Gastrin stimulated H+ secretion in amphibian gastric mucosa: effect of tetrodotoxin.
The role of neural mechanisms in gastrin stimulated H+ secretion was studied using amphibian gastric fundic mucosa. Spontaneously secreting mucosae were converted to resting state (zero H+ secretory rate) using Burimamide. Following removal of burimamide, 3 X 10(-6) M tetrodotoxin did not block gastrin stimulation of H+ secretion indicating that neural mechanisms are not required.


Clonal chromosome abnormalities in a so-called Dupuytren's subungual exostosis.
We report the first cytogenetic investigation of a Dupuytren's subungual exostosis. The clonal abnormalities found suggest that at least some of these heterotopic ossifications could be neoplastic in nature, instead of being a purely reactive process or exuberant growth in response to trauma.


Three new sesquiterpene lactone dimers from Carpesium macrocephalum.
Three new sesquiterpene lactone dimers (SLDs), carpedilactones E-G (1-3), together with two known monomeric units, ivalin (4) and alantolactone (5), were isolated from the acetonic extract of Carpesium macrocephalum. Their chemical structures were elucidated by IR, UV, HR-ESI-MS, NMR 1D and 2D experiments, and the absolute configuration of 1-3 was resolved according to the (1)H NMR and CD spectrographic features of 1,3-/2,4-linked SLDs. Furthermore, 1 was unambiguously confirmed by Cu-Kα X-ray crystallographic analysis. Additionally, compounds 1 and 2 were revealed with potent cytotoxicities against human colon cancer HCT116 cells with IC50 values of 2.27 and 3.30 μM, respectively.


[Care guidance and management of cooperative healthcare networks].
Selective agreements offer the possibility to the health insurers to influence the control of care, a chance that they urgently need because of cost pressure. The concepts of care can be developed top-down and then a health insurer can make an offer. Or these concepts are developed bottom-up that means a chance for the healthcare providers who want to actively shape the medical care. An essential component for all these concepts is to be able to calculate and administrate funding and control. Pathways are necessary for controlling the treatment which not only have to be developed but also have to be put into practice. The pathway acute sacroiliac pain developed by the Lübeck doctors' network will be described here as an example of a successful implementation.


[Stereotactic body radiation therapy for spine bone oligometastatic disease].
Stereotactic radiotherapy is an ever more common technique, regardless of the location treated. However, spinal stereotactic radiotherapy requires a particular technicality in order to ensure its proper realization. There is now a large literature defining the type of imaging to be used, the dose to be delivered and the delineation of target volumes. This technique can achieve a significant local control and an interesting analgesic efficiency. However, its place in relation to conventional radiotherapy remains limited because it requires MRI imaging and a significantly longer patient management during the treatment fraction. In this context, it is currently mainly restricted to oligometastatic patients or for re-irradiations.


Cell-mediated immunity to chemically xenogenized tumors--III. Generation of monoclonal antibodies interfering with reactivity to novel antigens.
To develop monoclonal antibodies (MAbs) recognizing drug-mediated tumor antigens on a chemically xenogenized murine lymphoma, hybridomas were constructed with splenocytes from histocompatible mice hyperimmunized with L5178Y cells antigenically altered by triazene treatment in vivo (clone D, derived from a polyclonal L5178Y/DTIC subline). Screening of supernatants with parental and xenogenized cells showed that nine MAbs displayed exclusive or preferential reactivity with clone D cells as detected by immunofluorescence, and failed, as a rule, to bind normal or unrelated malignant cells of the same or different haplotype. Moreover, no reactivity was displayed to the triazene-xenogenized variants of antigenically unrelated tumors. All nine MAbs, however, were capable of binding a panel of L5178Y/DTIC clones in addition to clone D. When the ability of these antibodies to interfere with the development of cell-mediated immunity to clone D cells in vitro was tested, it was found that the proliferative reaction and generation of cytolytic activity by syngeneic lymphocytes were inhibited by addition of several MAbs to the tumor--lymphocyte co-cultures.


Comparison of two ventilators used with the T-piece in paediatric anaesthesia.
The Nuffield 200 ventilator was compared with a new valveless ventilator (CW 200) in 20 children undergoing general anaesthesia for paediatric surgery. The new ventilator incorporates design features which overcome the main disadvantages of the Nuffield 200 and make it an inherently safer machine. At identical ventilator settings it produced a significantly greater tidal volume with a reduction in end-tidal carbon dioxide partial pressure. This may have advantages in avoiding pulmonary barotrauma in children.


Serum glypican4 and glycosylphosphatidylinositol-specific phospholipase D levels are associated with adipose tissue insulin resistance in obese subjects with different glucose metabolism status.
Glypican4 (GPC4) is a novel adipokine associated with obesity and insulin resistance. GPC4 was cleaved by the glycosylphosphatidylinositol-specific phospholipase D (GPLD1) in an anchored site of the glycosylphosphatidylinositol, and then was released into the extracellular environment. Herein, we investigated the changes of serum GPC4 and GPLD1 levels in obese subjects with different glucose metabolism status and their relationship with adipose tissue insulin resistance index (Adipo-IR) in Chinese north populations. A total of 221 obese subjects and 37 normal controls (NC) were recruited in this study. Obese subjects were divided into normal insulin (NI) group, hyperinsulinemia (HI) group, impaired glucose tolerance (IGT) group, and type 2 diabetes mellitus (DM) group. Serum GPC4, GPLD1, and adiponectin were determined by commercially available ELISA kits. Serum GPC4 levels in the HI, IGT, and DM groups were significantly higher than those in the NC and NI groups (2.27 ± 0.58 ng/mL, 2.21 ± 0.60 ng/mL, 2.49 ± 0.67 ng/mL vs. 1.70 ± 0.33 ng/mL, 1.93 ± 0.34 ng/mL, P < 0.05). GPC4 was positively correlated with GPLD1, which was the most important influencing factor of GPC4. Adipo-IR was independently and positively associated with serum GPC4 and GPLD1. For GPC4, after adjustment for confounders, the risk of adipose tissue insulin resistance in subjects with the highest tertile was 2.974-fold that of those with the lowest tertile (OR = 2.974, P = 0.013). For GPLD1, before adjustment for lipids, the increased probability still existed (Model 2, OR = 3.568, P = 0.003). GPC4 is an adipokine associated with adipose tissue insulin resistance, and its activity may be regulated by GPLD1. GPC4 may be a marker for adipose tissue insulin resistance in Chinese north obese populations.


Modular Monomers with Tunable Solubility: Synthesis of Highly Incompatible Block Copolymer Nano-Objects via RAFT Aqueous Dispersion Polymerization.
The high incompatibility of block copolymers consisting of a neutral stabilizer block and a polyelectrolyte core-forming block is exploited to drive phase segregation during polymerization-induced self-assembly (PISA). A modular approach to systematically tune the solubility of ionic monomers/polymers is developed to efficiently identify monomers suitable for aqueous dispersion polymerizations. The strong phase segregation ability of the neutral-polyelectrolyte block copolymers favors the formation of worms over a relatively broad composition range and even at very low solids. These findings suggest that the degree of incompatibility between the stabilizer block and the core-forming block should be considered as one of the key parameters when studying morphological transitions in PISA.


[Experimental study on berberin raised insulin sensitivity in insulin resistance rat models].
To observe the effects of berberin on insulin sensitivity in high fat diet rats. Before and after ingesting berberin, glucose insulin tolerance test was used to measure the insulin sensitivity, and determining fasting blood glucose, insulin, blood lipid and muscle triglyceride content. Compared with normal feeding rats, high fat feeding impaired insulin action (5.02 +/- 1.08 vs 8.72 +/- 0.91, P < 0.005), decreased liver glycogen level and raised fasting blood glucose, insulin and blood lipid levels. Berberin and metformin improved insulin resistance (6.31 +/- 0.95 and 6.24 +/- 0.65) and liver glycogen level in insulin resistance models, but had no effect on blood glucose, insulin, lipid levels and muscle triglyceride depots. It is confirmed that berberin could raise insulin sensitivity of high fat diet rats similar to metformin.


Inhibition of the Akt/NF-κB pathway is involved in the anti-gastritis effects of an ethanolic extract of the rhizome of Atractylodes macrocephala.
Gastritis can lead to ulcers and the development of gastric cancer. The rhizome of Atractylodes macrocephala Koidz. (Asteraceae), a traditional Chinese medicinal herb, is prescribed for the treatment of gastric disorders, hepatitis and rheumatism. Its bio-active compounds are considered to be particularly effective in this regard. However, the molecular processes of the herb's anti-inflammatory activity remain obscure. This study elucidates a mechanism upon which an ethanolic extract of this herb (Am-EE) exerts anti-inflammation effects in RAW264.7 macrophage cells (RAW cells) stimulated by lipopolysaccharide (LPS) treatment and HCl Ethanol-stimulated gastritis rats. To investigate the anti-gastritis activities of Am-EE and explore the mode of action. Ethanol (95%) was used to prepare Am-EE. The quality of the extract was monitored by HPLC analysis. The in vivo effects of this extract were examined in an HCl Ethanol-stimulated gastritis rat model, while LPS-stimulated RAW cells were used for in vitro assays. Cell viability and nitric oxide (NO) production were observed by MTT and Griess assays. Real-time PCR was used to examine mRNA expression. The PGE2 ELISA kit was employed to detect prostaglandin E2 (PGE2). Enzyme activities and protein contents were examined by immunoblotting. Luciferase reporter gene assays (LRA) were employed to observe nuclear transcription factor (NF)-κB activity. The SPSS (SPSS Inc., Chicago, Illinois, United States) application was used for statistical examination. HPLC analysis indicates that Am-EE contains atractylenolide-1 (AT-1, 1.33%, w/w) and atractylenolide-2 (AT-2, 1.25%, w/w) (Additional Figure. A1). Gastric tissue damage (induced by HCl Ethanol) was significantly decreased in SD rats following intra-gastric application of 35 mg/kg Am-EE. Indistinguishable to the anti-inflammation effects of 35 mg/kg ranitidine (gastric medication). Am-EE treatment also reduced LPS-mediated nitric oxide (NO) and prostaglandin E2 (PGE2) production. The mRNA and protein synthesis of inducible cyclooxygenase (COX)-2 and NO synthase (iNOS) was down-regulated following treatment in RAW cells. Am-EE decreased NF-κB (p50) nuclear protein levels and inhibited NF-κB-stimulated LRA activity in RAW cells. Lastly, Am-EE decreased the up-regulated levels of phosphorylated IκBα and Akt proteins in rat stomach lysates and in LPS challenged RAW cell samples. Our study illustrates that Am-EE suppresses the Akt/IκBα/NF-κB pathway and exerts an anti-inflammatory effect. These novel conclusions provide a pharmacological basis for the clinical use of the A. macrocephala rhizome in the treatment and prevention of gastritis and gastric cancer.


