paradigm that anticipated the important concepts of the modern Extended Evolutionary Synthesis such as the idea of net of life, the evolutionary role of apoptosis, the ideas of punctuated equilibrium, and the concept of metasystem transition.


The C terminus of p73 is essential for hippocampal development.
The p53 family member p73 has a complex gene structure, including alternative promoters and alternative splicing of the 3' UTR. This results in a complex range of isoforms whose biological relevance largely remains to be determined. By deleting exon 13 (which encodes a sterile α motif) from the Trp73 gene, we selectively engineered mice to replace the most abundantly expressed C-terminal isoform, p73α, with a shorter product of alternative splicing, p73β. These mice (Trp73Δ13/Δ13 ) display severe neurodevelopmental defects with significant functional and morphological abnormalities. Replacement of p73α with p73β results in the depletion of Cajal-Retzius (CR) cells in embryonic stages, thus depriving the developing hippocampus of the pool of neurons necessary for correct hippocampal architecture. Consequently, Trp73Δ13/Δ13 mice display severe hippocampal dysgenesis, reduced synaptic functionality and impaired learning and memory capabilities. Our data shed light on the relevance of p73 alternative splicing and show that the full-length C terminus of p73 is essential for hippocampal development.


Cardiac complications after laparoscopic large hiatal hernia repair. Is it related with staple fixation of the mesh? -Report of three cases.
Laparoscopic Nissen operation with mesh reinforcement remains being the most popular operation for large hiatal hernia repair. Complications related to mesh placement have been widely described. Cardiac complications are rare, but have a fatal outcome if they are misdiagnosed. We sought to outline our institutional experience of three patients who developed cardiac complications following a laparoscopic Nissen operation for large hiatal hernia repair. Laparoscopic hiatoplasty and Nissen fundoplication are safe and effective procedures for the hiatal hernia repair, but they are not exempt from complications. Fixation technique and material used must be taken into account. We have conducted a review of the literature on complications related to these procedures. In the differential diagnosis of hemodynamic instability after laparoscopic hiatal hernia repair, cardiac tamponade and other cardiac complications should be considered.


Use of endoscopic stents to treat anastomotic complications after bariatric surgery.
Complications after bariatric surgery often require longterm parenteral nutrition to achieve healing. Recently, endoscopic treatments have become available that provide healing while allowing for oral nutrition. The purpose of this study was to present outcomes of the largest series to date treating staple line complications after bariatric surgery with endoscopic covered stents. A retrospective evaluation was performed of all patients treated for staple line complications after bariatric surgery at a single tertiary care bariatric center. Acute postoperative leaks, chronic gastrocutaneous fistulas, and anastomotic strictures refractory to endoscopic dilation after both gastric bypass and sleeve gastrectomy were included. From January 2006 to June 2007, 19 patients (11 with acute leaks, 2 with chronic fistulas, and 6 with strictures) were treated with a total of 34 endoscopic silicone covered stents (23 polyester, 11 metal). Mean followup was 3.6 months. Immediate symptomatic improvement occurred in 90% (91% of acute leaks, 100% of fistulas, and 84% of strictures). Oral feeding was started in 79% of patients immediately after stenting. Resolution of leak or stricture after stent treatment occurred in 16 of 19 patients (84%). Healing of leak, fistula, and stricture occurred at means of 33 days, 46 days, and 7 days, respectively. Three patients (1 with leak, 1 with fistula, and 1 with stricture) had unsuccessful stent treatment. Migration of the stent occurred in 58% of 34 stents placed. Most migration was minimal, but three stents were removed surgically after distal small bowel migration. There was no mortality. Treatment of anastomotic complications after bariatric surgery with endoscopic covered stents allows rapid healing while simultaneously allowing for oral nutrition. The primary morbidity is stent migration.


Regulation of cancer cell death by a novel compound, C604, in a c-Myc-overexpressing cellular environment.
The proto-oncogene c-Myc has been implicated in a variety of cellular processes, such as proliferation, differentiation and apoptosis. Several c-Myc targets have been studied; however, selective regulation of c-Myc is not easy in cancer cells. Herein, we attempt to identify chemical compounds that induce cell death in c-Myc-overexpressing cells (STF-cMyc and STF-Control) by conducting MTS assays on approximately 4000 chemical compounds. One compound, C604, induced cell death in STF-cMyc cells but not STF-Control cells. Apoptotic proteins, including caspase-3 and poly(ADP-ribose) polymerase (PARP), were cleaved in C604-treated STF-cMyc cells. In addition, SW620, HCT116 and NCI-H23 cells, which exhibit higher basal levels of c-Myc, underwent apoptotic cell death in response to C604, suggesting a role for C604 as an inducer of apoptosis in cancer cells with c-Myc amplification. C604 induced cell cycle arrest at the G2/M phase in cells, which was not affected by apoptotic inhibitors. Interestingly, C604 induced accumulation of c-Myc and Cdc25A proteins. In summary, a chemical compound was identified that may induce cell death in cancer cells with c-Myc amplification specifically through an apoptotic pathway.


Downregulation of KRAB zinc finger proteins in 5-fluorouracil resistant colorectal cancer cells.
Radio-chemotherapy with 5-flu orouracil (5-FU) is the standard of care treatment for patients with colorectal cancer, but it is only effective for a third of them. Despite our understanding of the mechanism of action of 5-FU, drug resistance remains a significant limitation to the clinical use of 5-FU, as both intrinsic and acquired chemoresistance represents the major obstacles for the success of 5-FU-based chemotherapy. In order to identify the mechanism of acquired resistance, 5-FU chemoresistance was induced in CRC cell lines by passaging cells with increasing concentrations of 5-FU. To study global molecular changes, quantitative proteomics and transcriptomics analyses were performed on these cell lines, comparing the resistant cells as well as the effect of chemo and radiotherapy. Interestingly, a very high proportion of downregulated genes were annotated as transcription factors coding for Krüppel-associated box (KRAB) domain-containing zinc-finger proteins (KZFPs), the largest family of transcriptional repressors. Among nearly 350 KRAB-ZFPs, almost a quarter were downregulated after the induction of a 5-FU-resistance including a common one between the three CRC cell lines, ZNF649, whose role is still unknown. To confirm the observations of the proteomic and transcriptomic approaches, the abundance of 20 different KZFPs and control mRNAs was validated by RT-qPCR. In fact, several KZFPs were no longer detectable using qPCR in cell lines resistant to 5-FU, and the KZFPs that were downregulated only in one or two cell lines showed similar pattern of expression as measured by the omics approaches. This proteomic, transcriptomic and genomic analysis of intrinsic and acquired resistance highlights a possible new mechanism involved in the cellular adaptation to 5-FU and therefore identifies potential new therapeutic targets to overcome this resistance.


