Involvement of Arabidopsis glutaredoxin S14 in the maintenance of chlorophyll content.
Plant class-II glutaredoxins (GRXs) are oxidoreductases carrying a CGFS active site signature and are able to bind iron-sulfur clusters in vitro. In order to explore the physiological functions of the 2 plastidial class-II isoforms, GRXS14 and GRXS16, we generated knockdown and overexpression Arabidopsis thaliana lines and characterized their phenotypes using physiological and biochemical approaches. Plants deficient in one GRX did not display any growth defect, whereas the growth of plants lacking both was slowed. Plants overexpressing GRXS14 exhibited reduced chlorophyll content in control, high-light, and high-salt conditions. However, when exposed to prolonged darkness, plants lacking GRXS14 showed accelerated chlorophyll loss compared to wild-type and overexpression lines. We observed that the GRXS14 abundance and the proportion of reduced form were modified in wild type upon darkness and high salt. The dark treatment also resulted in decreased abundance of proteins involved in the maturation of iron-sulfur proteins. We propose that the phenotype of GRXS14-modified lines results from its participation in the control of chlorophyll content in relation with light and osmotic conditions, possibly through a dual action in regulating the redox status of biosynthetic enzymes and contributing to the biogenesis of iron-sulfur clusters, which are essential cofactors in chlorophyll metabolism.


Cardiopulmonary resuscitation artifact during electroencephalography.
Artifacts are signals recorded on the electroencephalogram (EEG) that are not cerebral in origin and can be divided into physiological and non-physiological artifacts. We present here an interesting non-physiological EEG artifact generated by cardiopulmonary resuscitation efforts.


An Atypical Case of Leishmaniasis Associated with Chronic Duodenitis in a Dog.
We describe an atypical case of duodenal leishmaniasis in a boxer dog presenting with chronic diarrhea and poor general condition. Antidiarrheic therapy was previously administered without success and inflammatory bowel disease localized to the small intestine was suspected, given the chronic clinical signs and by ruling out other known causes of gastrointestinal inflammation. Endoscopic biopsy of duodenum showed a moderate increase in lamina propria lymphocytes, plasma cells, and macrophages. Basophilic bodies were seen in the cytoplasm of numerous macrophages, suggestive of Leishmania spp, confirmed by immunostaining, and a diagnosis of granulomatous duodenitis associated to Leishmania infection was made. After 7 mo of therapy, a significant clinical improvement and weight gain were observed, and endoscopic histology showed no evidence of Leishmania. A progressive decline of anti-leishmanial antibody titer was also observed during follow-up. This report emphasizes the importance of atypical symptoms and the unusual location of visceral leishmaniasis, suggesting the need to consider leishmaniasis in the differential diagnosis of canine chronic enteritis, especially in endemic areas.


Enhanced anti-metastatic and anti-tumorigenic efficacy of Berbamine loaded lipid nanoparticles in vivo.
Research on metastasis is gaining momentum for effective cancer management. Berbamine (BBM) has the potency to act as a therapeutic in multiple cancers and cancer metastasis. However, the major limitation of the compound includes poor bioavailability at the tumor site due to short plasma half-life. Here, our major objective involved development of lipid based nanoparticles (NPs) loaded with BBM with an aim to circumvent the above problem. Moreover its, therapeutic potentiality was evaluated through various in vitro cellular studies and in vivo melanoma primary and experimental lung metastatic tumor model in C57BL/6 mice. Results of different cellular experiments demonstrated enhanced therapeutic efficacy of BBM-NPs in inhibiting metastasis, cell proliferation and growth as compared to native BBM in highly metastatic cancer cell lines. Further, in vivo results demonstrated suppression of primary B16F10 melanoma tumor growth in C57BL/6 mice model treated with BBM-NPs than that of native BBM. Importantly, a moderately cytotoxic dose of BBM-NPs was able to significantly suppress the incidence of B16F10 cells lung metastasis in vivo. Results indicated development of an effective approach for aggressive metastatic cancer.


Tachyphylactic properties of angiotensin II analogs with bulky and hydrophobic substituents at the N-terminus.
Tachyphylaxis, defined as the acute loss of response of some smooth muscles upon repeated stimulations with angiotensin II (Ang II), has been shown to be dependent mainly on the N-terminal region of the ligand. To further study the structural requirements for the induction of tachyphylaxis we have synthesized Ang II analogs containing the bulky and very lipophilic substituents 9-fluorenylmethyloxycarbonyl (Fmoc) and 9-fluorenylmethyl ester (OFm) at the alpha-amino (Nalpha-Fmoc-Ang II) or the beta-carboxyl ([Asp(OFm)1]-Ang II) groups of the Asp1 residue, respectively. In binding assays with Chinese hamster ovary cells transfected with the AT1 Ang II receptor, Nalpha-Fmoc-Ang II bound with high affinity, whereas [Asp(OFm)1]-Ang II showed lower affinity. In biological assays, these two analogs were full agonists and showed 30 and 3%, respectively, of the Ang II potency in contracting the guinea-pig ileum smooth muscle. The two analogs induced tachyphylaxis, in spite of the lack of a free amino group in Nalpha-Fmoc-Ang II. Thus, analogs with Fmoc- or OFm-type groups coupled to the Asp1 residue, whether at the amino or carboxyl functions, induce tachyphylaxis through an unreported mechanism. Based in these findings and those available from the literature, an alternate molecular interaction mode between Ang II N-terminal portion and the AT1 receptor is proposed to explain the tachyphylactic phenomenon.


Extracellular galectin-3 counteracts adhesion and exhibits chemoattraction in Helicobacter pylori-infected gastric cancer cells.
Galectin-3 (Gal-3) is a β-galactoside lectin that is upregulated and rapidly secreted by gastric epithelial cells in response to Helicobacter pylori infection. An earlier study reported the involvement of H. pylori cytotoxin-associated gene A (cagA) in the expression of intracellular Gal-3. However, the role of extracellular Gal-3 and its functional significance in H. pylori-infected cells remains uncharacterized. Data presented here demonstrate secretion of Gal-3 is an initial host response event in gastric epithelial cells during H. pylori infection and is independent of CagA. Previously, Gal-3 was shown to bind to H. pylori LPS. The present study elaborates the significance of this binding, as extracellular recombinant Gal-3 (rGal-3) was shown to inhibit the adhesion of H. pylori to the gastric epithelial cells. Interestingly, a decrease in H. pylori adhesion to host cells also resulted in a decrease in apoptosis. Furthermore, the study also demonstrated a chemoattractant role of extracellular rGal-3 in the recruitment of THP-1 monocytes. This study outlines the previously unidentified roles of extracellular Gal-3 where it acts as a negative regulator of H. pylori adhesion and apoptosis in gastric epithelial cells, and as a chemoattractant to THP-1 monocytes. Our findings could contribute to the better understanding of how Gal-3 acts as a modulator under H. pylori-induced pathological conditions.


Hypolipidaemic effect of chemically different mucilages in rats: a comparative study.
Different classes of fibres differ in their potential to lower lipid levels. In order to examine how chemically diverse fibres differ in their hypolipidaemic activity, mucilages of varying chemical composition isolated from three different sources were administered to experimental animals and the metabolism of lipids and lipoproteins was studied. The mucilages used were a galactomannan isolated from fenugreek (Trigonella foenum-graecum) seeds, a glucomannan from Dioscorea esculenta tubers and an arabinogalactan from Colocasia esculenta tubers. Rats were fed these mucilages at a dose of 4 mg/100 g body weight per d for 8 weeks and the changes in the levels of total cholesterol and triacylglycerols in serum, liver and aorta were analysed. All these mucilages decreased lipid levels both in serum and tissues. Among these mucilages, glucomannan showed the most hypolipidaemic effect followed by galactomannan and arabinogalactan. Further, hepatocytes were isolated from the livers of mucilage-fed rats and the synthesis and secretion of lipoproteins were studied using metabolic labelling. There was a decrease in the synthesis and secretion of apoB-containing lipoproteins, mainly VLDL, by hepatocytes isolated from mucilage-fed rats when compared to control (P<0.05). This was further confirmed by pulse chase analysis. Among the different mucilages, mannose-rich glucomannan showed the most effect followed by galactomannan, and mannose-free arabinogalactan showed minimal effect. Comparison of relative viscosity and water-holding capacity showed that mannan-rich mucilages like galactomannan and glucomannan, which showed greater hypolipidaemic effect, had greater relative viscosity and water-holding capacity. The present results suggested that the hypolipidaemic effect of dietary fibre involves a decrease in hepatic production of VLDL and further that it varies with the nature of the fibre.


Hereditary suprabasilar acantholytic mechanobullous dermatosis in buffaloes (Bubalus bubalis).
A skin disease characterized by trauma-induced sloughing of haired skin, hooves, and horns is described in four calves from a herd of Murrah buffaloes (Bubalus bubalis) in Brazil. Affected calves were detected shortly after birth by the presence of lesions affecting the distal extremities, the scapular and gluteal regions, and the tip of the tail. On histologic evaluation of affected skin, the lesions were characterized by suprabasilar vesicles and acantholysis affecting the epidermis and outer root sheath of the hair follicle infundibulum. The basal cell layer was intact and appeared as a single layer of cuboidal cells attached to the dermis. Ultrastructurally, the region between the stratum basale and the lower stratum spinosum had widened intercellular spaces with loss of desmosomal attachments, which led to the suprabasilar separation. The disease appears to be inherited as an autosomal recessive trait.


Phospholipase Cη2 Activation Redirects Vesicle Trafficking by Regulating F-actin.
PI(4,5)P2 localizes to sites of dense core vesicle exocytosis in neuroendocrine cells and is required for Ca(2+)-triggered vesicle exocytosis, but the impact of local PI(4,5)P2 hydrolysis on exocytosis is poorly understood. Previously, we reported that Ca(2+)-dependent activation of phospholipase Cη2 (PLCη2) catalyzes PI(4,5)P2 hydrolysis, which affected vesicle exocytosis by regulating the activities of the lipid-dependent priming factors CAPS (also known as CADPS) and ubiquitous Munc13-2 in PC12 cells. Here we describe an additional role for PLCη2 in vesicle exocytosis as a Ca(2+)-dependent regulator of the actin cytoskeleton. Depolarization of neuroendocrine PC12 cells with 56 or 95 mm KCl buffers increased peak Ca(2+) levels to ~400 or ~800 nm, respectively, but elicited similar numbers of vesicle exocytic events. However, 56 mm K(+) preferentially elicited the exocytosis of plasma membrane-resident vesicles, whereas 95 mm K(+) preferentially elicited the exocytosis of cytoplasmic vesicles arriving during stimulation. Depolarization with 95 mm K(+) but not with 56 mm K(+) activated PLCη2 to catalyze PI(4,5)P2 hydrolysis. The decrease in PI(4,5)P2 promoted F-actin disassembly, which increased exocytosis of newly arriving vesicles. Consistent with its role as a Ca(2+)-dependent regulator of the cortical actin cytoskeleton, PLCη2 localized with F-actin filaments. The results highlight the importance of PI(4,5)P2 for coordinating cytoskeletal dynamics with vesicle exocytosis and reveal a new role for PLCη2 as a Ca(2+)-dependent regulator of F-actin dynamics and vesicle trafficking.


