Selective feeding by the echinoid, Evechinus chloroticus, and the removal of plants from subtidal algal stands in Northern New Zealand.
Feeding choice of the echinoid Evechinus chloroticus was examined for six fucoid and one laminarian species of algae. Three experiments were conducted to determine the algal choice by echinoids under controlled conditions. In the first experiment, the seven algal species were presented to echinoids in laboratory conditions. The second experiment had replicates of the algal species placed randomly on a subtidal rocky reef where echinoids were abundant and randomly dispersed. For the third experiment, which was also field-based, replicates of one highly-ranked species, Ecklonia radiata, were presented to naturally dispersed Evechinus. In addition, a series of controlled observations was used to examine the order in which echinoids removed algae from mixed species stands on subtidal boulders and to determine if this was related to the experimentally demonstrated choices of algal species.The results of the first two experiments showed that there were differences between algal species in the amount of material grazed by echinoids. Rankings of algal species from the field experiment were not correlated with rankings from the laboratory experiment. The order of removal of algal species from natural stands was correlated with the laboratory-based experimental rankings of algal species, but not with the rankings from the field-based experiment or with algal species availability. There were differences between algal species in their vulnerability to grazing by echinoids, as measured by regression analyses on the amount of material grazed from algal replicates vs. the number of attached echinoids. Within each species, echinoid numbers exerted a non-linear effect on the removal of algal material. In the third experiment, where only one species of algae was presented, the echinoids still distributed themselves non-randomly amongst replicates, aggregating on some samples.Data on the finer scale distribution of algal species over the entire subtidal reef on which these experiments and observations were conducted indicate that Evechinus are not often presented with a choice of adult plants of several different species in natural stands.The evidence from this study supports the conclusion that feeding preferences by echinoids are labile and do not clearly exert the major influence on the removal of plants from natural stands. Preference, as determined from experimental rankings of algal species, is only one of a number of factors which may affect the removal of algae by echinoids. Other important factors are the density of echinoids present, algal susceptibility to removal, and the distribution and abundances of the various algal species and echinoids relative to each other. It is suggested that algal life history characteristics may be unaffected by echinoids and that coevolutionary arguments are not appropriate for describing echinoid-algal interactions.


Fibula fixation in the treatment of tibial pilon fractures - Is it really necessary?
There is a lack of consensus about the role of fibula fixation in these complex fractures, with only two clinical studies in the literature. We hypothesize that the fibula fracture need not be fixed in the tibial pilon fractures if primary stability can be achieved with tibial fixation alone. We reviewed 79 patients with operatively treated tibial pilon with associated fibula fractures from 2007 to 2017 and divided them into two groups; patients with fibula fracture fixation and those without fixation. The primary outcome measure was any mechanical complications. Secondary outcomes were wound complications and other morbidities. There were 54 (68.4%) patients with fibula fixation and 25 (31.6%) patients without fixation. There were no statistically significant differences in mechanical complications between the two groups. However, patients without fibula fixation were noted to have more wound complications (44% vs 25.9%, p = 0.108) although this was not statistically significant. In terms of removal of implant (ROI), there were no differences noted in patients with or without fibula fixation (33.3% vs 28%, p = 0.796). There were also no significant differences in ROI for those fixed with plate and screws when compared to those fixed with Rush rod and K wire within the group with fibula fixation. Fibula fixation in the treatment of tibial pilon fractures is not routinely necessary and does not result in decreased mechanical complications such as malunion, delayed union, nonunion and implant failure. Fibula fracture fixation should be reserved for cases where it may aid reduction or provide additional stability.


[The professional and familial status of female physicians in Switzerland].
A questionnaire on professional and family life was sent to all women doctors in Switzerland (N=2570). 70% were returned, 80% of the respondents are exercising their profession, though only 50% in full time jobs. The most important reason for not working is the presence of small children, mainly in doctors aged 30-40.


Regioselective synthesis and in vitro cytotoxicity evaluation of 3-thiooxindole derivatives: Tubulin polymerization inhibition and apoptosis inducing studies.
Herein, regiospecific nucleophilic ring-opening of spiroaziridine oxindoles has been established to afford 3-substituted-thiooxindole derivatives as anticancer agents. Among the new series, compounds 7d and 9c exhibited promising cytotoxic activity toward HCT-116 cells with IC50 values of 6.73 ± 0.36 and 6.64 ± 0.95 µM, respectively. Further, AO/EB, DCFDA, and DAPI staining studies were executed to establish the underlying apoptosis mechanism which displayed significant nuclear and morphological alterations. JC-1 staining and annexin V binding assay inferred the loss of mitochondrial membrane potential in HCT-116 cancer cells. Cell cycle analysis showed the treatment of 9c against HCT-116 cells, arrested the cell cycle in G2-M phase. In addition, tubulin binding assay revealed that compound 9c exhibited tubulin polymerase inhibition with IC50 value of 9.73 ± 0.18 μM. This inhibition of tubulin polymerase was further supported by binding interactions of 9c with tubulin through docking studies on PDB ID: 3E22.


Extracorporeal cardiopulmonary resuscitation after out-of-hospital cardiac arrest in a Danish health region.
Extracorporeal Cardiopulmonary Resuscitation (ECPR) has emerged as a feasible rescue therapy for refractory, normothermic out-of-hospital cardiac arrest (OHCA). Reported survival rates vary and comparison between studies is hampered by heterogeneous study populations, differences in bystander intervention and in pre-hospital emergency service organisation. We aimed to describe the first experiences, treatment details, complications and outcome with ECPR for OHCA in a Danish health region. Retrospective study of adult patients admitted at Aarhus University Hospital, Denmark between 1 January 2011 and 1 July 2015 with witnessed, refractory, normothermic OHCA treated with ECPR. OHCA was managed with pre-hospital advanced airway management and mechanical chest compression during transport. Relevant pre-hospital and in-hospital data were collected with special focus on low-flow time and ECPR duration. Survival to hospital discharge with Cerebral Performance Category (CPC) of 1 and 2 at hospital discharge was the primary endpoint. Twenty-one patients were included. Median pre-hospital low-flow time was 54 min [range 5-100] and median total low-flow time was 121 min [range 55-192]. Seven patients survived (33%). Survivors had a CPC score of 1 or 2 at hospital discharge. Five survivors had a shockable initial rhythm. In all survivors coronary occlusion was the presumed cause of cardiac arrest. Extracorporeal cardiopulmonary resuscitation is feasible as a rescue therapy in normothermic refractory OHCA in highly selected patients. Low-flow time was longer than previously reported. Survival with favourable neurological outcome is possible despite prolonged low-flow duration.


Disturbed hemodynamics and oxidative stress interaction in endothelial dysfunction and AAA progression: Focus on Nrf2 pathway.
Hemodynamic shear stress is one of the major factors that are involved in the pathogenesis of many cardiovascular diseases including atherosclerosis and abdominal aortic aneurysm (AAA), through its modulatory effect on the endothelial cell's redox homeostasis and mechanosensitive gene expression. Among important mechanisms, oxidative stress, endoplasmic reticulum stress activation, and the subsequent endothelial dysfunction are attributed to disturbed blood flow and low shear stress in the vascular curvature and bifurcations which are considered atheroprone regions and aneurysm occurrence spots. Many pathways were shown to be involved in AAA progression. Of particular interest from recent findings is, the (Nrf2)/Keap-1 pathway, where Nrf2 is a transcription factor that has antioxidant properties and is strongly associated with several CVDs, yet, the exact mechanism by which Nrf2 alleviates CVDs still to be elucidated. Nrf2 expression is closely affected by shear stress and was shown to participate in AAA. In the current review paper, we discussed the link between disturbed hemodynamics and its effect on Nrf2 as a mechanosensitive gene and its role in the development of endothelial dysfunction which is linked to the progression of AAA.


Local recurrence after curettage treatment of giant cell tumors in peripheral bones: retrospective study by the GSF-GETO (French Sarcoma and Bone Tumor Study Groups).
Curettage is a well-established treatment modality for giant cell tumors of bone. The purpose of this retrospective study by the French Sarcoma and Bone Tumor Study Groups (GSF-GETO) was to analyze various tumor-specific and surgery-specific factors that could influence the rate of local recurrence. Data was collected from patients with giant cells tumors of the appendicular skeletal who were treated by intralesional curettage. The hazard ratio for tumor recurrence was calculated for the different variables collected and a multifactorial analysis carried out. One hundred and ninety-three surgical procedures were included from nine centers. One hundred and seventy-one (89%) were primary tumors and 22 had been referred after one or more recurrences. The mean follow-up was 6 years and 11 months. The distal femur and proximal tibia were the most common locations: 42.5 and 34.2% of cases, respectively. The bone defect after curettage was filled in 176 cases (91.2%) and left empty in 16 cases. Local adjuvant treatment (phenol, alcohol, cryotherapy or combination treatment) was used in 39 cases (20.2%) and systemic adjuvant treatment used in 24 cases (calcitonin 11 and zoledronic acid 13). Local recurrence occurred in 71 cases (36.8%). Risk factors for local recurrence were an empty defect, a defect filled with autograft, and patients treated before 2005. Multivariate analysis showed that the only risk factors for local recurrence were a surgical procedure before 2005 (odds ratio 3.6 (95% CI: 1.2, 7.9) P=0.017) and a bone defect filled with autograft (odds ratio 3.9 [95% CI: 1.3, 11.6] P=0.013) CONCLUSION: Neither tumor-specific nor surgery-specific factors such as adjuvant treatment were found to be as risk factors for local recurrence after curettage of giant cell tumors in the appendicular skeleton. As recently reported, high-quality local curettage is probably the most effective technique to prevent local recurrence. The current study suggests that two factors associated with more recent management of these tumors in France, high-speed burring and centralization to skilled surgical teams, can improve the quality of curettage. 4, retrospective cohort study.


Is particulate or non-particulate steroid the determinant of periarticular injection efficacy for controlling postoperative TKR pain? Network meta-analysis.
Combining steroids for a periarticular injection (PAI) regiment has resulted in better pain control for postoperative TKR pain. Despite the available evidence, the most effective type of steroid for PAI still needs to be established. Network meta-analysis is conducted to analyze whether there is any difference in the effect of particulate compared to non-particulate periarticular steroid injection on post-TKR patients for pain control based on published literature. This study is conducted following the PRISMA guideline. In general, studies assessing the efficacy of periarticular injection analgesia added with either particulate (Triamcinolone, methylprednisolone, or prednisolone) or non-particulate (dexamethasone or betamethasone) steroid compared to the same regiment were analyzed. Ten studies were finally included from the 108 identified papers through database searching. VAS reduction on POD1 is found to be similar in particulate (0,91; CI95%: 0,45-1,37) compared to non-particulate (0,81; CI95%: 0,34-1,28) (Fig. 2). The difference becomes wider and favors non-particulate POD3. Subgroup analysis based on each steroid type was conducted. A stark difference can be observed for each pair of steroids (particulate and non-particulate), resulting in a similar cumulative effect of particulate and non-particulate steroids and inconsistent result on POD1 compared to POD3. From the available evidence, we concluded that particulate or non-particulate steroid does not significantly affect post-TKR pain management. Instead, the specific type of steroid contributes more to postoperative VAS reduction. Level III.