Evaluation of carotid arteries in stroke patients using color Doppler sonography: A prospective study conducted in a tertiary care hospital in South India.
Cerebral ischemic stroke is life-threatening and debilitating neurological disease, it is the third leading cause of death in the world. Studies have shown that there is a close relationship between carotid artery stenosis and ischemic cerebral vascular disease. This study is done to assess the carotid arteries with the help of color Doppler sonography and to correlate cerebrovascular accidents. The prospective study was carried out on 50 patients using purposive sampling technique. Risk factors such as hypertension, diabetes mellitus, smoking, and family history were documented. The data gathered from color Doppler examination consisted of peak systolic velocity of common carotid artery (CCA) and internal carotid artery (ICA), velocity ratios between CCA and ICA and plaque characteristics as seen on real-time image. The collected data were analyzed and presented in the form of tables, figures, graphs, and diagrams wherever necessary. As this study deals with the only frequency distribution of various factors, so no tests of significance were applied. The highest incidence of stroke was found in the male population in the age group of 60-69 years. Various risk factors included hypertension, diabetes mellitus, smoking, and family history. Of 50 patients, 12 patients showed significant stenosis (>60%). Atherosclerotic plaques were seen in 39 patients (78%). Color Doppler examination is an economic, safe, reproducible, and less time-consuming method of demonstrating the cause of cerebrovascular insufficiency in extracranial carotid artery system and will guide in instituting treatment modalities.


L-Homocysteine and L-homocystine stereospecifically induce endothelial nitric oxide synthase-dependent lipid peroxidation in endothelial cells.
Atherothrombotic cardiovascular disease associated with hyperhomocysteinemia has been proposed to result, at least in part, from increased vascular oxidative stress. Here we characterize one mechanism by which homocyteine may induce a vascular cell type-specific oxidative stress. Our results show that L-homocysteine at micromolar levels stereospecifically increases lipid peroxidation in cultured endothelial cells, but not in vascular smooth muscle cells or when medium is incubated in the absence of cells. Consistent with these observations, homocysteine also increases the formation of intracellular reactive oxygen species. The pro-oxidant effect of homocysteine can be fully replicated by an equivalent concentration of homocystine (i.e., an oxidized form of homocysteine), but not with cysteine or glutathione. Homocyst(e)ine-dependent lipid peroxidation is independent of H(2)O(2) and alterations in glutathione peroxidase activity, but dependent on superoxide. Mechanistically, the pro-oxidant effect of homocysteine appears to involve endothelial nitric oxide synthase (eNOS), as it is blocked by the eNOS inhibitor L-N(G)-nitroarginine methyl ester. Thus, homocyst(e)ine actively promotes oxidative stress in endothelial cells via an eNOS-dependent mechanism.


Minerals in the hair and nutrient intake of autistic children.
The concentrations of calcium, magnesium, zinc, copper, lead, and cadmium were determined in scalp hair samples from a group of 12 autistic children and a group of 12 nonautistic control children. The only statistically significant difference between median concentrations of minerals in the hair from the two groups was a 62% decrease in the concentration of cadmium in the hair of autistic children. This decrease was probably not physiologically significant. The nutrient intake of autistic children as a group was found to be adequate and typical of well-fed American children. It was concluded that the children in neither the autistic nor the nonautistic control group showed evidence of toxicity or deficiency of the minerals or nutrients studied, but because of food idiosyncracies nutrient intake should be monitored.


Conjunctival microangiopathy. An early sign of degenerative vascular disease?
Biomicroscopic examination of the bulbar conjunctival vessels regularly discloses degenerative microangiopathy in patients with overt arteriosclerotic cerebral vascular disease. Examination of a group of normotensive nondiabetic adults aged 21 to 39 years disclosed similar but less severe changes in 56 per cent of the men and 26 per cent of the women. The incidence was higher (88 per cent of the men and 45 per cent of the women) in those with a strong family history of early death from arteriosclerotic disease. There was no consistent correlation between the severity of the microangiopathy and the values for hematocrit, cholesterol, triglycerides or blood pressure. Conjunctival microangiopathy, like atherosclerosis of larger vessels, starts in the second and third decades and advances with age. We suggest that microangiopathic changes in the conjunctival vessels may provide the first readily detectable evidence of degenerative vascular disease.


Synthesis and Biological Activity of Manganese (II) Complexes of Phthalic and Isophthalic Acid: X-Ray Crystal Structures of [Mn(ph)(Phen)(2)(H(2)O)]. 4H(2)O, [Mn(Phen)(2)(H(2)O)(2)](2)(Isoph)(2)(Phen). 12H(2)O and {[Mn(Isoph)(bipy)](4). 2.75biby}(n)(phH(2) = Phthalic Acid; isoph = Isophthalic Acid; phen = 1,10-Phenanthroline; bipy = 2,2-Bipyridine).
Manganese(II) acetate reacts with phthalic acid (phH(2)) to give [Mn(ph)].0.5H(2)O (1). Reaction of 1 with 1,10-phenanthroline produces [Mn(ph)(phen)].2H(2)O (2) and [Mn(ph)(phen)(2)(H(2)O)].4H(2)O (3). Reaction of isophthalic acid (isophH(2)) with manganese(II) acetate results in the formation of [Mn(isoph)].2H(2)O (4). The addition of the N,N-donor ligands 1,10-phenanthroline or 2,2'-bipyridine to 4 leads to the formation of [Mn(2) (isoph)(2)(phen)(3))].4H(2)O (5), [(Mn(phen)(2)(H(2)O)(2)](2)(isoph)(2)(phen).12H(2)O (6) and {[Mn(isoph)(bipy)](4).2.75 biby}(n) (7), respectively. Molecular structures of 3, 6 and 7 were determined crystallographically. In 3 the phthalate ligand is bound to the manganese via just one of its carboxylate groups in a monodentate mode with the remaining coordination sites filled by four phenanthroline nitrogen and one water oxygen atoms. In 6 the isophthalates are uncoordinated with the octahedral manganese center ligated by two phenanthrolines and two waters. In 7 the Isophthalate ligands act as bridges resulting in a polymeric structure. One of the carboxylate groups is chelating a single manganese with the other binding two metal centres in a bridging bidentate mode. The phthalate and isophthalate complexes, the metal free ligands and a number of simple manganes salts were each tested for their ability, to inhibit the growth of Candida albicans. Only the "metal free" 1,10-phenanthroline and its manganese complexes were found to be active.