Testosterone synthesis by chicken follicular cells.
The roles of theca and of granulosa cells in the synthesis of testosterone (T) in ovarian follicle of hens have been studied. Theca cells alone synthesized no progesterone (P), and no or only negligible amounts of T. Granulosa cells, in contrast, without stimulation produced large amounts of P and small amounts of T. When incubated with ovine gonadotrophins, theca cells showed greater response than granulosa cells in synthesizing more T (2- to 2.5-fold increase). Combination of the two follicular cell types decreased synthesis of P, but increased that of T (9- to 17-fold). When 0.1 microgram of ovine luteinizing hormone (oLH) was added to the combined cells, T concentrations increased most dramatically, a 83-fold increase was seen after 12 h of incubation. Theca cells incubated with exogenous P also produced large amounts of T. These results indicated that in hens, theca cells may be the major site of follicular T synthesis, however, theca cells alone cannot synthesize T unless granulosa cells or P were added. It is suggested that granulosa cells may use P as a precursor, and that P is converted to T in the theca cells.


PRDM10 RCC: A Birt-Hogg-Dubé-like Syndrome Associated With Lipoma and Highly Penetrant, Aggressive Renal Tumors Morphologically Resembling Type 2 Papillary Renal Cell Carcinoma.
To characterize the clinical manifestations and genetic basis of a familial cancer syndrome in patients with lipomas and Birt-Hogg-Dubé-like clinical manifestations including fibrofolliculomas and trichodiscomas and kidney cancer. Genomic analysis of blood and renal tumor DNA was performed. Inheritance pattern, phenotypic manifestations, and clinical and surgical management were documented. Cutaneous, subcutaneous, and renal tumor pathologic features were characterized. Affected individuals were found to be at risk for a highly penetrant and lethal form of bilateral, multifocal papillary renal cell carcinoma. Whole genome sequencing identified a germline pathogenic variant in PRDM10 (c.2029 T>C, p.Cys677Arg), which cosegregated with disease. PRDM10 loss of heterozygosity was identified in kidney tumors. PRDM10 was predicted to abrogate expression of FLCN, a transcriptional target of PRDM10, which was confirmed by tumor expression of GPNMB, a TFE3/TFEB target and downstream biomarker of FLCN loss. In addition, a sporadic papillary RCC from the TCGA cohort was identified with a somatic PRDM10 mutation. We identified a germline PRDM10 pathogenic variant in association with a highly penetrant, aggressive form of familial papillary RCC, lipomas, and fibrofolliculomas/trichodiscomas. PRDM10 loss of heterozygosity and elevated GPNMB expression in renal tumors indicate that PRDM10 alteration leads to reduced FLCN expression, driving TFE3-induced tumor formation. These findings suggest that individuals with Birt-Hogg-Dubé-like manifestations and subcutaneous lipomas, but without a germline pathogenic FLCN variant, should be screened for germline PRDM10 variants. Importantly, kidney tumors identified in patients with a pathogenic PRDM10 variant should be managed with surgical resection instead of active surveillance.


Improving informed consent to chemotherapy: a randomized controlled trial of written information versus an interactive multimedia CD-ROM.
This randomized controlled trial aimed to determine whether an interactive CD-ROM improved cancer patients' recall of chemotherapy treatment information over standard written information, and whether demographic, cognitive, and psychological factors better predicted recall than this format of delivery. One-hundred-and-one new patients about to commence chemotherapy were randomized to receive written information or a CD-ROM containing treatment information before giving informed consent. Patients' recall, concentration, short-term memory, reading comprehension, anxiety, depression, and coping styles were assessed with standardized measures pre-treatment. Seventy-seven patients completed tests for recall of treatment information before their second chemotherapy session. Intention-to-treat analyses indicated no significant differences between the written information and CD-ROM groups across recall questions about number of drugs received (p=.43), treatment length (p=.23), and treatment goal (p=.69). Binary logistic regressions indicated that for groups combined different variables predicted each of the recall questions. An interactive CD-ROM did not improve cancer patients' recall of treatment information enough to warrant changes in consent procedures. Different variables predicted recall of different treatment aspects highlighting the complex nature of attempting to improve patient recall. Attending to the effect of depression on patient knowledge and understanding appears paramount.


Endogenous Aspergillus endophthalmitis in an immunocompetent individual.
We present an unusual case of Aspergillus fumigatus endogenous endophthalmitis in a 27 year old Hispanic male with no history of ocular trauma, surgery, hematologic malignancy, compromised immune system, or intravenous drug use. The patient presented with a two-day history of pain, redness, and visual acuity of bare count fingers in his right eye. He was originally suspected of having toxoplasmic retinochoroiditis, but clinically worsened on systemic anti-toxoplasma medication and corticosteroids. He subsequently underwent pars plana vitrectomy and treatment with intravenous and intravitreal amphotericin B. Aspergillus fumigatus was isolated and identified in the vitreous aspirate. With aggressive medical and surgical management, he eventually regained visual acuity of 20/30 in his right eye. This case illustrates the occurrence of endogenous Aspergillus endophthalmitis in a patient with no history of intravenous drug use, ocular trauma, or compromised immune system, and successful outcome with combined medical and surgical management.


[Students' perceptions comparing standardized and non-standardized oral exams in internal medicine].
Oral examinations are a useful tool to appraise certain medical skills compared to other examinations. However, they have some disadvantages that might be reduced with standardization. To compare students' perception comparing a standardized oral exam (SOE) versus a traditional, non-standardized oral exam (NSOE). During the first semester of 2013 a NSOE was applied to internal medicine undergraduate students. During the second semester, a SOE was applied. An anonymous and voluntary perception questionnaire, consisting in 10 questions based on a 5-level Likert scale, was answered by these students. Statistical analysis was done using the Mann-Whitney U test. Among the 118 students, 50.8% were evaluated using NSOE and 49.2% using SOE. Questionnaire response rate was 84%. Among respondents, 52% took the SOE and 48%, the NSOE. Students evaluated using SOE perceived that the degree of complexity of clinical cases was similar for all examinees (p < 0.05), that exam duration was standardized (p < 0.05), and that grades obtained were less influenced by the clinical site where the exam was taken (p < 0.05). However, anxiety level remained high in both groups, as well as the overall satisfaction experience. Standardization of an oral examination improves the perception of medical students about levels of difficulty, duration and external influences on the final grade.


Common-sense approaches to sharing tabular data alongside publication.
Numerous arguments strongly support the practice of open science, which offers several societal and individual benefits. For individual researchers, sharing research artifacts such as data can increase trust and transparency, improve the reproducibility of one's own work, and catalyze new collaborations. Despite a general appreciation of the benefits of data sharing, research data are often only available to the original investigators. For data that are shared, lack of useful metadata and documentation make them challenging to reuse. In this paper, we argue that a lack of incentives and infrastructure for making data useful is the biggest barrier to creating a culture of widespread data sharing. We compare data with code, examine computational environments in the context of their ability to facilitate the reproducibility of research, provide some practical guidance on how one can improve the chances of their data being reusable, and partially bridge the incentive gap. While previous papers have focused on describing ideal best practices for data and code, we focus on common-sense ideas for sharing tabular data for a target audience of academics working in data science adjacent fields who are about to submit for publication.


Caspar-like gene depletion reduces Leishmania infection in sand fly host Lutzomyia longipalpis.
Female phlebotomine sand flies Lutzomyia longipalpis naturally harbor populations of the medically important Leishmania infantum (syn. Leishmania chagasi) parasite in the gut, but the extent to which the parasite interacts with the immune system of the insect vector is unknown. To investigate the sand fly immune response and its interaction with the Leishmania parasite, we identified a homologue for caspar, a negative regulator of immune deficiency signaling pathway. We found that feeding antibiotics to adult female L. longipalpis resulted in an up-regulation of caspar expression relative to controls. caspar was differentially expressed when females were fed on gram-negative and gram-positive bacterial species. caspar expression was significantly down-regulated in females between 3 and 6 days after a blood feed containing Leishmania mexicana amastigotes. RNA interference was used to deplete caspar expression in female L. longipalpis, which were subsequently fed with Leishmania in a blood meal. Sand fly gut populations of both L. mexicana and L. infantum were significantly reduced in caspar-depleted females. The prevalence of L. infantum infection in the females fell from 85 to 45%. Our results provide the first insight into the operation of immune homeostasis in phlebotomine sand flies during the growth of bacterial and Leishmania populations in the digestive tract. We have demonstrated that the activation of the sand fly immune system, via depletion of a single gene, can lead to the abortion of Leishmania development and the disruption of transmission by the phlebotomine sand fly.


Coagulation effects of cyclosporine in liver transplantation.
Thromboembolic complications have been described in graft recipients receiving cyclosporine (CS). Whether these individuals have a hypercoagulable state when compared to healthy controls was evaluated. Recalcification times (RT) of saline-incubated citrated whole blood and endotoxin-incubated whole blood of both control and transplant patients were determined. There was no difference between the RT saline or RT endotoxin groups in both patient groups. These data suggest that CS alone has no procoagulant effects, but that additional factors such as endotoxin and/or graft-induced antigen production may provoke the thrombotic complications.


Impact of additional intracoronary nicorandil administration during fractional flow reserve measurement with intravenous adenosine 5'-triphosphate infusion.
Fractional flow reserve (FFR) is a useful index for determining the functional severity of epicardial coronary artery stenosis as an invasive physiological method. Although intravenous adenosine 5'-triphosphate (ATP) is generally used as a hyperemic agent for FFR measurement in Japan, there are some concerns about the variability of FFR measurement (short half-life, effect of caffeine, cyclic change). It is difficult to confirm sufficient maximum hyperemia after ATP infusion. Recent studies reported that nicorandil (NIC) could be an alternative to ATP as a hyperemic agent. Patients who underwent FFR assessments of angiographically intermediate lesions were included. All patients were asked to refrain from caffeine-containing products more than 12hours before FFR measurements. All patients first received intravenous (IV) ATP infusion (180μg/kg/min) for 3min to measure FFR (ATP-FFR). After additional intracoronary (IC) NIC administration (2mg/30s) during ATP infusion, FFR was measured again (NIC-FFR). To check cyclic change in FFR, we measured minimum and maximum FFR values during both ATP and NIC hyperemic phase. In this study, 94 patients with 94 lesions were enrolled. Mean FFR value was 0.81±0.10 in ATP-FFR infusion and 0.80±0.09 in NIC-FFR, respectively. ATP-FFR and NIC-FFR had a strong correlation on the whole (r=0.92, p<0.001). In 18 patients (19%), FFR values were significantly lower in NIC-FFR than in ATP-FFR. In one-third of those patients (6%), it was possible to change therapeutic strategy from deferral range (>0.80) to interventional range (≦0.80) after NIC-FFR measurements. Cyclic change in FFR was smaller in NIC-FFR than in ATP-FFR (0.03±0.02 vs. 0.06±0.05, p<0.0001). Additional IC NIC might be useful to confirm sufficient maximum hyperemia after IV ATP infusion in daily clinical practice. Furthermore, IC NIC could reduce cyclic change in FFR; thus, physicians might find it easier to determine FFR value during the procedure.