Awareness and Knowledge of the Adverse Effects of Dermal Fillers Among the Saudi Population: A Cross-Sectional Study.
Introduction Dermal filling for aesthetics and facial rejuvenation is one of the most common aesthetic procedures, with hyaluronic acid (HA) being the most commonly used filler due to its high safety profile. Nevertheless, adverse effects have been reported that people should be aware of before the procedure. This study aims to assess Saudi Arabians' awareness of dermal fillers, their side effects, and information sources. Methods This cross-sectional study used an online questionnaire to determine participants' level of knowledge, from January 2, 2022, to February 19, 2023. Statistical analysis and ordinal logistic regression were used to assess the respondents' knowledge of dermal fillers and other parameters. Results Of the 1,208 respondents, 290 reported using fillers, and 44% reported that complications were mentioned to them before the procedure. The results also showed that the primary source of information was social media (44.8%), followed by the Internet, physicians, and books. Respondents to whom physicians explained complications reported bruising, bluish discoloration at the injection site, redness, swelling, and accumulation of body cells under the skin, as discussed with them. Bruising and bluish discoloration were the significantly reported complications in people who received fillers, whereas lumps, epistaxis, ulceration/loss of skin, and swelling/accumulation were reported in those who did not receive fillers. Conclusion Although some adverse effects may occur with HA, its enormous advantages led to its use in facial rejuvenation. With social media as a major source of information, many respondents reported unlikely adverse effects as common ones, suggesting that information sources need to be corrected by physicians to raise awareness of the adverse effects of cosmetic procedures and enhance informed decision-making by patients.


Niacin bound chromium treatment induces myocardial Glut-4 translocation and caveolar interaction via Akt, AMPK and eNOS phosphorylation in streptozotocin induced diabetic rats after ischemia-reperfusion injury.
Diabetes, one of the major risk factors of metabolic syndrome culminates in the development of Ischemic Heart Disease (IHD). Refined diets that lack micronutrients, mainly trivalent chromium (Cr(3+)) have been identified as the contributor in the rising incidence of diabetes. We investigated the effect of niacin-bound chromium (NBC) during ischemia/reperfusion (IR) injury in streptozotocin induced diabetic rats. Rats were randomized into: Control (Con); Diabetic (Dia) and Diabetic rats fed with NBC (Dia+NBC). After 30 days of treatment, the isolated hearts were subjected to 30 min of global ischemia followed by 2 h of reperfusion. NBC treatment demonstrated significant increase in left ventricular functions and significant reduction in infarct size and cardiomyocyte apoptosis in Dia+NBC compared with Dia. Increased Glut-4 translocation to the lipid raft fractions was also observed in Dia+NBC compared to Dia. Reduced Cav-1 and increased Cav-3 expression along with phosphorylation of Akt, eNOS and AMPK might have resulted in increased Glut-4 translocation in Dia+NBC. Our results indicate that the cardioprotective effect of NBC is mediated by increased activation of AMPK, Akt and eNOS resulting in increased translocation of Glut-4 to the caveolar raft fractions thereby alleviating the effects of IR injury in the diabetic myocardium.


The proangiogenic phenotype of tumor-derived endothelial cells is reverted by the overexpression of platelet-activating factor acetylhydrolase.
We previously reported that human tumor-derived endothelial cells (TEC) have an angiogenic phenotype related to the autocrine production of several angiogenic factors. The purpose of the present study was to evaluate whether an enhanced synthesis of platelet-activating factor (PAF) might contribute to the proangiogenic characteristics of TEC and whether its inactivation might inhibit angiogenesis. To address the potential role of PAF in the proangiogenic characteristics of TEC, we engineered TEC to stably overexpress human plasma PAF-acetylhydrolase (PAF-AH), the major PAF-inactivating enzyme, and we evaluated in vitro and in vivo angiogenesis. TECs were able to synthesize a significantly enhanced amount of PAF compared with normal human microvascular endothelial cells when stimulated with thrombin, vascular endothelial growth factor, or soluble CD154. Transfection of TEC with PAF-AH (TEC-PAF-AH) significantly inhibited apoptosis resistance and spontaneous motility of TEC. In addition, PAF and vascular endothelial growth factor stimulation enhanced the motility and adhesion of TEC but not of TEC-PAF-AH. In vitro, TEC-PAF-AH lost the characteristic ability of TEC to form vessel-like structures when plated on Matrigel. Finally, when cells were injected s.c. within Matrigel in severe combined immunodeficiency mice or coimplanted with a renal carcinoma cell line, the overexpression of PAF-AH induced a significant reduction of functional vessel formation. These results suggest that inactivation of PAF, produced by TEC, by the overexpression of plasma PAF-AH affects survival, migration, and the angiogenic response of TEC both in vitro and in vivo.


Growth of broilers and quail fed Fusarium (Gibberella zeae)-infected corn and zearalenone (F-2).
There were no effects in commercial broilers after the long term ingesting of Fusarium-infected corn supplying 1, 10, and 30 p.p.m. zearalenone (F-2) in diets. Average gain and feed conversion were similar in all treatment groups. In the first feeding trial the average body weights were higher for males than for females, but the differences were not significant. Purified F-2, 30 P.P.M., was fed to broilers and no chronic effects were observed. Differences in mean body weights, between dietary treatments in the two Japanese quail lines were small and not significant after 4 weeks on diets containing 0, 10, and 25 p.p.m. F-2 from Fusarium infected corn.


Performing arts medicine-a bibliographic retrospective of the early literature: an historical examination of bibliographic references pre-1975.
Performing arts medicine (PAM) emerged as a medical specialty around 1985. Prior to this time, relatively few publications addressed the identification and concerns of musicians' and dancers' medical problems. To determine what number and types of publications occurred prior to the actual beginnings of PAM as a discipline, and to determine how these original topics compared with present-day publications, a retrospective review of the current bibliographic database of the Performing Arts Medicine Association (PAMA) was undertaken. Out of a total of 12,600 entries to date, 489 references were found published from 1798 through 1974, which represent only 3.9% of the current database listings. One-sixth of the references were originally written in a language other than English. Journal articles were by far the most numerous type of publication. Topics with the highest number of entries included the neurobiology of music (n=77), dental/orofacial matters (71), and biographical accounts of composers or musicians and their illnesses (59). Other frequently published topics included hearing loss, physiology of playing instruments, and instrumental technique and teaching. Early topics with multiple publications included composers' biographies, dystonias, and surgery to improve finger independence for playing piano. Subjects whose publications occurred principally in the last two decades of this review included dermatological disorders, hearing loss, and ballet physiology, teaching, and technique. Those which remain popular to the present day include hearing loss, performance anxiety, focal dystonia, and dental/orofacial problems.


Single-nucleotide polymorphisms based genetic risk score in the prediction of pancreatic cancer risk.
Disease-related single nucleotide polymorphisms (SNPs) based genetic risk score (GRS) has been proven to provide independent inherited risk other than family history in multiple cancer types. To evaluate the potential of GRS in the prediction of pancreatic cancer risk. In this case-control study (254 cases and 1200 controls), we aimed to evaluate the association between GRS and pancreatic ductal adenocarcinoma (PDAC) risk in the Chinese population. The GRS was calculated based on the genotype information of 18 PDAC-related SNPs for each study subject (personal genotyping information of the SNPs) and was weighted by external odd ratios (ORs). GRS was significantly different in cases and controls (1.96 ± 3.84 in PDACs vs 1.09 ± 0.94 in controls, P < 0.0001). Logistic regression revealed GRS to be associated with PDAC risk [OR = 1.23, 95% confidence interval (CI): 1.13-1.34, P < 0.0001]. GRS remained significantly associated with PDAC (OR = 1.36, 95%CI: 1.06-1.74, P = 0.015) after adjusting for age and sex. Further analysis revealed an association of increased risk for PDAC with higher GRS. Compared with low GRS (< 1.0), subjects with high GRS (2.0) were 99% more likely to have PDAC (OR: 1.99, 95%CI: 1.30-3.04, P = 0.002). Participants with intermediate GRS (1.0-1.9) were 39% more likely to have PDAC (OR: 1.39, 95%CI: 1.03-1.84, P = 0.031). A positive trend was observed (P trend = 0.0006). GRS based on PDAC-associated SNPs could provide independent information on PDAC risk and may be used to predict a high risk PDAC population.


[Bone echinococcosis. Apropos of a case of hydatid cyst of the spine].
The authors report a case of hydatid cyst of the vertebral column (L2-L3) simulating an acute abdominal syndrome with pain in the right iliac fossa. On exploration of the abdominal cavity, they detected the presence of a fluctuating retroperitoneal collection of fluid due to the migration of a hydatid abscess into the sheath of the right psoas muscle. Three surgical operations of curetage followed by wide drainage were carried out with simple operative sequelae.


Foetal "black bone" MRI: utility in assessment of the foetal spine.
Foetal CT has recently been added to the foetal imaging armamentarium, but this carries with it the risks of ionizing radiation, both to the mother and the foetus. Foetal "black bone" MRI is a new technique that allows assessment of the foetal skeleton without the risk of exposure to ionizing radiation and is a potential new sequence in foetal MRI examination. Retrospective review of all foetal MRI studies over the past 4- to 5-year period identified 36 cases where susceptibility weighted imaging was used. Cases were selected from this group to demonstrate the potential utility of this sequence. This sequence is most frequently useful not only in the assessment of spinal abnormalities, most commonly the bony abnormalities in myelomeningocele, but also in cases of scoliosis, segmentation anomalies and sacrococcygeal teratoma. Although the utility of this sequence is still being evaluated, it provides excellent contrast between the mineralized skeleton and surrounding soft tissues compared with standard half Fourier acquisition single-shot turbo-spin echo sequences. Further assessment is required to determine whether black bone MRI can more accurately evaluate the level of bony defect in spina bifida aperta, an important prognostic factor. Potential further uses include the assessment of skeletal dysplasias, evaluation of the skull base and craniofacial skeleton in certain congenital anomalies and the post-mortem evaluation of the foetal skeleton potentially obviating the need for necropsy. Foetal black bone MRI can be performed using susceptibility weighted imaging and allows better demonstration of the mineralized skeleton compared with standard sequences.