Unintentional extraction of an endothelialized bare metal stent.
The extraction of a previously endothelialized stent has been rarely reported in the literature. We report a case of a patient with unstable angina due to in-stent restenosis. During percutaneous coronary intervention, a stent was inadvertently dislodged in the ostium of the right coronary artery. Retrieval of the dislodged stent led to unintentional extraction of the previously endothelialized bare metal stent.


Emergence of the super antenna effect in mixed crystals of ytterbium and lutetium complexes showing near-infrared luminescence.
The synthesis of luminescent molecular crystalline materials requires a good understanding of the luminescence properties of crystals in which many molecules are densely packed. Previously, we studied the near-infrared (NIR) luminescence of a trivalent ytterbium (Yb(iii)) complex with a Schiff base ligand, tris[2-(5-methylsalicylideneimino)ethyl]amine (H3L). Herein, we extended our study on the Yb complex (YbL) to enhance and understand its solid-state luminescence via mixed crystallization with the lutetium complex (LuL). We prepared (YbL) x (LuL)1-x mixed crystals (x = 0.01, 0.05, 0.1, 0.2, 0.3, 0.5, and 0.7) and studied their NIR luminescence properties. The NIR luminescence intensity per Yb(iii) ion for (YbL)0.01(LuL)0.99 was determined to be two orders of magnitude larger than that for YbL. The excitation spectral shape of (YbL)0.01(LuL)0.99 was different from the absorption spectral shape of YbL but similar to that of LuL. We attribute this observation to the emergence of an intermolecular energy-migration path. In the mixed crystals, LuL molecules acted as a light-harvesting super antenna for Yb(iii) luminescence. Decay measurements of the NIR luminescence for (YbL) x (LuL)1-x with x > 0.2 showed mono-exponential decay, while (YbL) x (LuL)1-x with x < 0.1 showed a grow-in component, which reflected the lifetime of the intermediate state for energy migration. The decay lifetime values tended to increase with decreasing x, suggesting that Yb(iii) isolation resulted in a reduction in concentration quenching. We propose that the luminescence enhancement in the highly Yb-diluted conditions was mainly caused by an increase in the super antenna effect.


How people die in hospital general wards: a descriptive study.
To describe how patients die in hospital, 370 patients (age >18 years; in hospital for>24 hours) who died on the general wards of 40 Italian hospitals were assessed. Differences between patients whose death was expected and patients whose death was unexpected were evaluated. Data on treatments and care in proximity of death were collected after interviewing the nurse responsible for the patient within 72 hours of the patient's death, and from clinical and nursing records. For 58% of patients, death was highly expected. Symptom control was inadequate for the most severely ill patients: 75% experienced at least one "severe" symptom (42% pain and 45% dyspnea). Nurses tended to judge patients' global care as "good" or "very good" (76%), in spite of the persistence of symptoms and the scant use of analgesics. Despite some encouraging signs of sensitivity to end-of-life problems, acute inpatient institutions in Italy still deal inadequately with the needs of dying persons.


Calves' management conditions affect sperm count in adult bulls.
Early maternal separation may have long-lasting physiological effects on different organ systems. Although long-lasting effects of early maternal separation are mostly studied in connection with the development and function of the central nervous system hypothalamic-pituitary-adrenal axis, animal health, behaviour and productivity, there is a lack of information about its impacts on the reproductive system. In the dairy industry, calves are often separated from mothers 1 or 2 days after birth and are not nursed. In the present retrospective study based on data from an artificial insemination (AI) centre, we compared semen parameters and fertility in bulls that were separated from their mothers one day after birth with the semen parameters of bulls that remained with their mothers and were nursed for approximately 2 months. Semen parameters were followed in 3 consecutive years in 52 maternally separated and 22 nursed bulls. Ejaculate volume and total sperm count in ejaculate were significantly higher in nursed bulls in comparison to maternally separated bulls at the age 25-36 and 37-48 months, but interestingly, not at the age 12-24 months, during the first year in the AI centre. Non-return rates did not differ between separated and nursed bulls. The results suggest that early maternal separation causes long-lasting effects on the functioning of the male reproductive system, evident by reduced production of semen in adult bulls. The data suggest that with a standard of 20 million sperms per straw of frozen semen, 27-78 fewer straws can be obtained from one ejaculate of maternally separated bulls in comparison to the nursed bulls.


Marijuana use and risk of prediabetes and diabetes by middle adulthood: the Coronary Artery Risk Development in Young Adults (CARDIA) study.
The impact of marijuana use on metabolic health is largely unknown. This study sought to clarify the cross-sectional and longitudinal associations between self-reported marijuana use, and prediabetes (defined as fasting glucose 5.6-6.9 mmol/l, 2 h glucose post OGTT 7.8-11.0 mmol/l or HbA1c 5.7-6.4% [39-47 mmol/mol]) and diabetes. Data from the community-based Coronary Artery Risk Development in Young Adults (CARDIA) study were used to determine marijuana use and the presence of prediabetes and diabetes among participants. The association between marijuana use and the prevalence of prediabetes and diabetes was examined in 3,034 participants at CARDIA examination year 25 (2010-2011), while the incidence of prediabetes and diabetes according to previous marijuana use was assessed in 3,151 individuals who were free from prediabetes/diabetes at year 7 (1992-1993) and who returned for at least one of the four subsequent follow-up examinations over 18 years. The percentage of individuals who self-reported current use of marijuana declined over the course of the study's follow-up. After multivariable adjustment, higher odds of prediabetes were found for individuals who reported current use of marijuana (OR 1.65 [95% CI 1.15, 2.38]) and a lifetime use of 100 times or more (OR 1.49 [95% CI 1.06, 2.11]), compared with individuals who reported never using marijuana. There was no association between marijuana use and diabetes at CARDIA examination year 25. Over 18 years of follow-up, a greater risk of prediabetes (but not diabetes) was found for individuals who reported a lifetime use of marijuana of 100 times or more (HR 1.39 [95% CI 1.13, 1.71]), compared with individuals who had never used marijuana. Marijuana use in young adulthood is associated with an increased risk of prediabetes by middle adulthood, but not with the development of diabetes by this age.