Effects of dehydroepiandrosterone on aldosterone release in rat zona glomerulosa cells.
The present study was to investigate the effects and action mechanisms of dehydroepiandrosterone (DHEA) on steroidogenesis in rat adrenal zona glomerulosa cells (ZG). ZG cells were incubated with DHEA in the presence or absence of angiotensin II (AngII), a high concentration of potassium, 8-Br-cAMP, forskolin, 25-OH-cholesterol, pregnenolone, progesterone, deoxycorticosterone, corticosterone, A23187, or cyclopiazonic acid (CPA) at 37 degrees C for 1 h. The concentration of aldosterone or pregnenolone in the culture medium was then measured by radioimmunoassay (RIA). The cells were used to determine the cellular cAMP content. The data demonstrated that: (1) DHEA inhibited AngII-, high concentration of KCl-, forskolin-, 8-Br-cAMP-, 25-OH-cholesterol-, pregnenolone-, progesterone-, deoxycorticosterone-, corticosterone-, A23187-, or CPA-stimulated aldosterone release; (2) DHEA increased 25-OH-cholesterol-stimulated pregnenolone release but not when 25-OH-cholesterol was combined with trilostane; (3) DHEA noncompetitively inhibited aldosterone synthase but showed uncompetitive inhibition of P450scc. These results suggest that DHEA acts directly on rat ZG cells to diminish aldosterone secretion by inhibition of a post-cAMP pathway or by acting on intracellular Ca2+ mobilization. In addition it affects the function of post-P450scc steroidogenic enzymes.


[Efficacy and safety of secondary allogeneic hematopoietic stem cell transplantation in 70 patients with recurrent hematologic malignancies after transplantation].
Objectives: To investigate the role of donor change in the second hematopoietic stem cell transplantation (HSCT2) for hematological relapse of malignant hematology after the first transplantation (HSCT1) . Methods: We retrospectively analyzed patients with relapsed hematological malignancies who received HSCT2 at our single center between Mar 1998 and Dec 2020. A total of 70 patients were enrolled[49 males and 21 females; median age, 31.5 (3-61) yr]. Results: Forty-nine male and 21 female patients were enrolled in the trial. At the time of HSCT2, the median age was 31.5 (3-61) years old. Thirty-one patients were diagnosed with acute myeloid leukemia, 23 patients with ALL, and 16 patients with MDS or other malignant hematology disease. Thirty patients had HSCT2 with donor change, and 40 patients underwent HSCT2 without donor change. The median relapse time after HSCT1 was 245.5 (26-2 905) days. After HSCT2, 70 patients had neutrophil engraftment, and 62 (88.6%) had platelet engraftment. The cumulative incidence of platelet engraftment was (93.1±4.7) % in patients with donor change and (86.0±5.7) % in patients without donor change (P=0.636). The cumulative incidence of CMV infection in patients with and without donor change was (64.0±10.3) % and (37.0±7.8) % (P=0.053), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute graft versus host disease was (19.4±7.9) % vs (31.3±7.5) %, respectively (P=0.227). The cumulative incidence of TRM 100-day post HSCT2 was (9.2±5.1) % vs (6.7±4.6) % (P=0.648), and the cumulative incidence of chronic graft versus host disease at 1-yr post-HSCT2 was (36.7±11.4) % versus (65.6±9.1) % (P=0.031). With a median follow-up of 767 (271-4 936) days, 38 patients had complete remission (CR), and three patients had persistent disease. The CR rate was 92.7%. The cumulative incidences of overall survival (OS) and disease-free survival (DFS) 2 yr after HSCT2 were 25.8% and 23.7%, respectively. The cumulative incidence of relapse, OS, and DFS was (52.6±11.6) % vs (62.4±11.3) % (P=0.423), (28.3±8.6) % vs (23.8±7.5) % (P=0.643), and (28.3±8.6) % vs (22.3±7.7) % (P=0.787), respectively, in patients with changed donor compared with patients with the original donor. Relapses within 6 months post-HSCT1 and with persistent disease before HSCT2 were risk factors for OS, DFS, and CIR. Disease status before HSCT2 and early relapse (within 6 months post-HSCT1) was an independent risk factor for OS, DFS, and CIR post-HSCT2. Conclusion: Our findings indicate that changing donors did not affect the clinical outcome of HSCT2.


Percutaneous cervical pharyngostomy. A comfortable and convenient alternative to protracted nasogastric intubation.
For patients who require lengthy periods of enteral nutrition or gastrointestinal decompression, the use of a tube placed through a cervical pharyngostomy provides a convenient means of access to the upper gastrointestinal tract. The discomfort and complications of nasogastric intubation can be avoided, and the use of parenteral nutrition can be reduced in many cases where the gastrointestinal tract is functioning but the patient is unable to ingest food normally. The result of this technique in 42 patients over a 4 year period have been described herein. The patients found the method comfortable, cosmetically acceptable, and easily managed both in the hospital and at home. The technique of inserting the tube through the pyriform sinus is easy and safe to perform, and there have been no major complications in using the technique for periods up to 119 days. If accidentally displaced, the tube is easily reinserted through the neck without special equipment and with no discomfort. The method can provide a considerable improvement in the effectiveness of overall patient management. We suggest it could be more widely used in general surgical practice.


Cell contact-dependent functional selectivity of β2-adrenergic receptor ligands in stimulating cAMP accumulation and extracellular signal-regulated kinase phosphorylation.
Activation of β(2)-adrenegic receptor (β(2)-AR) leads to an increase in intracellular cAMP and activation of ERK. These two signals are activated by the interaction of the receptor with different transducer partners. We showed that the intrinsic activities of β(2)-AR ligands for stimulating cAMP production and ERK phosphorylation responses in HEK-293 cells were not correlated. The lack of correlation resulted mainly from the discrepancy between the intrinsic activities of two groups of ligands for these two responses: The first group consisted of clenbuterol, cimaterol, procaterol, and terbutaline which acted as full agonists for cAMP production but displayed very weak effect on ERK phosphorylation. The second group comprised adrenaline and noradrenaline which displayed higher intrinsic activity for the ERK phosphorylation than for the cAMP response. Thus, both groups behaved as functionally selective ligands. The functional selectivity of the first group was observable only in adherent cells when confluence was approximately 100%. When cell-cell contact was minimized either by decreasing the density of the adherent cells or by bringing the cells into suspension, the first group of ligands gained the ability to stimulate ERK phosphorylation without a change in their effect on cAMP production. In contrast, selectivity of the second group was independent of the adherence state of the cells. Our results show that the inherent "bias" of ligands in coupling a G protein-coupled receptor to different transducers may not always be revealed as functional selectivity when there is a "cross-talk" between the signaling pathways activated by the same receptor.


Drosophila Schip1 Links Expanded and Tao-1 to Regulate Hippo Signaling.
Regulation of organ size is essential in animal development, and Hippo (Hpo) signaling is a major conserved mechanism for controlling organ growth. In Drosophila, Hpo and Warts kinases are core components of this pathway and function as tumor suppressors by inhibiting Yorkie (Yki). Expanded (Ex) is a regulator of the Hpo activity, but how they are linked is unknown. Here, we show that Schip1, a Drosophila homolog of the mammalian Schwannomin interacting protein 1 (SCHIP1), provides a link between Ex and Hpo. Ex is required for apical localization of Schip1 in imaginal discs. Schip1 is necessary for promoting membrane localization and phosphorylation of Hpo by recruiting the Hpo kinase Tao-1. Taking these findings together, we conclude that Schip1 directly links Ex to Hpo signaling by recruiting Tao-1. This study provides insights into the mechanism of Tao-1 regulation and a potential growth control function for SCHIP1 in mammals.


[Inhibitors of proteolytic enzymes under abiotic stresses in plants (review)].
Data on the role of proteolytic enzyme inhibitors in plant adaptation to various unfavorable environmental abiotic factors--water deficiency, salinization of soil, extreme temperatures, etc.--and also probable functions of proteinases inhibitors in natural plant senescense are considered.


Sniffing, rearing and locomotor responses to the D-1 dopamine agonist R-SK&F 38393 and to apomorphine: differential interactions with the selective D-1 and D-2 antagonists SCH 23390 and metoclopramide.
The D-1 agonist R-SK&F 38393 induced non-stereotyped sniffing, rearing and locomotor responses that were blocked by the D-1 antagonist SCH 23390. The D-2 antagonist metoclopramide failed to block sniffing but blocked rearing and locomotion. Stereotyped sniffing and locomotion induced by apomorphine were each blocked by both antagonists. Either the criteria by which compounds are designated as D-1 or D-2 selective agents require revision, or else D-1 and D-2 mechanisms are able to reciprocally interact to influence the expression of behaviour initiated by stimulation of either receptor subtype.


Can self-care health books affect amount of contact with the primary health care team? A randomized controlled trial in general practice.
To investigate the effects of two differently styled self-care health books in general practice on the frequency and duration of patients' consultations and their views of the books. Random allocation of patients to either a descriptive or a decision-tree based self-care health book, or a no-book control condition. Three- and 12-months follow-up by postal questionnaire and monitoring of consultations. A large general practice in the South East of England. A total of 1967 volunteer, adult patients who attended the practice in 2001 participated. Demographics; health problems; use of health services; use and perceptions of the trial book; frequency and duration of consultations. Response rates to postal questionnaires at 3 and 12 months were 80% and 74%. In all, 48% consulted their allocated book, compared with 25% who consulted any healthcare book in the Control group. Those reporting health problems were more likely to have consulted their allocated book; 60% reported that the allocated book made them more likely to deal with a problem themselves and 40% reported themselves less likely to consult the practice. However, there were no differences in consultation rates or durations of consultations between the three groups. Handing out of self-care health books may provide qualitative benefits for patients but is unlikely to reduce attendance at the GP practice.