Shoulder pain and pneumoperitoneum following a diving accident.
We present the case of a diver who experienced the acute onset of shoulder pain after a rapid ascent. It was determined that the patient had decompression sickness ("the bends") of the right shoulder and pulmonary barotrauma resulting in secondary pneumoperitoneum. He underwent decompression, with prompt resolution of symptoms. Of the 14 cases of isolated pneumoperitoneum due to barotrauma reported in the world literature, three were due to gastric rupture. Shoulder pain in association with pneumoperitoneum may be due to diaphragmatic irritation or may be an isolated symptom of decompression sickness. Correctly determining the etiology of these findings is crucial to the appropriate management of the patient.


Evaluation of the teratogenicity of fluorescein sodium.
Pregnant rabbits in their first and second "trimesters" of gestation were used in a controlled study to evaluate the teratogenicity of fluorescein sodium. Injections of the drug were given in doses comparable to those planned for human administration. No abortions or defects apparent at birth or as delayed manifestations were evident as a result of the drug therapy.


Temporal dynamics of neural activity in an integration of visual and contextual information in an esthetic preference task.
While viewing works of art in galleries, we evaluate them by integrating at least two types of information: their visual properties (e.g., colors, symmetry, and proportion) and contextual information accompanying them (e.g., titles and names of artists). How rapidly the brain integrates visual and contextual information of artworks remains to be investigated. Using electroencephalography (EEG), we investigated neural activity when subjects with no professional experience in art viewed images of sculptures (masterpieces from the Classical and Renaissance periods, characterized by a canonical proportion of the golden ratio) and performed a five-scale rating of how appealing they were. At the beginning of each trial, we manipulated the expectations of the subjects for an upcoming sculpture by presenting information about its authenticity (either "genuine" or "fake"), although all images were actually taken from genuine artworks. The image of the sculpture was then presented, either in its original proportion or after being deformed by a photo-editing software. This 2 × 2 factorial design enabled us to identify whether each component of the EEG response was sensitive to contextual information (genuine or fake), visual information (original or deformed), or both. Results revealed that amplitudes of a positive EEG component emerging at 200-300ms after the presentation of the artworks (mainly distributed over the parietal cortex) were significantly modulated by both visual and contextual factors, indicating a rapid integration of these two types of information in the brain.


The variant surface glycoproteins of Trypanosoma equiperdum. Identification of a phosphorylated glycopeptide as the cross-reacting antigenic determinant.
The cross-reacting antigenic determinant in the variant surface glycoproteins (VSGs) of Trypanosoma equiperdum was studied by testing the ability of VSG glycopeptides to bind heterologous anti-VSG sera. VSG glycopeptide purification revealed the presence of 3 oligosaccharide sidechains on the mature VSG. These consist of two sidechains containing only mannose and glucosamine and a third containing galactose and mannose (in a 5:1 ratio) as well as phosphorous and ethanolamine. This phosphorylated fragment completely blocked the binding of VSG to heterologous anti-VSG and therefore contained the cross-reacting determinants.


Rapidly growing giant suprasellar tumor in a high-risk child: treatment strategy and role of neuroendoscopic surgery in slit-like ventricles.
Suprasellar tumors are common in the pediatric population and exhibit a wide range of pathological appearance and behavior. Although rare, pure suprasellar germinomas carry worse prognosis than other locations. We present a case of a 10-year-old girl treated with therapeutic anticoagulation for previous cardiac valvular replacement, who presented with rapidly growing giant (>4 cm) suprasellar germinoma. Neoadjuvant chemotheraphy was effective and the dilated ventricles became slit-like. The fine free-hand maneuver using a fine rigid-rod neuroendoscope. "Oi-Samii Handy Pro" made it possible to obtain the tissue diagnosis. Complete remission was achieved using neoadjuvant chemotherapy, minimally invasive neuroendoscopic surgery, then followed by specific chemoradiotherapy. The role of neuroendoscopic procedure, performed in a difficult situation with normalized size of the ventricles, was emphasized.


Striatal dopamine after cortical injury: a reexamination.
We reevaluated the effects of unilateral sensorimotor cortex ablation on dopamine and dihydroxyphenylacetic acid concentration in the left and right neostriatum. We found no evidence for an asymmetry of either dopamine or dihydroxyphenylacetic acid in control or sham-operated animals and cortical ablation had no effect on dopamine or dihydroxyphenylacetic acid concentrations. These results suggest that the influence of sensorimotor cortex lesions on extrapyramidal function does not involve changes in striatal dopamine concentrations or turnover.


Prior maternal separation stress alters the dendritic complexity of new hippocampal neurons and neuroinflammation in response to an inflammatory stressor in juvenile female rats.
Stress during critical periods of neurodevelopment is associated with an increased risk of developing stress-related psychiatric disorders, which are more common in women than men. Hippocampal neurogenesis (the birth of new neurons) is vulnerable to maternal separation (MS) and inflammatory stressors, and emerging evidence suggests that hippocampal neurogenesis is more sensitive to stress in the ventral hippocampus (vHi) than in the dorsal hippocampus (dHi). Although research into the effects of MS stress on hippocampal neurogenesis is well documented in male rodents, the effect in females remains underexplored. Similarly, reports on the impact of inflammatory stressors on hippocampal neurogenesis in females are limited, especially when female bias in the prevalence of stress-related psychiatric disorders begins to emerge. Thus, in this study we investigated the effects of MS followed by an inflammatory stressor (lipopolysaccharide, LPS) in early adolescence on peripheral and hippocampal inflammatory responses and hippocampal neurogenesis in juvenile female rats. We show that MS enhanced an LPS-induced increase in the pro-inflammatory cytokine IL-1β in the vHi but not in the dHi. However, microglial activation was similar following LPS alone or MS alone in both hippocampal regions, while MS prior to LPS reduced microglial activation in both dHi and vHi. The production of new neurons was unaffected by MS and LPS. MS and LPS independently reduced the dendritic complexity of new neurons, and MS exacerbated LPS-induced reductions in the complexity of distal dendrites of new neurons in the vHi but not dHi. These data highlight that MS differentially primes the physiological response to LPS in the juvenile female rat hippocampus.


Olanzapine counteracts stress-induced anxiety-like behavior in rats.
Atypical antipsychotics, such as olanzapine, have been reported to display anxiolytic properties as shown in several preclinical and clinical studies. Furthermore, several experimental evidences have shown that olanzapine reduces fear and anxiety in activated anxiety-like behavior test such as Geller-Seifter test, ultrasonic vocalization test and stress-induced EtOH consumption. Here, we hypothesized that the anxiolytic action of olanzapine might be due to via an indirect activation of the gamma-amino butyric acid (GABA)-ergic system through 3alpha-hydroxy-5alpha-pregnan-20-one [allopregnanolone (ALLO)], a potent neuroactive steroid that positively modulates the benzodiazepine-gamma-aminobutyric acid type A (GABA(A))/benzodiazepine receptors complex. To address this question, we used a preclinical animal test to screen for novel anxiolytic compounds - the elevated plus-maze (EPM) - in basal condition and after 45 min restrain stress after acute or repeated (21 days) administration of olanzapine (0.5mg/kg, i.p.). In this condition, we therefore study the effect of the 5-alpha-reductase inhibitor finasteride (FIN) (50mg/kg) after co-administration with olanzapine. FIN is an inhibitor of steroidogenic enzymes which acts by inhibiting type II 5-alpha reductase, the enzyme that converts into 5-alpha-reduced metabolites like the GABA(A) positive neuroactive steroid ALLO. Results showed an anxiolytic effect of the acute, but not of the chronic, treatment with olanzapine only in stressed rats. This anxiolytic effect was counteracted by the co-administration with FIN. These evidences suggest that the anxiolytic effects of olanzapine might be due to possible action of olanzapine on steroid function via activation of GABA system.


The effect of finish line preparation and layer thickness on the failure load and fractography of ZrO2 copings.
To prevent tooth weakening or pulp irritation, there is a need for a minimally invasive method of preparing single anterior crowns. Restoration dimensions for reduced coping thicknesses or less invasive finish line preparations are required. The purposed of this in vitro was to study investigate the fracture performance of high-strength zirconia copings, compare knife-edge margins with chamfer finish lines, and examine the effect of reducing the layer thickness from 0.5 mm to 0.3 mm. Y-TZP zirconia copings were manufactured on brass dies of a maxillary central incisor. Forty copings, with 2 layer thicknesses (0.5 and 0.3 mm), and 2 finish line preparations (knife edge and chamfer; n=10) were cemented using a conventional glass ionomer cement and stored in distilled water at 37 degrees C for 24 hours. The copings were vertically loaded until fracture using a universal testing machine. Data were analyzed by 2-way ANOVA (alpha=.05). Fractographic examination was performed using scanning electron microscopy and confocal laser scanning microscopy. A significantly higher mean failure load was measured for knife-edge (0.5 mm, 1110 +/-175 N; 0.3 mm, 730 +/-160 N) versus chamfer (0.5 mm, 697 +/-126 N; 0.3 mm, 455 +/-79 N) preparations (P<.001), and for 0.5-mm versus 0.3-mm thickness layers (P<.001). Knife-edge preparations present a promising alternative to chamfer finish lines; the fracture load required for knife-edge preparations was 38% greater than that required for chamfer preparations, regardless of coping thickness. Reducing the thickness of a single crown coping from 0.5 to 0.3 mm resulted in a 35% reduction in fracture load required for either preparation type.


Measurement of ventricular relaxation. An alternative index of isovolumic relaxation to the time constant.
The time constant (T) is commonly used for representing the isovolumic fall in left ventricular pressure (LVP) because the isovolumic fall is monoexponential under most circumstances. However, the determination of T is cumbersome due to the requirement of a set of LVP versus time values in fitting a monoexponential function. RT64, which is the time from the minimum value of the time derivative of LVP (-dp/dtmax) to 36% of -dP/dtmax, can be derived beat-by-beat, on-line, and may be a simple alternative to T. Through the use of 240 pairs of values derived from six conscious instrumented dogs treated with different cardiovascular active agents, RT64 and T were found to be significantly correlated (r = 0.835, p less than 0.05) according to the equation RT64 = 0.725T + 10.2. In conclusion, RT64 may provide a simple alternative to T in representing the isovolumic relaxation process of the left ventricle.