Comparative biochemical and pharmacological properties of epidermal secretions from Ariid catfish of the Arabian Gulf.
1. Comparative biochemical and pharmacological studies on epidermal secretions from three species of Ariid catfish were carried out to determine whether they share common properties. 2. Protein compositions are generally similar, but show some differences in size and numbers of proteins. 3. Lipids also differ. However, seasonal and dietary changes in lipid compositions exceed the differences among species. 4. Enzymes in the secretions appear common to each fish species, though some differences are noted in relative activities. 5. Toxicity responses of rabbits to injections with secretions from each of the catfish species indicated that two were lethal, with similar lethal dose levels when injected intravenously. 6. Secretions from all three catfish induced changes in plasma enzyme levels indicative of heart and liver damage, and also induced changes in blood glucose and cholesterol levels.


Surgical Management of Adnexal Masses in the Pediatric and Adolescent Age Group: Our Experience.
Adnexal masses in girls represent a wide pathological spectrum. We performed a retrospective analysis of clinical and diagnostic aspects of adnexal masses in girls. To analyze the clinical characteristics and surgical management of adnexal masses in children and adolescents. Retrospective observational analysis from 2000 to 2020. This analysis was performed on 28 children under the age of 17 years with adnexal masses who were managed by us at tertiary care centers of Delhi-NCR. Patients were analyzed based on their age at the time of admission, their presenting complaints, clinical and radiological findings, tumor markers, management, and follow-up. The age ranged between newborn and 17 years. Abdominal pain, nausea with vomiting, and abdominal lump was the most common presenting complaints. Pelvic ultrasound with or without color Doppler done in all patients and computed tomography, magnetic resonance imaging was performed in seven patients preoperatively. Adnexal masses were unilateral in 26 (92.85%) patients and bilateral in 2 (7.15%) patients. Five babies had antenatal diagnosis of ovarian cysts. Serum alpha fetoprotein (AFP) and beta-human chorionic gonadotropin (b-HCG) were normal in all 19 tested patients. Cancer antigen 125 (CA-125) was raised in three ovarian tumors out of 9 tested patients. Laparoscopy was performed in 23 out of 28 patients (30 ovaries). Ovarian cyst torsion was present in 50% patients. Ovarian cystectomy was done in 10 (33.3%) patients. Six (20%) ovaries were saved by detorsion of the ovary and deroofing of the cyst with or without ovarian biopsy. Oophorectomy was done in five (16.7%) patients. Salpingo-oopherectomy had to be done in seven (23.3%) patients. Histopathology revealed functional nonneoplastic lesions in 18 cases (66.7%), benign neoplastic lesions in 8 cases (29.6%), and malignant neoplastic lesion in 1 case (3.7%). Adnexal masses in children are generally benign. AFP, b-HCG, and CA-125 in ovarian torsion are within normal limits. Urgent surgery is required if torsion is established. The ovary should be preserved wherever possible.


A systematic review of patient-reported outcome measures for chronic suppurative otitis media.
The purpose of this review was to systematically appraise the world literature to identify existing patient-reported outcome measures (PROMs) for the assessment of outcomes in patients with chronic suppurative otitis media, to verify the diversity of the individual questionnaire items, to report the methods employed to evaluate the questionnaires, and to identify areas for development in the future. Embase (January 1980-November 2014), MEDLINE (January 1946-November 2014), Cumulative Index to Nursing and Allied Health Literature (January 1981-November 2014), and PsycINFO (January 1806-November 2014). A systematic literature search was independently undertaken by the two authors according to predefined inclusion and exclusion criteria. Nine original articles were identified, which overall outlined the evaluation of four different questionnaires. This systematic appraisal of the world literature has identified four PROM questionnaires for use in patients with chronic suppurative otitis media. All four questionnaires evaluate reliability and validity using different psychometric methods. The Chronic Ear Survey questionnaire has been most broadly evaluated and disseminated. All four questionnaires assess static health status. There are many advantages to developing a dynamic one-hit questionnaire to assess the health status of patients having undergone an intervention for chronic suppurative otitis media. NA Laryngoscope, 126:1458-1463, 2016.


The levonorgestrel-releasing intrauterine device potentiates stress reactivity.
The levonorgestrel-releasing intrauterine device (LNG-IUD) is currently recommended as a first-line contraceptive with an exclusively local intrauterine influence. However, recent clinical trials have identified side effects of LNG-IUD that appear to be systemically mediated, including depressed mood and emotional lability. We performed two experimental studies and a cross-sectional study. For each study, women were included from three groups: LNG-IUD (0.02mg/24h), oral ethinylestradiol/levonorgestrel (0.03mg/0.15mg; EE30/LNG) and natural cycling (NC). Study 1-Salivary cortisol was measured at baseline and at defined intervals following the Trier Social Stress Test (TSST). Heart rate was monitored continuously throughout the TSST. Study 2-Salivary cortisol and serum total cortisol were evaluated relative to low-dose (1μg) adrenocorticotropic hormone (ACTH) administration. Study 3-Hair cortisol was measured as a naturalistic index of long-term cortisol exposure. Women using LNG-IUD had an exaggerated salivary cortisol response to the TSST (24.95±13.45 nmol/L, 95% CI 17.49-32.40), compared to EE30/LNG (3.27±2.83 nmol/L, 95% CI 1.71-4.84) and NC (10.85±11.03nmol/L, 95% CI 6.30-15.40) (P<0.0001). Heart rate was significantly potentiated during the TSST in women using LNG-IUD (P=0.047). In response to ACTH challenge, women using LNG-IUD and EE30/LNG had a blunted salivary cortisol response, compared to NC (P<0.0001). Women using LNG-IUD had significantly elevated levels of hair cortisol compared to EE30/LNG or NC (P<0.0001). Our findings suggest that LNG-IUD contraception induces a centrally-mediated sensitization of both autonomic and hypothalamic-pituitary-adrenal (HPA) axis responsivity. LNG-IUD sensitization of HPA axis responsivity was observed acutely under standardized laboratory conditions, as well as chronically under naturalistic conditions.