Dissipation of clodinafop-propargyl and its metabolite in wheat field ecosystem.
The dissipation and residues of clodinafop-propargyl and clodinafop in wheat and soil were investigated by high performance liquid chromatography-tandem mass spectrometry. Clodinafop-propargyl rapidly degraded to the acid derivative-clodinafop as major metabolite in plant and soil. The half-lives of clodinafop-propargyl were 2.35-11.20 days in soil and 6.00 days in wheat plant. The half-lives of clodinafop were 7.04-11.22 days in soil and 0.67-1.24 days in wheat plant. The residues of clodinafop-propargyl and clodinafop in wheat grain, wheat straw and soil were below the detection limit.


Complexity of bidirectional transcription and alternative splicing at human RCAN3 locus.
Human RCAN3 (regulator of calcineurin 3) belongs to the human RCAN gene family.In this study we provide, with in silico and in vitro analyses, the first detailed description of the human multi-transcript RCAN3 locus. Its analysis revealed that it is composed of a multigene system that includes at least 21 RCAN3 alternative spliced isoforms (16 of them identified here for the first time) and a new RCAN3 antisense gene (RCAN3AS). In particular, we cloned RCAN3-1,3,4,5 (lacking exon 2), RCAN3-1a,2,3,4,5, RCAN3-1a,3,4,5, RCAN3-1b,2,3,4,5, RCAN3-1c,2,3,4,5, RCAN3-1c,2,4,5 and RCAN3-1c,3,4,5, isoforms that present a different 5' untranslated region when compared to RCAN3. Moreover, in order to verify the possible 5' incompleteness of previously identified cDNA isoforms with the reference exon 1, ten more alternative isoforms were retrieved. Bioinformatic searches allowed us to identify RCAN3AS, which overlaps in part with exon 1a, on the opposite strand, for which four different RCAN3AS isoforms were cloned.In order to analyze the different expression patterns of RCAN3 alternative first exons and of RCAN3AS mRNA isoforms, RT-PCR was performed in 17 human tissues. Finally, analyses of RCAN3 and RCAN3AS genomic sequences were performed to identify possible promoter regions, to examine donor and acceptor splice sequences and to compare evolutionary conservation, in particular of alternative exon 1 or 1c--exon 2 junctions in different species.The description of its number of transcripts, of their expression patterns and of their regulatory regions can be important to clarify the functions of RCAN3 gene in different pathways and cellular processes.


Age-dependence of the nerve fibre growth-promoting effects of hippocampus and exogenous nerve growth factor on cultured rat septum and superior cervical ganglion.
Explants of hippocampus from rats at various ages evoked an intense nerve fibre growth from cocultured superior cervical ganglion and septum explants taken from newborn rats. The addition of antiserum to nerve growth factor (NGF) into the culture medium inhibited the outgrowth of nerve fibres from superior cervical ganglia, while septum explants still extended nerve fibres in the same medium. Septum explants responded to added NGF, as well as to cocultured hippocampus, during the first postnatal week only, whereas ganglia extended nerve fibres in NGF-containing cultures throughout the postnatal period and even at the age of 6 months if superoptimal concentration of NGF was used. The present results suggest that hippocampus releases NGF and some other growth factor(s) in culture throughout the postnatal period from birth to adulthood. On the other hand, the capacity of septum to extend nerve fibres in response to the growth factors appears to be restricted to the first postnatal week.


Epigenetic status of argininosuccinate synthetase and argininosuccinate lyase modulates autophagy and cell death in glioblastoma.
Arginine deprivation, either by nutritional starvation or exposure to ADI-PEG20, induces adaptive transcriptional upregulation of ASS1 and ASL in glioblastoma multiforme ex vivo cultures and cell lines. This adaptive transcriptional upregulation is blocked by neoplasia-specific CpG island methylation in either gene, causing arginine auxotrophy and cell death. In cells with methylated ASS1 or ASL CpG islands, ADI-PEG20 initially induces a protective autophagic response, but abrogation of this by chloroquine accelerates and potentiates cytotoxicity. Concomitant methylation in the CpG islands of both ASS1 and ASL, observed in a subset of cases, confers hypersensitivity to ADI-PEG20. Cancer stem cells positive for CD133 and methylation in the ASL CpG island retain sensitivity to ADI-PEG20. Our results show for the first time that epigenetic changes occur in both of the two key genes of arginine biosynthesis in human cancer and confer sensitivity to therapeutic arginine deprivation. We demonstrate that methylation status of the CpG islands, rather than expression levels per se of the genes, predicts sensitivity to arginine deprivation. Our results suggest a novel therapeutic strategy for this invariably fatal central nervous system neoplasm for which we have identified robust biomarkers and which overcomes the limitations to conventional chemotherapy imposed by the blood/brain barrier.


Intra- and interobserver reproducibility of transvaginal ultrasound for the detection and measurement of endometriotic lesions of the bowel.
The number and invasion depth of endometriotic bowel lesions, total length of bowel affected by endometriosis, lesion-to-anal verge distance, and extent of pouch of Douglas obliteration are important factors in preoperatively determining risk and complexity of endometriosis surgery. The intra- and interobserver reproducibility of transvaginal ultrasound in the evaluation of many of these parameters has not yet been investigated. Our study aimed to assess the intra- and interobserver reproducibility of transvaginal ultrasound between an experienced and less experienced examiner for all of these parameters. This prospective observational cross-sectional study was conducted between July 2019 and November 2020. Fifty consecutive premenopausal women who underwent transvaginal ultrasound examination in our clinic for the first time, were examined by the same two operators during the same attendance. Outcomes of interest were the inter-rater reproducibility of transvaginal ultrasound for detecting the presence, number, depth and size of bowel endometriotic nodules, lesion-to-anal-verge distance, total length of bowel affected, and pouch of Douglas obliteration. The intraobserver reproducibility was assessed for the continuous parameters. Cohen's kappa (κ) statistic, Cohen's weighted kappa (κ), proportions of agreement, intraclass correlation coefficient (ICC) and Bland-Altman limits of agreement were used to assess the reproducibility of the parameters. The inter-rater agreement and reliability were very good for identifying bowel endometriosis, the number and invasion depth of bowel nodules, determining whether the maximum nodule length was <3 cm, and lesion-to-anal-verge distance <8 cm (proportion of agreement 0.92, 0.94, 0.97, 0.94, 0.96; κ 0.92, 0.91, 0.92, 0.82, 0.89). The inter-rater agreement and reliability were good for assessing pouch of Douglas obliteration (proportion of agreement 0.86, κ 0.80). The intra-rater reliability for the mean nodule diameter (ICC 0.93 and 0.97) and total length of bowel affected (ICC 0.94 and 0.91) were excellent for operators A and B, respectively. The inter-rater reliability for the mean nodule diameter was good (ICC 0.80), and moderate for the total length of bowel affected (ICC 0.70). The Bland-Altman limits of agreement demonstrated clinically acceptable ranges for these two parameters. This study demonstrated a high intra- and inter-rater reproducibility of transvaginal ultrasound in the diagnosis of bowel endometriosis and measurement of its various components.


Changes in angiotensin II receptors in dopamine-rich regions of the mouse brain with age and ethanol consumption.
The density of angiotensin II (Ang II) receptors was determined in three dopaminergic nerve terminal-rich brain regions (caudate putamen, nucleus accumbens, and ventral pallidum) of mice that were given either water (control) or 20% w/v ethanol (EtOH) to drink for either 2-8 weeks (young) or 46 weeks (old). The receptors were labeled with 125I-sarcosine1, isoleucine8 angiotensin II (125I-SI Ang II) and measured by quantitative densitometric image analysis (receptor autoradiography) or by saturation binding assays on homogenates of these brain regions. The selective AT2 receptor subtype antagonist PD 123319 (10 microM) was used to inhibit 125I-SI Ang II binding to AT2 receptors to determine AT1 receptor density in brain sections. In young control mice the density of Ang II receptor binding sites in the caudate putamen was 407+/-26 fmol/g, in the nucleus accumbens the density was 346+/-27 fmol/g, and in the ventral pallidum the density was 317+/-27 fmol/g. Less than 5% of specific 125I-SI Ang II binding was displaced by PD 123319, suggesting that nearly all of the Ang II receptors in these brain regions were the AT1 subtype. The Bmax in homogenates of these three regions in young control mice was 11.0+/-2.1 fmol/mg protein. The KD was 0.49+/-0.13. Ang II receptors in old mouse brains were decreased, respectively, by 32%, 35% and 30% in the caudate putamen, nucleus accumbens and ventral pallidum (p<0.001). Ang II receptors were slightly, but not significantly increased in both young and old EtOH-consuming mice.


Dyspnea: a sensory experience.
Dyspnea--an unpleasant or uncomfortable awareness of breathing or need to breathe--is a common symptom of patients with cardiopulmonary disease. Although often thought of as a single symptom, dyspnea probably subsumes many sensations. Experimental conditions used to induce dyspnea are characterized by discrete groups or clusters of descriptive phrases. Similarly, as the language of dyspnea is refined further, different disease states may be distinguishable by the nuances of breathlessness described by patients. Evidence is gathering that the sensations of dyspnea are modified by information from a variety of receptors throughout the respiratory system. The sense of effort, although still important in the breathlessness associated with mechanical loads, is insufficient to explain the dyspnea arising from a number of experimental and clinical conditions. As our understanding of the interactions between effort and afferent information from the respiratory system grows, new therapeutic interventions to alleviate dyspnea are likely to follow.


Comparison of high-frequency oscillatory ventilation and high-frequency jet ventilation in cats with normal lungs.
Four adult cats received alternating high-frequency oscillatory ventilation (HFOV) and high-frequency jet ventilation (HFJV) at equivalent proximal airway pressures. Physiologic measurements were made before and after each ventilator change. Proximal airway pressures were then adjusted as necessary to reestablish normal pH and PaCO2 values. Aortic, pulmonary artery, and central venous pressures were monitored. Cardiac outputs were measured. Pulmonary and systemic vascular resistance, intrapulmonary shunt, and alveolar-arterial oxygen gradient were determined. Following the change from HFOV to HFJV at similar proximal airway pressures, HFJV always produced higher pH values (P less than 0.0001), higher PaO2 values (P less than 0.05), lower PaCO2 values (P less than 0.0001), as well as higher cardiac outputs (P less than 0.01), lower pulmonary artery pressures (P less than 0.001), and lower pulmonary vascular resistances (P less than 0.001). Following the reciprocal crossover, from HFJV to HFOV, HFJV pH values were again higher (P less than 0.001), and PaCO2 values were again lower (P less than 0.001). A comparison of HFOV and HFJV at similar pH and PaCO2 values showed that HFOV consistently required higher peak inspiratory pressures (P less than 0.001), higher mean airway pressure (P less than 0.001), and higher pressure wave amplitudes (P less than 0.001). Under the circumstances of this study, HFJV produced better gas exchange at lower proximal airway pressures.