A convenient procedure for bismuth-mediated Barbier-type allylation of aldehydes in water containing fluoride ions.
A new and convenient procedure for synthesis of homoallylic alcohols in generally good to excellent yields has been developed. The bismuth-mediated Barbier-type allylation of aldehydes (aromatic, aliphatic, alicyclic and heterocyclic) with allyl bromide has been carried out smoothly in water in the presence of fluoride ions.


Molecular Targets of Triple-Negative Breast Cancer: Where Do We Stand?
Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer. Due to its heterogeneity and lack of hormone receptor expression, this subtype is more likely to metastasize and resist treatment attempts than are other forms of breast cancer. Due to the absence of targetable receptors, chemotherapy and breast conserving surgery have been the predominant treatment options for patients. However, resistance to chemotherapy and local recurrence of the tumors is frequent. Emerging immunotherapies have begun to change treatment plans for patients diagnosed with TNBC. In this review, we discuss the various immune pathways identified in TNBC and the role they play as targets for new potential treatment choices. Various therapeutic options that inhibit key pathways in cellular growth cycles, DNA repair mechanisms, epithelial mesenchymal transition, and immunosuppression have been shown to improve survival in patients with this disease. With promising results thus far, continued studies of immunotherapy and neoadjuvant therapy options for TNBC are likely to alter the treatment course for these diagnoses in the future.


Inhibition of cathepsin S confers sensitivity to methyl protodioscin in oral cancer cells via activation of p38 MAPK/JNK signaling pathways.
Oral cancer is one of the most common cancers in the world. Approximately 90% of oral cancers are subtyped to oral squamous cell carcinoma (OSCC). Despite advances in diagnostic techniques and improvement in treatment modalities, the prognosis remains poor. Therefore, an effective chemotherapy mechanism that enhances tumor sensitivity to chemotherapeutics is urgently needed. Methyl protodioscin (MP) is a furostanol bisglycoside with a wide range of beneficial effects, including anti-inflammatory and anti-cancer properties. The aim of the present study was to determine the antitumor activity of MP on OSCC and its underlying mechanisms. Our results show that treatment of OSCC cells with MP potently inhibited cell viability. Moreover, MP leading to cell cycle arrest at G2/M phase, which subsequently activates caspase-3, -8, -9 and PARP to induce cell apoptosis. Meanwhile, we also demonstrate that MP induces a robust autophagy in OSCC cells. The results indicate cathepsin S (CTSS) is involved in MP-induced apoptosis and autophagy by modulation of p38 MAPK and JNK1/2 pathways. These findings may provide rationale to combine MP with CTSS blockade for the effective treatment of OSCC.


Attribution and driving force of nitrogen losses from the Taihu Lake Basin by the InVEST and GeoDetector models.
Quantifying temporal and spatial changes in reactive nitrogen (Nr) losses from a watershed and exploring its main drivers are the key to watershed water quality improvements. Huge Nr losses continue to threaten the safety of the water environment in the Taihu Lake Basin (TLB). Here, the InVEST and GeoDetector models were combined to estimate Nr losses in the TLB from 1990 to 2020 and explore driving forces. Different scenarios for Nr losses were compared, showing that Nr loss peaked at 181.66 × 103 t in 2000. The key factors affecting Nr loss are land use, followed by elevation, soil, and slope factors, and their mean q-values were 0.82, 0.52, 0.51, and 0.48, respectively. The scenario analysis revealed that Nr losses increased under the business-as-usual and economic development scenarios, while ecological conservation, increased nutrient use efficiency, and reduced nutrient application all contribute to a reduction in Nr losses. The findings provide a scientific reference for Nr loss control and future planning in the TLB.


A piezoelectric drop-on-demand generator for accurate samples in capillary electrophoresis.
In this work, we propose a piezoelectric droplet generator for injection of well-defined amounts of sample in capillary electrophoresis. We demonstrate stable, precise and drop-on-demand droplet formation for various solutions, with precise control of waveform driving piezoelectric crystal inside the ink-jet head. By tuning the waveform, we can also manipulate the droplet size and delivery frequency. This injector was used in sampling for capillary electrophoresis. As a state-of-the-art application, the analysis of theobromine, caffeine and theophiline using micellar electrokinetic chromatography was developed. The volume of sample (single droplet) analyzed in this experiment was 179 pL (RSD=1.2%, n=10). The detection limits for caffeine, theobromine, and theophiline are 0.02, 0.08 and 0.06 mM L(-1), respectively. Compared with conventional methods, the combination of picoliter droplet dispenser with capillary electrophoresis allows precise and accurate sampling, as well as for reduced sample consumption, which will prove to be an efficient tool in quantitative separation and analysis.


FDW028, a novel FUT8 inhibitor, impels lysosomal proteolysis of B7-H3 via chaperone-mediated autophagy pathway and exhibits potent efficacy against metastatic colorectal cancer.
Metastatic colorectal cancer (mCRC) is a major cause of cancer-related mortality due to the absence of effective therapeutics. Thus, it is urgent to discover new drugs for mCRC. Fucosyltransferase 8 (FUT8) is a potential therapeutic target with high level in most malignant cancers including CRC. FUT8 mediates the core fucosylation of CD276 (B7-H3), a key immune checkpoint molecule (ICM), in CRC. FUT8-silence-induced defucosylation at N104 on B7-H3 attracts heat shock protein family A member 8 (HSPA8, also known as HSC70) to bind with 106-110 SLRLQ motif and consequently propels lysosomal proteolysis of B7-H3 through the chaperone-mediated autophagy (CMA) pathway. Then we report the development and characterization of a potent and highly selective small-molecule inhibitor of FUT8, named FDW028, which evidently prolongs the survival of mice with CRC pulmonary metastases (CRPM). FDW028 exhibits potent anti-tumor activity by defucosylation and impelling lysosomal degradation of B7-H3 through the CMA pathway. Taken together, FUT8 inhibition destabilizes B7-H3 through CMA-mediated lysosomal proteolysis, and FDW028 acts as a potent therapeutic candidate against mCRC by targeting FUT8. FDW028, an inhibitor specifically targeted FUT8, promotes defucosylation and consequent HSC70/LAMP2A-mediated lysosomal degradation of B7-H3, and exhibits potent anti-mCRC activities.


A quantitative sutdy of vertebral displacement and angulation in the normal cervical spine under axial load.
Cervical traction of one-third the person's weight was applied for 3 minutes to normal subjects. The mean and standard deviation of displacement and rotation between adjacent cervical vertebra was calculated in the sagittal plane. The average separation between adjacent vertebra was 0.7 mm with a standard deviation of 0.5 mm. The average angular motion between adjacent vertebra was 0.9 degrees with a standard deviation of 2.4 degrees.


The first two cell-fate decisions of preimplantation mouse embryo development are not functionally independent.
During mouse preimplantation embryo development, three distinct cell lineages are formed, represented by the differentiating trophectoderm (TE), primitive endoderm (PrE) and the pluripotent epiblast (EPI). Classically, lineage derivation has been presented as a two-step process whereby outer TE cells are first segregated from inner-cell mass (ICM), followed by ICM refinement into either the PrE or EPI. As ICM founders can be produced following the fourth or fifth cleavage divisions, their potential to equally contribute to EPI and PrE is contested. Thus, modelling the early sequestration of ICM founders from TE-differentiation after the fourth cleavage division, we examined ICM lineage contribution of varying sized cell clones unable to initiate TE-differentiation. Such TE-inhibited ICM cells do not equally contribute to EPI and PrE and are significantly biased to form EPI. This bias is not caused by enhanced expression of the EPI marker Nanog, nor correlated with reduced apical polarity but associated with reduced expression of PrE-related gene transcripts (Dab2 and Lrp2) and down-regulation of plasma membrane associated Fgfr2. Our results favour a unifying model were the three cell lineages are guided in an integrated, yet flexible, fate decision centred on relative exposure of founder cells to TE-differentiative cues.


Relationship between regeneration of cell surface glycoproteins in trypsin-treated chick embryo fibroblasts and cell adhesion to the substratum.
The ability of cells to adhere to a substratum was altered by treatment with trypsin but was restored after a 1.5-h culture. A concomitant incorporation of [3H] leucine and [14C] glucosamine in the trypsin-sensitive cell surface glycoproteins was observed and almost reached a plateau within 1.50 h following the treatment with trypsin.


Gluteal compartment syndrome following elective unilateral internal iliac artery embolization before endovascular abdominal aortic aneurysm repair.
During endovascular abdominal aortic aneurysm repair, aneurysmal involvement of the common or internal iliac arteries occasionally necessitates elective occlusion of one or both internal iliac arteries. Although elective internal iliac artery occlusion is often well tolerated, it can result in complications such as buttock claudication or rest pain, impotence, and colon ischemia. We report a case of gluteal compartment syndrome following elective unilateral internal iliac artery embolization prior to endovascular abdominal aortic aneurysm repair. On the first postoperative day, the patient developed sciatic nerve palsy, rhabdomyolysis, and renal failure, which promptly resolved after emergent operative exploration of his left buttock and debridement of all grossly necrotic muscle. This case emphasizes the point that, although elective internal iliac artery interruption is usually benign, it can have serious and unexpected complications that necessitate expeditious treatment for complete recovery.


Surface free energy predominates in cell adhesion to hydroxyapatite through wettability.
The initial adhesion of cells to biomaterials is critical in the regulation of subsequent cell behaviors. The purpose of this study was to investigate a mechanism through which the surface wettability of biomaterials can be improved and determine the effects of biomaterial surface characteristics on cellular behaviors. We investigated the surface characteristics of various types of hydroxyapatite after sintering in different atmospheres and examined the effects of various surface characteristics on cell adhesion to study cell-biomaterial interactions. Sintering atmosphere affects the polarization capacity of hydroxyapatite by changing hydroxide ion content and grain size. Compared with hydroxyapatite sintered in air, hydroxyapatite sintered in saturated water vapor had a higher polarization capacity that increased surface free energy and improved wettability, which in turn accelerated cell adhesion. We determined the optimal conditions of hydroxyapatite polarization for the improvement of surface wettability and acceleration of cell adhesion.


Transnational tobacco companies and the mechanism of externalization: A realist synthesis.
Externalization theory assumes that risks and costs are systematically displaced from high-income countries (HICs) to low- and middle-income countries (LMICs). We review how and why transnational tobacco companies (TTCs) influence the local circumstances of LMICs that trigger externalization mechanisms, leading to tobacco-attributable risk outcomes. Our realist synthesis of scientific evidence and gray literature identifies externalization mechanisms with risk outcomes at the level of health policy, smoking trends, and tobacco production. The results reveal the mediating role of local and global third parties and intermediaries. Externalization mechanisms produce systematic tobacco-attributable inequalities between places located in HICs and those located in LMICs.