Hepatic abscess following biliary tract surgery. Etiology, treatment and results.
Experience of seven consecutive cases of liver abscess following biliary tract surgery is presented. The age range was 41-83 years, and six of the patients were women. The interval from operation to appearance of abscess was 10 days to 14 months. Primary surgical drainage was used in two patients, who remained clinically well 6 months and 2 years later. Four of five patients with initially percutaneous drainage subsequently underwent operative drainage, but one refused further surgery and died 8 days later of sepsis. Multiple factors may predispose to both cholangitis and hepatic abscess following biliary tract surgery. Radiologic investigation of abscess must also focus on identifying underlying biliary pathology. Bactericholia and obstructed bile flow are two of the most important etiologic factors in hepatic abscess after biliary surgery. Experience with these cases suggests that a surgical approach may be preferable to percutaneous techniques in management also of the associated biliary pathology.


Condensation reactions and formation of amides, esters, and nitriles under hydrothermal conditions.
Hydrothermal pyrolysis experiments were performed to assess condensation (dehydration) reactions to amide, ester, and nitrile functionalities from lipid precursors. Beside product formation, organic compound alteration and stability were also evaluated. Mixtures of nonadecanoic acid, hexadecanedioic acid, or hexadecanamide with water, ammonium bicarbonate, and oxalic acid were heated at 300 degrees C for 72 h. In addition, mixtures of ammonium bicarbonate and oxalic acid solutions were used to test the abiotic formation of organic nitrogen compounds at the same temperature. The resulting products were condensation compounds such as amides, nitriles, and minor quantities of N-methylalkyl amides, alkanols, and esters. Mixtures of alkyl amide in water or oxalic acid yielded mainly hydrolysis and dehydration products, and with ammonium bicarbonate and oxalic acid the yield of condensation products was enhanced. The synthesis experiments with oxalic acid and ammonium bicarbonate solutions yielded homologous series of alkyl amides, alkyl amines, alkanes, and alkanoic acids, all with no carbon number predominances. These organic nitrogen compounds are stable and survive under the elevated temperatures of hydrothermal fluids.


Infants' perception of lightness changes related to cast shadows.
When humans perceive the lightness of an object's surface in shadows there is an implicit assumption that cast shadows dim the surface. In two experiments, we investigated whether 5- to 8-month-old infants make this assumption about shadows. According to this shadow assumption, the apparent change in lightness produced by shadows on an object's surface are attributed to blocked light sources. If infants can use the shadow assumption to perceive the object's lightness in shadows, they will also be able to detect unnatural lightness changes in shadows. We compared the infants' looking times to the unnatural and the natural lightness changes in the shadow when an object (duck) goes through the cast shadow. In Experiment 1, we examined whether infants could detect the unnatural lightness changes of the object's surface in shadows. We created computer-graphic movies of unnatural and natural lightness changes to the duck's surface. Our results showed that 7- to 8-month-olds but not 5- to 6-month-olds significantly preferred the movie with the unnatural changes in lightness, indicating that only the older infants could detect these changes. In Experiment 2, we confirmed that the infants' preference was based on the detection of unnatural lightness changes according to the shadow assumption. The natural and the unnatural lightness changes of Experiment 1 were presented without cast shadows. Under these conditions, neither younger nor older infants showed a significant preference. Taken together, the experiments showed that 7- to 8-month-old infants could detect the unnaturalness of a surface's lightness changes produced by shadows. In conclusion, our findings suggest that 7- to 8-month-old infants can perceive an object's lightness in shadows by using an assumption that cast shadows dim the surface of an object.


Estimating conditional distributions using a method based on S-distributions reference percentile curves for body mass index in Spanish children.
Reference intervals are a fundamental tool for characterizing the health status in a given population and play a central role in defining diagnostic values in clinical applications. Estimation of the conditional distribution of a variable, as the body mass index (BMI), is necessary for providing reference values when there is a trend as a function of the covariate. We studied 1453 boys and young between 5 and 16 years old measured in a study carried out in the schools of Lleida (Spain). BMI conditional distributions with age have been derived using a new parametric method based on the one proposed by Sorribas et al. [Stat. Med. (2000) 19:697-713]. This method is based on S-distributions as a parametric model for the distribution and uses maximum likelihood estimation of the conditional distribution. The methods commonly used for estimating reference curves are based on a smoothing of sample quantiles using different techniques. However, these methods do not provide information on the conditional distribution of the target variable. Our method provides an estimation of such distribution and the corresponding reference curves for the quantiles as a function of a covariate, in our case age. The suggested methodology provides appropriate reference quantiles for the BMI. Our results allow characterizing the change in distribution within the age range considered. Besides describing a raise in BMI with age, we observe an increase in dispersion around puberty. This must be considered when using BMI as a diagnostic variable.


Further evidence that preoptic anterior hypothalamic GABAergic neurons are part of the GnRH pulse and surge generator.
The in vivo release rates of GABA from the preoptic/anterior hypothalamic area (PO/AH) of ovariectomized rats were assessed by means of a focal perfusion cannula system. Seven days after surgery all animals received a sc silastic capsule implant containing either estradiol-17 beta (E2) or corn oil, and they were perfused 3 days later. Perfusate fractions were sampled at 5-min intervals and blood was collected every 10 min over a period of 5 h. In ovariectomized animals PO/AH GABA release was pulsatile without any diurnal rhythm. Prior to frequency analysis by means of the pulsar-programme, LH and GABA values were z-transformed. Significant LH peaks of all examined ovariectomized rats were superimposed and GABA data were arranged accordingly. It became evident that LH episodes are preceded by a significant reduction of preoptic anterior hypothalamic GABA release. The secretion patterns of GABA and LH were profoundly affected by E2 replacement. During early noon when LH levels were low, constantly elevated hypothalamic GABA release rates were observed in E2-substituted rats in comparison to ovariectomized rats. GABA release rates fell significantly during the E2-induced LH surge. Our previous demonstration of the existence of a large number of estrogen-respective GABAergic neurons in the PO/AH is suggestive of these neurons changing their activity in response to estrogen treatment. We conclude that these estrogen-respective GABAergic neurons are involved in the generation of GnRH pulses as well as in the generation of the so-called positive feedback effect of E2 on LH release.(ABSTRACT TRUNCATED AT 250 WORDS)


Case report of parathyroid carcinoma with raised urinary catecholamines: a diagnostic dilemma.
Parathyroid carcinoma is often misdiagnosed as thyroid carcinoma clinically and also with fine needle aspiration cytology. Moreover in cases misdiagnosed as thyroid carcinoma pre operatively, raised urinary catecholamines may mislead to a diagnosis of MEN2 A. We report a case of a patient admitted to the surgery department ofour hospital with a swelling in the thyroid region, raised urinary catecholamines and urinary VMA levels, with hypercalciuria and elevated parathyroid hormone levels. It was clinically suspected as thyroid carcinoma with parathyroid adenoma and associated MEN 2A syndrome.


[A parotid gland lymphoma presenting with steroid-responsive recurrent sialadenitis: a case report].
Parotid gland located lymphomas are rarely seen. The most common lymphomas involving salivary gland include B-cell MALT (mucosa-associated lymphoid tissue) lymphomas. Of them, extranodal marginal zone B-cell lymphomas are the most frequently seen pathologies. They usually present with painless swelling of the parotid gland. The diagnosis is often based on parotidectomy. In this article, we report a 46-year-old male patient who was admitted with recurrent sialadenitis attacks which responded well to steroid treatment for three years, but recur after the cessation of the therapy. With the initial diagnosis of recurrent parotitis, the patient was scheduled for total parotidectomy for the definitive diagnosis and treatment. When the frozen-section of specimens during superficial parotidectomy revealed lymphoma, the operation was terminated.


[Characteristics of endogenous proteolysis in preparations of human erythrocyte membranes].
Endoproteolytic activity in human erythrocyte membrane preparations has been examined at 37 degrees C by one- and two-dimensional electrophoresis. Two-dimensional mapping has shown that the presence of leukocyte enzymes in erythrocytes prepared in a regular manner (centrifugation) cannot be excluded. Sedimentation in the 1.5% dextran 500,000 with the following erythrocyte purification on HBS-cellulose has made it possible to prepare erythrocyte membranes characterized by low level endoproteolytic activity without leukocyte enzymes. The marker peptide has been found. It is likely to be a specific product of the enzyme activity of membrane localization.


Synthesis of extended polyphosphacumulenes.
Addition of two equivalents of (Me(3)Si)(2)CLiCl to the C-[(diphenyl) (diisopropylamino)phosphonio]-P-(diisopropylamino)phosphaalkene 2 affords the 1sigma(4),3sigma(3)-diphosphabuta-1,2,3-triene E1 in 55 % yield. Derivative E1 was fully characterized, including a single-crystal X-ray diffraction study. Alkylation of E1 with methyl trifluoromethanesulfonate gives rise to the first C-phosphonio-bis(methylene)phosphorane 5, which was isolated in 84 % yield. Because the second carbon center is also nucleophilic, cumulene E1 reacts as a "pincer" with BF(3)OEt(2), leading to the formation of a novel four-membered PCBC heterocycle 6 with a betaine-like structure. Addition of three equivalents of P-[diphenyl(diisopropylamino)]methylene phosphorane to (diisopropylamino)dichlorophosphane, followed by addition of one equivalent of CCl(4), and subsequent deprotonation with lithium hexamethyldisilazide gave rise to 1sigma(4),3sigma(3),5sigma(4)-triphosphapenta-1,2,3,4-tetraene F1, which was isolated in 62 % yield.


