Platinum- and gold-catalyzed cycloisomerization reactions of hydroxylated enynes.
Exposure of enynes containing a hydroxyl group at one of the propargylic positions to catalytic amounts of either PtCl2 or (PPh3)AuCl/AgSbF6 results in a selective rearrangement with formation of bicyclo[3.1.0]hexan-3-one derivatives. The same products are obtained by a "one-pot" process on treatment of an alkynal with allylchlorodimethylsilane (4) and PtCl2 via a reaction cascade involving an initial platinum-catalyzed allylation followed by the cycloisomerization of the homoallylic alcohol formed in situ. This novel skeletal reorganization process was implemented into a concise total synthesis of the terpenes sabinone (18) and sabinol (19). Furthermore it is shown that conversion of the hydroxylated enynes into the corresponding acetates followed by reaction with a cationic gold catalyst formed from (PPh3)AuCl and AgSbF6 opens entry into isomeric products bearing the ketone function at the C-2 position of the bicyclo[3.1.0]hexane skeleton. The outcome of a deuterium labeling experiment and the analysis of the stereochemical course of the cycloisomerization reaction are consistent with the formation of cyclopropylmethyl platinum carbene species as reactive intermediates.


[Analysis of psychosocial factors in epidemiologic study of cardiologic examination--preliminary results of Warsaw POL-MONICA].
Several epidemiological studies have focused on influence of psychosocial factors on intensity of cardiovascular diseases in general population. In 1988 Warsaw POL-MONICA PROJECT was performed covering the population of 710 men and 723 women, aged 35-64. We found that 25.1% men and 25.8% women had type A behaviour pattern (TABP). TABP was rare represented in the older age group and in low-educated persons. Extreme sleep disturbances were observed significantly (p < 0.001) more often in women (10.7%) than in men (4.9%) and the percentage increased with age. Extreme sleep disturbances were also found more often among elementary educated persons (16%) versus the others (p < 0.001). Low social support level was observed twice often in women (29.7%) than in men (14.8%) and the percentage increased with age and with lower education level (p < 0.001). Extreme stress level was found more often in women (13.3%) than in men (5.6%) (p < 0.001) and in the oldest age-group. In both sex-groups mean anger levels decreased with age (p < 0.05). Mean anxiety levels didn't differ significantly neither in age-groups nor in education categories.


Genome-wide association mapping and genomic prediction for CBSD resistance in Manihot esculenta.
Cassava (Manihot esculenta Crantz) is an important security crop that faces severe yield loses due to cassava brown streak disease (CBSD). Motivated by the slow progress of conventional breeding, genetic improvement of cassava is undergoing rapid change due to the implementation of quantitative trait loci mapping, Genome-wide association mapping (GWAS), and genomic selection (GS). In this study, two breeding panels were genotyped for SNP markers using genotyping by sequencing and phenotyped for foliar and CBSD root symptoms at five locations in Uganda. Our GWAS study found two regions associated to CBSD, one on chromosome 4 which co-localizes with a Manihot glaziovii introgression segment and one on chromosome 11, which contains a cluster of nucleotide-binding site-leucine-rich repeat (NBS-LRR) genes. We evaluated the potential of GS to improve CBSD resistance by assessing the accuracy of seven prediction models. Predictive accuracy values varied between CBSD foliar severity traits at 3 months after planting (MAP) (0.27-0.32), 6 MAP (0.40-0.42) and root severity (0.31-0.42). For all traits, Random Forest and reproducing kernel Hilbert spaces regression showed the highest predictive accuracies. Our results provide an insight into the genetics of CBSD resistance to guide CBSD marker-assisted breeding and highlight the potential of GS to improve cassava breeding.


Successful pregnancy with the use of vaginal pessary in a patient with a very short cervix. A case report.
Preterm birth is one of the causes of perinatal morbidity and mortality. The traditional treatment for a short cervix has been the cerclage in addition with the progesterone administration. Recently, the idea of using vaginal pessaries as a new less invasive method of treatment for the same indication is under discussion. The case of a 29-year-old pregnant woman with an extremely short cervix and the treatment, she underwent during her second pregnancy, is presented. In order to avoid a preterm delivery the patient was treated with the use of a vaginal pessary. After the placement of the pessary and its removal after 37 weeks of gestation, a full term delivery was performed. The pessary was symptom free throughout. In conclusion, the cervical pessary may offer a safe and easy alternative to cerclage for the treatment of cervical insufficiency and prevention of preterm birth.


Moderate immigration may promote a peak of cooperation among natives.
In a world of hardening borders, nations may deprive themselves of enjoying the benefits of cooperative immigrants. Here we analyze the effect of efficient cooperative immigrants on a population playing public goods games. We considered a population structured on a square lattice with individuals playing public goods games with their neighbors. The demographics are determined by stochastic birth, death, and migration. The strategies spread through imitation dynamics. Our model shows that cooperation among natives can emerge due to social contagion of good role-model agents that can provide better quality public goods. Only a small fraction of efficient cooperators, among immigrants, is enough to trigger cooperation across the native population. We see that native cooperation achieves its peak at moderate values of immigration rate. Such efficient immigrant cooperators act as nucleation centers for the growth of cooperative clusters, which eventually dominate defection.


Alterations in the endothelial G-protein coupled receptor pathway in epicardial arteries and subendocardial arterioles in compensated left ventricular hypertrophy.
The present study was designed to compare alterations of endothelium-dependent vasorelaxation in coronary epicardial arteries and subendocardial arterioles occurring in left ventricular hypertrophy (LVH) secondary to 60 days of aortic banding in a porcine model. Development of LVH was documented by echocardiogram and the endothelial function of subendocardial and epicardial vessels was studied by constructing concentration-response curves in a pressure myograph and standard organ chambers, respectively. 5-HT induced relaxations were reduced (p<0.05) in both vessel types isolated from pigs with LVH. Dilations of subendocardial arterioles and epicardial vessels to UK14304 were depressed by LVH. In the presence of Nomega-nitro-L-arginine (L-NNA), EDHF solely accounts for BK-induced relaxations; it fully compensates for the loss of NO in arterioles, but only partially in epicardial arteries isolated from LVH swine. Endothelium-independent relaxations induced by SNP were not altered in both vessel types from the LVH group. In a porcine model of LVH secondary to 60 days of aortic banding, the associated coronary endothelial dysfunction preferentially involves Gi-protein mediated relaxations in arterioles and arteries but also affects Gq-protein mediated relaxations in epicardial coronary arteries.


Schistosoma mansoni: DNA synthesis in males and females from mixed and single-sex infections.
The pattern of DNA synthesis in male and female Schistosoma mansoni from mixed and single-sex infections in mice has been determined biochemically and autoradiographically using the incorporation of [3H]-thymidine as a specific marker of DNA synthesis. During early development (up to 35 days post-infection (p.i.] adult males and females from mixed infections had a comparable specific activity of DNA. In males, from 35 days p.i. onwards, the specific activity of DNA decreased rapidly to become significantly different from that observed in females. In single-sex infections DNA synthesis in females was depressed compared to that observed in males from single-sex infections and was also significantly different (P less than or equal to 0.01) from DNA synthesis in females from mixed infections. There was no significant difference in DNA synthesis between males from single or mixed infections. DNA synthesis in both sexes was found to be sensitive to hydroxyurea treatment, the inhibition in sexually mature females being approximately 75% and in males approximately 45%. Autoradiography using both light microscope and electron microscope techniques revealed that the testes and ovary had labelled cells. In male schistosomes the only other labelled cells were small undifferentiated cells found scattered through the tissues. In females the vitelline gland had large numbers of densely labelled nuclei within Stage 1 vitelline cells, as well as numerous small undifferentiated cells.