The influence of men on HPV vaccination of their spouse/partner in China.
Men involvement in HPV vaccine advocacy is important in a patriarchal society. This study aimed to investigate the influence of men on HPV vaccination of adult women. An online cross-sectional survey was undertaken between June and August 2019. Participants were fathers of children enrolled in schools in Fujian Province. A total of 1953 participants responded to our survey. Just over 60% reported they would definitely or likely support their spouse/partner to receive HPV vaccine. Physician recommendation (adjusted odds ratio [aOR] = 5.68, 95%CI = 3.89-6.86) and spouse/partner communication about HPV vaccination (aOR = 5.30, 95%CI = 3.72-7.55) were significant covariates associated with higher willingness to support women's HPV vaccination. Perceiving HPV vaccination as only for women who have had multiple sex partners and HPV vaccination as a sensitive topic were significantly associated with lower willingness to support HPV vaccination. Over two-thirds (67.3%) reported joint HPV vaccination decision-making and 2.8% reported that it was entirely the man's decision. The role of men in HPV vaccine acceptance and hesitancy among adult women is evident in China and warrants educational interventions to target men to enhance women's HPV vaccination uptake.


On azimuthally propagating equatorial atmospheric waves.
We investigate the existence of solutions to a recent model for large-scale equatorial waves, derived recently by an asymptotic method driven by the thin-shell approximation of the Earth's atmosphere in rotating spherical coordinates.


Strain-dependent damage in mouse lung after carbon ion irradiation.
To examine whether inherent factors produce differences in lung morbidity in response to carbon ion (C-ion) irradiation, and to identify the molecules that have a key role in strain-dependent adverse effects in the lung. Three strains of female mice (C3H/He Slc, C57BL/6J Jms Slc, and A/J Jms Slc) were locally irradiated in the thorax with either C-ion beams (290 MeV/n, in 6 cm spread-out Bragg peak) or with ¹³⁷Cs γ-rays as a reference beam. We performed survival assays and histologic examination of the lung with hematoxylin-eosin and Masson's trichrome staining. In addition, we performed immunohistochemical staining for hyaluronic acid (HA), CD44, and Mac3 and assayed for gene expression. The survival data in mice showed a between-strain variance after C-ion irradiation with 10 Gy. The median survival time of C3H/He was significantly shortened after C-ion irradiation at the higher dose of 12.5 Gy. Histologic examination revealed early-phase hemorrhagic pneumonitis in C3H/He and late-phase focal fibrotic lesions in C57BL/6J after C-ion irradiation with 10 Gy. Pleural effusion was apparent in C57BL/6J and A/J mice, 168 days after C-ion irradiation with 10 Gy. Microarray analysis of irradiated lung tissue in the three mouse strains identified differential expression changes in growth differentiation factor 15 (Gdf15), which regulates macrophage function, and hyaluronan synthase 1 (Has1), which plays a role in HA metabolism. Immunohistochemistry showed that the number of CD44-positive cells, a surrogate marker for HA accumulation, and Mac3-positive cells, a marker for macrophage infiltration in irradiated lung, varied significantly among the three mouse strains during the early phase. This study demonstrated a strain-dependent differential response in mice to C-ion thoracic irradiation. Our findings identified candidate molecules that could be implicated in the between-strain variance to early hemorrhagic pneumonitis after C-ion irradiation.


[Laser membranotomy of acute subhyaloidal hemorrhage after indirect ocular trauma].
Subhyaloidal premacular hemorrhage (SPH) causes a painless acute loss of vision with central scotoma. Typically, it can be caused by vascular retinal diseases or in the context of a Valsalva retinopathy. Ocular trauma is a less common cause of SPH. This case report describes a 54-year-old male who presented with a painless decrease of vision in the left eye after blunt frontal trauma to the forehead during a car accident. A car accident resulted in an abrupt deceleration of the head by hitting the windscreen. There was no direct trauma to the eyes. The initial visual acuity of the affected left eye was 0.1 and the visual acuity of the right eye was 1.0. Funduscopy verified an incomplete detachment of the posterior vitreous body with rupture of a retinal venous vessel of the temporal upper vascular arch and prominent SPH. Furthermore, a cystoid macular edema was detected. For internal drainage a neodymium-doped yttrium aluminium garnet (Nd:YAG) laser membranotomy of the posterior vitreous body was performed 1 day after the trauma. On the first postoperative day visual acuity increased to 0.32 with a complete resolution of the macular edema. During the follow-up, visual acuity was 1.0 after 3 months and 1.25 after 6 months. Acceleration and subsequent deceleration can result in a relevant transfer of force to the vitreoretinal interface as an indirect trauma. The Nd:YAG laser membranotomy is a minimally invasive treatment option for SPH after indirect ocular trauma.


[Anemia prevalence in heart failure. GESAIC study results].
There is a great variability in the prevalence of anemia in heart failure (HF) according to cohort based studies where the majority of patients have depressed left ventricular ejection fraction (LVEF). Our study has aimed to evaluate the prevalence of anemia in HF within the usual hospital clinical practice. An initial analysis was made of a prospective cohort of inpatients with HF admitted during 3 months in 15 Internal Medicine Services including all health system levels. We used the World Health Organization (WHO) criteria to define anemia (hemoglobin [Hb] < 12 g/l in women and < 13 g/l in men) and a value > or = 45% as preserved LVEF. A total of 391 patients with an average age of 77.9 +/- 9.4; 239 women (61.1%). The 52.7% of the cases had anemia. Regarding multiple associated factors to anemia in the bivariant analysis, the regression model indicated the following variables: preserved LVEF (odds ratio [OR] 3.03), not being HF debut (OR 1.85), glomerular filtration (OR 0.97), functional class III-IV of the New York Heart Association (NYHA) (OR 0.53), arterial vascular disease (OR 0.41), antiaggregant treatment (OR 0.56) and treatment with nitrites (OR 0.48). Prevalence of anemia in HF is very high in usual clinical practice, that most frequently occurs in subjects with preserved LVEF.


In vitro susceptibilities of oxacillin-resistant Staphylococcus aureus to dapsone and sulfamethoxazole alone and in combination with trimethoprim.
The in vitro activity of trimethoprim plus dapsone against oxacillin-resistant Staphylococcus aureus was comparable to that of trimethoprim plus sulfamethoxazole. Because of its different pharmacologic properties, dapsone may be a useful agent in combination with trimethoprim for the treatment of patients colonized with oxacillin-resistant S. aureus.


Phamacokinetic-pharmacodynamic modelling of behavioural responses.
Drug concentrations at the site of action in studies on behavioural pharmacology, are seldom constant. Therefore, observed changes in behaviour can be due to the natural time course of behavioural processes, but equally to changes in drug concentration, and it is therefore crucial to separate the former from the latter. One solution is keeping drug concentrations constant. However, one can also exploit the variation in drug concentration caused by absorption, distribution and elimination of a drug. This is done by simultaneous measurement of drug effect and concentration, while the drug enters and leaves a biologically relevant compartment, such as blood or cerebrospinal fluid. The concept of determining concentration-effect curves in individual animals, by monitoring in parallel drug effect and changes in concentration in one single experiment, has not yet found wide application in behavioural studies. The fact that behavioural processes, like any other physiological process, change over time, may have contributed to the scarcity of pharmacokinetic-pharmacodynamic (PK/PD) studies in behavioural pharmacology. However, there are now mathematical techniques that allow PK/PD modelling even if the effect parameter changes over time or cannot be properly assessed in every instance. Here we use PK/PD modelling to characterize fear-induced ultrasonic vocalizations and the anxiolytic effect of buspirone. This approach reduces the number of animals required to assess concentration-effect relationships. More importantly, it allows the identification of differences in individual drug response over a wide range of concentrations. Consequently, we suggest that PK/PD modelling can be used as a tool to study drug-induced changes in behavioural response. An introduction in PK/PD modelling is presented.


Constraining crustal silica on ancient Earth.
Accurately quantifying the composition of continental crust on Hadean and Archean Earth is critical to our understanding of the physiography, tectonics, and climate of our planet at the dawn of life. One longstanding paradigm involves the growth of a relatively mafic planetary crust over the first 1 to 2 billion years of Earth history, implying a lack of modern plate tectonics and a paucity of subaerial crust, and consequently lacking an efficient mechanism to regulate climate. Others have proposed a more uniformitarian view in which Archean and Hadean continents were only slightly more mafic than at present. Apart from complications in assessing early crustal composition introduced by crustal preservation and sampling biases, effects such as the secular cooling of Earth's mantle and the biologically driven oxidation of Earth's atmosphere have not been fully investigated. We find that the former complicates efforts to infer crustal silica from compatible or incompatible element abundances, while the latter undermines estimates of crustal silica content inferred from terrigenous sediments. Accounting for these complications, we find that the data are most parsimoniously explained by a model with nearly constant crustal silica since at least the early Archean.


Alcanivorax limicola sp. nov., isolated from a soda alkali-saline soil.
An alkaliphilic and aerobic bacterium, designated as strain JB21T, was isolated from a soda alkali-saline soil sample in Heilongjiang, Northeast China. Strain JB21T is a Gram-stain-negative, rod-shaped, non-motile and amylase-positive bacterium. Growth occurred at 15-45 °C (optimum, 35-37 °C), in the presence of 0-15.0% (w/v) NaCl (optimum, 1.0%) and at pH 6.5-10.5 (optimum, pH 8.5-9.5). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain JB21T was most closely related to type strains of the genus Alcanivorax, with the highest sequence similarity to Alcanivorax indicus SW127T (96.3%), and shared 95.4-93.1% sequence identity with other valid type strains of this genus. The major cellular fatty acids identified were C16:0 and summed feature 8 (C18:1ω6c and/or C18:1ω7c). The polar lipids comprised phosphatidylethanolamine, phosphatidylglycerol and one unidentified phospholipid. The genomic G + C content of strain JB21T was 61.3 mol%. The digital DNA-DNA hybridization (dDDH) estimation and average nucleotide identity (ANI) between strain JB21T and type strains of the genus Alcanivorax were 18.3-23.2% and 69.2-79.0%, respectively. On the basis of its phenotypic and phylogenetic characteristics, we suggest the creation of a new species within the Alcanivorax genus, named Alcanivorax limicola sp. nov., type strain JB21T (= CGMCC 1.16632T = JCM 33717T).


Correlation between serum linezolid concentration and the development of thrombocytopenia.
We evaluated the possible association between trough linezolid (LZD) concentrations and platelet counts using a dose-response curve with a logit model equation. We demonstrated that trough LZD concentrations correlated with platelet counts. A significant decrease in platelet count was observed in patients with trough LZD concentrations higher than 22.1 μg/ml.