Predictive Value of Exhaled Nitric Oxide and Blood Eosinophil Count in the Assessment of Airway Eosinophilia in COPD.
Fractional exhaled nitric oxide (FENO50) level and peripheral blood eosinophil count may serve as indicators of airway eosinophilia. The aim of this study was to estimate the diagnostic value of these markers for detecting airway eosinophilia in patients with stable chronic obstructive pulmonary disease (COPD) and those experiencing an acute exacerbation (AECOPD). FENO50 levels, sputum and blood eosinophil counts were assessed in 53 clinically stable ex-smoker COPD patients and 67 ex-smoker COPD patients experiencing a severe exacerbation. In AECOPD, clinical variables were measured at the time of hospital admission and discharge following treatment. In stable COPD, blood eosinophil count but not FENO50 level was found to be a good predictor of airway eosinophilia (area under the receiver operating characteristic curve [ROC AUC]: ≥0.82). The sensitivity and the specificity of the test ranged between 75% and 98%, the negative predictive value (NPV) was high (>90%). In AECOPD, FENO50 was predictive for airway eosinophilia (ROC AUC: >0.8) with high NPV (>88%), but with lower sensitivity and specificity (64-70%). In contrast, the predictive accuracy of blood eosinophil count for airway eosinophilia in AECOPD was modest (ROC AUC: 0.54-0.63). The combined use of the two markers provided only limited additional benefit. Correlation analyses supported ROC curve findings. In stable COPD the peripheral blood eosinophil count, while in AECOPD the FENO50 level is a good surrogate marker of airway eosinophilia.


The effects of perioperative pain management techniques on food consumption and body weight after laparotomy in rats.
We examined the effects of two perioperative pain management techniques on recovery after laparotomy, as assessed by body weight (BW) and food consumption (FC). All rats received a preoperative intrathecal mixture of morphine plus bupivacaine combined with one of two treatments: (a) injection of slow-release morphine at the end of the surgery or (b) an antiinflammatory drug, interleukin-1 receptor antagonist (IL-1ra), combined with the preoperative mixture. Laparotomy significantly decreased FC and BW. Both analgesic treatments resulted in a faster recovery of FC and BW. This beneficial effect was more pronounced in the group receiving preoperative analgesics combined with IL-1ra. Effective perioperative pain management can improve postoperative recovery. We studied the effects of two preoperative pain management techniques on recovery after laparotomy in rats. Both analgesic treatments resulted in a faster recovery, especially preoperative analgesics combined with interleukin-1 receptor antagonist.


Genesis and properties of wetland soils by VIS-NIR-SWIR as a technique for environmental monitoring.
Wetlands are important ecosystems characterized by redoximorphic environments producing typical soil forming processes and organic carbon accumulation. Assessments and management of these areas are dependent on knowledge about soil characteristics and variability. By reflectance spectroscopy, information about soils can be obtained since their spectral behaviors are directly related to their chemical, physical, and mineralogical properties reflecting the pedogenetic processes and environment conditions. Our aims were: (a) to characterize the main soil classes of wetlands regarding their spectral behaviors in VIS-NIR-SWIR (350-2500 nm) and relate them to pedogenesis and environmental conditions, (b) to determine spectral ranges (bands) with greater expression of the main soil properties, (c) to identify spectral variations and similarities between hydromorphic soils from wetlands and other soils under different moisture conditions, and (d) to propose spectral models to quantify some chemical and physical soil properties used as environmental quality indicators. Nine soil profiles from the Pantanal region (Mato Grosso State, Brazil) and one from the Serra do Espinhaço Meridional (Minas Gerais State, Brazil) were investigated. Spectral morphology interpretation allowed identifying horizon differences regarding shape, absorption features and reflectance intensity. Some pedogenetic processes of wetland soils related to organic carbon accumulation and oxide iron variation were identified by spectra. Principal Component Analysis allowed discriminating soils from wetland and outside this area (oxidic environment). Quantification of organic carbon was possible with R2 of 0.90 and low error. Quantification of clay content was masked by soils with organic carbon content over 2% where it was not possible to quantify with high R2 and low error both properties when dataset has soil samples with high organic carbon content. By reflectance spectroscopy, important characteristics of wetland soils can be identified and used to distinguish from soils of different environments at low costs, reduced time, and with environmental quality.


A context-sensitive mechanism in hippocampal CA1 networks.
This paper presents a possible context-sensitive mechanism in a neural network and at single neuron levels based on the experiments of hippocampal CA1 and their theoretical models. First, the spatiotemporal learning rule (STLR, non-Hebbian) and the Hebbian rule (HEBB) are experimentally shown to coexist in dendrite-soma interactions in single hippocampal pyramidal cells of CA1. Second, the functional differences between STLR and HEBB are theoretically shown in pattern separation and pattern completion. Third, the interaction between STLR and HEBB in neural levels is proposed to play an important role in forming a selective context determined by value information, which is related to expected reward and behavioral estimation.


Bipolar affective disorder and creativity: implications and clinical management.
Research on the relationship between creativity and mental illness is summarized, and studies documenting a relationship in writers between creativity and affective illness (particularly bipolar illness) are described. Writers have a high prevalence of affective illness, and both affective illness and creativity have increased frequency in their first-degree relatives. The clinical management of the creative individual is challenging. In general, creative individuals are most productive when their affective symptoms are under good control.


KOTMIN13, a Korean herbal medicine alleviates allergic inflammation in vivo and in vitro.
The ethanol extract of KOTMIN13, composed of Inula japonica Flowers, Trichosanthes kirilowii Semen, Peucedanum praeruptorum Radix, and Allium macrostemon Bulbs, was investigated for its anti-asthmatic and anti-allergic activities. The anti-asthmatic effects of KOTMIN13 were evaluated on ovalbumin (OVA)-induced murine asthma model. Anti-allergic properties of KOTMIN13 in bone-marrow derived mast cells (BMMC) and passive cutaneous anaphylaxis (PCA) in vivo were also examined. In asthma model, KOTMIN13 effectively suppressed airway hyperresponsiveness induced by aerosolized methacholine when compared to the levels of OVA-induced mice. KOTMIN13 treatment reduced the total leukocytes, eosinophil percentage, and Th2 cytokines in the bronchoalveolar lavage fluids in OVA-induced mice. The increased levels of eotaxin and Th2 cytokines in the lung as well as serum IgE were decreased by KOTMIN13. The histological analysis shows that the increased inflammatory cell infiltration and mucus secretion were also reduced. In addition, the degranulation and leukotriene C4 production were inhibited in BMMC with IC50 values of 3.9 μg/ml and 1.7 μg/ml, respectively. Furthermore, KOTMIN13 treatment attenuated mast-mediated PCA reaction. These results demonstrate that KOTMIN13 has anti-asthmatic and anti-allergic effects in vivo and in vitro models.


Synthesis of interleukin-1-like activity by normal rat chondrocytes in culture.
Chondrocytes prepared from the articular cartilage of young rats synthesize and secrete an interleukin-1-like activity into the medium. The physical and biochemical properties of this IL-1-like activity are similar to macrophage-derived IL-1. Immunological studies suggest that this activity is related to IL-1 alpha. Isolated chondrocytes and those grown in culture can express Ia.


Smoker and ex-smoker reactions to cigarettes claiming reduced risk.
The tobacco industry is introducing modified tobacco products claiming to reduce the risk of smoking (potential reduced exposure products, PREPs). If PREPs are perceived as safe, they may deter smokers from quitting and encourage re-initiation by smokers who have quit. To assess smokers' and ex-smokers' perceptions of PREPs and the impact of PREP claims on interest in quitting (among smokers) or in resuming smoking (ex-smokers). A random-digit-dialled survey of US smokers and ex-smokers. We used Eclipse, a modified PREP cigarette, as an exemplar PREP. During the survey, the interviewer read risk reduction claims made for Eclipse by its manufacturer, assessing smokers' interest in quitting before and after the exposure. 1000 current cigarette smokers and 499 ex-smokers (300 quit within the last two years), over 18 years old. Perception of risk reduction from Eclipse; interest in using Eclipse; smokers' interest in quitting was assessed using a stage of change approach (pre- and post-exposure to claims). 91% of smokers thought Eclipse was safer than regular cigarettes. 24% believed Eclipse was completely safe. 57.4% of smokers were interested in using Eclipse; interest was greatest among smokers who were contemplating quitting. Exposure to Eclipse's claims was followed by reduced interest in quitting. Among all ex-smokers, interest in Eclipse was 6.2%, but interest was 15.2% among young adults (18-25 years) who had stopped smoking within two years. There is substantial risk that smokers will overinterpret reduced risk claims made for modified tobacco products. PREPs appeal to smokers who are contemplating quitting and exposure to reduced risk product claims appears to reduce smokers' readiness to quit. PREPs also appealed to young adults who had recently stopped smoking. Thus, reduced risk tobacco product claims can undermine adult cessation and youth prevention, possibly resulting in increased harm even if the products are less toxic.


Continuing medical education: a challenge to the Italian Scientific Societies of Laboratory Medicine.
In the modern health service, it is no longer acceptable for any clinician or other professional to abstain from continuing education after qualification. This is particularly true in the field of laboratory medicine because of the dramatic changes that have occurred in the organization, number and types of tests, and role of medical laboratories. In Italy, a program for continuing education in medicine (Educazione Continua in Medicina (ECM)) has recently been promoted by the National Government. Continuing education (CE) in laboratory medicine should include all educational activities that are pertinent to a person's professional skills, activities, interests, and growth. Continuing education can take many forms. In particular, a variety of programs are available that enable employees to improve their knowledge and skills while reducing their travel and absence from the laboratory. The present paper describes the recent redefinition of the mission, aims and structure of the Scientific Division of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC) and the role it plays in making available to all associates a program for continuing education in the field of Laboratory Medicine. The activation of a national program for continuing education in medicine (ECM) in Italy provides a great opportunity for all professionals of the healthcare sector and for laboratorians, in particular. This educational project offers an unrivalled opportunity for the Italian Scientific Societies of Laboratory Medicine to weave quality improvement into their relationships with associates, thus reappraising their missions and goals.