Parental longevity, carotid atherosclerosis, and aortic arterial stiffness in adult offspring.
We examined the associations of parental longevity with carotid intima-media thickness, carotid plaques, and aortic arterial stiffness in adult offspring. A population of 1117 volunteers who participated in the SUVIMAX Vascular Study (mean age, 59.7 years; 49.0% women) were included. Carotid-femoral pulse-wave velocity (PWV) was used to assess aortic stiffness. Carotid B-mode ultrasound examination included measurements (at sites free of plaque) of intima-media thickness at the common carotid arteries and assessment of atherosclerotic plaques in the extracranial carotid arteries. The prevalence of carotid plaques in subjects whose fathers had died at <65 years, in those whose fathers were alive at 65 years but who had died by 80 years, and in those whose fathers were alive at 80 years was 40.4%, 30.4%, and 28.9%, respectively (P<0.001). The multivariate odds ratios of carotid plaques in the 3 groups of paternal longevity, adjusted for conventional cardiovascular risk factors, were 1, 0.68 (95% CI, 0.48 to 0.96), and 0.69 (95% CI, 0.49 to 0.98), respectively. The mean common carotid arteries intima-media thickness was higher in subjects with premature paternal death in univariate (P<0.007) but not in multivariate (P=0.39) analyses. Mean PWV decreased with increasing paternal longevity in both univariate and multivariate analyses. The multivariate-adjusted means of PWV in the 3 groups of paternal longevity were 11.9+/-0.14, 11.7+/-0.12, and 11.0+/-0.12 m/s (P<0.0001), respectively. In contrast, neither B-mode ultrasound measurements nor PWV measurements were associated with maternal longevity. These results may indicate that there are modifications of structure and function of large arteries according to paternal longevity.


Insulin resistance has no impact on ghrelin suppression in pregnancy.
Ghrelin is reduced in various states of insulin resistance. The aim of this study was to examine the relationship between ghrelin and glucose metabolism during pregnancy - a natural insulin-resistant state - in women with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) or gestational diabetes mellitus (GDM) and potential changes 3 months after delivery. A total of 54 women, 37 pregnant and with various degrees of insulin resistance and 24 postpartum (PP, seven of them also studied during pregnancy) were studied. Ghrelin plasma concentrations at fasting and 60' following glucose loading (75 g-2 h-oral glucose tolerance test), area under the curve of plasma glucose (G-AUC(OGTT)) and insulin sensitivity [homeostatic model assessment (HOMA) and oral glucose sensitivity index (OGIS) indices, respectively] were determined. Both baseline and 60' ghrelin concentrations were to a comparable degree ( approximately by 65%) suppressed in NGT, IGT and GDM as compared to the PP group (the latter being indistinguishable from NGT regarding glucose tolerance and insulin sensitivity). In all women studied both during and after pregnancy, ghrelin levels rose from pregnancy to PP (mean increase 313.8%; P < 0.03). There was no correlation between baseline ghrelin and insulin sensitivity as estimated from both baseline (HOMA) and dynamic (OGTT:OGIS) glucose and insulin data. Ghrelin is substantially decreased during pregnancy, but glucose-induced ghrelin suppression is preserved at a lower level. There is apparently no relation to the degree of insulin resistance.


The experience of seeking help for postnatal depression.
This qualitative study sought to explore women's experiences of support and treatment for postnatal depression. In-depth interviews from seven women were analysed using the phenomenological method described by Creswell (1998). Findings indicate that partners provided women the most support. The women did not know where to seek professional help, often being identified and helped by the maternal health nurse who monitors and guides the progress of their babies' development. Hospital programs were criticised for not informing and involving family. The women were dissatisfied with hospital doctors and their GPs claiming they had limited time for counselling, preferring to prescribe medication that alleviated symptoms but reinforced feelings of inadequacy. Recommendations are made to involve families and to use the unique position of the maternal health nurse in assessing new mothers.


[Diagnostic value of cystatin C and neutrophil gelatinase-associated lipocalin in primary glomerulopathies].
To study an association between clinical and morphological evidence and the serum and daily urinary levels of cystatin C (CysC) and neutrophil gelatinase-associated lipocalin (NGAL) in patients with primary glomerulopathies. The investigation included 104 patients; morphological examination showed minimal change disease in 15 (14.4%) patients, focal segmental glomerulosclerosis in 24 (23.1%), membrane nephropathy in 32 (30.8%), and IgA nephropathy (mesangioproliferative glomerulonephritis) in 33 (31.7%). The investigators analyzed the clinical type of nephropathy, performed conventional laboratory and instrumental examinations, and determined the level of CysC (by immunoturbodimetry) and NGAL (by enzyme immunoassay) in the serum and daily urine taken before kidney biopsy. The degree of glomerulosclerosis, tubulointerstititial sclerosis, and tubular atrophy was semiquantitatively estimated. Urinary CysC and NGAL excretion correlated with the degree of glomerulosclerosis and proteinuria and the reduced glomerular filtration rate (GFR) regardless of the method of its determination. The urinary level of NGAL positively correlated with the degree of tubular atrophy. The GFR value determined from serum CysC and creatinine levels more precisely reflected the degree of glomerulosclerosis. The tubulointerstitial compartment in primary glomerulopathies should be determined not only by morphological changes, but also by tubular function parameters by estimating the urinary excretion of biomarkers. The urinary content of CysC reflects tubular epithelial dysfunction whereas that of NGAL also characterizes tubular atrophy. To estimate the degree of glomerulosclerosis, it is more preferable to use the GFR calculated from the blood concentrations of CysC and creatinine, by keeping in mind clinical findings (using Chronic Kidney Disease Epidemiology Collaboration formula, 2012).


In silico design, synthesis, and assays of specific substrates for proteinase 3: influence of fluorogenic and charged groups.
Neutrophil serine proteases are specific regulators of the immune response, and proteinase 3 is a major target antigen in antineutrophil cytoplasmic antibody-associated vasculitis. FRET peptides containing 2-aminobenzoic acid (Abz) and N-(2,4-dinitrophenyl)ethylenediamine (EDDnp) as fluorophore and quencher groups, respectively, have been widely used to probe proteases specificity. Using in silico design followed by enzymatic assays, we show that Abz and EDDnp significantly contribute to substrate hydrolysis by PR3. We also propose a new substrate specific for PR3.


[Secondary anterior sphincteroplasty for anal incontinence after delivery].
The prevalence of anal sphincter rupture at vaginal delivery is from 0.5 to 2.5 %. More than 50 % of these patients may need a secondary anterior sphincteroplasty because of anal incontinence. We present prospective series of 29 women (median age 45 years) operated with an overlapping anterior sphincteroplasty from 1996 to 2001. The patients were examined with anal ultrasonography (n = 23), manometry (n = 19) and neurophysiologically (n = 13), and divided into group 1 (n = 19) with anal sphincter rupture and group 2 (n = 10) with sphincter rupture as well as pudendal neuropathy. All patients (n = 29) were examined with the Cleveland Clinic incontinence score before and median eight (2-64) months after operation. Median incontinence score before and after operation was 11.0 (0-22) versus 5.0 (0-16) (p = 0.002) for group 1; 18.0 (15-24) versus 15.5 (11-24) (p = 0.034) for group 2. There was also a significant difference between the groups concerning incontinence scores both preoperatively (p = 0.045) and postoperatively (p = 0.028). An improvement of continence was seen in 15 (79 %) of the patients in group 1 compared to 4 patients (40 %) in group 2. In group 1 a significant increase of median resting and squeeze pressures was seen. Anterior sphincteroplasty improves anal continence considerably in patients with isolated sphincter rupture. However, patients with evidence of pudendal neuropathy must be informed that they should expect only a minor improvement in continence after operation.