Surface and liquid-crystalline properties of FmHnFm triblock semifluorinated n-alkanes.
A series of triblock semifluorinated n-alkanes of the general formula: F(CF2)m(CH2)n(CF2)mF, (in short FmHnFm), where m=10, 12, and n=6, 8, and 12 have been synthesized and employed for liquid crystalline studies and Langmuir monolayer characterization. Differential scanning calorimetry (DSC) measurements together with texture observation with polarizing microscope (POM) revealed the presence of liquid crystalline smectic phases for all the investigated homologs. The behavior of the studied molecules spread at the free water surface has also been investigated. Our results show for the first time that these unusual film-forming materials, which are completely hydrophobic in nature and do not possess any polar group in their structure, are surface active and form insoluble (Langmuir) monolayers at the air/water interface. Due to the fact that these molecules are chemically inert and, similar to the semifluorinated diblocks, are not toxic, they may be destined for biomedical uses as gas carriers and contrast agents, as well as in drug delivery systems.


Preparation and characterization of amine functional nano-hydroxyapatite/chitosan bionanocomposite for bone tissue engineering applications.
In this study, three different types of scaffolds including a uniquely modified composite scaffold - namely chitosan (CTS), nano-hydroxyapatite/chitosan composite (CTS+nHAP), and amine group (NH2) modified nano-hydroxyapatite/chitosan composite (CTS+nHAP-NH2) scaffolds - were synthesized for bone tissue engineering (BTE) purposes. As results of the study, it was found that all scaffold types were biodegradable with CTS and CTS+nHAP scaffolds losing up to 15% of their initial weight, while the CTS+nHAP-NH2 scaffold showing 10% of weight loss after six weeks of lysozyme treatment. In addition, all three types of scaffolds were shown to be biocompatible, and amongst them CTS+nHAP-NH2 scaffolds supported the most cell proliferation in WST-1 assay and expressed the least and acceptable level of cytotoxicity in lactate dehydrogenase (LDH) test for human bone mesenchymal stem cells (hBM-MSCs). Finally, during osteoinductivity assessment, CTS+nHAP-NH2 nearly tripled initial alkaline phosphatase (ALP) activity when whereas both CTS and CTS+nHAP scaffolds only doubled. These results indicate that all synthesized scaffold types under investigation have certain potential to be used in bone tissue engineering approaches with CTS+nHAP-NH2 scaffold being the most promising and applicable one. In the future, we plan to intensify our studies on osteogenic differentiation on our scaffolds on a detailed molecular level and to include in vivo studies for pre-clinical purposes.


Neuropeptides and gamma-aminobutyric acid in the vestibular nuclei of the rat: an immunohistochemical analysis. I. Distribution.
The distribution of substance P, Leu-enkephalin and gamma-aminobutyric acid (GABA) containing structures in the rat vestibular nuclei were investigated by means of an indirect immunofluorescent method using specific antisera to substance P, Leu-enkephalin and glutamic acid decarboxylase (GAD), respectively. Numerous positive neurons and fibers containing these three substances were found in the medial vestibular nucleus. Most of them were situated in the caudal part of the nucleus and those in the rostral part were concentrated dorsally. In the descending vestibular nucleus, a large number of substance P, Leu-enkephalin and GAD containing neurons were evenly distributed among longitudinally directing fiber bundles. A number of positive fibers with these substances were also observed. The lateral vestibular nucleus contained numerous coarse GAD-immunoreactive fibers surrounding Deiters' neurons, while substance P-immunoreactive and Leu-enkephalin-immunoreactive fibers were rather poorly distributed in this nucleus as well as in the superior vestibular nucleus.


On the (Un)greenness of Biocatalysis: Some Challenging Figures and Some Promising Options.
Biocatalysis is generally regarded as a "green" technology. This statement is justified by the mild reaction conditions, the use of aqueous reaction media-with water as the paradigm of green solvents-, and the renewable nature of the biocatalysts. However, researchers making these statements frequently do not take into account the entire picture of their processes. Aspects like water consumption, wastewater production, titers, and metrics of the (diluted?) biocatalytic processes are important as well. With those figures at hand, many biocatalytic reactions do not appear so green anymore. This article critically discusses some common wrong assumptions given for biocatalytic approaches, with regard to their environmental impact, and actual greenness. Some promising biocatalytic approaches, such as the use of biphasic systems involving biogenic solvents, deep-eutectic-solvents (and biogenic ionic liquids), water-free media, solvent-free processes, are briefly introduced, showing that enzyme catalysis can actually be a robust sustainable alternative for chemical processes.


Effect of interferon therapy on first and second recurrence after resection of hepatitis C virus-related hepatocellular carcinoma.
Several investigators have shown that interferon (IFN) therapy can suppress the recurrence of hepatocellular carcinoma (HCC) after curative treatment. We investigated the effect of IFN therapy on the first and second HCC recurrence following hepatic resection of hepatitis C virus (HCV)-related HCC. Subjects included 166 patients who had undergone curative resection for a single HCV-related HCC. We analyzed the outcome after initial hepatic resection and risk factors of a second HCC recurrence following treatment for the first HCC recurrence. Using multivariate analysis, a non-sustained virological response (non-SVR) was significantly associated with a high incidence of first HCC recurrence. The rate of second HCC recurrence tended to be higher in the non-SVR group than in the SVR group. In the patients with recurrence of multiple tumors or who received non-curative treatment for recurrent HCC, the second HCC recurrence rates were significantly higher. Multivariate analysis demonstrated that non-curative treatment for first HCC recurrence was an independent risk factor for a second HCC recurrence. Among the patients who received curative treatment for their first HCC recurrence, the rates of second recurrence were significantly higher in the non-SVR group than in the SVR group. Multivariate analysis also revealed that SVR was independently associated with prevention of a second HCC recurrence. These results suggest that on first HCC recurrence, a curative treatment should be considered in order to prevent a second recurrence if possible. In addition, IFN therapy contributes to improved prognosis after curative treatment, even in patients with recurrent HCC.


Anatomically induced changes in rice leaf mesophyll conductance explain the variation in photosynthetic nitrogen use efficiency under contrasting nitrogen supply.
The ratio of CO2 mesophyll conductance (gm) to Ribulose-1, 5-bisphosphate carboxylase/oxygenase (Rubisco) content has been suggested to positively affect photosynthetic nitrogen use efficiency (PNUE). The anatomical basis of gm has been quantified, but information on the relationship between cell-level anatomies and PNUE is less advanced. Here, hydroponic experiments were conducted in rice plants supplied with ammonium (NH4+) and nitrate (NO3-) under three N levels (low, 0.71 mM; intermediate, 2.86 mM; high, 7.14 mM) to investigate the gas exchange parameters, leaf anatomical structure and PNUE. The results showed a lower PNUE in plants supplied with high nitrogen and NH4+, which was positively correlated with the gm/Rubisco ratio. A one-dimensional within-leaf model revealed that the resistance to CO2 diffusion in the liquid phase (rliq) dominated the overall mesophyll resistance (rm), in which CO2 transfer resistance in the cell wall, cytoplasm and stroma were significantly affected by nitrogen supply. The chloroplast surface area exposed to intercellular space (Sc) per Rubisco rather than the gm/Sc ratio was positively correlated with PNUE and was thus considered a key component influencing PNUE. In conclusion, our study emphasized that Sc was the most important anatomical trait in coordinating gm and PNUE with contrasting N supply.


Co-overexpression of Brassica juncea NPR1 (BjNPR1) and Trigonella foenum-graecum defensin (Tfgd) in transgenic peanut provides comprehensive but varied protection against Aspergillus flavus and Cercospora arachidicola.
Coexpression of two antifungal genes ( NPR1 and defensin ) in transgenic peanut results in the development of resistance to two major fungal pathogens, Aspergillus flavus and Cercospora arachidicola. Fungal diseases have been one of the principal causes of crop losses with no exception to peanut (Arachis hypogeae L.), a major oilseed crop in Asia and Africa. To address this problem, breeding for fungal disease resistance has been successful to some extent against specific pathogens. However, combating more than one fungal pathogen via breeding is a major limitation in peanut. In the present study, we demonstrated the potential use of co-overexpression of two genes, NPR1 and defensin isolated from Brassica juncea and Trigonella foenum-graecum respectively; that offered resistance towards Aspergillus flavus in peanut. The transgenic plants not only resisted the mycelial growth but also did not accumulate aflatoxin in the seeds. Resistance was also demonstrated against another pathogen, Cercospora arachidicola at varied levels; the transgenic plants showed both reduction in the number of spots and delay in the onset of disease. PCR, Southern and Western blot analysis confirmed stable integration and expression of the transgenes in the transgenic plants. The combinatorial use of the two pathogen resistance genes presents a novel approach to mitigate two important fungal pathogens of peanut.


CRISPR/Cas9-Mediated Gene Correction in Newborn Rabbits with Hereditary Tyrosinemia Type I.
Patients with hereditary tyrosinemia type I (HT1) present acute and irreversible liver and kidney damage during infancy. CRISPR-Cas9-mediated gene correction during infancy may provide a promising approach to treat patients with HT1. However, all previous studies were performed on adult HT1 rodent models, which cannot authentically recapitulate some symptoms of human patients. The efficacy and safety should be verified in large animals to translate precise gene therapy to clinical practice. Here, we delivered CRISPR-Cas9 and donor templates via adeno-associated virus to newborn HT1 rabbits. The lethal phenotypes could be rescued, and notably, these HT1 rabbits reached adulthood normally without 2-(2-nitro-4-trifluoromethylbenzyol)-1,3 cyclohexanedione administration and even gave birth to offspring. Adeno-associated virus (AAV)-treated HT1 rabbits displayed normal liver and kidney structures and functions. Homology-directed repair-mediated precise gene corrections and non-homologous end joining-mediated out-of-frame to in-frame corrections in the livers were observed with efficiencies of 0.90%-3.71% and 2.39%-6.35%, respectively, which appeared to be sufficient to recover liver function and decrease liver and kidney damage. This study provides useful large-animal preclinical data for rescuing hepatocyte-related monogenetic metabolic disorders with precise gene therapy.