A new model to assess staphylococcal adhesion to intraocular lenses under in vitro flow conditions.
Adhesion of staphylococcal cells to intraocular lenses coated with heparin was studied under in vitro flow conditions (280 microl min(-1)) at 37 degrees C. The intraocular lenses were incubated with human cerebrospinal fluid for 1 h or with cerebrospinal fluid including 0.50% plasma for 12 h, prior to bacterial challenge. Two strains of Staphylococcus epidermidis selected for this study, were isolated from biomaterial-associated infections. Bacterial adhesion was quantitated by bioluminescence and visualized by fluorescence microscopy of acridine orange stained bacteria. Surface coating with heparin significantly decreased bacterial adhesion of both strains after incubation with cerebrospinal fluid including 0.50% plasma for 12 h (p = 0.0209). However, no difference in bacterial adhesion was obtained between intraocular lenses with and without heparin, after incubation with cerebrospinal fluid for 1 h (p = 0.327). Microscopy showed that more bacteria were present on intraocular lenses without heparin than on intraocular lenses with heparin. The results show that preincubation with a proteinaceous fluid influences subsequent bacterial adhesion to the polymer surface. The results suggest that IOLs with heparin coating may be less prone to bacterial adhesion under perfusion conditions after surface conditioning in human CSF with 0.50% plasma and a preincubation period of 12 h. Heparin coating might be a valuable tool to decrease implant-associated bacterial endophthalmitis.


Healthcare utilisation in the last year of life in internal medicine, young-old versus old-old.
With increasing cost of healthcare in our aging society, a consistent pain point is that of end-of-life care. It is particularly difficult to prognosticate in non-cancer patients, leading to more healthcare utilisation without improving quality of life. Additionally, older adults do not age homogenously. Hence, we seek to characterise healthcare utilisation in young-old and old-old at the end-of-life. We conducted a single-site retrospective review of decedents under department of Advanced Internal Medicine (AIM) over a year. Young-old is defined as 65-79 years; old-old as 80 years and above. Data collected was demographic characteristics; clinical data including Charlson Comorbidity Index (CCI), FRAIL-NH and advance care planning (ACP); healthcare utilisation including days spent in hospital, hospital admissions, length of stay of terminal admission and clinic visits; and quality of end-of-life care including investigations and symptomatic control. Documentation was individually reviewed for quality of communication. One hundred eighty-nine older adult decedents. Old-old decedents were mostly females (63% vs. 42%, p = 0.004), higher CCI scores (7.7 vs 6.6, p = 0.007), similarly frail with lower polypharmacy (62.9% vs 71.9%, p = 0.01). ACP uptake was low in both, old-old 15.9% vs. young-old 17.5%. Poor prognosis was conveyed to family, though conversation did not result in moderating extent of care. Old-old had less healthcare utilisation. Adjusting for sex, multimorbidity and frailty, old-old decedents had 7.3 ± 3.5 less hospital days in their final year. Further adjusting for cognition and residence, old-old had 0.5 ± 0.3 less hospital admissions. When accounted for home care services, old-old spent 2.7 ± 0.8 less hospital days in their last admission. There was high healthcare utilisation in older adults, but especially young-old. Enhanced education and goal-setting are needed in the acute care setting. ACP needs to be reinforced in acute care with further research to evaluate if it reduces unnecessary utilisation at end-of-life.


Incorporation of peptides in phospholipid aggregates using ultrasound.
This study presents the highlights of ultrasonic effects on peptides incorporated on phospholipid aggregates (liposomes). These liposomes or vesicles are known as transport agents in skin drug delivery and for hair treatment. They might be a good model to deliver larger peptides into hair to restore fibre strength after hair coloration, modelling, permanent wave and/or straightening. The preparation of liposomes 1,2-dipalmitoyl-sn-glycerol-3-phosphocholine (DPPC) with peptides (LLLLK LLLLK LLLLK LLLLK; LLLLL LCLCL LLKAK AK) was made by the thin film hydration method. The LUVs (uni-lamellar vesicles) were obtained by sonication, applying different experimental conditions, such as depth (mm) and power intensity (%). Photon-correlation spectroscopy (PCS) and electronic microscopy (EM) results confirmed that the incorporation of these peptides, with different sequence of amino acids, presented differences on the diameter, zeta-potential of membrane surface and shape of liposomes. The liposomes that included peptide LLLLK LLLLK LLLLK LLLLK present an increased in zeta-potential values after using ultrasound and an "amorphous" aspect. Conversely, the liposomes that incorporated the peptide LLLLL LCLCL LLKAK AK presented a define shape (rod shape) and the potential surface of liposome did not change significantly by the use of ultrasound.


Molecular and cellular responses to short exposure to bisphenols A, F, and S and eluates of microplastics in C. elegans.
Bisphenol F (BPF) and bisphenol S (BPS) have been developed as an alternative to bisphenol A (BPA), a well-known endocrine disruptor, leading to their detection in the aquatic environment. In this work, we used the animal model Caenorhabditis elegans to improve our understanding of their potential effects on the biota and the environment. Our findings demonstrated that, after 24 h exposure, all the bisphenols examined increased the number of apoptotic corpses and the expression of the detoxifying enzymes SOD-3 and GST-4, without affecting the ROS levels, while BPA and BPS significantly enhanced DNA fragmentation. Furthermore, similarly to BPA, BPF and BPS did not alter the lifespan through the activation of SEK-1 and SKN-1 pathways. Thus, this study raises the attention of the risks associated with exposure to BPA alternatives. We also examined the effects of microplastic (MP) eluates on C. elegans. Aqueous extracts of weathered microplastic samples, both at high and low degradation state and pellets, have been evaluated for their effects on lifespan, DNA fragmentation, germline apoptosis, and oxidative stress response. Overall, our findings showed that eluates of low degraded plastics exert a greater toxic effect on the nematode C. elegans compared with the aqueous sample of high degraded plastic fragments and pellets.