[Gene analysis of maple syrup urine disease (MSUD)].
Maple syrup urine disease (MSUD), an autosomal recessive hereditary metabolic disorder, is due to defective oxidative decarboxylation of the branched-chain alpha-ketoacids (BCKAs) derived from transamination of the three branched-chain amino acids, valine, leucine and isoleucine. The oxidative decarboxylation of three BCKAs is catalysed by the branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex. BCKDH consists of three catalytic components: E1, E2 and E3. The E1 component is further composed of two subunits, E1 alpha and E1 beta. To clarify the mechanisms involved in MSUD, measurements of the enzyme activity in cultured cells, measurements of the generation time in cultured cells, complementation analysis and immunoblot analysis were performed. To further elucidate the molecular mechanisms of MSUD, we and others isolated and characterized cDNAs encoding BCKDH-E1 alpha, E1 beta, E2 and E3. The human genome structures of BCKDH -E1 alpha, E1 beta and E2 were also characterized. Gene mutations in E1 alpha, E1 beta and E2, respectively, were identified at the molecular level in three cases of classical MSUD. It became clear that the molecular mechanisms of MSUD involved not only the function of each subunit but also the protein-protein interactions between each subunit. In an attempt to further analyse the molecular basis of MSUD, we carried out complementation analyses by somatic cell hybridization, and identified the affected component of BCKDH complex in the MSUD patient. Furthermore, to rapidly screen for gene mutations, we used PCR-SSCP analysis. Seventeen patients with MSUD were examined using these methods. Defects of E1 alpha, E1 beta and E2 subunits were suspected in 8, 5, and 4 patients, respectively, by complementation analysis.(ABSTRACT TRUNCATED AT 250 WORDS)


Differential and chaotic calcium signatures in the symbiosis signaling pathway of legumes.
Understanding how the cell uses a limited set of proteins to transduce very different signals into specific cellular responses is a central goal of cell biology and signal transduction disciplines. Although multifunctionality in signal transduction is widespread, the mechanisms that allow differential modes of signaling in multifunctional signaling pathways are not well defined. In legume plants, a common symbiosis signaling pathway composed of at least seven proteins mediates infection by both mycorrhizal fungi and rhizobial bacteria. Here we show that the symbiosis signaling pathway in legumes differentially transduces both bacterial and fungal signals (inputs) to generate alternative calcium responses (outputs). We show that these differential calcium responses are dependent on the same proteins, DMI1 and DMI2, for their activation, indicating an inherent flexibility in this signaling pathway. By using Lyapunov and other mathematical analyses, we discovered that both bacterial-induced and fungal-induced calcium responses are chaotic in nature. Chaotic systems require minimal energy to produce a wide spectrum of outputs in response to marginally different inputs. The flexibility provided by chaotic systems is consistent with the need to transduce two different signals, one from rhizobial bacteria and one from mycorrhizal fungi, by using common components of a single signaling pathway.


Emergence/re-emergence of Echinococcus spp.--a global update.
This review provides an update of the biological aspects of the genus Echinococcus and focuses on newly recognized endemic areas. Infection with the intermediate cystic stage of all species of Echinococcus causes disease and incapacity in animals and humans, and in the most serious cases, death of the host. Transmission of Echinococcus to new continents has occurred during European colonisation and the parasite has often taken advantage of Echinococcus-naive wildlife populations in these new environments, incorporating them into its transmission pattern. Echinococcus granulosus consists of a complex of 10 strains. Host specificities of these strains have important implications for transmission and control. As a result of human behaviour and/or political instability in a number of countries Echinococcus is re-emerging as an important public health issue. The importance of wildlife reservoirs in perpetuating transmission and as a source of infection for domestic animals and humans is addressed. The review also refers to the transmission pattern of a recently described new species, Echinococcus shiquicus, from China.


Manifestation of Kohn anomaly in 1/f fluctuations in metallic carbon nanotubes.
Low-frequency noise in metallic single walled carbon nanotubes is shown to be strongly dependent on the Fermi level position and the applied electric field across the nanotube. Resonance-like enhancement observed near optical phonon energy only when the Fermi level lies near the Dirac point is correlated to Raman G-band softening and broadening. The results suggest that the competition between zone-center and zone-boundary phonon scattering is the underlying origin of the large enhancement and resonance-like behavior of 1/f noise.


Hounsfield unit as a predictor of symptomatic vasospasm and hydrocephalus in good-grade subarachnoid hemorrhage treated with endovascular coiling.
Patients with good-grade subarachnoid hemorrhage (SAH) often expect favorable outcomes; however, several patients may experience secondary neurological deterioration. Hydrocephalus and vasospasm are significant complications affecting SAH prognosis. We aimed to evaluate the relationship between the incidence of symptomatic vasospasm or hydrocephalus and the Hounsfield unit (HU) value of the subarachnoid space on brain computed tomography (CT) in patients with good-grade SAH treated with endovascular coiling. We conducted a retrospective analysis of consecutive initially good-grade pure SAH patients (Hunt-Hess grade I or II, modified Fisher scale I or III) with ruptured anterior circulation aneurysms treated with endovascular coiling in a single tertiary neurosurgical center between January 2010 and December 2019. The HU value within each cisterns of enrolled patients was measured, and after setting an appropriate cutoff value, it was investigated whether it could be a predictor of the occurrence of vasospasm and hydrocephalus. The study included 108 eligible patients (34 males, mean age 60.88±12.26 years): 26 (24.1%) showed symptomatic vasospasm and 31 (28.7%) developed hydrocephalus. Patients with symptomatic vasospasm had a greater proportion of those with Hunt-Hess grade II (77% vs. 51%, P=0.021) and modified Fisher scale III scores (58% vs. 22%, P=0.001). The hydrocephalus group presented an older mean age (65.90 vs. 58.86 years, P=0.006) and a greater proportion of Hunt-Hess grade II (74% vs. 51%, P=0.025) and modified Fisher scale III cases (45% vs. 25%, P=0.037). The mean HU values of the Sylvian cistern (53.23 vs. 43.99, P<0.001) and basal cisterns (47.04 vs. 40.18, P=0.003) were higher in the vasospasm group. In the hydrocephalus group, only the basal cistern HU value was significantly higher (45.60 vs. 40.32, P=0.016). The area under the receiver operating characteristic (ROC) curve to determine the best cut-off HU value for the prediction of patients with symptomatic vasospasm revealed a Sylvian cistern HU value of 50.375 (sensitivity: 0.692, specificity: 0.683) and basal cistern HU value of 44.875 (sensitivity: 0.615, specificity: 0.659). Multivariable logistic analysis showed that age >70 years and Sylvian cistern HU value were independent predictors of any neurological complication at 1 year. The HU value of the subarachnoid space on brain CT can predict vasospasm, hydrocephalus, and long-term prognosis in good-grade SAH patients.


[Semiological features and risk factors associated with osteoarthritis of the hip in Ouagadougou (Burkina Faso)].
To study the epidemiological and clinical aspects of osteoarthritis (OA) of the hip in Ouagadougou, as well as its risk factors. This retrospective study covered cases treated over a 3-year period (February 2006 through January 2009) in the internal medicine department of the Yalgado Ouedraogo Teaching Hospital of Ouagadougou (Burkina Faso) and the surgery department of the private hospital Notre-Dame-de la Paix of Ouagadougou. All patients included had OA of the hip that met the Kellgren and Lawrence criteria. There were 46 patients who met the study criteria, but only 40 files could be used. The patients' mean age was 46.4 years ± 15.2 years (range 25-80 years; 10 patients were older than 56 years). Men accounted for more than half (n=23, 57.5%). The mean duration of disease was 6.2 years ± 4.5 years (range: 1-19 years). The right hip alone was concerned in 20 patients (50%), the left hip in 16 (40%), and the OA was bilateral in four (10%). Seventeen patients had sickle cell disease (42.5%), 11 SC and 6 SS. The risk factors included necrosis of the femoral head in 19 cases (59.37%), hip dysplasia in 6 (18.74%), hip trauma in 3 (9.37%), inflammatory arthropathy in 3 more (9.37%), and epiphysitis in one (3.13%). The OA of the hip was primary in 8 cases (20%). Three patients were at stage 1, 9 at stage 2, 15 at stage 3, and 13 at stage 4 according to the Arlet-Ficat classification. OA of the hip arises in a young population and is dominated by secondary OA. The dominant risk factor was aseptic necrosis of the femoral head associated with sickle cell disease. In view of the small number of patients with primary OA, no definitive conclusions can be drawn about it.


Social factors and dental health in the urban adolescents of Isfahan, Iran.
The aim of this study is to determine the dental caries and oral health behavior status of urban adolescents in Iran. Also it assesses the influence of the socioeconomic background on their oral health outcomes. A cross-sectional study was conducted in the students living in the city of Isfahan, Iran. 597 adolescents by 13 to 17 years old participated in the study. The asset-based wealth index, household income and parents' educational history were the indicators of socioeconomic status. Data on tooth brushing frequency and smoking experience were collected, and the adolescents were examined for their dental health status. The index of DMFT was recorded by two calibrated examiners considering the criteria of World Health Organization. Bivariate analysis and multivariate regressions were employed to explore the association between dental caries status and socioeconomic variables. The DMFT mean (SD) of the study population was 2.79(2.7) with attributable 50, 4 and 46 percent to D, M and F components and 26% caries- free prevalence. Nearly 19% of the students presented twice daily brushing and 3% of respondents had smoking experience. Dental caries did not show any linear relationship with the social indicators when the DMFT was modeled by the wealth index, parents' educational level and family income adjusted for age and gender. Without adjustment, lower income has increased the chance of untreated tooth decay, 2.5 times among the students. Despite the supporting findings on inequalities in oral health, this study did not show a direct association between socio economic backgrounds of the adolescents with their dental health/disease. The hypothesized balanced risk exposure is considered to justify the results, but it needs to be studied by further comprehensive analysis.


Patient-reported outcome measures for transthyretin cardiac amyloidosis: the ITALY study.
Transthyretin cardiac amyloidosis (ATTR-CA) has a deep impact on the quality of life (QoL), yet no specific patient-reported outcome measures (PROMs) for ATTR-CA exist. The ITALY study involved 5 Italian referral centres (Pisa, Pavia, Ferrara, Florence, Messina) enrolling consecutive outpatients with ATTR-CA. Two 30-item questionnaires were created for wild-type (wt) and variant (v) ATTR-CA. Scores ranged from 100 (best condition) to 0 (worst condition). Out of 140 patients enrolled (77% with ATTRwt-CA), 115 repeated the re-evaluation at 6 months. At baseline, only 30% of patients needed help to fill out the questionnaires. Among baseline variables, all KCCQ and SF-36 domains were univariate predictors of ITALY scores in ATTRwt-CA patients, with the KCCQ Symptom Summary score (beta coefficient 0.759), Social Limitations (0.781), and Overall summary score (0.786) being the strongest predictors. The SF-36 Emotional well-being score (0.608), the KCCQ Overall summary score (0.656), and the SF-36 Energy/fatigue score (0.669) were the strongest univariate predictors of ITALY scores in ATTRv-CA. Similar results were found at 6 months. The ITALY questionnaires are the first specific PROMs for ATTRwt- and ATTRv-CA. Questionnaire completion is feasible. ITALY scores display close relationships with non-ATTR-specific measures of QoL.