Trial-based economic evaluation of the system-integrated activation of community health volunteers in rural Ghana.
Globally, steps to revitalise programmes deploying community health workers (CHWs) on a national scale have been growing, but few economic evaluations have been done on system-integrated CHW programmes. Ghana has dual cadres of CHWs: community health officers (CHOs) and community health volunteers (CHVs). CHO plays a major role in primary health services but has suffered from chronic staff shortages. We activated CHVs in communities to mitigate the negative impact due to CHO shortages. The CHVs conducted home visits and provided health education to prevent childhood diseases. We evaluated the cost-effectiveness and cost-benefit of activating CHVs. In a cluster-randomised trial with 40 communities in rural Ghana, the changes in disease incidence were inferred from a statistical model using a Bayesian generalised linear multilevel model. We evaluated the total incremental cost, benefit, and effectiveness for the intervention from an economic model. In cost-effectiveness analysis, disability-adjusted life years (DALYs) were estimated using a decision tree model. In the cost-benefit analysis, the cost-benefit ratio and net present value of benefit were estimated using a decision tree model, and a standardised sensitivity analysis was conducted. The decision tree model was a one-year cycle and run over 10-years. Costs, benefits, and effectiveness were discounted at a rate of 3% per year. According to the cost-effectiveness analysis, the programme was highly likely to exceed the WHO-CHOICE threshold (1-3 times GDP per capita), but it was unlikely to exceed the conservative threshold (10-50% of GDP per capita). In the cost-benefit analysis, the mean and median cost-benefit ratios were 6.4 and 4.8, respectively. We found the potential economic strengths in the cost-benefit analysis. To integrate CHW programmes with national health systems, we need more research to find the most effective scope of work for CHWs.


Pattern dystrophies of the retinal pigment epithelium. The study of three generations in a family.
Three members of a family in one generation were affected by a pattern dystrophy of the retinal pigment epithelium. The patients present typical hyperpigmented macular RPE lesions in a butterfly-shaped to (macro-)reticular pattern, and were all asymptomatic. Examination of 26 family members in 3 generations suggests autosomal recessive inheritance. The family showed some cases of congenital deutanomaly, and a female subject presented both disorders.


Presynaptic Adenosine Receptor-Mediated Regulation of Diverse Thalamocortical Short-Term Plasticity in the Mouse Whisker Pathway.
Short-term synaptic plasticity (STP) sets the sensitivity of a synapse to incoming activity and determines the temporal patterns that it best transmits. In "driver" thalamocortical (TC) synaptic populations, STP is dominated by depression during stimulation from rest. However, during ongoing stimulation, lemniscal TC connections onto layer 4 neurons in mouse barrel cortex express variable STP. Each synapse responds to input trains with a distinct pattern of depression or facilitation around its mean steady-state response. As a result, in common with other synaptic populations, lemniscal TC synapses express diverse rather than uniform dynamics, allowing for a rich representation of temporally varying stimuli. Here, we show that this STP diversity is regulated presynaptically. Presynaptic adenosine receptors of the A1R type, but not kainate receptors (KARs), modulate STP behavior. Blocking the receptors does not eliminate diversity, indicating that diversity is related to heterogeneous expression of multiple mechanisms in the pathway from presynaptic calcium influx to neurotransmitter release.


The Effectiveness of Pharmacological Synchronization of the Estrous Cycle in Hinds (Cervus elaphus L.): A Pilot Field Trial.
The aim was to estimate the effective pharmacological method of the estrous cycle synchronization by checking the effects of synchronization by measurement of progesterone (P4) and 17-beta estradiol (E2) concentration by RIA and artificial insemination. The experiment was performed at the red deer farm in Rudzie (North-East Poland; 3 year's old). The herd (N = 14) was kept away from bulls and was divided in two groups of seven animals. In the Group I, CIDR insert (0.3 g of P4) was applicated intravaginally for 12 days; a second insert replaced the first one for the next 12 days, and next 200 IU of equine chorionic gonadotropin (eCG) was injected intramuscularly (Folligon). Estrus was expected 48 h after eCG injection. In the Group II, Chronogest sponge (20 mg of flugestone acetate) was applicated intravaginally and after 7 days replaced with second chronogest sponge for 7 days. After removing the sponge, on the same day eCG was injected and estrus was expected after 48 h. Artificial insemination was provided with frozen-thawed semen twice: 12 and 24 h after expected estrus. The peripheral blood from the jugular vein was collected each time when the inserts or sponge were applicated and 40 days after insemination. The concentration of P4 and E2 in plasma was measured by RIA. The effectiveness of insemination was monitored by pregnancy-associated glycoproteins determination and observed by the number of calves born. Two pregnancies were confirmed in Group I and five in Group II based on PAG concentration. One newborn was observed in Group I and five in Group II. Both methods of synchronization are effective in hinds based on the received profile of steroids. Although the sponge shape in case of chronogest is better comparing with CIDR, which was not completely deposited in the vagina of hind, potentially leads to bacteria inflammation, and it disturbs the rightful endocrine regulation. Moreover, pregnancy rate and hormone responsiveness were better in Group II.


Identification and quantification of six-ring C₂₆H₁₆ cata-condensed polycyclic aromatic hydrocarbons in a complex mixture of polycyclic aromatic hydrocarbons from coal tar.
We applied a combination of normal-phase liquid chromatography (NPLC) with ultraviolet-visible spectroscopy and gas chromatography with mass spectrometry (GC/MS) for the fractionation, identification, and quantification of six ring C26H16 cata-condensed polycyclic aromatic hydrocarbons, PAHs, in the Standard Reference Material 1597a, Complex Mixture of PAHs from Coal Tar. For the characterization analysis, we calculated the GC retention indices of 17 C26H16 PAH authentic reference standards using the Rxi-PAH and DB-5 GC columns. Then, we used NPLC with ultraviolet-visible spectroscopy to isolate the fractions containing the C26H16 PAHs, and subsequently, we used GC/MS to establish the identity and quantity of the C26H16 PAHs using authentic reference standards. Following this procedure, 12 C26H16 cata-condensed PAHs benzo[c]pentaphene, dibenzo[f,k]tetraphene, benzo[h]pentaphene, dibenzo[a,l]tetracene, dibenzo[c,k]tetraphene, naphtho[2,3-c]tetraphene, dibenzo[a,c]tetracene, benzo[b]picene, dibenzo[a,j]tetracene, naphtho[2,1-a]tetracene, dibenzo[c,p]chrysene, and dibenzo[a,f]tetraphene were identified and quantified for the first time, and benzo[c]picene was quantified for the first time in an environmental combustion sample.


[Piroxicam, diazepam and placebo in the treatment of temporomandibular joint dysfunction. Double blind study].
The effects of Piroxicam, Diazepam, and a Placebo on patients of different degrees of Stomatognathic System Dysfunction were studied. No statistically significant differences were found between the therapeutic effects of Piroxicam, Diazepam and a placebo.


Dislocation-free Ge Nano-crystals via Pattern Independent Selective Ge Heteroepitaxy on Si Nano-Tip Wafers.
The integration of dislocation-free Ge nano-islands was realized via selective molecular beam epitaxy on Si nano-tip patterned substrates. The Si-tip wafers feature a rectangular array of nanometer sized Si tips with (001) facet exposed among a SiO2 matrix. These wafers were fabricated by complementary metal-oxide-semiconductor (CMOS) compatible nanotechnology. Calculations based on nucleation theory predict that the selective growth occurs close to thermodynamic equilibrium, where condensation of Ge adatoms on SiO2 is disfavored due to the extremely short re-evaporation time and diffusion length. The growth selectivity is ensured by the desorption-limited growth regime leading to the observed pattern independence, i.e. the absence of loading effect commonly encountered in chemical vapor deposition. The growth condition of high temperature and low deposition rate is responsible for the observed high crystalline quality of the Ge islands which is also associated with negligible Si-Ge intermixing owing to geometric hindrance by the Si nano-tip approach. Single island as well as area-averaged characterization methods demonstrate that Ge islands are dislocation-free and heteroepitaxial strain is fully relaxed. Such well-ordered high quality Ge islands present a step towards the achievement of materials suitable for optical applications.


Preparative chromatography for obtaining pure samples of rosaniline, magenta II, and new fuchsine.
A simple low pressure liquid chromatographic method is reported that can separate the basic fuchsine homologues, rosaniline, magenta II and new fuchsine from an impure commercial dye. The chromatographic purity of the separated dyes is > 90%. All homologues were obtained in multi-milligram amounts per chromatographic run; precise yields depend on the composition of the starting material and potentially may be greater. This is a useful preparative procedure for generating chromatographically pure samples of basic fuchsine homologues, especially those that cannot be obtained in pure form by direct synthesis.


Obstetric violence in the perception of multiparous women.
To know the perception of multiparous women about their experiences with obstetric violence. Qualitative descriptive study carried out from January to May 2019 in basic health units in the city of Rio Grande, Rio Grande do Sul. Twenty multiparous women from the community participated in the study. Data were collected through interviews and submitted to content analysis. Two subcategories were constructed: Obstetric Violence in primiparous women, where women suffered verbal violence to collaborate during fetal expulsion in labor; Obstetric violence in multiparous women, where there was verbal and physical violence related to the fact that the women had many children. Obstetric violence in health institutions is experienced by many women. The trauma suffered will follow them through their lives. The naturalization of violent practices during labor and birth should be avoided, in order to ensure respectful and non-discriminatory care.


Comprehensive comparison of classic Soxhlet extraction with Soxtec extraction, ultrasonication extraction, supercritical fluid extraction, microwave assisted extraction and accelerated solvent extraction for the determination of polychlorinated biphenyls in soil.
This paper compares the extraction effectiveness of six different commonly applied extraction techniques for the determination of PCBs in soil. The techniques included are Soxhlet, Soxtec, ultrasonication extraction, supercritical fluid extraction, microwave-assisted extraction and accelerated solvent extraction. For none of the techniques were the extraction conditions optimized, but instead the extraction parameters were based on the experience from previous successful investigation published by a number of research groups worldwide. In general, all extraction techniques were capable of producing accurate data for one native PCB contaminated soil diluted with another soil sample to obtain two concentration levels. It could therefore be concluded that any of the investigated techniques can be used with success if the extraction conditions applied are chosen wisely.


Effect of hemothorax on experimental empyema thoracis in the guinea pig.
An experimental model for empyema thoracis in the Duncan-Harley guinea pig is introduced. Empyema thoracis development and early death (less than 14 days after bacterial inoculation) were noted after various concentrations and species were inoculated into the pleural space with a piece of umbilical tape, which was used as a cofactor. The effect of concomitant hemothorax was also tested. Group I (N = 90) had intrapleural inoculation of umbilical tape and various concentrations (10(4), 10(6), 10(8) organisms/ml) of various bacterial species, which included Staphylococcus aureus (N = 30), Escherichia coli (N = 30), and Bacteroides fragilis (N = 30). Group II (N = 90) had intrapleural inoculation of umbilical tape, 1 ml of autologous blood, and the same varying concentrations and species of bacteria as Group I. The observation period was 14 days, during which time early deaths were noted. Fifty-eight percent of the staphylococcal group of animals, 37% of the E. coli group of animals, and none of the B. fragilis group of animals developed empyema. Animals with empyema developed significant weight loss (p less than 0.05) and roentgenographic evidence of empyema, which was supported by postmortem pleural reaction and pneumonia scores (p less than 0.05). Higher concentrations of inoculated bacteria produced a higher incidence of empyema in the S. aureus and E. coli groups (p less than 0.05), but concomitant hemothorax did not increase the already high incidence of empyema and early death in the E. coli group. Empyema caused by B. fragilis did not develop, even with cofactors of umbilical tape and blood. Anaerobic infections in this model may require the presence of other aerobic or facultative organisms, the presence of necrotic lung, prior malnutrition, or a combination thereof.