The test-negative design for estimating influenza vaccine effectiveness.
The test-negative design has emerged in recent years as the preferred method for estimating influenza vaccine effectiveness (VE) in observational studies. However, the methodologic basis of this design has not been formally developed. In this paper we develop the rationale and underlying assumptions of the test-negative study. Under the test-negative design for influenza VE, study subjects are all persons who seek care for an acute respiratory illness (ARI). All subjects are tested for influenza infection. Influenza VE is estimated from the ratio of the odds of vaccination among subjects testing positive for influenza to the odds of vaccination among subjects testing negative. With the assumptions that (a) the distribution of non-influenza causes of ARI does not vary by influenza vaccination status, and (b) VE does not vary by health care-seeking behavior, the VE estimate from the sample can generalized to the full source population that gave rise to the study sample. Based on our derivation of this design, we show that test-negative studies of influenza VE can produce biased VE estimates if they include persons seeking care for ARI when influenza is not circulating or do not adjust for calendar time. The test-negative design is less susceptible to bias due to misclassification of infection and to confounding by health care-seeking behavior, relative to traditional case-control or cohort studies. The cost of the test-negative design is the additional, difficult-to-test assumptions that incidence of non-influenza respiratory infections is similar between vaccinated and unvaccinated groups within any stratum of care-seeking behavior, and that influenza VE does not vary across care-seeking strata.


Impact of a brief dietary self-monitoring intervention on weight change and CPAP adherence in patients with obstructive sleep apnea.
Weight loss can decrease the severity of obstructive sleep apnea (OSA) in many obese individuals; however, very few studies have investigated the effects of behavioral weight loss interventions for patients with OSA. The aims of this pilot study were to determine the feasibility and initial effects on weight and continuous positive airway pressure (CPAP) use of a brief minimal-contact self-monitoring-based weight loss intervention (SM). An additional aim was to investigate the association between weight loss and CPAP adherence. Forty obese men and women diagnosed with mild or moderate OSA were randomized to either the SM or an attention-control (AC) condition. SM participants completed daily dietary logs for 6 weeks. Participants were weighed at baseline, post-treatment (6 weeks), and at a 6-week follow up. Recruitment and retention were good in this study and attrition rates did not differ significantly by group. Intent to treat repeated measures ANOVA indicated a main effect of time (but not group), such that both groups lost weight over time. Pearson r correlations between weight change and CPAP adherence indicated that among SM participants, 6-week weight loss was correlated with CPAP adherence at post-treatment and follow-up, such that SM participants with greater weight loss at 6 weeks had greater CPAP adherence at 6 and 12 weeks. This study provides initial support for the beneficial effects of a minimal-contact weight loss intervention for patients with obstructive sleep apnea and highlights a possible association between weight loss and CPAP adherence.


Eshelby Twist as a Possible Source of Lattice Rotation in a Perfectly Ordered Protein/Silica Structure Grown by a Simple Organism.
The formation mechanism of a perfectly ordered protein/silica structure in the axial filament of the anchor spicule of the silica sponge Monorhaphis chuni is suggested. Experimental evidence shows that the growth of this architecture is realized by a thermodynamically driven dislocation-mediated spiral growth mechanism, resulting in a specific rotation of the mesoscopic crystal lattice (Eshelby twist).


Effect of the Associated Methanogen Methanobrevibacter thaueri on the Dynamic Profile of End and Intermediate Metabolites of Anaerobic Fungus Piromyces sp. F1.
Although the scheme of metabolic pathways involved in the production of the major end products has been described, the dynamic profile of metabolites of anaerobic fungi co-cultured with methanogens is limited, especially for the intermediate metabolites. In the present study, the fermentation of the co-culture of Piromyces sp. F1 and Methanobrevibacter thaueri on glucose was investigated. The presence of methanogens shortened the growth lag time of anaerobic fungi and enhanced the total gas production. The occurrence of the maximum cell dry weight and the disappearance of most of the substrate were observed at 24 h for the co-culture and 48 h for the fungal mono-culture. In the co-culture, hydrogen was detected at a very low level during fermentation, and formate transitorily accumulated at 24 h and disappeared at 48 h, resulting in an increase of pH. Acetate was higher during the fermentation in the co-culture (P < 0.05), while lactate and ethanol were higher only in the initial stage of fermentation (P < 0.05). After 48 h, lactate in the mono-culture became much higher than that in the co-culture (P < 0.05), and ethanol tended to remain the same in both cultures. Moreover, malate tended to be exhausted in the co-culture, while it accumulated in the mono-culture. Citrate was also detected in both co-culture and mono-culture. Collectively, these results suggest that methanogen enhanced the malate pathway and weakened the lactate pathway of anaerobic fungus.


Childhood emotional abuse, dissociation, and suicidality among patients with drug dependency in Turkey.
The aim of the present study was to determine the prevalence and correlates of dissociative disorders among patients with drug dependency. The Dissociative Experiences Scale (DES) was used to screen 104 consecutive patients at an addiction treatment center. Thirty-seven patients who had scores >or=30 were compared with 21 patients who scored <10 on the DES. Both groups were then evaluated using the Dissociative Disorders Interview Schedule and the Structured Clinical Interview for Dissociative Disorders (SCID-D). The interviewers were blind to the DES scores. Twenty-seven patients (26.0%) had a dissociative disorder according to the SCID-D. Dissociative patients were younger than the non-dissociative group. History of suicide attempt and/or childhood emotional abuse was significant predictors of a dissociative disorder. The majority (59.3%) of dissociative drug users reported that dissociative experiences had existed prior to substance use. More patients in the dissociative disorder than in the non-dissociative group stopped their treatment prematurely. A considerable proportion of drug users have a dissociative disorder, which may also interfere with treatment process. The relatively young age of this subgroup of patients and frequent reports of childhood emotional abuse underline potential preventive benefits of early intervention among adolescents with developmental trauma history and dissociative psychopathology.


Interferon stimulation creates chromatin marks and establishes transcriptional memory.
Epigenetic memory for signal-dependent transcription has remained elusive. So far, the concept of epigenetic memory has been largely limited to cell-autonomous, preprogrammed processes such as development and metabolism. Here we show that IFNβ stimulation creates transcriptional memory in fibroblasts, conferring faster and greater transcription upon restimulation. The memory was inherited through multiple cell divisions and led to improved antiviral protection. Of ∼2,000 IFNβ-stimulated genes (ISGs), about half exhibited memory, which we define as memory ISGs. The rest, designated nonmemory ISGs, did not show memory. Surprisingly, mechanistic analysis showed that IFN memory was not due to enhanced IFN signaling or retention of transcription factors on the ISGs. We demonstrated that this memory was attributed to accelerated recruitment of RNA polymerase II and transcription/chromatin factors, which coincided with acquisition of the histone H3.3 and H3K36me3 chromatin marks on memory ISGs. Similar memory was observed in bone marrow macrophages after IFNγ stimulation, suggesting that IFN stimulation modifies the shape of the innate immune response. Together, external signals can establish epigenetic memory in mammalian cells that imparts lasting adaptive performance upon various somatic cells.