Evidence for Structural and Functional Alterations of Frontal-Executive and Corticolimbic Circuits in Late-Life Depression and Relationship to Mild Cognitive Impairment and Dementia: A Systematic Review.
Depression is a risk factor for developing Alzheimer's disease and Related Dementia (ADRD). We conducted a systematic review between 2008 and October 2018, to evaluate the evidence for a conceptual mechanistic model linking depression and ADRD, focusing on frontal-executive and corticolimbic circuits. We focused on two neuroimaging modalities: diffusion-weighted imaging measuring white matter tract disruptions and resting-state functional MRI measuring alterations in network dynamics in late-life depression (LLD), mild cognitive impairment (MCI), and LLD+MCI vs. healthy control (HC) individuals. Our data synthesis revealed that in some but not all studies, impairment of both frontal-executive and corticolimbic circuits, as well as impairment of global brain topology was present in LLD, MCI, and LLD+MCI vs. HC groups. Further, posterior midline regions (posterior cingulate cortex and precuneus) appeared to have the most structural and functional alterations in all patient groups. Future cohort and longitudinal studies are required to address the heterogeneity of findings, and to clarify which subgroups of people with LLD are at highest risk for developing MCI and ADRD.


Prospects for Recyclable Multilayer Packaging: A Case Study.
Food preservation is an essential application for polymers, particularly in packaging. Complex multilayer films, such as those used for modified atmosphere packaging (MAP), extend the shelf life of sensitive foods. These mostly contain various polymers to achieve the necessary combination of mechanic, optic, and barrier properties that limit their recyclability. As the European Union's Circular Economy Action Plan calls for sustainable products and business models, including waste prevention policies and recycling quotas, with plastic packaging being a high priority, solutions towards more sustainable multilayer packaging are urgently needed. This study evaluated and compared the recycling potential of functionally equivalent PET (polyethylene terephthalate) and PP (polypropylene) post-consumer MAP through structure analysis and recycling simulation. The structure analysis revealed that both types of MAP contained functional (stability) and barrier layers (oxygen and moisture). The recycling simulation showed that the PP-based packaging was recyclable 10 times, maintaining its mechanical properties and functionality. At the same time, the PET-based MAP resulted in a highly brittle material that was unsuitable for reprocessing into similar economic value products. The secondary material from the PP-based MAP was successfully manufactured into films, demonstrating the functional possibility of closed-loop recycling. The transition from a linear to a circular economy for MAP is currently still limited by safety concerns due to a lack of sufficient and efficient purification methods, but the proper design of multilayers for recyclability is a first step towards circularity.


Antigenic experience dictates functional role of glycogen synthase kinase-3 in human CD4+ T cell responses.
Signals induced by the TCR and CD28 costimulatory pathway have been shown to lead to the inactivation of the constitutively active enzyme, glycogen synthase kinase-3 (GSK3), which has been implicated in the regulation of IL-2 and T cell proliferation. However, it is unknown whether GSK3 plays a similar role in naive and memory CD4(+) T cell responses. Here we demonstrate a divergence in the dependency on the inactivation of GSK3 in the proliferative responses of human naive and memory CD4(+) T cells. We find that although CD28 costimulation increases the frequency of phospho-GSK3 inactivation in TCR-stimulated naive and memory CD4(+) T cells, memory cells are less reliant on GSK3 inactivation for their proliferative responses. Rather we find that GSK3beta plays a previously unrecognized role in the selective regulation of the IL-10 recall response by human memory CD4(+) T cells. Furthermore, GSK3beta-inactivated memory CD4(+) T cells acquired the capacity to suppress the bystander proliferation of CD4(+) T cells in an IL-10-dependent, cell contact-independent manner. Our findings reveal a dichotomy present in the function of GSK3 in distinct human CD4(+) T cell populations.


A Pilot Cross-Sectional Study of Postpartum Wrist Pain in an Urban Chinese Population: Its Prevalence and Risk Factors.
Wrist pain after childbirth is commonly encountered in clinical practice. Little is known about the prevalence of this musculoskeletal disorder which is important to overall maternal health. To examine the prevalence of and risk factors for de novo wrist pain in women after childbirth. A pilot cross-sectional survey. A telephone interview was conducted 2 months after childbirth among women who delivered at a tertiary hospital in Hong Kong. The prevalence of de novo wrist pain was recorded; its severity was rated using the numerical rating scale and Patient-Rated Wrist Evaluation (PRWE) with pain and functional subscale scores. In total, 259 women aged 32.8 ± 4.0 years participated; 149 women (57.5%) developed wrist pain after childbirth and 125 (84%) had persistent wrist pain 2 months postpartum. The majority had moderate (43.5%) to severe (21%) wrist pain. Bilateral involvement was common (56.8%), with most of the pain (59.3%) located on the radial side of the wrist. Primiparity was associated with wrist pain development (odds ratio 2.62, 95% confidence interval 1.33 - 5.16, P = 0.01); pain intensity was negatively correlated with the baby's birth weight (beta = -1.059, P = 0.013). Mean PRWE pain and function scores were 22.8 ± 10.3 and 15.6 ± 10.7, respectively. Cross-sectional survey is prone to volunteer bias, though recent literature indicates that the bias may not substantially affect the internal validity of the study. Wrist pain is prevalent after childbirth; future studies may consider looking into its exact pathology, long-term consequences, and overall effect on maternal health. Wrist pain, DeQuervain disease, postpartum, childbirth, mothers, prevalence, cross sectional study, survey.


Amentoflavone inhibits colorectal cancer epithelial-mesenchymal transition via the miR-16-5p/HMGA2/β-catenin pathway.
Amentoflavone is a type of bioflavonoid that exists in many Chinese medicines and has anti-inflammatory, antioxidant, antiviral, and anticancer effects. However, the effect of amentoflavone on epithelial to mesenchymal transition (EMT) in human colorectal cancer (CRC) has not been studied. In this study, we aim to explore the effect of amentoflavone on EMT in CRC. The effects of long noncoding RNA (lncRNA) miR-16-5p on proliferation, migration, and invasion were determined by in vitro and in vivo experiments. A luciferase reporter assay was carried out to reveal the interaction between miR-16-5p and targeted genes. Reverse transcription polymerase chain reaction (RT-PCR) was used to evaluate the expression of miR-16-5p. A western blot assay was used to detect the expression of targeted genes in CRC cells. The results showed that amentoflavone significantly inhibited CRC migration, invasion, and EMT by increasing miR-16-5p expression. Mechanistically, amentoflavone induced inactivation of the Wnt/β-catenin pathway via miR-16-5p, directly targeting 3'-UTR of HMGA2 to suppress HMGA2 expression in CRC. Clinically, combined miR-16-5p and HMGA2 levels may serve as a predictor for poor prognosis in patients with CRC. Furthermore, an in vivo PDX model suggested that amentoflavone exhibited antitumor effects in vivo via the miR-16-5p/HMGA2/β-catenin pathway. This is the first study to show that amentoflavone inhibits CRC EMT via the miR-16/HMGA2/β-catenin pathway. Amentoflavone may be beneficial in treating CRC patients in the clinic.


[The use of the Stone Sweeper catheter for stone disease of the upper urinary tract].
The treatment of patients with a great burden of stones is very difficult and often requires complex treatments including different kinds of surgery, associated in some cases with ureteral stents. We present the case of a patient with complex renoureteral stone disease in whom we used the stone sweeper stent before SWL. The catheter is a 6.5 Fr radial expanding stent with small baskets, a special structure designed to extract small stones < 5mm. The placement and retrieval of bilateral stents were performed without complications, extracting several small stones inside the baskets. The Stone Sweeper stent may play an important role in the treatment of patients with great stone burden; by dilating the ureter and helping the passage of stones and capturing small residual fragments it may decrease the need of new treatments. Currently, more clinic and research tests with this stent are necessary to determine proper indications and associated complications.