Electrochemical, pharmacological and electrophysiological evidence of rapid dopamine release and removal in the rat caudate nucleus following electrical stimulation of the median forebrain bundle.
Fast cyclic voltammetry was used to monitor the release of electroactive material in the striatum following electrical stimulation of the median forebrain bundle. The released material was shown to be dopamine by electrochemical, pharmacological and neurophysiological means. The material gave a voltammogram identical to that of iontophoretically applied dopamine but not DOPAC. Release was increased by L-DOPA, the metabolic precursor of dopamine. NSD 1015, an inhibitor of dopa decarboxylase, and alpha-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor decreased release. Reserpine, which disrupts vesicular dopamine storage, abolished release. Parachlorophenylalanine, a tryptophan hydroxylase inhibitor, had no effect. Finally, square wave stimulation was only effective when pulses longer than 0.5 ms were used. This indicated stimulation of very fine unmyelinated fibres, consistent with the known morphology of nigrostriatal dopamine fibres.


Polymyositis and dermatomyositis biomarkers.
Polymyositis (PM) and dermatomyositis (DM) are the two subtypes of idiopathic inflammatory myositis and are characterized as symmetrical progressive muscle weakness in the proximal extremities. PM/DM affect multiple organs and systems, including the cardiovascular, respiratory and digestive tract systems. An in-depth understanding of PM/DM biomarkers will facilitate development of simple and accurate strategies for diagnosis, treatment, and prognosis prediction. This review summarized the classic biomarkers of PM/DM, including anti-aminoacyl tRNA synthetases (ARS) antibody, anti-Mi-2 antibody, anti-melanoma differentiation-associated gene 5 (MDA5) antibody, anti-transcription intermediary factor 1-γ (TIF1-γ) antibody, anti-nuclear matrix protein 2 (NXP2) antibody, among others. Among them, anti-aminoacyl tRNA synthetases antibody is the most classic. In addition, many potential novel biomarkers were also discussed in this review, including anti-HSC70 antibody, YKL-40, interferons, myxovirus resistance protein 2, regenerating islet-derived protein 3-α, interleukin (IL)-17, IL-35, microRNA (miR)-1 and so on. Among the biomarkers of PM/DM described in this review, classic biomarkers have become the mainstream biomarkers to assist clinicians in diagnosis due to their early discovery, in-depth research, and widespread application. The novel biomarkers also have potential and broad research prospects, which will make immeasurable contributions to exploring biomarker-based classification standards and expanding their application value.


Dataset for evaluating fitness index using Adaptive Neuro-Fuzzy Inference System.
With the current global downturn, the organizations need to develop new strategies and innovative approaches to ensure that every aspect of sustainability is achieved. For this purpose, the organizations need an indicator that measures the fitness if an organization. The purpose of this project is to analyze the 'Fitness' of an organization using the dataset related to leanness, agility and sustainability in ANFIS (Adaptive Neuro-Fuzzy Inference System) in order to determine whether the company is fit enough to sustain in global markets or not. The project does so by integrating both neural networks and fuzzy logic principles with lean, agility and sustainability principles. FIT manufacturing is the integration of Lean, Agile and sustainability manufacturing in one system as a whole which would help in attaining maximum output and sustain effectively in global markets. FIT Manufacturing adopts an integrated approach towards the use of Lean, Agility and Sustainability to achieve a level of fitness that is unique to each company. The database in the paper contains lean, agile and sustainable indices reviewed by experts. FIT does not prescribe that every aspect of Lean, Agile and Sustainability methodologies must be applied to every company, but a selective mix of components will provide the optimum conditions for a company to prosper.


Cytokine profile in patients with acute bacterial meningitis.
Bacterial meningitis is a life-threatening disease with high mortality and common long-term sequelae. The inflammatory response in the subarachnoid space, modulated by different cytokines, plays a major role in the pathogenesis of acute central nervous system infections. We aimed to examine correlations of interleukin (IL)-6, IL-8, IL-10, IL-12(p40), and tumor necrosis factor (TNF)-α levels with disease severity, complications, and outcome in patients with acute bacterial meningitis. The study involved 30 patients with bacterial meningitis/meningoencephalitis admitted to the University Hospital St. George, Plovdiv over a period of 4 years. Patients were selected based on clinical presentation and laboratory abnormalities, consistent with a neuroinfection. Enzyme-linked immunosorbent assay was used to measure the studied cytokines in both cerebrospinal fluid (CSF) and serum in parallel. For microbiological diagnosis multiplex, polymerase chain reaction, and CSF culture were used. In patients with acute bacterial meningitis CSF levels of IL-6, IL-8, IL-10, and TNF-α are significantly increased than in serum. CSF TNF-α, CSF IL-8, and CSF IL-10 had a moderate negative correlation to CSF glucose. It was found that serum IL-8 is significantly elevated in patients who experienced neurological complications, have severe clinical course, and in deceased patients. CSF IL-10 is increased only in patients with severe acute bacterial meningitis. Among patients with acute bacterial meningitis serum IL-8 could delineate these with increased risk of neurological complications, severe clinical course, and fatal outcome. Serum IL-8 and CSF IL-10 could be used as indicators of disease severity.


Liposome-targeted recombinant human acid sphingomyelinase: Production, formulation, and in vitro evaluation.
Niemann-Pick disease type B is a hereditary rare condition caused by deficiency of the acid sphingomyelinase (ASM) that is needed for lysosomal hydrolysis of sphingomyelin to ceramide and phosphocholine. This deficiency leads to a massive accumulation of sphingomyelin in cells throughout the body, predominantly in the liver, spleen and lungs. Currently, there is no effective treatment available. Olipudase alfa (recombinant human acid sphingomyelinase; rhASM) is an investigational drug that has shown promising results. However, dose-dependent toxicity was observed in mice upon the intravenous administration of rhASM, potentially due to the systemic release of ceramide upon the extracellular degradation of sphingomyelin by rhASM. Using a nanocarrier to deliver the rhASM to cells could improve the therapeutic window by shielding the rhASM to prevent the off-target degradation of sphingomyelin. For this aim, we recombinantly expressed hASM in human cells and loaded it into different liposomal formulations at a drug-to-lipid ratio of 4% (w/w). Among four formulations, the liposomal rhASM formulation with the composition DPPC:DOPS:BMP:CHOL:DiD (59:20:10:10:1 mol%) was selected because of its superiority concerning the encapsulation efficiency of rhASM (21%) and cellular uptake by fibroblasts and macrophages. The selected liposomal rhASM formulation significantly reduced the accumulated lyso-sphingomyelin in NPD-B fibroblasts by 71%, part of this effect was stimulated by the used lipids, compared to 55% when using the free rhASM enzyme. More importantly, the undesired extracellular degradation of sphingomyelin was reduced when using the selected liposomal rhASM by 61% relative to the free rhASM. The presented in vitro data indicate that the liposomal rhASM is effective and may provide a safer intervention than free rhASM.


Advanced mucosal neoplasia of the anorectal junction: endoscopic resection technique and outcomes (with videos).
EMR at the anorectal junction (ARJ) is technically challenging. Issues of safety and procedural efficacy dictate that surgery is still performed as the primary management for noninvasive lesions in most centers. Modifications to the standard EMR technique may help to address the unique features and achieve safe and curative resection of most lesions. To describe an effective and safe, modified EMR technique to remove advanced mucosal neoplasia (AMN) of the ARJ. Prospective, observational cohort study. Academic, tertiary care referral center. Patients undergoing EMR for AMN at the ARJ over 4.5 years, from June 2008 to December 2012. Use of long-acting local anesthetic in the submucosal injectate, endoscopic resection over the dentate line and hemorrhoidal columns, prophylactic antibiotics for resection of lesions at high risk for bacteremia, and cap and gastroscope-assisted resection. Procedural success and safety. Twenty-six patients with lesions involving the ARJ were referred for EMR (males 53.8%, median age 63, median lesion size 40 mm). Two patients went directly to surgery because of an endoscopic diagnosis of adenocarcinoma. EMR was performed in 24 lesions with complete adenoma clearance achieved in 100%. Four patients were admitted to the hospital. Focal adenoma recurrence was seen in 4 of 18 patients (22%) at first surveillance colonoscopy and was managed by snare diathermy resection. No recurrences were found at the second follow-up colonoscopy. Procedural success, adenoma recurrence, and admission rates were similar between EMRs performed at the ARJ and proximal rectum on univariate analysis (all P > .05). Single tertiary center, nonrandomized study. Simple modifications to the EMR technique allow safe and effective treatment of AMN at the ARJ on an outpatient basis and should be the first-line management when the risk of invasive disease is low.


Application of hierarchical clustering to multi-parametric MR in prostate: Differentiation of tumor and normal tissue with high accuracy.
Hierarchical clustering (HC), an unsupervised machine learning (ML) technique, was applied to multi-parametric MR (mp-MR) for prostate cancer (PCa). The aim of this study is to demonstrate HC can diagnose PCa in a straightforward interpretable way, in contrast to deep learning (DL) techniques. HC was constructed using mp-MR including intravoxel incoherent motion, diffusion kurtosis imaging, and dynamic contrast-enhanced MRI from 40 tumor and normal tissues in peripheral zone (PZ) and 23 tumor and normal tissues in transition zone (TZ). HC model was optimized by assessing the combinations of several dissimilarity and linkage methods. Goodness of HC model was validated by internal methods. Accuracy for differentiating tumor and normal tissue by optimal HC model was 96.3% in PZ and 97.8% in TZ, comparable to current clinical standards. Relationship between input (DWI and permeability parameters) and output (tumor and normal tissue cluster) was shown by heat maps, consistent with literature. HC can accurately differentiate PCa and normal tissue, comparable to state-of-the-art diffusion based parameters. Contrary to DL techniques, HC is an operator-independent ML technique producing results that can be interpreted such that the results can be knowledgeably judged.


A comparison of procedures in teaching self-help skills: increasing assistance, time delay, and observational learning.
The effectiveness and efficiency of two prompt-fading procedures were compared during the instruction of two self-help skills to four pairs of developmentally delayed preschoolers. In addition, the effect of observational learning was examined. Within a combined multiple probe and parallel treatments design, one member of each pair received direct instruction on the two skills. One skill was taught using an increasing assistance prompting procedure and the other skill was taught using a constant time delay procedure. The other member of the pair was prompted to observe the instruction, but was not taught directly. Reliability of scoring and procedural integrity were estimated, and social validity of outcomes considered. Findings indicated a slight but discernible advantage of using the time delay procedure rather than the increasing assistance procedure to teach complex, chained-response tasks. Further, considerable learning resulted solely from the observation of instruction.