Needlestick injuries and other occupational exposures to body fluids amongst employees and medical students of a German university: incidence and follow-up.
The aim of this study was to obtain data concerning the incidence, reporting and follow-up of occupational exposure to blood or other body fluids (OEB). A questionnaire was distributed to employees and medical students (N=787) and official reports of OEB during the year 2003 (N=203) and their consequent follow-up (N=100) were evaluated. The percentages of needlestick injuries were 29.5% for students and 22.5% for employees. Incidence rates per 1000 employee days were 0.61 for needlestick injuries or sharp object injuries and 0.27 for mucocutaneous exposure to body fluids. The mean rate of underreporting was approximately 45%. Contrary to expectations, only 4.3% of nurses and 3.9% of doctors officially reported an OEB in 2003. The number of persons who did not attend for a serological test increased during the follow-up period. Considering all documented test results, 35 out of 100 affected persons were lost to follow-up due to default of appearance. As a consequence, the employer should provide safety devices and enforce didactical interventions with practical training and incident reporting. Periodical occupational health medicals, including serological testing, should be mandatory for all employees, including medical students and student nurses. To increase compliance after OEB, a short follow-up period using improved laboratory tests requires further discussion.


Prognostic significance of polygraphic recordings in newborn infants on ventilation.
In a prospective study, 79 preterm and fullterm newborn infants who had been on assisted ventilation for at least five days were recorded polygraphically between the fifth and eighth day of life. 73 were still intubated and on assisted ventilation at the time of recording. 61 of the infants were again recorded polygraphically between 14 and 34 days after birth. The findings of both first and second recordings correlated with psychomotor development up to one year, or with postmortem examinations. The first recordings were highly significant to the prognosis, especially for infants whose gestations were more than 33 weeks. The second polygram showed a similar correlation with later development. Neurological examinations were performed on the same day as the first polygraphic recording: they were less significant prognostically for the preterm infants compared with polygraphic findings, and of no prognostic significance for the fullterm infants.


Synergistical Coupling Interconnected ZnS/SnS2 Nanoboxes with Polypyrrole-Derived N/S Dual-Doped Carbon for Boosting High-Performance Sodium Storage.
Metal sulfides possess tremendous potentials owing to their high specific capacity for sodium storage. However, the huge volume expansion, accompanied with structural collapse and unsatisfied electric conductivity upon continuous cycling, always lead to inferior rate capability and severe cycling fading. In this work, binary metal sulfide (ZnS/SnS2 ) nanoboxes confined in N/S dual-doped carbon shell (ZSS@NSC) are fabricated through a facile co-precipitation method involving the wrapping of polypyrrole, and subsequent in situ sulfidation process. Such a well-designed heterogeneity between ZnS and SnS2 provides rapid Na+ insertion and enhanced charge transport by creating an electric field at the heterointerface. More significantly, the formation of polypyrrole-derived N/S dual-doped carbon is synergistically coupled with the ZnS/SnS2 to create a unique and robust architecture, further strengthening the interconnect function at the heterointerface, which improves electric/ion transfer and mitigates the volume variation during the long-term cycling process. Herein, this as-prepared ZSS@NSC exhibits satisfied specific capacity, excellent rate property, and superior cyclic stability (a reversible capacity of 456.2 mAh g-1 with excellent capacity retention of 97.2% after 700 stable cycles at ultrahigh rate of 5 A g-1 ). The boosted Na-storage properties demonstrate that the optimized strategy of structure-engineering has a broad prospect to promote energy storage applications.


Chronic microaspiration of bile acids induces lung fibrosis through multiple mechanisms in rats.
Gastroesophageal reflux (GER) and microaspiration of duodenogastric refluxate have been recognized as a risk factor for pulmonary fibrosis. Recent evidence suggests that bile acid microaspiration may contribute to the development of lung fibrosis. However, the molecular evidence is scarce and the underlying mechanisms remain to be elucidated. We have recently demonstrated that bile acids induce activation of alveolar epithelial cells (AECs) and lung fibroblasts in vitro In the present study, a rat model of bile acid microaspiration was established by weekly intratracheal instillation of three major bile acids including chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), and lithocholic acid (LCA). Repeated microaspiration of CDCA, DCA, and LCA caused fibrotic changes, including alveolar wall thickening and extensive collagen deposition, in rat lungs. Bile acid microaspiration also induced alveolar epithelial-mesenchymal transition (EMT), as indicated by up-regulation of mesenchymal markers α-smooth muscle actin (α-SMA) and vimentin, as well as down-regulaton of epithelial markers E-cadherin and cytokeratin in alveolar epithelium of rat lungs. The expression of fibrogenic mediators, including transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and periostin, was significantly elevated in rat lungs exposed to microaspiration of bile acids. Furthermore, microaspiration of bile acids also induced p-Smad3 and farnesoid X receptor (FXR) expression in rat lungs. Our findings suggest that microaspiration of bile acids could promote the development of pulmonary fibrosis in vivo, possibly via stimulating fibrogenic mediator expression and activating TGF-β1/Smad3 signaling and FXR.


Combined effects of temperature and the herbicide diuron on Photosystem II activity of the tropical seagrass Halophila ovalis.
Tropical seagrasses are at their highest risk of exposure to photosystem II (PSII) herbicides when elevated rainfall and runoff from farms transports these toxicants into coastal habitats during summer, coinciding with periods of elevated temperature. PSII herbicides, such as diuron, can increase the sensitivity of corals to thermal stress, but little is known of the potential for herbicides to impact the thermal optima of tropical seagrass. Here we employed a well-plate approach to experimentally assess the effects of diuron on the photosynthetic performance of Halophila ovalis leaves across a 25 °C temperature range (36 combinations of these stressors across 15-40 °C). The thermal optimum for photosynthetic efficiency (▵) in H. ovalis was 31 °C while lower and higher temperatures reduced ▵ as did all elevated concentrations of diuron. There were significant interactions between the effects of temperature and diuron, with a majority of the combined stresses causing sub-additive (antagonistic) effects. However, both stressors caused negative responses and the sum of the responses was greater than that caused by temperature or diuron alone. These results indicate that improving water quality (reducing herbicide in runoff) is likely to maximise seagrass health during extreme temperature events that will become more common as the climate changes.


[A case of repeated postoperative recurrence of gastric cancer treated via laparoscopic approach].
A 74-year-old man who had undergone distal gastrectomy was diagnosed with metastasis to the spleen and transverse colon 27 months after the operation, and 6 courses of combination therapy with S-1 and cisplatin (CDDP) were administered. However, both lesions showed progressive disease (PD) after chemotherapy. Massive gastrointestinal hemorrhage from colon metastases was observed following the administration of irinotecan(CPT-11). Therefore, total remnant gastrectomy, splenectomy, and partial transverse colectomy were performed via the laparoscopic approach. Chemotherapy using paclitaxe(l PTX) was initiated after surgery. However, bowel obstruction due to intestinal metastatic lesions developed after 4 courses of PTX therapy, and right hemicolectomy and partial resection of the small intestine were performed laparoscopically. Although combination therapy of capecitabine and CDDP were administered, the patient died 28 months after the diagnosis of recurrent disease. Typically, surgical intervention is rarely effective in cases of recurrent disease from gastric cancer. However, a favorable quality of life was obtained in the case of our patient with aggressive multimodal therapy that included laparoscopic surgery.


[Dynamic stereovisometry].
An original method of dynamic stereovisometry and a device for its realization Stereovisotest have been developed for examining the stereoscopic vision. Dynamic stereovisometry permitted the detection of positive and negative thresholds of stereoperception starting from the age of 4 years with an accuracy of 1 second of arc. The mean age-specific thresholds of stereoscopic vision were determined for a random sample of 1810 subjects aged 4 to 60 with binocular vision. For children aged 4 to 6 the mean threshold is 80 seconds of arc, in schoolchildren and adolescents it gradually reduces to 55 seconds of arc by the age of 16-20, from 21 to 40 the threshold remains at the level of 45 seconds of arc, after which it starts to increase and reaches 60 seconds of arc by 60. Stereoscopic vision of subjects whose profession requires precise vision was examined and criteria for vision assessment offered. Training of stereoscopic vision using the Stereovisotest device were carried out. The possibility of raising the thresholds of stereoscopic perception to physiological ones has been demonstrated.


Tetra-aqua-bis-[2-(4-pyridyl-sulfan-yl)acetato-κN]nickel(II).
In the centrosymmetric title complex, [Ni(C(7)H(6)NO(2)S)(2)(H(2)O)(4)], the Ni(II) atom, located on a centre of inversion, is coordinated by two N atoms from two 2-(4-pyridyl-sulfan-yl)acetate ligands and four water O atoms in an octa-hedral geometry. In the crystal, inter-molecular O-H⋯O hydrogen bonds between the coordinated water mol-ecules and the carboxyl-ate group of the anionic 2-(4-pyridyl-sulfan-yl)acetate ligands link these discrete mononuclear units into a three-dimensional network.


Differential actions of the medial region of caudal medulla on autonomic nerve activities.
1. The inhibitory effects produced by activation of the medial region of caudal medulla on activities of the left and right cardiac sympathetic, vagus and greater splanchnic nerves were studied in chloralose-urethane anaesthetized cats. 2. Electrical stimulation of the medial region produced an 80-92% inhibition of the sympathetic nerve activities, and a 45% and 58% inhibition of the left and right cardiac vagal nerve activities, respectively. There were no significant differences between effects elicited in the left and right autonomic nerves. Similar but smaller inhibitory effects were produced by micro-injection of sodium glutamate (0.5 mol/L) or DL-homocysteic acid (50 mmol/L) to the same medullary sites. 3. These data suggest that neurons residing in the medial medullary region exert strong inhibitory effects on autonomic nerve activities. Since the vasculature is principally innervated by sympathetic nerves, inhibition of sympathetic nerve activities might be the principal factor responsible for the depressor effects caused by activation of the medial region of caudal medulla. The heart is innervated both by sympathetic and parasympathetic nerves. Thus, their simultaneous inhibition during activation of the medial region elicits only a weak and variable inhibition of the heart.