Gait deficiencies associated with peripheral artery disease are different than chronic obstructive pulmonary disease.
Previous studies have indicated that patients with peripheral artery disease (PAD), display significant differences in their kinetic and kinematic gait characteristics when compared to healthy, aged-matched controls. The ability of patients with chronic obstructive pulmonary disease (COPD) to ambulate is also limited. These limitations are likely due to pathology-driven muscle morphology and physiology alterations establish in PAD and COP, respectively. Gait changes in PAD were compared to gait changes due to COPD to further understand how altered limb muscle due to disease can alter walking patterns. Both groups were independently compared to healthy controls. It was hypothesized that both patients with PAD and COPD would demonstrate similar differences in gait when compared to healthy controls. Patients with PAD (n=25), patients with COPD (n=16), and healthy older control subjects (n=25) performed five walking trials at self-selected speeds. Sagittal plane joint kinematic and kinetic group means were compared. Peak values for hip flexion angle, braking impulse, and propulsive impulse were significantly reduced in patients with symptomatic PAD compared to patients with COPD. After adjusting for walking velocity, significant reductions (p<0.05) in the peak values for hip flexion angle, dorsiflexor moment, ankle power generation, propulsion force, braking impulse, and propulsive impulse were found in patients with PAD compared to healthy controls. No significant differences were observed between patients with COPD and controls. The results of this study demonstrate that while gait patterns are impaired for patients with PAD, this is not apparent for patients with COPD (without PAD). PAD (without COPD) causes changes to the muscle function of the lower limbs that affects gait even when subjects walk from a fully rested state. Altered muscle function in patients with COPD does not have a similar effect.


Heterogeneous responsiveness of normolipemic women to n-3 long chain fatty acid supplementation. Changes in serum lipids and apoproteins.
The effect of 10 day-low dosage of n-3 long chain fatty acids (390 mg/day of EPA and 252 mg/day of DHA) on lipid and apolipoprotein (Apo) concentrations has been studied in nine normolipidaemic women aged 28.9 +/- 4.2 years. n-3 fatty acid supplementation did not significantly decrease total cholesterol and triglyceride levels but markedly decreased the Apo A1 and Apo B concentrations (12.7%, p < 0.01 and 23.1%, p < 0.001, respectively), while the Apo A1/Apo B ratio significantly increased (14.8%, p < 0.02). In contrast to the individual variations found for triglycerides and cholesterol, Apo changes indicate a fairly homogeneous response to the fish oil supplement. In seven women Apo A1 decreased (> 10%), whereas Apo B decreased (> 10%) in all of them. The Apo A1/Apo B ratio increased (> 10%) in five of these nine women. Changes in Apo A-1 and Apo B did not significantly correlate with changes in serum lipids. These findings suggest that short-term supplementation with low amount of n-3 long chain fatty acids, EPA and DHA, influences the serum Apo content more than the lipid levels in normolipidaemic women.


Evolution of High Cellulolytic Activity in Symbiotic Streptomyces through Selection of Expanded Gene Content and Coordinated Gene Expression.
The evolution of cellulose degradation was a defining event in the history of life. Without efficient decomposition and recycling, dead plant biomass would quickly accumulate and become inaccessible to terrestrial food webs and the global carbon cycle. On land, the primary drivers of plant biomass deconstruction are fungi and bacteria in the soil or associated with herbivorous eukaryotes. While the ecological importance of plant-decomposing microbes is well established, little is known about the distribution or evolution of cellulolytic activity in any bacterial genus. Here we show that in Streptomyces, a genus of Actinobacteria abundant in soil and symbiotic niches, the ability to rapidly degrade cellulose is largely restricted to two clades of host-associated strains and is not a conserved characteristic of the Streptomyces genus or host-associated strains. Our comparative genomics identify that while plant biomass degrading genes (CAZy) are widespread in Streptomyces, key enzyme families are enriched in highly cellulolytic strains. Transcriptomic analyses demonstrate that cellulolytic strains express a suite of multi-domain CAZy enzymes that are coregulated by the CebR transcriptional regulator. Using targeted gene deletions, we verify the importance of a highly expressed cellulase (GH6 family cellobiohydrolase) and the CebR transcriptional repressor to the cellulolytic phenotype. Evolutionary analyses identify complex genomic modifications that drive plant biomass deconstruction in Streptomyces, including acquisition and selective retention of CAZy genes and transcriptional regulators. Our results suggest that host-associated niches have selected some symbiotic Streptomyces for increased cellulose degrading activity and that symbiotic bacteria are a rich biochemical and enzymatic resource for biotechnology.


Rapid mapping of urinary schistosomiasis: An appraisal of the diagnostic efficacy of some questionnaire-based indices among high school students in Katsina State, northwestern Nigeria.
In sub-Saharan Africa, over 200 million individuals are estimated to be infected with urinary and intestinal schistosomiasis. In a bid to lay a foundation for effective future control programme, this study was carried out with the aim of assessing the diagnostic efficacy of some questionnaire-based rapid assessment indices of urinary schistosomiasis. A total number of 1,363 subjects were enrolled for the study. Questionnaires were administered basically in English and Hausa languages by trained personnel. Following informed consent, terminal urine samples were collected between 09:40 AM and 2:00 PM using clean 20 ml capacity universal bottles. 10μl of each urine residue was examined for the eggs of S. haematobium using x10 objective nose of Motic Binocular Light Microscope (China). The average age ± Standard Deviation (SD) of school children examined was 15.30 ± 2.30 years and 40.87% were females. The overall prevalence and geometric mean intensity of S. haematobium infection were 26.41% (24.10─28.85) and 6.59 (5.59─7.75) eggs / 10 ml of urine respectively. Interestingly, a questionnaire equivalence of the prevalence obtained in this survey was 26.41% (24.10─28.85) for Rapid Assessment Procedure based on self-reported blood in urine. The results of correlation analyses demonstrated significant associations between the prevalence of S. haematobium infection and contact with potentially infested open water sources (r = 0.741; P = 0.006). By regression model, cases of respondents with self-reported blood in urine are expected to rise to 24.75% if prevalence of the infection shoots up to 26.5%. The best RAP performance was obtained with self-reported blood in urine. Based on the overall prevalence value, the study area was at a "moderate-risk" of endemicity for urinary schistosomiasis. Chemotherapeutic intervention with Praziquantel, the rationale behind rapid assessment procedure for schistosomiasis, has been recommended to be carried out once in every 2 years for such communities.


Protein prenylation: enzymes, therapeutics, and biotechnology applications.
Protein prenylation is a ubiquitous covalent post-translational modification found in all eukaryotic cells, comprising attachment of either a farnesyl or a geranylgeranyl isoprenoid. It is essential for the proper cellular activity of numerous proteins, including Ras family GTPases and heterotrimeric G-proteins. Inhibition of prenylation has been extensively investigated to suppress the activity of oncogenic Ras proteins to achieve antitumor activity. Here, we review the biochemistry of the prenyltransferase enzymes and numerous isoprenoid analogs synthesized to investigate various aspects of prenylation and prenyltransferases. We also give an account of the current status of prenyltransferase inhibitors as potential therapeutics against several diseases including cancers, progeria, aging, parasitic diseases, and bacterial and viral infections. Finally, we discuss recent progress in utilizing protein prenylation for site-specific protein labeling for various biotechnology applications.


Treatment-resistant depression.
Our ability to treat depression has improved with the availability of receptor-specific and chemically diverse groups of antidepressants. Even now, most of the short-term studies indicate that about 20% of depressed patients remain resistant to treatment. Therefore, it is important to properly assess the treatment-resistant depressed (TRD) patients and to separate the truly refractory patients from those inadequately treated. Undiagnosed medical conditions should be eliminated. TRD is neither a clinically nor a biologically identifiable entity. As there are no established methods for the treatment of TRD, all options should be considered. The clinician can be enriched by the knowledge of the treatment modalities available, and yet, in treating an individual patient, clinical skills, intuitive judgment, family history of response to drugs and side effects, all play a vital role. Several of the approaches described in the paper indicate available methods and their merits in general but there is no way of ascertaining by which particular method a patient should be treated. The three common methods of treatment are substitution of one antidepressant drug for another, combination therapies and augmentation techniques. These are based on clinical experiences and not research findings. Therefore the treatment of TRD patients is more an art than a science. The physician should assess all the psychopathological, phenomenological and psychosocial variables to appropriately treat an individual patient.