Risk factors for wheezing in primary health care settings in the tropics.
The International Study of Wheezing in Infants (EISL) is a cross-sectional, population-based study, based on ISAAC (http://www.isaac.auckland.ac.nz). It uses a validated questionnaire on early wheezing and risk/protective factors. To apply the EISL questionnaire regarding wheezing events in 0- to 12-month-old infants with or without atopic background searching for risk factors in the tropics. The population was toddlers coming in for a checkup or 12-months' vaccination in primary health care clinics of a tropical city. Apart from child factors (eg, daycare attendance), we evaluated home factors (eg, air conditioning, bathroom, carpet, >6 persons, pollution) and mothers' factors (eg, education level, employment, cellphone). Data analysis was descriptive and case-control, with as cases atopic (AW) or non-atopic (NAW) wheezing children vs healthy controls. Wheezing-associated factors were evaluated using multivariate analysis, adjusted for the relation of AW/NAW with factors that were significant in prior univariate analysis. The study included 999 toddlers. Any wheeze: 31.3%, recurrent wheeze (≥3 episodes): 12.1%. Major risk factors for AW (OR; 95%CI) included smoking (11.39; 2.36-54.99), common cold before 3 months of life (3.72; 2.59-5.36), mold (3.48; 2.28-5.30), kitchen indoors (2.40; 1.27-4.54), and pets (1.69; 1.09-2.62); breastfeeding was almost protective. For NAW, common cold and pets were risk factors, but cesarean section (0.44; 0.23-0.82), more than 1 sibling (0.33; 0.18-0.61), and breastfeeding for longer than 3 months (0.50; 0.28-0.91) were protective. Wheezing is a health care burden. We found potential new risk factors for AW, some possibly unique for tropical climates. We suggest testing several hypotheses: could early AW be reduced in the tropics by attacking mold growth? Enhancing cooking place ventilation? Keeping pets outside? Or by postponing daycare attendance until after 4 months of age and avoiding (passive) smoking during pregnancy?


Pain-relieving effects of processed Aconiti tuber in CCI-neuropathic rats.
Neuropathic pain is often refractory to conventional pain therapies and thus requires exploration of effective drugs. We evaluated if processed Aconiti tuber (PAT), a traditional oriental herbal medicine that has been used as an analgesic, relieves neuropathic pain in the rat chronic constriction injury (CCI) model. Ten to 14 days after CCI in the right hind paw, six groups of rats received oral placebo, or PAT at 0.5, 1, 2, 3, or 5 g/kg. Additional groups received oral PAT, 2 g/kg, after pretreatment with intraperitoneal naloxone; intraperitoneal nor-binaltorphimine (norBNI); or intrathecal norBNI. As indicators of mechanical allodynia and thermal hyperalgesia, the pressure threshold of paw withdrawal (PWT) in response to linearly increasing pressure, and latency to paw withdrawal (PWL) in response to radiant heat, were measured before and after drug administration. Oral PAT dose-dependently increased PWT and PWL, which had been decreased due to CCI. The increases in PWT and PWL by oral PAT were inhibited by intraperitoneal and intrathecal norBNI: a selective kappa-opioid receptor antagonist, but not by intraperitoneal naloxone. These results indicate that oral PAT can alleviate mechanical allodynia and thermal hyperalgesia, dose-dependently, via spinal kappa-opioid receptor mechanisms in a rat CCI neuropathic pain model.


Prevalence of a Salmonella subspecies diarizonae in Norwegian sheep herds.
We studied the prevalence of Salmonella enterica subspecies diarizonae serovar 61:k:1,5,(7) (S. IIIb 61:k:1,5,(7)) in 133 Norwegian sheep herds from throughout the country. We used a nested case-control study to identify major risk factors. Two pooled samples (one from lambs and one from adult sheep) were collected from each herd from (10 different) abattoirs. The regional prevalence varied from 0 to 45%, and was more prevalent in adults than in lambs. Sixteen of the 133 herds tested positive to S. IIIb 61:k:1,5,(7), and these positive herds were included in the questionnaire-based nested case-control part of the study. The controls were stratified according to abattoir. Above-median herd size, having white crossbreed sheep, and higher annual replacement percentage were the most evident risk factors.


Influence of perinatal deltamethrin exposure at distinct developmental stages on motor activity, learning and memory.
Perinatal exposure to deltamethrin (DM) causes attention-deficit/ hyperactivity disorder-like behaviors. However, the vulnerable time window to DM exposure and the possible mechanism are obscure. We aimed to identify the critical window(s) at perinatal stages for DM exposure and the possible mechanism. Pregnant mice were exposed to DM (0.5 mg/kg) at three different prenatal stages [gestational day (GD) 0-5, 6-15 and 16-birth (16-B)] and early postnatal stage (PD 0-10). Locomotor activity, learning and memory were evaluated using open field and Y-maze test, respectively. Nissl staining and western blots were used to examine the neuronal loss and the protein expression, respectively. Perinatal exposures to DM had no effect on reproductive and growth index of offspring. However, mice receiving DM exposure during GD 16-B displayed significantly higher mortality suggesting GD 16-B is the most vulnerable time window to DM exposure. Prenatal but not early postnatal DM exposure impaired locomotor activity, learning and memory, and caused neuron loss in the dentate gyrus of male offspring. However, neither prenatal nor postnatal DM exposure affected mouse behavior of female offspring. Prenatal DM exposures decreased the protein levels of NR2A and NR2B in both hippocampi and cerebral cortices of male offspring. However, female mice receiving DM exposure at GD 16-B but not other stages displayed increased expression levels of NR2A and NR2B in hippocampi. Prenatal but not early postnatal DM exposure impairs the neuron development in male but not female mice. Altered NMDA receptor expression may correlate to DM-induced behavioral deficits.


Effect of the antioxidant action of Ginkgo biloba extract (EGb 761) on aging and oxidative stress.
Aging is responsible for oxidative damage to DNA, protein, lipid, and other macromolecules linked to tissue alterations. The resultant damage contributes significantly to degenerative diseases, to include those of the brain, sensorial tissues, and cardiovascular system. To protect cellular components from oxyradical attack, especially lipoperoxidation, a substantial interest in the use of antioxidants has evolved. A free radical scavenger, Ginkgo biloba extract (EGb 761) may be effective in fighting the oxidative stress related to aging. Many data support the efficacy of EGb 761 in biological model systems. In aging processes, EGb 761 may ameliorate the mitochondria respiratory chain function by quenching the superoxide anion, and the hydroxyl and peroxyl radicals. It protects the brain by facilitating the uptake of neurotransmitters and by reducing ischemia-reperfusion episodes and level of apoptosis. Moreover, in sensorial tissues, EGb 761 reduces apoptosis in the olfactive bulb and in the retinal pigmented epithelium of the eye, and protects against the lipoperoxidation alteration of the retina that results in a decrease of the electroretinogram response. In the cardiovascular system, by a direct effect on oxidative low density lipoproteins, EGb 761 may decrease atherosclerosis evolution, and is shown to accelerate cardiac mechanical recovery after ischemia-reperfusion. In conclusion, the antioxidant effects of EGb 761 noted in many experimental data, may explain the therapeutic efficacy observed in clinical trials of the elderly. These beneficial properties seem in part to come from the activity of EGb 761 constituents, such as flavonoids and terpens.


Hemangiopericytoma of the median nerve.
This is a case report of a hemangiopericytoma located within the median nerve at the wrist in a 79-year-old man. The tumor was removed without loss of function.


[Exploratory eye movement in children with ADHD].
To explore the character of the exploratory eye movement in ADHD children. The eye mark recorder (model IV) was used to record the eye movements in 33 ADHD children and 33 normal controls matched by age and sex, using t-test to compare the differences of the numbers of eye fixations, total eye scanning lengths, mean eye scanning lengths, cognitive search scores, responsive search scores and D values between the two groups. ADHD children showed significantly fewer frequent numbers of eye fixations and longer mean eye scanning lengths than the normal controls. The responsive search score of ADHD children was significantly lower than that of the control group. ADHD children had a positive D value and the normal controls had a negative D value. ADHD children had fewer frequent numbers of eye fixation, longer mean eye scanning length and lower responsive search score than the normal controls, which may be the evidence of executive dysfunctions.


Role of Stress-Induced Proteins RpoS and YicC in the Persistence of Salmonella enterica subsp. enterica Serotype Typhimurium in Tomato Plants.
Understanding the functional role of bacterial genes in the persistence of Salmonella in plant organs can facilitate the development of agricultural practices to mitigate food safety risks associated with the consumption of fresh produce contaminated with Salmonella spp. Our study showed that Salmonella enterica subsp. enterica serotype Typhimurium (strain MDD14) persisted less in inoculated tomato plants than other Salmonella Typhimurium strains tested (JSG210, JSG626, JSG634, JSG637, JSG3444, and EV030415; P < 0.01). In-vitro assays performed in limited-nutrient conditions (growth rate, biofilm production, and motility) were inconclusive in explaining the in-planta phenotype observed with MDD14. Whole-genome sequencing combined with non-synonymous single nucleotide variations analysis was performed to identify genomic differences between MDD14 and the other Salmonella Typhimurium strains. The genome of MDD14 contained a truncated version (123 bp N-terminal) of yicC and a mutated version of rpoS (two non-synonymous substitutions, i.e., G66E and R82C), which are two stress-induced proteins involved in iron acquisition, environmental sensing, and cell envelope integrity. The rpoS and yicC genes were deleted in Salmonella Typhimurium JSG210 with the Lambda Red recombining system. Both mutants had limited persistence in tomato plant organs, similar to that of MDD14. In conclusion, we demonstrated that YicC and RpoS are involved in the persistence of Salmonella in tomato plants in greenhouse conditions and, thus, could represent potential targets to mitigate persistence of Salmonella spp. in planta. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Increased serum phospholipase A2 activity after non-heart-beating donor liver transplantation and association with ischemia-reperfusion injury.
Secretory phospholipase A(2) (sPLA(2)) degrades cell membrane phospholipids and plays an important role in the synthesis of pro-inflammatory lipid mediators (arachidonic acid and cytokines) during inflammatory events such as ischemia-reperfusion injury after liver transplantation (LTx). A role for sPLA(2) in LTx from non-heart-beating donors (NHBD) has never been demonstrated. Furthermore data on the natural sPLA(2) inhibition capacity are scarce. Using our previously validated pig model of NHBD-LTx, we evaluated changes in sPLA(2) enzyme activity in serum early after reperfusion of livers exposed to warm ischemia. Porcine livers were exposed to incremental periods of warm ischemia, procured, and transplanted after 4 h of cold storage. In serum samples, collected prior to and after reperfusion, sPLA(2) enzyme activity, tumor necrosis factor-alpha, and interleukin-6 levels were determined. After reperfusion, sPLA(2) activity increased and peaked significantly at 60 min in recipients with primary nonfunction (PNF). Tumor necrosis factor-alpha and interleukin-6 peaked later (at 180 min) in these PNF recipients. We observed a strong natural inhibition of sPLA(2) activity in serum at baseline; this inhibition was substantial reduced 1 h after reperfusion in both PNF and non-PNF recipients. In the non-PNF recipients, however, this natural PLA(2) inhibition was restored within 24 h after reperfusion. This study suggests that an increased sPLA(2) activity and a reduced inhibition may play an important role in the pathogenesis of ischemia-reperfusion injury of NHBD liver grafts.