Feasibility and safety of computed tomography-guided intrapulmonary injection of indocyanine green for localization of peripheral pulmonary ground-glass nodules.
The early surgical intervention for pulmonary ground-glass nodules (GGNs) has become increasingly important, but accurate identification of these nodules during thoracoscopic surgery poses challenges due to the need for sublobar resections and reliance on visual and tactile perception alone. The prognosis of the procedure is closely tied to the use of precise positioning technology. Thus, it is crucial to develop an accurate positioning technology that can improve patient prognosis. Clinical data from the cardiothoracic department of a tertiary hospital in Shanghai were collected and analyzed between January 2020 and December 2021. The patients were categorized into 2 groups: an indocyanine green (ICG) group and a hook-wire group. Outcome measures including success rate, complications, procedure time, localization-related pain, and interval time were assessed. Adverse events and reactions were reported and compared between the 2 groups. A total of 62 patients (17 males and 45 females, aged 50.5±13.2 years) were in the ICG group, while 66 patients (23 males and 43 females, aged 48.4±12.9 years) were localized in the hook-wire group. The success rate was comparable between the 2 groups. However, the ICG group showed significant advantages over the hook-wire group in terms of procedure time (22.6±4.4 vs. 24.1±4.9 min; P=0.012), localization-related pain (P<0.001), and interval time [median and interquartile range (IQR): 3 (0.7, 104.9) vs. 1.2 (0.5, 3.3) h; P<0.001]. In the ICG group, there were 11 cases of pneumothorax, 4 cases of hemothorax, and 2 cases of ICG diffusion. In the hook-wire group, there were 24 cases of pneumothorax, 25 cases of hemothorax, and 2 cases of dislodgement. The ICG group had fewer complications, including pneumothorax (P=0.018) and hemothorax (P=0.007), compared to the hook-wire group. Computed tomography (CT)-guided intrapulmonary injection of ICG for preoperative localization of peripheral pulmonary GGNs is a practical and safe technique. It offers advantages in terms of reduced procedure time, localization-related pain, and interval time compared to the hook-wire method. Moreover, the ICG technique results in fewer complications, making it a valuable preoperative localization technique worthy of popularization.


Association between visual inspection of the cervix with acetic acid examination and high-risk human papillomavirus infection, Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis in Papua New Guinea.
Papua New Guinea (PNG) has among the highest estimated burdens of cervical cancer globally but currently has no national cervical screening program. Visual inspection of the cervix with acetic acid (VIA) is a low-cost screening strategy endorsed by the World Health Organization that has been adopted in many low-resource settings but not previously evaluated in PNG. To evaluate the association between VIA examination findings and high-risk HPV (hrHPV) infection; and the impact of concomitant genital Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis on the interpretation of VIA findings. A prospective clinical cohort study among women aged 30-59 years attending Well Woman Clinics in PNG. Main outcome measures were VIA examination findings and laboratory-confirmed hrHPV, C. trachomatis, N. gonorrhoeae and T. vaginalis. A total of 614 women were enrolled, of whom 87.5% (537/614) underwent VIA, and 12.5% (77/614) did not due to pre-existing cervicitis or inability to visualise the transformation zone. Among the 537 women who underwent VIA, 21.6% were VIA positive, 63.7% VIA negative, and 14.7% had indeterminate findings. The prevalence of hrHPV infection (n = 614) was 14.7%; C. trachomatis, 7.5%; N. gonorrhoeae, 8.0%; and T. vaginalis, 15.0%. VIA positive women were more likely to have HPV16 (odds ratio: 5.0; 95%CI: 1.6-15.6; P = 0.006) but there was no association between HPV18/45, all hrHPV types (combined), C. trachomatis, N. gonorrhoeae or T. vaginalis. VIA positivity was associated with HPV16, but not with other hrHPV infections, nor with genital C. trachomatis, N. gonorrhoeae or T. vaginalis in this setting.


Protein biomarkers for breast cancer prevention.
Protein biomarkers suitable for the prevention of breast cancer must be extremely sensitive, easily detectable and highly correlated with the disease. They should be expressed in the reversible phase of carcinogenesis. Among the large number of candidate tumour-associated proteins, those related to the oestrogen/chorionic gonadotropin/insulin pathway seem to be of most interest because these can be causally implicated. They presumably are the first to express differently and are open to hormonal treatments. The biomarkers that give information on membrane receptor-modulated signal transduction should be considered as well. Up to now, only tamoxifen has shown some preventive activity, suggesting that the oestrogen pathway is useful indeed. Fenretinide and recombinant human chorionic gonatotropin (hCG) are also promising. But the financial requirements and the very long assessment periods largely prevent current research. This is precisely why we badly need to give priority to molecular biology research, in particular in the protein compartment There is widespread belief that advanced proteomics together with increased informatics can provide specific combinations of disease-related expression profiles that could identify high-risk groups with much more reliability and allow us to monitor preventive strategies.


Common cortical and thalamic mechanisms for language and motor functions.
Evidence for common mechanisms in the human brain for motor and language functions is reviewed, particularly evidence derived from electrical-stimulation mapping during cortical and thalamic operations in awake patients. Several systems in the dominant hemisphere are identified where language and motor function share common mechanisms, including a lateral thalamic attentional system and a lateral perisylvian cortical system common to sequential movement and speech sound identification, where precise timing may be a common mechanism.


Cardiac and central nervous system vasculitis in a child with dermatomyositis.
Cerebral vasculitis and clinically important myocardial inflammation are rare in juvenile dermatomyositis. We report a previously healthy 6-year-old girl with dermatomyositis who died after a fulminating clinical deterioration. Postmortem examination of the heart revealed characteristic endothelial tubuloreticular aggregates and evidence of capillary necrosis and secondary thrombosis, associated with extensive hemorrhagic myocardial necrosis. Endothelial necrosis was also evident in the cerebrocortical capillaries.


Impaired corticomuscular coherence during isometric elbow flexion contractions in humans with cervical spinal cord injury.
After spinal cord injury (SCI), the reorganization of the neuromuscular system leads to increased antagonist muscles' co-activation-that is, increased antagonist vs. agonist muscles activation ratio-during voluntary contractions. Increased muscle co-activation is supposed to result from reduced cortical influences on spinal mechanisms inhibiting antagonist muscles. The assessment of the residual interactions between cortical and muscles activity with corticomuscular coherence (CMC) in participants with SCI producing different force levels may shed new lights on the regulation of muscle co-activation. To achieve this aim, we compared the net joint torque, the muscle co-activation and the CMC ~ 10 and ~ 20 Hz with both agonist and antagonist muscles in participants with SCI and healthy participants performing actual isometric elbow flexion contractions at three force levels. For all participants, overall CMC and muscle co-activation decreased with the increase in the net joint torque, but only CMC ~ 10 Hz was correlated with muscle co-activation. Participants with SCI had greater muscle co-activation and lower CMC ~ 10 Hz, at the highest force levels. These results emphasize the importance of CMC as a mechanism that could take part in the modulation of muscle co-activation to maintain a specific force level. Lower CMC ~ 10 Hz in SCI participants may reflect the decreased cortical influence on spinal mechanisms, leading to increased muscle co-activation, although plasticity of the corticomuscular coupling seems to be preserved after SCI to modulate the force level. Clinically, the CMC may efficiently evaluate the residual integrity of the neuromuscular system after SCI and the effects of rehabilitation.


A sensitive radioligand binding assay for timolol in plasma.
A sensitive and reproducible radioreceptor assay (RRA) is described for the determination of low picogram levels of timolol in plasma. The plasma or serum samples (1 mL) are prepared by selectively extracting timolol with lipophilic solvents or, alternatively, only plasma (serum) proteins are precipitated prior to binding assay. The recovery of timolol is at least 90% during the sample preparation. In the radioligand binding assay, timolol and the nonselective beta-antagonist [3H](-)-CGP-12177 compete for the binding sites present in the rat reticulocyte membranes. The detection limit for timolol (30 pg/mL) exceeds 50 times the sensitivity of the GC-MS techniques for timolol. The RRA results and GC results obtained from the same clinical samples correlate excellently (r = 0.99). There was no evidence for interference caused by timolol metabolites in the RRA. Timolol concentrations in plasma following its oral and even ocular administration were possible to monitor using the RRA. The method can be modified to also measure several other beta-antagonist drugs in picogram per milliliter quantities.


Pain relief following percutaneous vertebroplasty: results of a series of 283 consecutive patients treated in a single institution.
The aim of this study was to assess if percutaneous vertebroplasty (PVP) could relieve back pain, reduce drug consumption, and improve the mobility of patients with metastases and vertebral compression fractures. From August 2002 to July 2004, 283 patients (216 females; mean age: 73.8 +/- 9.9 years) underwent PVP on 749 vertebrae. Pain was evaluated with the pain intensity numeric rating scale (PI-NRS) (0 = no pain; 10 = worst pain) before the procedure and at the end point in September 2004 (follow-up:1-24 months; median: 7 months). A reduction of at least two points of the PI-NRS score was considered clinically relevant. Two hundred four patients were available for evaluation at the end point. Overall results showed a reduction of the median pain score from 8 at baseline to 1 at the end point (p < 0.0001); a clinically relevant pain reduction was observed in 176/205 patients (86%); 89/147 patients (61%) gave up a brace support (p < 0.0001); and 117/190 patients (62%) gave up drug therapy. Results were similar in different subgroups stratified according to age, underlying pathology, number of fractured or treated vertebrae, and length of follow-up. This study adds evidence that PVP is effective in treating painful vertebral fractures. A significant reduction in drug assumption and significant mobility improvement can also be achieved.


Images of health technology in national and local strategies.
This paper examines the potential of various models relating technology to society and institutional structures to inform health policy. Among the models discussed are various versions of technological determinism, social constructivism, actor network theory and critical theory. The paper considers recent developments in policy and strategy that aim to shape the way the UK's National Health Service (NHS) integrates Information and Communication Technologies (ICTs) into health care and considers what these alternative models highlight or emphasise, and how they might influence the activities of setting local implementation strategies. Contemporary ICTs are often presented as having a particular relevance and power in reforming or transforming the delivery of health care. Understanding how such technologies might be conceived of, implemented and become an integral part of some future health care system is an important and challenging task that requires innovative theoretical treatments.


Price effects of a hospital merger: Heterogeneity across health insurers, hospital products, and hospital locations.
In most studies on hospital merger effects, the unit of observation is the merged hospital, whereas the observed price is the weighted average across hospital products and across payers. However, little is known about whether price effects vary between hospital locations, products, and payers. We expand existing bargaining models to allow for heterogeneous price effects and use a difference-in-differences model in which price changes at the merging hospitals are compared with price changes at comparison hospitals. We find evidence of heterogeneous price effects across health insurers, hospital products and hospital locations. These findings have implications for ex ante merger scrutiny.