Hazards of intravenous verapamil for sustained ventricular tachycardia.
In 11 of 25 patients (44%) with sustained ventricular tachycardia (VT) who received intravenous verapamil (5 to 10 mg), acute severe hypotension or loss of consciousness developed, necessitating immediate cardioversion. Comparison of these 11 patients with the 14 who did not have adverse effects after verapamil revealed no significant difference in age, heart disease, ejection fraction, blood pressure before verapamil administration, other oral or intravenous drugs use, verapamil dose or VT characteristics (rate and morphologic pattern). Although most patients with severe adverse effects after verapamil had prior myocardial infarction, deterioration also occurred in patients without coronary disease and in patients with a normal left ventricular ejection fraction. VT terminated after verapamil infusion in 6 patients. No single electrocardiographic morphologic pattern characterized these patients. A control group of 25 patients presenting with hemodynamically stable VT who received other antiarrhythmic agents was examined. Hypotension developed in only 1 patient during acute therapy and did not require emergency cardioversion. Thus, although verapamil may terminate VT, severe adverse effects occur much more often. Use of verapamil to differentiate supraventricular tachycardia with aberrant conduction from ventricular tachycardia is hazardous.


One-Year Outcomes of Oral Treatment With Alga Capsules Containing Low Levels of 9-cis-β-Carotene in RDH5-Related Fundus Albipunctatus.
This study aimed to clarify the effect of 1-year oral treatment with 9-cis-β-carotene-rich alga Dunaliella bardawil (Dunaliella supplementation) using full-field electroretinography (ERG) in patients with RDH5-related fundus albipunctatus (FAP). Prospective, interventional case series. The study included 12 patients (23 eyes) with RDH5-related FAP. Twelve patients (23 eyes) with RDH5-related FAP received Dunaliella supplementation (total daily dose of β-carotene was 74.0 mg, comprising 28.4 mg 9-cis-β-carotene and 45.6 mg all-trans-β-carotene at a ratio of 1:1.6) for 1 year and underwent ophthalmic examinations, including full-field ERG at baseline, 3 months, and 1 year after the initial treatment. The main outcome was changes in the amplitudes of responses of full-field ERG before and after treatment. A linear mixed-effects model was used to evaluate the adjusted mean difference between the amplitude of each response pretreatment and posttreatment. Prolonged dark adaptation (DA) responses at 3 months revealed a significant impairment in the b-wave of DA 0.01 (adjusted mean difference, -34.7, 95% CI, -66.8 to -2.73, P = .041) and a-wave of DA 3.0 (-29.0, 95% CI, -50.6 to -7.41, P = .013) and DA 10.0 (-40.4, 95% CI, -67.8 to -13.0, P = .007), which were also observed at 1 year. Additionally, prolonged DA and light adaptation (LA) responses revealed statistically significant impairment at 1 year in the b-wave of DA 3.0 (-43.8, 95% CI, -82.9 to -4.78, P = .035), DA 10.0 (-59.7, 95% CI, -101.8 to -17.61, P = .009), LA 3.0 (-7.31, 95% CI, -13.6 to -1.04, P = .029), and LA 3.0 flicker (-7.53, 95% CI, -12.7 to -2.34, P = .007). Our study results suggest that Dunaliella supplementation comprising low levels of 9-cis-β-carotene compared with those reported in a previous study (1:1 ratio) adversely affects ERG amplitudes in patients with RDH5-related FAP.


The validity of an interview to assess a patient's drug taking.
The most practical method of assessing patient compliance is to ask the patient for a self-report; but, how valid is such a report? This study compared one particular interview question to a pill-count measure by studying 98 patients who visited their family physician, received medication instructions, and were interviewed in their homes ten days later. The interview question identified 80 percent of the true noncompliers, as assessed by the pill count (sensitivity). However, the interview question was not equally sensitive for all subgroups of patients. Results for younger patients, patients receiving renewals rather than new prescriptions, and patients taking more than one drug were not as accurate, showing sensitivities of 75 percent, 40 percent, and 60 percent, respectively.


Changes in social behaviour of rats following chronic treatment with gamma-endorphin antiserum injected into the nucleus accumbens.
Treatment with gamma-endorphin antiserum twice daily for 12 days, by injection into the nucleus accumbens did not change the basal level of social activity or explorative behaviour when pairs of rats were tested in a social interaction test. The decrease in social interactions due to increased light level as observed in placebo-treated rats, was not present in animals treated with gamma-endorphin antiserum. Significantly more freezing and fly-responses were observed in the rats treated with antiserum, as reactions to penetrating sound stimuli. These changed responses to light and sound stimuli persisted for at least 3 days following discontinuation of treatment. It is concluded that treatment with gamma-endorphin antiserum, injected into the nucleus accumbens results in disturbances in the integration of environmental stimuli in social behaviour and in enhanced responsiveness to stressful stimuli. It is suggested that these effects may be related to increased dopaminergic transmission in some dopaminergic systems in the nucleus accumbens, implicating these systems in the environmental control over social behaviour.


Efficient Adsorption of Sulfamethazine onto Modified Activated Carbon: A Plausible Adsorption Mechanism.
Activated carbon (AC) was modified by FeCl3. Batch experiments were carried out to evaluate the characteristics of equilibrium, kinetics and thermodynamics of Sulfamethazine adsorption onto original and modified AC. The results showed that Fe3+ treatment changed the surface area, pore volume and surface zeta potential and increased the number of surface oxygenic functional groups. The adsorption of Sulfamethazine on modified activated carbon (MAC) was significantly improved. Isotherm test results revealed that the adsorption isotherms of Sulfamethazine on MAC fit the Freundlich, Langmuir and Temkin equations well. The maximum adsorption quantity of Sulfamethazine on MAC was 17.2414 mg/g at 25 °C. The adsorption kinetics of Sulfamethazine on AC and MAC can be characterized by the pseudo-second-order model. The adsorption process was affected by membrane diffusion, surface adsorption and internal diffusion. The adsorption quantities of Sulfamethazine first increased and then decreased for pH between 3 and 10. The removal efficiencies decreased with increasing temperature, which is favorable for adsorption at low temperature. It was also found that the mechanisms of adsorption included micropore capture and electrostatic, hydrogen bonding, π-π electron donor-acceptor (EDA) and coordination interactions as well as other interactions.