T cell kinetics reveal expansion of distinct lung T cell subsets in acute versus in resolved influenza virus infection.
Influenza virus infection is restricted to airway-associated tissues and elicits both cellular and humoral responses ultimately resulting in generation of memory cells able to initiate a rapid immune response against re-infections. Resident memory T cells confer protection at the site of infection where lung-resident memory T cells are important for protecting the host against homologous and heterologous influenza virus infections. Mapping kinetics of local and systemic T cell memory formation is needed to better understand the role different T cells have in viral control and protection. After infecting BALB/c mice with influenza virus strain A/Puerto Rico/8/1934 H1N1 the main proportion of activated T cells and B cells expressing the early activation marker CD69 was detected in lungs and lung-draining mediastinal lymph nodes. Increased frequencies of activated cells were also observed in the peripheral lymphoid organs spleen, inguinal lymph nodes and mesenteric lymph nodes. Likewise, antigen-specific T cells were most abundant in lungs and mediastinal lymph nodes but present in all organs studied. CD8+CD103-CD49a+ lung-resident T cells expanded simultaneously with timing of viral clearance whereas CD8+CD103+CD49a+ lung-resident T cells was the most abundant subset after resolution of infection and antigen-specific, lung-resident T cells were detected up to seven months after infection. In conclusion, the results in this detailed kinetic study demonstrate that influenza virus infection elicits adaptive immune responses mainly in respiratory tract-associated tissues and that distinct subsets of lung-resident T cells expand at different time points during infection. These findings contribute to the understanding of the adaptive immune response locally and systemically following influenza virus infection and call for further studies on the roles of the lung-resident T cell subsets.


Chemokine CXCL12 and its receptors in the developing central nervous system: emerging themes and future perspectives.
Homeostatic chemokine CXCL12 (also known as SDF-1) and its receptor CXCR4 are indispensable for the normal development of the nervous system. This chemokine system plays a plethora of functions in numerous neural developmental processes, from which the underlying molecular and cellular mechanisms are beginning to be unravelled. Recent identification of CXCR7 as a second receptor for CXCL12 provides opportunities to gain deeper insights into how CXCL12 operates in the nervous system. Here, we review the diverse roles of CXCL12 in the developing central nervous system, summarize the recent progress in uncovering CXCR7 functions, and discuss the emerging common themes from these works and future perspectives.


[The traffic elbow. A series of 9 cases].
"Traffic elbow" is a condition occurring when high energy trauma involves a patient's elbow resting on the window of the car or completely outside it. This is a prospective study over 30 months of 9 patients with "traffic elbow" and therefore sufferring complex open trauma to the elbow. There were 8 men and 1 woman with a median delay of 4 hours before arrival in hospital. The dominant member was affected in 3 cases. The severity of the lesions, using the Mangled Extremity Severity Score (MESS), was more than 7, comprising lesions corresponding to type 1 of the complex trauma of the superior member (TCMS) in 2 patients and a MESS score of between 3 and 6 corresponding to types 2 or 3 of the TCMS for the other 7 patients. The therapeutic possibilities are limited considering the frequent context of polytrauma. In 4 cases we performed a debridement and external humero-ulnar fixation, in 3 cases a debridement and stabilization with Kirschner's wires completed by a fenestrated cast, and in 2 cases a lifesaving amputation. All patients, except those that had had amputation, developed deep sepsis that resolved after adequate treatment. Assessment of the non-amputee patients according to the Mayo Performance Score, yielded more than 70% of bad results. The authors stress the gravity of these lesions whose prognosis is guarded both concerning mobility of the elbow and the frequent neurovascular complications.


Systematic Literature Review of Spinal Cord Stimulation in Patients With Chronic Back Pain Without Prior Spine Surgery.
Low back pain is the leading cause of disability worldwide and one of the most common reasons for seeking healthcare. Despite numerous care strategies, patients with low back pain continue to exhibit poor outcomes. Spinal cord stimulation (SCS) is an evidence-based therapeutic modality for patients with failed back surgery syndrome. For patients without a surgical lesion or history, minimally invasive interventions that provide long-term reduction of chronic back pain are needed. Therefore, we conducted a systematic review of the evidence on SCS therapy in patients with chronic back pain who have not undergone spinal surgery. A systematic literature search was performed to identify studies reporting outcomes for SCS in chronic back pain patients (with or without secondary radicular leg pain) without prior surgery using date limits from database inception to February 2021. Study results were analyzed and described qualitatively. A total of ten primary studies (16 publications) were included. The included studies consistently demonstrated favorable outcomes in terms of pain reduction and functional improvement following SCS therapy. Improvements also occurred in quality of life scores; however, not all studies reported statistically significant findings. Additionally, the studies reported that SCS resulted in high patient satisfaction, reductions in opioid use, and an acceptable safety profile, although these data were more limited. Findings suggest that SCS is a promising, safe, minimally invasive, and reversible alternative option for managing chronic back pain in patients who have not undergone spinal surgery.


Preauricular transmasseteric anteroparotid approach for extracorporeal fixation of mandibular condyle fractures.
Free grafting or extracorporeal fixation of traumatically displaced mandibular condyles is sometimes required in patients with severe anteromedial displacement of condylar head. Majority of the published studies report the use of a submandibular, retromandibular or preauricular incisions for the access which have demerits of limited visibility, access and potential to cause damage to facial nerve and other parotid gland related complications. This retrospective clinical case record study was done to evaluate the preauricular transmasseteric anteroparotid (P-TMAP) approach for open reduction and extracorporeal fixation of displaced and dislocated high condylar fractures of the mandible. This retrospective study involved search of clinical case records of seven patients with displaced and dislocated high condylar fractures treated by open reduction and extracorporeal fixation over a 3-year period. The parameters assessed were as follows: a) the ease of access for retrieval, reimplantation and fixation of the proximal segment; b) the postoperative approach related complications; c) the adequacy of anatomical reduction and stability of fixation; d) the occlusal changes; and the e) TMJ function and radiological changes. Accessibility and visibility were good. Accurate anatomical reduction and fixation were achieved in all the patients. The recorded complications were minimal and transient. Facial nerve (buccal branch) palsy was noted in one patient with spontaneous resolution within 3 months. No cases of sialocele or Frey's syndrome were seen. The P-TMAP approach provides good access for open reduction and extracorporeal fixation of severely displaced condylar fractures. It facilitates retrieval, transplantation, repositioning, fixing the condyle and also reduces the chances of requirement of a vertical ramus osteotomy. It gives straight-line access to condylar head and ramus thereby permitting perpendicular placement of screws with minimal risk of damage to the facial nerve.


Fertility Intentions and Residential Relocations.
This research addresses the question of whether fertility intentions (before conception) are associated with residential relocations and the distance of the relocation. We empirically tested this using data from two birth cohorts (aged 24-28 and 34-38 in the first survey wave) of the German Family Panel (pairfam) and event history analysis. Bivariate analyses showed that coupled individuals relocated at a higher rate if they intended to have a(nother) child. We found substantial heterogeneity according to individuals' age and parental status, particularly for outside-town relocations. Childless individuals of average age at family formation-a highly mobile group-relocated at a lower rate if they intended to have a child. In contrast, older individuals who already had children-the least-mobile group-relocated at a higher rate if they intended to have another child. Multivariate analyses show that these associations are largely due to adjustments in housing and other living conditions. Our results suggest that anticipatory relocations (before conception) to adapt to growing household size are importantly nuanced by the opportunities and rationales of couples to adjust their living conditions over the life course. Our research contributes to the understanding of residential mobility as a by-product of fertility decisions and, more broadly, evidences that intentions matter and need to be considered in the analysis of family life courses.


Influence of individual nodes for continuous-time susceptible-infected-susceptible dynamics on synthetic and real-world networks.
In the study of epidemic dynamics a fundamental question is whether a pathogen initially affecting only one individual will give rise to a limited outbreak or to a widespread pandemic. The answer to this question crucially depends not only on the parameters describing the infection and recovery processes but also on where, in the network of interactions, the infection starts from. We study the dependence on the location of the initial seed for the susceptible-infected-susceptible epidemic dynamics in continuous time on networks. We first derive analytical predictions for the dependence on the initial node of three indicators of spreading influence (probability to originate an infinite outbreak, average duration, and size of finite outbreaks) and compare them with numerical simulations on random uncorrelated networks, finding a very good agreement. We then show that the same theoretical approach works fairly well also on a set of real-world topologies of diverse nature. We conclude by briefly investigating which topological network features determine deviations from the theoretical predictions.