A clinical study on Pandu Roga, iron deficiency anemia, with Trikatrayadi Lauha suspension in children.
Nutritional iron deficiency is the most common cause of anemia in India. The nearest correlation of iron deficiency anemia (IDA) can be made with Pandu Roga in Ayurveda. As the IDA is a very common prevalent disease in the society and the side effects of oral allopathic iron preparations are very common, therefore to get a better alternative, an Ayurvedic herbomineral medicine, the Trikatrayadi Lauha, was subjected to a clinical trial in children suffering from IDA. Evaluation of safety and efficacy of the compound Trikatrayadi Lauha suspension in children with IDA. Randomized, double-blind placebo-controlled clinical study. The study was conducted on 123 children of IDA for a period of 10 weeks. Clinical features and hematological parameters were documented before, during and after treatment. Observations of the study were analyzed and findings were evaluated by using statistical methods (Student's t test) The present study shows that the trial drug Trikatrayadi Lauha suspension is effective to improve clinical features and hematological parameters significantly. The medicine is effective to increase the hemoglobin level 1.94 g/dL (8.52 -10.46 g/dL, P < 0.001) in 5 weeks and 3.33g/dL (8.52 -11.85g/dL, P < 0.001) in 10 weeks. No adverse effect of the trial drug was observed during the study. The results suggest that Trikatrayadi Lauha is significantly effective in the management of IDA in children.


Coverage and factors associated with tetanus toxoid vaccination status among females of reproductive age in Peshawar.
To estimate the coverage and determine the factors associated with tetanus toxoid vaccination status among females of reproductive age. Cross-sectional study. District Peshawar, NWFP, from July to September 2002. A total of 646 females of reproductive age (15-49) years were selected from both urban and rural areas of Peshawar through stratified cluster sampling. A pre-tested structured questionnaire was administered to females. Two logistic regression models were built, one for all females and one for married females only. Overall 65.0% females were vaccinated (95% confidence interval (CI) (61.3%, 68.6%). For all females, the variables that were significantly associated with vaccination status were marital status (OR= 8.5, 95% CI (4.7, 15.6)), source of information regarding tetanus toxoid (TT) vaccination, knowledge regarding TT vaccination, visits of lady health worker (LHW) to a household (OR = 2.3, 95% CI (1.4, 3.9) and restriction on TT vaccination (OR = 28.7, 95% CI (3.5, 237.9)). For the married females, the variables that were significantly associated with vaccination status were source of information; visits of LHW to a household (OR = 2.8, 95% CI (1.5 to 5.2)) and an interaction between knowledge regarding TT vaccination and antenatal care visits. These findings are of public health concern as a majority of females is not vaccinated according to WHO recommendations. It is recommended that maternal and neonatal tetanus (MNT) vaccination campaigns should include lady health workers at implementation stage.


Utilization of isoniazid prophylaxis therapy and its associated factors among HIV positive clients taking antiretroviral therapy at Fre Semaetat primary hospital, Hawzien districts, Tigrai, Northern Ethiopia.
Isoniazid prophylaxis therapy is a significant public health intervention to prevent the progression of latent tuberculosis to active tuberculosis disease among people living with HIV. Those with HIV are at high risk to develop active Tuberculosis from latent Tuberculosis than those without HIV. Even though there is strong evidence supporting Isoniazid Prophylaxis therapy for Tuberculosis prevention, there is limited information about the implementation of isoniazid prophylaxis therapy in Ethiopia as well as in the study area. To determine the effects of Isoniazid Prophylaxis therapy and its associated factors among HIV positive clients taking antiretroviral therapy at Fre Semaetat primary Hospital, Hawzien districts, Tigray, northern Ethiopia. Institutional based cross-sectional study design was conducted from April to August 2019 among HIV positive clients who came to Fre Semaetat primary Hospital. Data related to socio-demographic characteristics and associated risk factors were taken from 372 HIV positive clients who were selected by a simple random sampling method. Data was coded and cleaned by using SPSS version 23.0 for the final analysis. A total of 372 HIV positive clients taking antiretroviral therapy were included in the study. Of those, the overall prevalence that took and completed their Isoniazid Prophylaxis therapy for 6 months was found to be 231(62.1%). From those who completed Isoniazid Prophylaxis therapy (IPT), 13(3.5%) was developed active Tuberculosis (TB) incidence. Gender, co-trimexazol Prophylaxis therapy users, HIV positive clients who took Anti-pain and married clients were the predictor among statistically significant variables of Isoniazid Prophylaxis therapy. Isoniazid Prophylaxis therapy utilization found to below. Therefore, health education and counseling of patients who are in their first 2 months of therapy should be strengthened further. Prophylaxis should be given by service providers, medication side effects should be addressed rapidly.


Creative cross-organizational collaboration: coming to a project near you.
Historically, the pharmaceutical industry has provided investors with robust growth and patients with a range of life-enhancing treatments; academic institutions conducted early-stage research largely supported by the government; disease foundations funded projects in their areas of interest; and venture capital built exciting new startups with bold ambitions. Today, those institutions are all facing scientific, economic and operating challenges. As a result, they are experimenting with new organizational and funding models. We consider some of those models in the life sciences in general, as well as in the development and delivery of novel regenerative medicines. In particular, the changing roles of the venture capital and disease foundation communities are considered in the context of academic and commercial collaborations.


Measurement of peak esophageal luminal cross-sectional area utilizing nadir intraluminal impedance.
Multichannel intraluminal impedance (MII) is currently used to monitor gastroesophageal reflux and esophageal bolus clearance. We describe a novel methodology to measure maximal luminal cross-sectional area (CSA) during bolus transport from MII measurements. Studies were conducted in-vitro (test tubes) and in-vivo (healthy subjects). Concurrent MII, high resolution manometry, and intraluminal ultrasound (US) images were recorded 7-cm above the lower esophageal sphincter. Swallows with two concentrations of saline, 0.1 and 0.5 N, of bolus volumes 5, 10, and 15 cc were performed. The CSA was estimated by solving two algebraic Ohm's law equations, resulting from the two saline solutions. The CSA calculated from impedance method was compared with the CSA measured from the intraluminal US images. The CSA measured in duplicate from B-mode US images showed a mean difference between the two manual delineations to be near zero, and the repeatability coefficient was within 7.7% of the mean of the two CSA measurements. The calculated CSA from the impedance measurements strongly correlated with the US measured CSA (R(2) ≅ 0.98). A detailed statistical analysis of the impedance and US measured CSA data indicated that the 95% limits of agreement between the two methods ranged from -9.1 to 13 mm(2) . The root mean square error of the two measurements was 4.8% of the mean US-measured CSA. We describe a novel methodology to measure peak esophageal luminal CSA from the nadir impedance during peristalsis. Further studies are needed to determine if it is possible to measure patterns of luminal distension during peristalsis across the entire length of the esophagus from the MII recordings.


Determination of ibuprofen, naproxen and diclofenac in aqueous samples using a multi-template molecularly imprinted polymer as selective adsorbent for solid-phase extraction.
This study describes the application of multi-template molecularly imprinted polymer (MIP) as selective sorbent in the solid-phase extraction (SPE) of naproxen, ibuprofen and diclofenac from wastewater and river water. MIP was synthesized at 70°C by employing naproxen, ibuprofen and diclofenac as multi-templates, ethylene glycol dimethacrylate, 2-vinyl pyridine and toluene as cross-linker, functional monomer and porogen, respectively. Wastewater and river water samples (pH 2.5) were percolated through SPE cartridge packed with 50mg of the MIP. The cartridge was washed with 2mL of methanol-water 10:90% (v:v) prior to elution with 2mL of acetic acid-acetonitrile 20:80% (v:v). Quantification of eluted compounds was performed with high performance liquid chromatography equipped with photo diode array detection. The detection limits were 0.15, 1.00 and 0.63μgL(-1) for naproxen, ibuprofen and diclofenac, respectively. Recoveries for naproxen, ibuprofen and diclofenac in deionized water spiked at 5 and 50μgL(-1) were greater than 80%. Ibuprofen was the most frequently detected compound with maximum concentrations of 221, 67.9 and 11.4μgL(-1) in wastewater influent, effluent and river water, respectively.


Super-additive interaction of the reinforcing effects of cocaine and H1-antihistamines in rhesus monkeys.
Histamine H1 receptor antagonists can be sedating and have behavioral effects, including reinforcing and discriminative stimulus effects in non-humans, that predict abuse liability. Previous research has suggested that antihistamines can enhance the effects of some drugs of abuse. We have reported a synergistic interaction between cocaine and diphenhydramine (DPH) in a self-administration assay with monkeys. The present study was designed to extend those findings to other combinations of cocaine and DPH, and to the mixture of cocaine and another H1-antihistamine, pyrilamine. Rhesus monkeys were prepared with chronic i.v. catheters and allowed to self-administer cocaine, DPH or pyrilamine alone or as mixtures under a progressive-ratio schedule of reinforcement. Cocaine, DPH and pyrilamine alone maintained self-administration and cocaine was the stronger reinforcer. When cocaine was combined with DPH or pyrilamine in a 1:1, 1:2 or 2:1 ratio of the ED(50)s, the combinations were super-additive as reinforcers. Reinforcing strength of the combinations was greater than that of the antihistamines alone but not greater than cocaine. The data support the prediction that the combination of cocaine and histamine H1 receptor antagonists could have enhanced potential for abuse relative to either drug alone. The interaction may involve dopamine systems in the CNS.