Decreasing myopic lacquer crack and widening parapapillary gamma zone: case report.
Myopic axial elongation may be due to an equatorial enlargement of Bruch's membrane (BM), leading to a prolate eye shape and increasing strain with BM and the retinal pigment epithelium (RPE) layer at the posterior pole. The increased BM strain may cause an enlargement of Bruch's membrane opening (BMO) of the optic nerve head, with the subsequent development and enlargement of parapapillary gamma zone as BM-free parapapillary zone. The increased strain within BM and RPE may also cause lacquer cracks (LCs) as linear breaks in the RPE and / or BM. Studies suggested that a more marked gamma zone enlargement is associated with lower prevalence of LCs or macular BM defects. Here report on the disappearance of a LC during a 10-year follow-up of a highly myopic eye, concurrent with a marked increase in gamma zone. A 56-year-old woman showed in her right eye (axial length measured 30.69 mm) a LC, vertically oval optic disc, and parapapillary gamma zone in 2001. When re-examined in 2006, gamma zone had enlarged, while the LC was no longer detectable. In 2011, the LC was not visible neither upon ophthalmoscopy and or upon optical coherence tomography (OCT), while gamma zone had further enlarged. The gamma zone enlargement occurred in a direction perpendicular to the direction of the former LC. The observation suggest that a LC can decrease in width, in temporal association with an enlargement of gamma zone. It fits with the notion that an enlargement of the BMO (i.e., enlarging gamma zone) may lead to a relaxation of the BM strain and subsequently to a decrease in the width of the LC.


Randomised trial of cervical cerclage, with and without occlusion, for the prevention of preterm birth in women suspected for cervical insufficiency.
To evaluate the effect of cerclage, with and without cervical occlusion. Multicentre, stratified, randomised controlled trial. Hospital-based multicentre study with 18 tertiary centres from nine countries. Women with a history of cervical insufficiency (prophylactic trial) and women with a short cervix (therapeutic trial) were recruited from August 2006 to August 2011. A centralised telephone randomisation service with a computer system was used to randomise women to cervical cerclage with or without cervical occlusion. Only the analyst performing the interim analyses was blinded. The take-home baby rate (number of infants discharged alive from the hospital), gestational age at delivery, and the number of days in the neonatal intensive care unit (NICU). Women (n = 309) were stratified into the prophylactic trial (n = 213) or the therapeutic trial (n = 96). The trial stopped early due to slow recruitment and an interim analysis showing no benefit of occlusion. Final analysis comprised 197 women in the prophylactic trial and 87 women in the therapeutic trial. No added effect of cervical occlusion was found in terms of the take-home baby rate in the prophylactic trial (92 versus 90%, RR 1.03, 95% CI 0.94-1.12) or in the therapeutic trial (81 versus 85%, RR 0.96, 95% CI 0.79-1.16). No effect of cervical occlusion was found in terms of gestational age at delivery and number of days the neonate spent in the NICU. Cervical occlusion was associated with no harm. Cervical occlusion with cerclage had no significant additional effect.


Pulsatile luteinizing hormone-releasing hormone therapy in women with polycystic ovary syndrome.
Induction of ovulation with pulsatile luteinizing hormone-releasing hormone (LH-RH) therapy was attempted in 48 women with polycystic ovary disease (PCOD) and clomiphene citrate (CC) resistant anovulation. Fourteen women ovulated regularly, 23 ovulated variably, but 11 did not ovulate at all. Fifty-two of the 108 cycles of pulsatile LH-RH therapy alone (15 mu gm per pulse, one pulse every 90 minutes) administered through the subcutaneous route were ovulatory. In patients who did not ovulate on subcutaneous LH-RH, treatment with CC (100 mg per day for 5 days) was added to the LH-RH therapy in an additional 33 cycles, of which 21 were ovulatory. In those who did not respond to the combination of treatments, the same dose of LH-RH was administered intravenously: 14 of 29 cycles of intravenous therapy were ovulatory. The overall cumulative conception rate after 6 months of therapy was 60%. When recalculated for ovulatory cycles alone it was 90%, indicating that failure of ovulation was the only cause of the failure of conception. Analysis of the clinical and endocrine findings indicated that failure to ovulate was associated with obesity and hyperandrogenization. Ten of the 23 conceptions ended in miscarriage, 8 within 4 weeks of ovulation. The authors conclude that infertility in patients with PCOD is not optimally corrected by pulsatile LH-RH therapy.


Determination of chromium in estuarine waters by catalytic cathodic stripping voltammetry using a vibrating silver amalgam microwire electrode.
Chromium (Cr(VI)) in water can be determined by adsorptive catalytic cathodic stripping voltammetry in the presence of diethylenetriaminepentaacetic acid (DTPA) and nitrate on the hanging mercury drop electrode (HMDE). Predominately Cr(VI) is detected and the water is UV-digested to convert all Cr to Cr(VI) prior to analysis. We develop here an alternative to the HMDE by using a silver amalgam electrode based on a vibrating microwire. The microwire electrodes were 12.5 μm in diameter and electrochemically coated with mercury, and were stable for a week. Conditions were re-optimised, and we used a DTPA concentration of 5mM, 30 mM acetate pH buffer (pH 5.5 in seawater and pH 5.8 in pure water), and 1.5M nitrate solution. The microwire was reactivated prior to each scan by applying a negative potential (-3V) for 2s which removed all deposited Cr. The detection limit for chromium in pH buffer was found to be 0.2 nM Cr(VI) and in seawater 0.3 nM Cr(VI) at a deposition time of 30s. The response increased linearly with the concentration of Cr(VI) up to 60 nM Cr(VI) in seawater. The limit of detection is less good than using the HMDE, but the linear range is good and the microwire electrode could form the basis of apparatus for flow-analysis. The method was successfully tested on water samples from the estuary of the river Mersey (Liverpool Bay) giving chromium concentrations between 1.48 nM and 2.29 nM.


Gene transfer via nucleofection into adult and embryonic stem cells.
The use of embryonic and adult stem cells as therapeutic agents is gaining momentum. A major impediment in the use of stem cells for genetic disorders is their ability to undergo genetic modification. The recognition of various site-specific integration methods open up a new avenue for gene therapy in stem cells. However, this necessitates efficient delivery of DNA molecule into cells. Most commercially used liposome-mediated transfection reagents are toxic or work poorly with stem cells. Electroporation, while effective in transfecting stem cells, is rather harsh and leads to excessive cell death. Nucleofection, a technology by Amaxa, uses a combination of electric pulse in an appropriate media, which decreases the toxicity and promotes efficient transfection of stem cells. Various types of adult and embryonic stem cells can be successfully transfected using this method, as described in this chapter.


Deep tissue afferents, but not cutaneous afferents, mediate transcutaneous electrical nerve stimulation-Induced antihyperalgesia.
In this study we investigated the involvement of cutaneous versus knee joint afferents in the antihyperalgesia produced by transcutaneous electrical nerve stimulation (TENS) by differentially blocking primary afferents with local anesthetics. Hyperalgesia was induced in rats by inflaming one knee joint with 3% kaolin-carrageenan and assessed by measuring paw withdrawal latency to heat before and 4 hours after injection. Skin surrounding the inflamed knee joint was anesthetized using an anesthetic cream (EMLA). Low (4 Hz) or high (100 Hz) frequency TENS was then applied to the anesthetized skin. In another group, 2% lidocaine gel was injected into the inflamed knee joint, and low or high frequency TENS was applied. Control experiments were done using vehicles. In control and EMLA groups, both low and high frequency TENS completely reversed hyperalgesia. However, injection of lidocaine into the knee joint prevented antihyperalgesia produced by both low and high frequency TENS. Recordings of cord dorsum potentials showed that both low and high frequency TENS at sensory intensity activates only large diameter afferent fibers. Increasing intensity to twice the motor threshold recruits Adelta afferent fibers. Furthermore, application of EMLA cream to the skin reduces the amplitude of the cord dorsum potential by 40% to 70% for both high and low frequency TENS, confirming a loss of large diameter primary afferent input after EMLA is applied to the skin. Thus, inactivation of joint afferents, but not cutaneous afferents, prevents the antihyperalgesia effects of TENS. We conclude that large diameter primary afferent fibers from deep tissue are required and that activation of cutaneous afferents is not sufficient for TENS-induced antihyperalgesia. Transcutaneous electrical nerve stimulation (TENS) is an accepted clinical modality used for pain relief. It is generally believed that TENS analgesia is caused mainly by cutaneous afferent activation. In this study by differentially blocking cutaneous and deep tissue primary afferents, we show that the activation of large diameter primary afferents from deep somatic tissues, and not cutaneous afferents, are pivotal in causing TENS analgesia.


Serum antibody production by oral immunization with dextran B512.
Serum antibodies to dextran were detected when dextran B512 was orally administered to C3H/He mice. The amounts of serum antibodies were increased along with the dose of orally administered dextran B512. For serum antibody production, differences were observed among the strains of mice. C3H/He, C57BL/6 and CBA mice produced high levels of serum antibodies to dextran, while BALB/c and DBA/2 mice produced low levels of serum antibodies. The serum antibodies had groove-type combining sites, as determined by ELISA inhibitory assay.


Kinetics and mechanism of Ru(III) and Hg(II) co-catalyzed oxidation of D-galactose and D-ribose by N-bromoacetamide in perchloric acid.
Kinetics of oxidation of reducing sugars D-galactose (Gal) and D-ribose (Rib) by N-bromoacetamide (NBA) in the presence of ruthenium(III) chloride as a homogeneous catalyst and in perchloric acid medium, using mercuric acetate as a scavenger for Br(minus sign) ions, as well as a co-catalyst, have been investigated. The kinetic results indicate that the first-order kinetics in NBA at lower concentrations tend towards zero order at its higher concentrations. The reactions follow identical kinetics, being first order in the [sugar] and [Ru(III)]. Inverse fractional order in [H(+)] and [acetamide] were observed. A positive effect of [Hg(OAc)(2)] and [Cl(minus sign)] was found, whereas a change in ionic strength (mu) has no effect on oxidation velocity. Formic acid and D-lyxonic acid (for Gal) and formic acid and L-erythronic acid (for Rib) were identified as main oxidation products of reactions. The various activation parameters have been computed and recorded. A suitable mechanism consistent with experimental findings has been proposed.