Nonequilibrium-molecular-dynamics investigation of the presmectic behavior of the viscosities of a Gay-Berne nematic liquid crystal.
Using the method of nonequilibrium molecular dynamics, the behavior of the Miesowicz, Helfrich, and Leslie viscosities as functions of temperature and density are investigated. In particular, attention is focused on the region immediately preceding the nematic-smectic phase transition. The Miesowicz viscosity eta1 for the orientation parallel to the direction of flow and the Helfrich viscosity eta12 are both found to increase rapidly as the phase transition is approached. In most of the cases investigated, a critical exponent nu=1 / 3 is found. Values closer to nu=1 / 4 are also found, but in these cases, the errors are sufficiently large for nu=1 / 3 to be possible. No nonregular behavior of the viscosity coefficients eta2, eta3, gamma1, and gamma2 in the presmectic region was detected.


Mortality in nursing home residents stratified according to subtype of dementia: a longitudinal study over three years.
There are several subtypes of dementia caused by different pathophysiology and with different clinical characteristics. Irrespective subtype, the disease is progressive, eventually leading to the need for care and supervision on a 24/7 basis, often provided in nursing homes (NH). The progression rate and course of the disease might vary according to subtype. The aim of this study was to explore whether the mortality rate for NH residents varied according to the subtype of dementia. NH residents were followed from admission to NH over a period of 36 months or until death with annual follow-up examinations. Demographic and clinical data were collected. The diagnosis of dementia and its subtype at baseline (BL) were set according to international accepted criteria. Kaplan-Meier analysis was performed to estimate median survival time. A Cox regression model was estimated to assess the impact of dementia diagnosis and demographic and clinical variables on mortality. A total of 1349 participants were included. When compared to persons with Alzheimer's disease (AD), persons with frontotemporal dementia (FTD) and dementia with Lewy bodies or Parkinson's disease dementia (DLB/PDD) were younger and had more neuropsychiatric symptoms. Median survival for the total sample was 2.3 years (95% confidence interval: 2.2-2.5). When compared to persons with AD, having no dementia or unspecified dementia was associated with higher mortality, while we found similar mortality in other subtypes of dementia. Higher age, male gender, poorer general health, higher dependency in activities of daily living, and more affective symptoms were associated with higher mortality. Mortality did not differ across the subtypes of dementia, except in persons with unspecified dementia or without dementia, where we found a higher mortality. With a median survival of 2.3 years, NH residents are in the last stage of their lives and care and medical follow-up should focus on a palliative approach. However, identifying the subtype of dementia might help carers to better understand and address neuropsychiatric symptoms and to customize medical treatment.


Comparison of Two Lipid Emulsions on the Incidence of Parenteral Nutrition Associated Cholestasis in Neonates.
Lipid emulsion contributes to parenteral nutrition associated cholestasis (PNAC). For decades, soybean oil-based intravenous lipid emulsion (SO-ILE) was the predominant product. Recently, a multicomponent lipid emulsion containing soybean oil, medium-chain triglycerides, olive oil and fish oil (SMOF-ILE) has been used off-label in neonatal care. This study evaluates the incidence of PNAC in neonates who received SMOF-ILE or SO-ILE. This was a retrospective review of neonates who received SMOF-ILE or SO-ILE for at least 14 days. Patients receiving SMOF-ILE were matched based on gestational age (GA) and birth weight to a historical cohort receiving SO-ILE. The primary outcomes were the incidences of PNAC among all patients and patients without intestinal failure. The secondary outcomes were clinical outcomes and incidence of PNAC stratified by GA. Clinical outcomes included liver function tests, growth parameters, and development of retinopathy of prematurity and intraventricular hemorrhage. Forty-three neonates who received SMOF-ILE were matched to 43 neonates who received SOILE. There were no significant differences in baseline characteristics. The incidence of PNAC in the total population was 12% in the SMOF-ILE cohort and 23% in the SO-ILE cohort (p = 0.26). The lipid dosage of SMOF-ILE was significantly higher at time of peak direct serum bilirubin concentration compared with SO-ILE cohort (p = 0.05). Clinically significant differences were noted in laboratory endpoints in several subgroups. There was no significant difference in the incidence of PNAC among neonates in a SMOFILE cohort compared with a historical SO-ILE cohort.


Effect of chenodeoxycholic acid and sodium hydrogen sulfide in dinitro benzene sulfonic acid (DNBS)--Induced ulcerative colitis in rats.
Ulcerative colitis is a chronic inflammatory condition in which the inflammatory response confined to the colon. There is a need to explore the new targets for UC such as Farnesoid X receptor and hydrogen sulfide pathway. Wistar rats of either sex (200-250 g) were used. 2,4-Dinitrobenzene sulfonic acid (DNBS) (25mg/rat) given by rectal route into the colon to induced symptoms of ulcerative colitis. Chenodeoxycholic acid (CDCA) (10 and 20mg/kg) and sodium hydrogen sulfide (NaHS) (10 and 30 μmol/kg) and a inhibitor of cystathionine-γ-lyase enzyme (CSE) i.e. dl-propargylglycine (10mg/kg) treatment given along with 2,4-dinitrobenzene sulfonic acid. The disease activity index was assessed by daily change in body weight and rectal bleed score and change in length of colon. Oxidative stress markers (reduced glutathione, malondialdehyde (MDA), nitrite, and catalase and myeloperoxidase enzyme activity), serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) levels in blood serum, and cardiac hemodynamic were performed on last day. The administration of DNBS intra-rectally in rats produced loss of body weight and bloody diarrhea with significant increase in oxidative stress markers in the colon. CDCA (10 and 20mg/kg) and NaHS (10 and 30 μmol/kg) significantly attenuated DNBS-induced UC in rats. The combination of CDCA (10mg/kg) and NaHS (10 μmol/kg) showed synergetic effect whereas; dl-propargylglycine reversed the protective effect of CDCA. The observed beneficial effects following CDCA may be due to its action through activation of CSE enzyme which leads to hydrogen sulfide generation.