Failure of tacrolimus to prevent aspirin-induced respiratory reactions in patients with aspirin-exacerbated respiratory disease.
In patients with aspirin-exacerbated respiratory disease (AERD), pretreatment with asthma controller medications (leukotriene modifiers, inhaled or systemic corticosteroids, and salmeterol) partially modifies the severity of aspirin-induced asthmatic reactions. A recent study showed that pretreatment with tacrolimus completely prevented aspirin-induced respiratory reactions and might allow silent aspirin desensitization. Ten patients with rhinosinusitis, nasal polyps, and asthma had a history of asthma attacks after ingesting aspirin and nonsteroidal anti-inflammatory drugs. All underwent baseline oral aspirin challenges and had typical respiratory reactions. They were then randomized to receive tacrolimus (0.1 mg/kg weight; 8 patients) or placebo (2 patients) in a double-blind protocol before rechallenge with aspirin using the previous provoking dose of aspirin. In addition, respiratory reactions sustained by 50 consecutive patients with AERD during 2004 were recorded, analyzed, and compared with the tacrolimus/placebo-treated patients to determine whether there were any differences. Tacrolimus pretreatment failed to block respiratory reactions to provoking doses of aspirin in 5 of 8 patients with AERD, and in the other 3 patients did not block higher doses of aspirin. The results of oral aspirin challenges in the control population of 50 patients were compared with either the baseline or postchallenge data from the tacrolimus-pretreated or placebo-pretreated patients with AERD, and there were no significant differences. Use of tacrolimus as add-on pretreatment to prevent reactions to aspirin in patients with AERD or to achieve the goal of silent aspirin desensitization could not be accomplished.


The role of antibiotic prophylaxis in mesh repair of primary inguinal hernias using prolene hernia system: a randomized prospective double-blind control trial.
Antibiotic prophylaxis is being commonly used in mesh repair of inguinal hernia but its role has been questioned in a recent Cochrane analysis performed in 2003. Routine use of antibiotic prophylaxis in mesh repair of inguinal hernia can lead to bacterial resistance and increase in cost. In a present double-blind placebo controlled trial involving 120 patients undergoing inguinal hernia repair using prolene hernia system, we did not find any benefit of the routine use of antibiotic prophylaxis in terms of wound infection rate.


The cell biology of vision.
Humans possess the remarkable ability to perceive color, shape, and motion, and to differentiate between light intensities varied by over nine orders of magnitude. Phototransduction--the process in which absorbed photons are converted into electrical responses--is the first stage of visual processing, and occurs in the outer segment, the light-sensing organelle of the photoreceptor cell. Studies of genes linked to human inherited blindness have been crucial to understanding the biogenesis of the outer segment and membrane-trafficking of photoreceptors.


Growth and physicochemical properties of L-phenylalaninium maleate: a novel nonlinear optical crystal.
Single crystals of novel organic nonlinear optical material, L-phenylalaninium maleate (LPM) having dimensions up to 10 × 6 × 6 mm(3) were grown by slow evaporation solution growth technique at room temperature. The grown crystals were confirmed by single crystal X-ray diffraction studies and the various functional groups were identified by FT-IR spectroscopic analysis. The optical properties were studied by optical absorption, second harmonic generation (SHG), photoconductivity and photoluminescence (PL) studies and reported for the first time. The optical band gap energy and SHG efficiency were found to be 4.85 eV and 1.5 times higher than KDP crystals. Negative photoconducting nature was confirmed by photoconductivity studies. Photoluminescence studies confirm the suitability of the sample for blue and green radiations. The title compound was also subjected to TG/DTA analysis and dielectric studies. Layer like growth pattern was analyzed by SEM micrograph.


High-resolution array-based comparative genomic hybridization of bladder cancers identifies mouse double minute 4 (MDM4) as an amplification target exclusive of MDM2 and TP53.
Loss of p53 function in urothelial cell carcinoma (UCC) by mutation or inactivation disrupts normal cell cycle checkpoints, generating a favorable milieu for genomic instability, a hallmark of UCC. The aim of this study was to characterize novel DNA copy number changes to identify putative therapeutic targets. We report our findings using array comparative genomic hybridization on a whole-genome BAC/PAC/cosmid array with a median clone interval of 0.97 Mb to study a series of UCC cases. TP53 status was determined by direct sequencing, and an in-house tissue microarray was constructed to identify protein expression of target genes. Array comparative genomic hybridization allowed identification of novel regions of copy number changes in addition to those already known from previous studies. A novel amplification previously unreported in UCC was identified at 1q32. A chromosome 1 tile path array was used to analyze tumors that showed gains and amplification; the mouse double minute 4 (MDM4) homologue was identified as the amplified gene. MDM4 mRNA expression correlated with copy number and tumor grade. Copy number changes of MDM4 and MDM2 occurred exclusively in tumors with wild-type p53. Overexpression of MDM4 corresponded to disruption of p53 transcriptional activity. Immunohistochemistry on an independent series by tissue microarray identified an inverse relationship between Mdm4 and Mdm2, with Mdm4 expression highest in invasive UCC. The data indicate that gain/amplification and overexpression of MDM4 is a novel molecular mechanism by which a subset of UCC escapes p53-dependent growth control, thus providing new avenues for therapeutic intervention.


Fitting methods for constructing energy-dependent efficiency curves and their application to ionization chamber measurements.
An ionization chamber without and with an iron liner (absorber) was calibrated by a set of radionuclide activity standards of the Physikalisch-Technische Bundesanstalt (PTB). The ionization chamber is used as a secondary standard measuring system for activity at the Slovak Institute of Metrology (SMU). Energy-dependent photon-efficiency curves were established for the ionization chamber in defined measurement geometry without and with the liner, and radionuclide efficiencies were calculated. Programmed calculation with an analytical efficiency function and a nonlinear regression algorithm of Microsoft (MS) Excel for fitting was used. Efficiencies from bremsstrahlung of pure beta-particle emitters were calibrated achieving a 10% accuracy level. Such efficiency components are added to obtain the total radionuclide efficiency of photon emitters after beta decay. The method yields differences of experimental and calculated radionuclide efficiencies for most of the photon-emitting radionuclides in the order of a few percent.


Feasibility and diagnostic accuracy of an electronic nose in children with asthma and cystic fibrosis.
The measurement of volatile organic compounds (VOCs) in exhaled breath is a promising tool for diagnosing and monitoring various lung diseases in children. Gas chromatography mass spectrometry (GC-MS) analysis is a frequently used standard technique for VOCs analysis. However, as GC-MS is an expensive and time-consuming technique, hand-held devices or electronic noses have been developed. Recently, the Aeonose was introduced as an easy-to-use hand-held eNose capable of point-of-care testing. Although first results using this eNose in adults are promising, studies in children are lacking. We therefore performed a cross-sectional study in 55 children and adolescents ≥6 years of age (20 children with moderate to severe asthma, 13 children with CF, and 22 healthy controls). The feasibility of the Aeonose was high (>98% successful measurements). The diagnostic accuracy was high for discriminating asthma from CF (Area Under the Receiver Operating Characteristic Curve [AUC] 0.90 [95% Confidence Interval 0.78-1.00] sensitivity 89% [65%-98%], specificity 77% [46%-94%]), and for the distinction between CF and healthy controls (AUC 0.87 [0.74-1.00], sensitivity 85% [54%-97%], specificity 77% [54%-91%]). However, the diagnostic accuracy for the discrimination between asthma and healthy controls was modest (AUC 0.79 [0.63-0.94], sensitivity 74% [49%-90%], specificity 91% [69%-98%]). This is the first study to report test results of the Aeonose in children and adolescents ≥6 years. This eNose showed a high feasibility with modest to good diagnostic accuracies in asthma and CF. This study was registered at clinicaltrial.gov (NCT03377686).


Therapeutic effects of flunitrazepam in dystonias and torticollis. Preliminary communication.
A new form of clinical treatment is proposed for dystonias and torticollis using flunitrazepam (FN), a powerful agonist of all benzodiazepine receptors of GABA neurons. FN has a specific effect in dystonic patients, specially those in which the hypnotic effect of this drug is absent or diminished, thus suggesting the existence of two different neurochemical categories of dystonias.


Phenotypic defects from the expression of wild-type and pathogenic TATA-binding proteins in new Drosophila models of Spinocerebellar Ataxia Type 17.
Spinocerebellar Ataxia Type 17 (SCA17) is the most recently identified member of the polyglutamine (polyQ) family of disorders, resulting from abnormal CAG/CAA expansion in the TATA box-binding protein (TBP), an initiation factor essential for of all eukaryotic transcription. A largely autosomal dominant inherited disease, SCA17, is unique in both its heterogeneous clinical presentation and low incidence of genetic anticipation, the phenomenon in which subsequent generations inherit longer polyQ expansions that yield earlier and more severe symptom onset. Like other polyQ disease family members, SCA17 patients experience progressive ataxia and dementia, and treatments are limited to preventing symptoms and increasing quality of life. Here, we report 2 new Drosophila models that express human TBP with polyQ repeats in either wild-type or SCA17 patient range. We find that TBP expression has age- and tissue-specific effects on neurodegeneration, with polyQ-expanded SCA17 protein expression generally having more severe effects. In addition, SCA17 model flies accumulate more aggregation-prone TBP, with a greater proportion localizing to the nucleus. These new lines provide a new resource for the biochemical characterization of SCA17 pathology and the future identification of therapeutic targets.


Biosynthesis and preparation of T-2 Toxin, HT-2 Toxin and Neosolantol.
Biosynthesis of trichothecenes by strains ofF. sporotriahioides KF 9 6 and KF 530 was performed on rice as a medium. Three toxins in significant amounts were produced, with yield: T-2 toxin 0.7g from 600g of drv culture, being the highest of the three metabolites, HT-2 toxin 0.06g an Neosolaniol 0.015g. Toxins were extracted with methanol from ground and defatted dry culture. Liquid/liquid partition, using chloroform/water saturated solution of sodium bicarbonate as a preliminary purification was applied. Silicagel and charcoal columns were used in further purification. Toxin were separated by preparative TLC and crystallized from methanol.


Spectrofluorimetric determination of famotidine in pharmaceutical preparations and biological fluids. Application to stability studies.
A simple, economic, selective, and stability indicating spectrofluorimetric method was developed for the determination of famotidine (FMT); is based on its reaction with 9, 10-phenanthraquinone in alkaline medium to give a highly fluorescent derivative measured at 560 nm after excitation at 283 nm. The fluorescence intensity-concentration plot was rectilinear over the concentration range of 50-600 ng/ml with minimum quantification limit (LOQ) of 13.0 ng/ml and minimum detection limit (LOD) of 4.3 ng/ml. The factors affecting the development of the fluorescence intensity of the reaction product were carefully studied and optimized. The method was applied for the determination of FMT in its dosage forms. The stability of the compound was studied, and the proposed method was found to be stability indicating one. The results obtained were in good agreement with those obtained by the official method. Furthermore, the method was applied for the determination of FMT in spiked and real human plasma. The mean % recovery (n = 4) was found to be 99.94 +/- 0.24, and 105.13 +/- 0.64 for spiked and real human plasma, respectively. The composition of the reaction product as well as its stability constant was also investigated. Moreover, the method was utilized to investigate the kinetics of both alkaline and oxidative induced degradation of the drug. The apparent first order rate constant and half life time of the degradation product was calculated. A proposal of the reaction pathway was postulated.