Interplay between cytochrome c and gibberellins during Arabidopsis vegetative development.
We studied the effect of reducing the levels of the mitochondrial electron carrier cytochrome c (CYTc) in Arabidopsis thaliana. Plants with CYTc deficiency have delayed growth and development, and reach flowering several days later than the wild-type but with the same number of leaves. CYTc-deficient plants accumulate starch and glucose during the day, and contain lower levels of active gibberellins (GA) and higher levels of DELLA proteins, involved in GA signaling. GA treatment abolishes the developmental delay and reduces glucose accumulation in CYTc-deficient plants, which also show a lower raise in ATP levels in response to glucose. Treatment of wild-type plants with inhibitors of mitochondrial energy production limits plant growth and increases the levels of DELLA proteins, thus mimicking the effects of CYTc deficiency. In addition, an increase in the amount of CYTc decreases DELLA protein levels and expedites growth, and this depends on active GA synthesis. We conclude that CYTc levels impinge on the activity of the GA pathway, most likely through changes in mitochondrial energy production. In this way, hormone-dependent growth would be coupled to the activity of components of the mitochondrial respiratory chain.


Analysis of the stent expansion in a stenosed artery using finite element method: application to stent versus stent study.
In this article, finite element method is used to investigate the mechanical behavior of a stent and to determine the biomechanical interaction between the stent and the artery in a stenting procedure. The main objective of this study is to reach to a model close to a real condition of coronary stent placement. Unlike most of the models proposed in the literature, all the steps of the deployment of a stent in the stenotic vessel (i.e. pressure increasing, constant load pressure and pressure decreasing) are simulated in this article to show the behavior of the stent in different stages of implantation. The results indicate that the first step of deployment, that is, pressure increasing, plays a main role in the success of stent implantation. So that, in order to compare the behavior of different types of stents, it is sufficient to compare their behavior at the end of pressure increasing step. In order to show the application of the findings in stent versus stent studies, three commercially available stents (the Palmaz-Schatz, Multi-Link and NIR stents) are modeled and their behavior is compared at the end of pressure increasing step. The effect of stent design on the restenosis rate is investigated. According to the findings, the possibility of restenosis is lower for Multi-Link and NIR stents in comparison with Palmaz-Schatz stent which is in good agreement with clinical results. Therefore, the testing methodology outlined here is proposed as a simple and economical alternative for "stent versus stent" complicated clinical trials.


A 10-year-old girl with coexistent moyamoya disease and Graves' disease.
There are rare reports of young women with moyamoya disease associated with Graves' disease; we are unaware of any previous reports of this association in prepubescent girls. We report a 10-year-old girl who presented with multiple bilateral strokes. Cerebral angiography demonstrated moderate to severe stenosis of her bilateral distal internal carotid arteries and proximal anterior and middle cerebral arteries, which was greater on the right. Thyroid function tests demonstrated suppressed thyroid-stimulating hormone and elevated thyroid hormone levels. Serum antiphospholipid antibody screen demonstrated mild elevations of antiocardiolipin IgG. Possible mechanisms predisposing individuals to concurrent moyamoya and Graves' disease are discussed.


Pharmacological dissection of Ca2+ channels in the rat aorta by Ca2+ entry modulators.
Ca2+ agonists, Bay K 8644 and CGP 28392, induced concentration-dependent contractions in segments of rat aorta partially depolarized with 15 mmol/l K+. The responses caused by Bay K 8644 were greater than those elicited by CGP 28392. The actions of these Ca2+ agonists were blocked by nifedipine. CGP 28392 and mainly Bay K 8644 increased the contractions induced by different K+ concentrations but did not alter those caused by noradrenaline (NA) and higher K+ concentrations. Bay K 8644 enhanced and nifedipine reduced the contractions elicited by Ca2+ addition in a Ca2(+)-free solution containing K+ (25, 50 or 75 mmol/l). This enhancement was blocked by nifedipine. Nifedipine and verapamil reduced more effectively the responses induced by K+ than those caused by NA; they did not modify contractions evoked by Ca2+ ionophore A23187. They also reduced the increases in K+ contractions elicited by CGP 28392 and Bay K 8644. Bay K 8644 increased 45Ca2+ uptake induced by K+ and did not affect that caused by NA. Nifedipine blocked this increase as well as 45Ca2+ uptake elicited by NA and K+. Basal 45Ca2+ efflux was not modified by verapamil and Bay K 8644. NA and K+ significantly increased this efflux in normal solution, but not in Ca2(+)-free medium. Bay K 8644 enhanced 45Ca2+ efflux induced by K+ in normal medium, whereas it did not affect those elicited by NA and K+ in a solution without Ca2+. This Ca2+ agonist had scant ability to induce Ca2+ efflux in a Ca2(+)-free medium. These results indicate that in this vascular preparation: (1) Ca2+ agonists (Bay K 8644 particularly) have the ability to produce Ca2+ influx (and subsequent contraction) and Ca2+ efflux by activation of voltage-operated Ca2+ channels (VOCs), only when they are preactivated with K+; (2) VOCs and receptor-operated Ca2+ channels (ROCs) appear to constitute two different populations, and (3) Ca2+ antagonists possess, in comparison with Ca2+ agonists, a small range of selectivity to block only VOCs; the latter drugs are better to pharmacologically discriminate between VOCs and ROCs in the rat aorta.


Synthesis of (+)-bullatacin via the highly diastereoselective [3+2] annulation reaction of a racemic aldehyde and a nonracemic allylsilane.
[reaction: see text] A total synthesis of (+)-bullatacin has been accomplished via a diastereoselective [3+2] annulation reaction of the highly enantiomerically enriched allylsilane 3 and racemic aldehyde 4, which provides the key bis-tetrahydrofuran fragment 15 with > or = 20:1 ds.


Sleep duration and sleep efficiency in UK long-distance heavy goods vehicle drivers.
To profile sleep duration and sleep efficiency in UK long-distance heavy goods vehicle (HGV) drivers and explore demographic, occupational and lifestyle predictors of sleep. Cross-sectional analyses were carried out on 329 HGV drivers (98.5% men) recruited across an international logistics company within the midland's region, UK. Sleep duration and efficiency were assessed via wrist-worn accelerometry (GENEActiv) over 8 days. Proportions of drivers with short sleep duration (<6 hour/24 hours and <7 hour/24 hours) and inadequate sleep efficiency (<85%) were calculated. Demographic, occupational and lifestyle data were collected via questionnaires and device-based measures. Logistic regression assessed predictors of short sleep duration and inadequate sleep efficiency. 58% of drivers had a mean sleep duration of <6 hour/24 hours, 91% demonstrated <7-hour sleep/24 hours and 72% achieved <85% sleep efficiency. Sleeping <6 hour/24 hours was less likely in morning (OR 0.45, 95% CI 0.21 to 0.94) and afternoon (OR 0.24, CI 0.10 to 0.60) shift workers (vs night) and if never smoked (vs current smokers) (OR 0.45, CI -0.22 to 0.92). The likelihood of sleeping <7 hour/24 hours reduced with age (OR 0.92, CI 0.87 to 0.98). The likelihood of presenting inadequate sleep efficiency reduced with age (OR 0.96, CI 0.93 to 0.99) and overweight body mass index category (vs obese) (OR 0.47, CI 0.27 to 0.82). The high prevalence of short sleep duration and insufficient sleep quality (efficiency) rate suggest that many HGV drivers have increased risk of excessive daytime sleepiness, road traffic accidents and chronic disease. Future sleep research in UK HGV cohorts is warranted given the road safety and public health implications.