COVID-19 vaccine strategies for Aotearoa New Zealand: a mathematical modelling study.
Background: COVID-19 elimination measures, including border closures have been applied in New Zealand. We have modelled the potential effect of vaccination programmes for opening borders. Methods: We used a deterministic age-stratified Susceptible, Exposed, Infectious, Recovered (SEIR) model. We minimised spread by varying the age-stratified vaccine allocation to find the minimum herd immunity requirements (the effective reproduction number Reff<1 with closed borders) under various vaccine effectiveness (VE) scenarios and R0 values. We ran two-year open-border simulations for two vaccine strategies: minimising Reff and targeting high-risk groups. Findings: Targeting of high-risk groups will result in lower hospitalisations and deaths in most scenarios. Reaching the herd immunity threshold (HIT) with a vaccine of 90% VE against disease and 80% VE against infection requires at least 86•5% total population uptake for R0=4•5 (with high vaccination coverage for 30-49-year-olds) and 98•1% uptake for R0=6. In a two-year open-border scenario with 10 overseas cases daily and 90% total population vaccine uptake (including 0-15 year olds) with the same vaccine, the strategy of targeting high-risk groups is close to achieving HIT, with an estimated 11,400 total hospitalisations (peak 324 active and 36 new daily cases in hospitals), and 1,030 total deaths. Interpretation: Targeting high-risk groups for vaccination will result in fewer hospitalisations and deaths with open borders compared to targeting reduced transmission. With a highly effective vaccine and a high total uptake, opening borders will result in increasing cases, hospitalisations, and deaths. Other public health and social measures will still be required as part of an effective pandemic response. Funding: This project was funded by the Health Research Council [20/1018]. Research in context.


Differential activation of signal transduction pathways mediating oxidative burst by chicken heterophils in response to stimulation with lipopolysaccharide and lipoteichoic acid.
Toll-like receptors (TLRs) have been previously shown to mediate oxidative burst in chicken heterophils. This study was conducted to begin to map the molecular pathways that regulate TLR-mediated oxidative burst. Peripheral blood heterophils from neonatal chicks were isolated and exposed to known inhibitors of signal transduction pathways for either 20 min (genistein, verapamil, or chelerythrine) or 120 min (pertussis toxin) at 39 degrees C. The cells were then stimulated for 30 min at 39 degrees C with Salmonella enteritidis lipopolysaccharide (LPS) or Staphylococcus aureus lipoteichoic acid (LTA). The heterophil oxidative burst was then quantitated by luminol-dependent chemiluminescence (LDCL). Genistein (a tyrosine kinase inhibitor), verapamil (a calcium channel blocker), chelerythrine (a protein kinase C inhibitor), and pertussis toxin (a G-protein inhibitor) significantly reduced LPS-stimulated oxidative burst in chicken heterophils by 34, 50, 63, and 51%, respectively. Although genistein had a statistically significant effect on reducing LPS-stimulated LDCL biologically it seems to play only a minor role within the oxidative burst pathway. Heterophils stimulated with the gram-positive TLR agonist, LTA, activated a different signal transduction pathway since chelerythrine was the only inhibitor that significantly reduced (72%) LTA-stimulated oxidative burst. These findings demonstrate that distinct signal transduction pathways differentially regulate the stimulation of oxidative burst in avian heterophils. Pertussis toxin-sensitive, protein kinase C-dependent, Ca(++)-dependent G proteins appear to regulate oxidative burst of avian heterophils stimulated with gram-negative agonist LPS; whereas, a protein kinase C-dependent signal transduction pathway plays the major role activating the oxidative burst of avian heterophils stimulated with gram-positive agonists. The distinct differences in the response of heterophils to these two agonists illustrate the specificity of TLRs to pathogen-associated molecular patterns (PAMP)s.


CytoMCS: A Multiple Maximum Common Subgraph Detection Tool for Cytoscape.
Comparative analysis of biological networks is a major problem in computational integrative systems biology. By computing the maximum common edge subgraph between a set of networks, one is able to detect conserved substructures between them and quantify their topological similarity. To aid such analyses we have developed CytoMCS, a Cytoscape app for computing inexact solutions to the maximum common edge subgraph problem for two or more graphs. Our algorithm uses an iterative local search heuristic for computing conserved subgraphs, optimizing a squared edge conservation score that is able to detect not only fully conserved edges but also partially conserved edges. It can be applied to any set of directed or undirected, simple graphs loaded as networks into Cytoscape, e.g. protein-protein interaction networks or gene regulatory networks. CytoMCS is available as a Cytoscape app at http://apps.cytoscape.org/apps/cytomcs.


Prevalence and Risk Factors for Human T-Cell Lymphotropic Virus (HTLV) in Blood Donors in Brazil-A 10-Year Study (2007-2016).
It is unknown whether HTLV-1/2 prevalence has been stable or changing with time in Brazil. We present a 10-year (2007-2016) analysis of HTLV-1/2 infection in first-time blood donors from four blood banks in Brazil. The Brazilian blood centers participating in this multicenter Recipient Epidemiology and Donor Evaluation Study (REDS) are located in Recife in the Northeast and in São Paulo, Rio de Janeiro and Belo Horizonte located in the Southeast of the country. A previous REDS study using the same database from 2007 to 2009 showed that the prevalence per 100,000 donors was 222 in Recife, 83 in Belo Horizonte and 101 in São Paulo. From 2007 to 2016, HTLV-1/2 prevalence was calculated by year, blood center and birth cohort. Covariates included age, gender, schooling, self-reported skin color and type of donation. From 1,092,174 first-blood donations, in the general analysis, HTLV-1/2 infection predominated in females, donors over 50 years of age, black skin color and less educated. The average prevalence was 228 per 100,000 donors in Recife, 222 in Rio de Janeiro, 104 in Belo Horizonte and 103 in São Paulo. In the 10-year analysis, HTLV-1/2 prevalence was stable, but a trend was observed toward an increase in HTLV-1/2 infection among younger people (p < 0.001), males (p = 0.049), those with white skin color (p < 0.001), and higher education (p = 0.014). Therefore, this 10-year surveillance of the infection showed stable HTLV-1/2 prevalence overall but a trend toward increased prevalence among the younger and more educated donors despite Brazilian policies to control sexually transmitted infections being in place for more than 10 years.


Integration of devices into long-term condition management: a synthesis of qualitative studies.
Understanding peoples' responses to and ability to incorporate technology for managing long-term conditions into their everyday lives is relevant for informing the development and implementation of new technologies as part of future long-term condition management in domestic environments. Future research and theory building can be facilitated by the synthesis of existing qualitative studies. A systematic search for qualitative studies of health technologies at home was undertaken on OVID CINAHL, OVID Medline and CSA databases for the period 1996-2006. Studies (n = 12) that met the inclusion criteria were synthesized and their analyses subjected to qualitative meta-synthesis. Analyses clustered into five themes: (1) managing multiple uncertainties; (2) the reconstruction of identity; (3) the struggle to remain autonomous while allowing dependence; (4) coming to terms with living a technology-assisted life; and (5) the usability of devices. These translated into a line of argument synthesis in which technology takes on the status of a personified ;other' around which a set of personal and relational attributions are subsequently constructed. These allow the extension of existing illness work to incorporate new technologies. Ambivalence about the value of technologies that are designed to assist with the management of a long-term condition reflects experiences of the disruptive effects of health technologies on personal identities and strategies of managing illness. At the same time, they are highly valued because they provided new opportunities to complete aspects of illness work that were previously impossible.


Perceived Truthfulness of Reduced Lung Cancer Risk Advertising Claims Influences Consumers' Intention to try and to Purchase Snus.
The objective of the current study was to evaluate the impact of a reduced risk claim about lung cancer, presented in various formats, on smokers' and non-smokers' interest in trying Camel Snus and intention to purchase Camel Snus. We varied claim formats by varying advertising messages for Camel Snus in 4 ways (1) text only; (2) bar chart; (3) text/testimonial; and (4) bar chart/testimonial. 3001 participants were recruited from a web-based consumer specialty panel via an email invitation. In 2015, a second study was conducted, using similar methods, where 3001 additional participants were recruited. Overall, controlling for other factors, the presence of an MRTP claim was not significantly related to interest in trying snus [X2 (4) = 8.567, P = .073], or purchase intentions [X2 (4) = 1.148, P = .887]. Relative to a control ad where no explicit health risk claim was made, the Graphic + testimonial [OR = 1.29] or Text only [OR = 1.41] claims did significantly increase interest in trying Camel Snus. However, the adverting format did not impact interest in purchasing Camel Snus. While current smokeless tobacco users (95%) and smokers (59%) expressed interest in trying Camel Snus, non-tobacco users (7%) showed low interest in trying or purchasing Camel Snus (P < .001). Interest in trying Camel Snus was stronger in younger smokers compared to older smokers. Among current smokers, worry about lung cancer (the key focus of the reduced risk claim) was not associated with interest in trying Camel Snus or with purchase intention [OR = .91, 95% CI: .72, 1.14] or intention to purchase snus [OR = 1.07, 95% CI: .86, 1.32]. Future research should evaluate how claim and messaging formats influence perceived truthfulness and whether this effect differs among sub-groups of consumers, such as adolescents, those with tobacco-related disease, and former smokers. It will also be helpful to understand whether perceptions of ad truthfulness result in changes in product use patterns over time. In sum, giving people truthful, credible information about relative product risks, such as through authorized MRTP claims, is important, but such information is likely insufficient to get smokers to switch.


Increasing activity attendance and engagement in individuals with dementia using descriptive prompts.
The effects of providing descriptive prompts to increase activity attendance and engagement in 6 individuals with dementia were evaluated using a reversal design. The results showed that providing descriptive prompts increased activity attendance and engagement for all participants. The results support the use of antecedent interventions for increasing appropriate behavior by individuals with dementia.


Polymer translocation under time-dependent driving forces: resonant activation induced by attractive polymer-pore interactions.
We study the driven translocation of polymers under time-dependent driving forces using N-particle Langevin dynamics simulations. We consider the force to be either sinusoidally oscillating in time or dichotomic noise with exponential correlation time, to mimic both plausible experimental setups and naturally occurring biological conditions. In addition, we consider both the case of purely repulsive polymer-pore interactions and the case with additional attractive polymer-pore interactions, typically occurring inside biological pores. We find that the nature of the interaction fundamentally affects the translocation dynamics. For the non-attractive pore, the translocation time crosses over to a fast translocation regime as the frequency of the driving force decreases. In the attractive pore case, because of a free energy well induced inside the pore, the translocation time can be a minimum at the optimal frequency of the force, the so-called resonant activation. In the latter case, we examine the effect of various physical parameters on the resonant activation, and explain our observations using simple theoretical arguments.