Distance estimation in a dynamic simulated environment: a visual field dependence problem?
Egocentric distance estimation implies that the subject perceives his own location in the environment. In a simulated environment, subjects have to transpose perceptively their own observation point in order to assume their virtual body position. As only visual information specifies this position, their ability to perceive the camera viewpoint should be linked to the field dependence independence factor (FDI). Field-independent subjects underestimated the mid-distance between their own virtual body position and a far-located target; their bisection was located between the projective (2-D) and the simulated (3-D) mid-distance which indicates their difficulty in considering the in-depth simulated spatial references. High correlations between the vertical estimation in the rod-and-frame test and the egocentric-distance-estimation task (with shifted camera) suggest a similar perceptive process in both tasks. This result is confirmed by the better performances of the field-dependent subjects in this condition. In conclusion, we discuss the relationship between FDI and the sense of presence in virtual environments.


Type II hiatal hernias: do they exist or are they actually parahiatal hernias?
Type II hiatal hernias (HH) are characterized by a portion of the gastric fundus located above the esophageal hiatus adjacent to the esophagus while the gastroesophageal junction (GEJ) remains fixed below the esophageal hiatus. This type of HH has been called the "true" paraesophageal hernia (PEH) because the fundus appears to the side of the esophagus. In our experience, Type II HHs are occasionally identified on radiographic testing, however they are rarely, if ever, confirmed intraoperatively. This led to our question: Does Type II HH exist? We searched for evidence of type II HH in three locations: 1. Retrospective review of all first-time PEH repairs (excluding Type I HHs and re-operative cases) performed at the University of Washington Medical Center from 1994 to 2021; 2. Operative videos available on YouTube and WebSurg websites; and 3. Abstracts from the SAGES annual meetings from 2005 to 2021. We found no evidence of Type II HH in any of our three searches. We performed 846 PEH repairs: 760 Type III, 75 Type IV, and 11 parahiatal. Upon website video review, we found only one possible type II hernia, though it too was likely a para-hiatal hernia. No video or case presentations of a type II HH were identified within SAGES annual meeting abstracts. Type II HHs do not exist as they are currently defined. Although uncommon, parahiatal hernia can easily be misinterpreted as Type II HH. We should consider changing the hiatal hernia classification system to prevent ongoing clinical confusion.


Is an isolated cleft lip an isolated anomaly?
It is well known that patients with cleft lip/palate or cleft palate can have associated anomalies. However, there is a relative paucity of information about the possible anomalies associated with an isolated cleft lip. A recent study (Vallino et al., 2008) showed that children with cleft lip and/or alveolus often develop cleft palate-related issues. This inspired us to investigate our population. A questionnaire was sent to the parents of 214 children with cleft lip and/or alveolus; 161 questionnaires were returned (response rate (RR): 75%) and included in our study. The study consisted of 91 boys and 70 girls (0.3-13.1 years: mean 6.8 ± 3.5 years). Speech and/or language problems were reported in 34% and ventilation tube insertion in 21% of children with ≥6 years' follow-up. Of the children in that group, 33% reported to have undergone an episode of acute otitis media and 11% reported five episodes or more. Additional congenital anomalies were found in 4% of children with a cleft lip and in 16% of children with a cleft lip/alveolus. Our results demonstrate that an isolated cleft lip can often be described as an isolated anomaly, although children with cleft lip and/or alveolus develop cleft palate-related issues more often than anticipated. Therefore, we suggest an intensive monitoring and treatment of children with these types of clefts.


Hemopexin: structure, function, and regulation.
Hemopexin (HPX) is the plasma protein with the highest binding affinity to heme among known proteins. It is mainly expressed in liver, and belongs to acute phase reactants, the synthesis of which is induced after inflammation. Heme is potentially highly toxic because of its ability to intercalate into lipid membrane and to produce hydroxyl radicals. The binding strength between heme and HPX, and the presence of a specific heme-HPX receptor able to catabolize the complex and to induce intracellular antioxidant activities, suggest that hemopexin is the major vehicle for the transportation of heme in the plasma, thus preventing heme-mediated oxidative stress and heme-bound iron loss. In this review, we discuss the experimental data that support this view and show that the most important physiological role of HPX is to act as an antioxidant after blood heme overload, rather than to participate in iron metabolism. Particular attention is also put on the structure of the protein and on its regulation during the acute phase reaction.


Targeting Neuroimmune Interactions in Diabetic Neuropathy with Nanomedicine.
Significance: Diabetes is a major source of neuropathy and neuropathic pain that is set to continue growing in prevalence. Diabetic peripheral neuropathy (DPN) and pain associated with diabetes are not adequately managed by current treatment regimens. Perhaps the greatest difficulty in treating DPN is the complex pathophysiology, which involves aspects of metabolic disruption and neurotrophic deficits, along with neuroimmune interactions. There is, therefore, an urgent need to pursue novel therapeutic options targeting the key cellular and molecular players. Recent Advances: To that end, cellular targeting becomes an increasingly compelling drug delivery option as our knowledge of neuroimmune interactions continues to mount. These nanomedicine-based approaches afford a potentially unparalleled specificity and longevity of drug targeting, using novel or established compounds, all while minimizing off-target effects. Critical Issues: The DPN therapeutics directly targeted at the nervous system make up the bulk of currently available treatment options. However, there are significant opportunities based on the targeting of non-neuronal cells and neuroimmune interactions in DPN. Future Directions: Nanomedicine-based agents represent an exciting opportunity for the treatment of DPN with the goals of improving the efficacy and safety profile of analgesia, as well as restoring peripheral neuroregenerative capacity. Antioxid. Redox Signal. 36, 122-143.


Facing a Clinical Challenge: Limited Empirical Support for Toddler Speech Sound Production Intervention Approaches.
Speech sound production intervention in early childhood is relatively rare despite empirical and theoretical support for providing this type of targeted therapy for toddlers. Challenges perpetuate the present clinical condition including those related to treatment decision making (e.g., intervention approach). Although there are numerous speech sound production treatment approaches appropriate for the pediatric population, a much smaller proportion are proposed to be appropriate for children under the age of 3 years. Of these, five approaches (i.e., core vocabulary, cycles, naturalist recast, stimulability, and psycholinguistic intervention) were selected for review because they can be used to treat functional speech sound disorders produced by toddlers and none required additional clinician training for implementation. We found the empirical evidence supporting the use of these approaches with children under the age of 3 years scant to nonexistent. Due to the lack of empirical evidence, early intervention speech-language pathologists must primarily rely on internal factors (e.g., clinician experience and client/caregiver perspectives) to support evidence-based intervention decisions in the absence of external empirical support. Clinical action steps such as careful documentation of approaches used/discontinued and associated individual client outcomes are necessary for evidence-based decision making until more robust empirical evidence is established.


Embryonic asymmetry: left TGFbeta at the right time?
Vertebrates have consistent differences between their left and right sides. In all species, nodal, a transforming growth factor beta superfamily signalling protein, is involved in a late step in the pathways that specify such asymmetry in the embryo. Earlier components seem not so well conserved.


HLA class II antigen expression in conjunctival precancerous lesions and squamous cell carcinomas.
The expression of human leukocyte antigen (HLA) class II molecules on the cell surface is necessary for the presentation of peptide antigens to helper CD4 T lymphocytes of the immune system. We studied the immunoexpression of HLA class II antigen in conjunctival precursor lesions and conjunctival squamous cell carcinomas. HLA class II antigen expression was analyzed in 8 conjunctival dysplasias, 6 carcinomas in situ and in 7 conjunctival squamous cell carcinomas, by immunoperoxidase staining with monoclonal antibody to HLA class II antigen on the archival clinical samples. Immunoanalysis was done by a semi quantitative method based on the intensity of staining and the percentage of stained cells. HLA class II antigen immunoexpression was heterogeneous in 8 conjunctival dysplasias and in 6 carcinoma in situ and negative in 7 conjunctival squamous cell carcinomas. Human leukocyte class II antigen immunoexpression is decreased in conjunctival precancerous and squamous cell carcinomas.