The emerging roles of nitric oxide and its associated scavengers, phytoglobins, in plant-symbiotic interactions.
A key feature in the establishment of symbiosis between plants and microbes is the maintenance of the balance between the production of the small redox-related molecule, nitric oxide (NO) and its cognate scavenging pathways. During the establishment of symbiosis, a transition from a normoxic to a microoxic environment often takes place triggering the production of NO from nitrite via a reductive production pathway. Plant hemoglobins (phytoglobins) are a central tenant of NO scavenging, with NO homeostasis maintained via the phytoglobin-NO cycle. While the first plant hemoglobin (leghemoglobin), associated with the symbiotic relationship between leguminous plants and bacterial Rhizobium species, was discovered in 1939, most other plant hemoglobins, identified only in the 1990s, were considered as non-symbiotic. From recent studies, it is becoming evident that the role of Phytogbs1 in the establishment and maintenance of plant-bacterial and plant-fungal symbiosis is also essential in roots. Consequently, the division of plant hemoglobins into symbiotic and non-symbiotic groups becomes less justified. While the main function of Phytogbs1 is related to the regulation of NO levels, participation of these proteins in the establishment of symbiotic relationships between plants and microorganisms represents another important dimension among the other processes in which these key redox-regulatory proteins play a central role.


Percutaneous mesenteric venous thrombectomy and thrombolysis: successful treatment followed by liver transplantation.
Mesenteric vein thrombosis (MVT) is a rare cause of intestinal ischemia. Because of its nonspecific symptoms, diagnosis is often delayed. We describe a patient with liver cirrhosis who developed acute MVT while waiting for liver transplantation. Surgical intervention carried a high risk because of her underlying cirrhosis. Mesenteric venous thrombectomy and thrombolysis were performed with an AngioJet (Possis Medical, Minneapolis, MN) thrombectomy device and streptokinase infusion through transjugular route. The patient subsequently received an orthotopic liver transplant. We also present a review of the literature about the occurrence and treatment options for MVT.


Circadian rhythms and exercise - re-setting the clock in metabolic disease.
Perturbed diurnal rhythms are becoming increasingly evident as deleterious events in the pathology of metabolic diseases. Exercise is well characterized as a crucial intervention in the prevention and treatment of individuals with metabolic diseases. Little is known, however, regarding optimizing the timing of exercise bouts in order to maximize their health benefits. Furthermore, exercise is a potent modulator of skeletal muscle metabolism, and it is clear that skeletal muscle has a strong circadian profile. In humans, mitochondrial function peaks in the late afternoon, and the circadian clock might be inherently impaired in myotubes from patients with metabolic disease. Timing exercise bouts to coordinate with an individual's circadian rhythms might be an efficacious strategy to optimize the health benefits of exercise. The role of exercise as a Zeitgeber can also be used as a tool in combating metabolic disease. Shift work is known to induce acute insulin resistance, and appropriately timed exercise might improve health markers in shift workers who are at risk of metabolic disease. In this Review, we discuss the literature regarding diurnal skeletal muscle metabolism and the interaction with exercise bouts at different times of the day to combat metabolic disease.


Growth cone pathfinding: a competition between deterministic and stochastic events.
Growth cone migratory patterns show evidence of both deterministic and stochastic search modes. We quantitatively examine how these two different migration modes affect the growth cone's pathfinding response, by simulating growth cone contact with a repulsive cue and measuring the resultant turn angle. We develop a dimensionless number, we call the determinism ratio Psi, to define the ratio of deterministic to stochastic influences driving the growth cone's migration in response to an external guidance cue. We find that the growth cone can exhibit three distinct types of turning behaviors depending on the magnitude of Psi. We conclude, within the context of these in silico studies, that only when deterministic and stochastic migration factors are in balance (i.e. Psi ~ 1) can the growth cone respond constructively to guidance cues.


Use of thymic grafts or thymic factors to augment immunologic recovery after bone marrow transplantation: brief report with 2 to 12 years' follow-up.
Thymus tissue implants, thymic epithelial cells obtained from third party donors sharing one HLA-A and -B locus with the recipient, or the thymic hormones thymosin fraction 5 and thymopentin were given to recipients of HLA-identical sibling bone marrow to prevent chronic graft-versus-host disease (GVHD) and accelerate immunologic reconstitution. The clinical courses of 17 patients receiving thymus tissue and 18 patients receiving thymic hormones were reported initially 5 years ago and showed no difference in the incidence of chronic GVHD or immunologic recovery from those of concurrent or historical controls. We report here for the first time nine new patients who received thymus tissue implants with modifications of the culture method to lower the number of lymphocytes in the transplanted tissue with the intent of reducing rejection of the thymus tissue grafts. The clinical outcomes and immunologic functions of these nine patients were similar to those of the recipients of the earlier thymus tissue implants. With follow-up now ranging from 2.2 to 12.3 years (median 6.7) for the total group, 16 patients are alive. Seven never developed chronic GVHD. Nine were treated for chronic GVHD, seven of whom recovered and are leading normal lives, one has chronic pulmonary insufficiency, and one is disabled from chronic GVHD. We conclude that thymus tissue grafts or thymic epithelial cells partially HLA-matched to the recipient, thymosin fraction 5, or thymopentin used as described were not effective in reducing the incidence of chronic GVHD, improving immunologic recovery, or altering long-term survival.


Effect of Salt Stress on Growth, Physiological Parameters, and Ionic Concentration of Water Dropwort (Oenanthe javanica) Cultivars.
Salt stress is an important environmental limiting factor. Water dropwort (Oenanthe javanica) is an important vegetable in East Asia; however, its phenotypic and physiological response is poorly explored. For this purpose, 48 cultivars of water dropwort were grown hydroponically and treated with 0, 50, 100, and 200 mm NaCl for 14 days. Than their phenotypic responses were evaluated, afterward, physiological studies were carried out in selected sensitive and tolerant cultivars. In the present study, the potential tolerant (V11E0022) and sensitive (V11E0135) cultivars were selected by screening 48 cultivars based on their phenotype under four different levels of salt concentrations (0, 50, 100, and 200 mm). The results depicted that plant height, number of branches and leaves were less effected in V11E0022, and most severe reduction was observed in V11E0135 in comparison with others. Than the changes in biomass, ion contents, accumulation of reactive oxygen species, and activities of antioxidant enzymes and non-enzymatic antioxidants were determined in the leaves and roots of the selected cultivars. The potential tolerant cultivar (V11E0022) showed less reduction of water content and demonstrated low levels of Na+ uptake, malondialdehyde, and hydrogen peroxide (H2O2) in both leaves and roots. Moreover, the tolerant cultivar (V11E0022) showed high antioxidant activities of ascorbate peroxidase (APX), superoxide dismutase, peroxidase, catalase (CAT), reduced glutathione (GSH), and high accumulation of proline and soluble sugars compared to the sensitive cultivar (V11E0135). These results suggest the potential tolerance of V11E0022 cultivar against salt stress with low detrimental effects and a good antioxidant defense system. The observations also suggest good antioxidant capacity of water dropwort against salt stress. The findings of the present study also suggest that the number of branches and leaves, GSH, proline, soluble sugars, APX, and CAT could serve as the efficient markers for understanding the defense mechanisms of water dropwort under the conditions of salt stress.


Graft-versus-host disease: unexpected presentation with simultaneous hepatitis and pancreatitis.
We report the case of a 37-year-old man with a previous bone marrow transplantation presenting with abdominal pain, diarrhoea and jaundice. Laboratory evaluation showed marked elevated liver enzymes, amylase and lipase with ultrasonographic evidence of acute alithiasic pancreatitis. Liver biopsy was compatible with graft-versus-host disease and toxic hepatitis. The patient rapidly improved after increasing immunosuppression. Although gastrointestinal manifestations are common in graft-versus-host disease, clinical acute pancreatitis is rarely seen. Patients with graft versus host are seldom managed by gastroenterologists and hepatologists. An awareness of this condition is essential for the experienced clinician.


Multi-institutional development and validation of a novel histologic grading system for colonic graft-versus-host disease.
Graft-versus-host disease (GVHD) remains a major complication for patients who have undergone hematopoietic stem cell transplantation. The Lerner system is the most widely used histologic grading score for gastrointestinal GVHD but its clinic utility is debated. The aim of our study was to develop a novel histologic grading system for gastrointestinal GVHD that incorporates independent evaluation of both apoptotic counts and crypt destruction. Colonic biopsies taken to assess for GVHD were retrospectively assessed for: Crypt damage (No crypt dropout or ulceration-0; crypt dropout without ulceration-1; ulceration-2) and crypt apoptotic counts (No apoptosis-0; 1-6 apoptotic bodies per 10 contiguous crypts-1; >6apoptotic bodies per 10 contiguous crypts-2). The two scores were added together to get an overall grade (0-4). Alternative apoptotic cutoff points were examined. An apoptotic cutoff of >9 apoptotic bodies per 10 contiguous crypts marginally improved the area under the curve (AUC), but the AUCs from the resulting novel grade calculations were not significantly different (p = 0.10). Lerner grading was also applied. The study group consisted of an initial analysis cohort (n = 191) and a second validation cohort from a separate institution (n = 97). In the initial analysis cohort, our histologic grading system provided prognostic stratification for GVHD-related death within 6 months (p = 0.0004, AUC = 0.705). The Lerner system performed similarly in terms of providing prognostic stratification for GVHD-related death (p = 0.0001, AUC = 0.707). In the external validation cohort, our histologic grading system was not associated with GVHD-related death (p = 0.14, AUC = 0.621), but the Lerner system was associated with GVHD-related death (p = 0.048, AUC = 0.663). While our grading system may have some advantages compared to the Lerner system, due to lack of reproducibility we do not currently recommend widespread adoption of this system. Nonetheless, we present a standardized tool for assessing both apoptosis and crypt damage. Future studies assessing alternative histologic grading systems with external validation and further examination the lower apoptotic threshold for GVHD diagnosis are warranted.


An analysis of provider attitudes toward end-of-life decision-making.
The explosion of technological and biomedical interventions over the past half century appears to have enhanced the medical profession's ability to prolong life at a faster pace than society's ability to develop comprehensive bioethical laws governing end-of-life decisions. This study was conducted to determine if there was a correlation between educational and occupational backgrounds and participants' perceptions of end-of-life care. Study participants came from various areas and levels of healthcare at a large federal healthcare facility and included nurses, doctors, pharmacists, dietitians, administrators, and others. Participants completed a questionnaire providing both sociodemographic information and perceptions of end-of-life care. Respondents were classified by type of education or background (technical, professional, or medical) and by level of involvement with patient care (direct or indirect). While the results showed a general consensus about the importance of respecting patients' end-of-life wishes, there were differences among respondents in regard to specific issues.