Use of ethylenediaminetetraacetic acid in pulp mills and effects on metal mobility and primary production.
Over the last decade, the use of ethylenediaminetetraacetic acid (EDTA) has increased by a factor of three within the Swedish pulp industry. The effects of pulp mill wastewater in combination with EDTA on metal mobility and the consequences for ecologically relevant organisms have been studied. Ethylenediaminetetraacetic acid was added to pulp mill effluent water in the laboratory and compared to wastewater without EDTA. Degradation of the water was followed over a experimental period up to eight weeks and samples were taken five times for chemical analysis and at the beginning and the end for biological tests. Half a year later, the experiment was repeated. The results from both experiments showed that EDTA markedly increased the solubility of zinc, cadmium, lead, iron, nickel, and copper, whereas the solubility of vanadium, molybdenum, thallium, arsenic, and chromium was not changed by the presence of EDTA. No measurable degradation of EDTA occurred even after 5.5 months. The toxicity of the pulp mill effluent water was low, and only a slight toxic effect was observed on the reproduction of Ceramium strictum. The most pronounced effect was a stimulation in the growth of three algal species in 5 to 20% (v/v) total effluent wastewater with and without EDTA. The presence of EDTA in the dissolved fraction of the pulp mill effluent water increased the growth stimulation in 20 to 40% (v/v), possibly because of the increased availability of essential metals like iron, zinc, and copper. The capacity of the pulp mill wastewater to support algal growth was nearly as good as a rich nutrient medium for algae. The combination of poorly degradable EDTA and the increasing availability of metals might further enhance eutrophication in the recipient areas of pulp mills.


Turnover of CD4+ and CD8+ T lymphocytes in HIV-1 infection as measured by Ki-67 antigen.
We investigated CD4+ and CD8+ T cell turnover in both healthy and HIV-1-infected adults by measuring the nuclear antigen Ki-67 specific for cell proliferation. The mean growth fraction, corresponding to the expression of Ki-67, was 1.1% for CD4(+) T cells and 1.0% in CD8(+) T cells in healthy adults, and 6.5 and 4.3% in HIV-1-infected individuals, respectively. Analysis of CD45RA+ and CD45RO+ T cell subsets revealed a selective expansion of the CD8+ CD45RO+ subset in HIV-1-positive individuals. On the basis of the growth fraction, we derived the potential doubling time and the daily turnover of CD4+ and CD8+ T cells. In HIV-1-infected individuals, the mean potential doubling time of T cells was five times shorter than that of healthy adults. The mean daily turnover of CD4+ and CD8+ T cells in HIV-1-infected individuals was increased 2- and 6-fold, respectively, with more than 40-fold interindividual variation. In patients with <200 CD4+ counts, CD4+ turnover dropped markedly, whereas CD8+ turnover remained elevated. The large variations in CD4+ T cell turnover might be relevant to individual differences in disease progression.


Postoperative bleeding adversely affects total knee arthroplasty outcomes in hemophilia.
Hemophilic arthropathy can result in severe degenerative arthritis and functional limitations in the knees of relatively young patients. Total knee arthroplasty (TKA) provides pain relief and gain of function in advanced-stage hemophilic arthropathy cases. However, little is known about the long-term effects of early major postoperative bleeding (MPOB) in people with hemophilia (PWH). The aim of this study was to evaluate the effects of early MPOB on the final functional outcome, complications, and implant survival of TKA in a single-center hemophilia cohort. PWH who underwent TKA between 1998 and 2019 in a single center were reviewed. Demographic data, clinical data, and radiographic images were evaluated. Hospital for Special Surgery (HSS), Knee Society Score (KSS), and Knee Society Function Score (KSS-F) scores were used to determine function. Patients with early bleeding complications (wound dehiscence, ecchymosis, hemarthrosis, hematoma formation, prolonged or recurrent bleeding attacks) were defined as the bleeding group. Patients who did not experience these complications were assigned to the control group. The bleeding group was compared with controls. Survival of the primary arthroplasty was analyzed by Kaplan-Meier curves. Forty-five TKAs in 29 patients were included in the study. TKA led to an increase in the mean range of motion from 46.08° to 84.59° (P < 0.01). HSS scores increased from 48.33 preoperatively to 82.67 postoperatively (P < 0.01). There were improvements in both KSS and KSS-F scores from 34.22 and 53.3 preoperatively to 82.00 and 84.63 (P < 0.01), respectively. Ten patients (10 TKAs) (34%) experienced major bleeding during the postoperative period. Six of these patients had moderate hemophilia, and four had severe hemophilia. Three of these patients had hemarthroses (10.2%), one patient had a hematoma (3.4%), one patient had hemorrhagic bullae formation (3.4%), and five had excessive/prolonged bleeding from the wound (17%). The bleeding group (34%) had significantly worse HSS (63.78 vs 92.75, P < 0.001), KSS (61.78 vs 93.25, P < 0.001), and KSS-F (60.71 vs 96.25, P = 0.005) scores compared with controls. Preoperative and postoperative flexion contractures were positively correlated (+0.33, P = 0.003). One of the patients with postoperative hemarthrosis also had an accompanying transient common peroneal nerve palsy, and one patient (3.4%) had a periprosthetic fracture. Three knees (6.6%), two of whom were in the bleeding group, developed periprosthetic infections. Four knees (8.8%) in three patients underwent revision surgery, and two knees (4.4%) ended up in arthrodeses. Kaplan-Meier analysis revealed a mean survival duration of 17.04 years for the bleeding group and 22.15 years for the control group (P = 0.83). Survival rates were 80.0% for the bleeding group and 96.4% for the control group (P = 0.83). In this study, MPOB after TKA in PWH was common and led to significantly worse function. MPOB after TKA in PWH was associated with a higher rate of complications and lower survival rates, although the differences were not statistically significant. Efforts must be made to avoid MPOB after TKA in PWH.


Diabetes Mellitus and Lower Extremity Peripheral Artery Disease.
Lower extremity peripheral artery disease, or often simply called peripheral artery disease (PAD), is a common cardiovascular disease, as coronary artery disease is. Atherosclerotic disease of the arteries of the lower extremity, or arteriosclerosis obliterans, accounts for the vast majority of PAD today. Rest pain, nonhealing ulcers, and gangrenes associated with chronic ischemia (i.e., Fontaine stage III and IV or Rutherford category 4 to 6) are referred to as chronic limb-threatening ischemia (CLTI), formally called critical limb ischemia (CLI). This narrative review focuses on atherosclerotic PAD, especially CLTI, mainly highlighting its link with diabetes mellitus (DM). This article will first overview the clinical impact of DM in patients with symptomatic PAD and that of symptomatic PAD in patients with DM, followed by the clinical features of CLTI, which will be discussed from a viewpoint of its prognosis, patient profile, onset, and seasonality. DM poses a great clinical impact on CLTI, and vice versa. Patient profile appears different between DM patients complicated with CLTI and the general population with DM. Furthermore, although CLTI is pathologically rooted in atherosclerosis as is acute coronary syndrome (ACS), CLTI has considerably different clinical features compared with ACS. CLTI has an extremely poor prognosis even after revascularization, and there is ample room for improvement in terms of its prognosis. Some measures might be needed in healthcare and clinical settings before revascularization: e.g., DM control and regular ischemia risk evaluation before CLTI onset, proper diagnosis at CLTI onset, and prompt referral to a vascular specialist after CLTI onset, although its evidence is still scanty. Piling up evidence of patients with CLTI, by patients with CLTI, and for patients with CLTI is needed.


Interaction of high-molecular-weight basic fibroblast growth factor with endothelium: biological activity and intracellular fate of human recombinant M(r) 24,000 bFGF.
The single-copy gene of human basic fibroblast growth factor (bFGF) encodes four co-expressed isoforms, with an apparent molecular weight (M(r)) of 24 kD, 22.5 kD, 22 kD, and 18 kD, co-translated from a single mRNA. As a tool for the study of the role exerted by the different bFGF isoforms in the biology of endothelial cells, human recombinant 24-kD bFGF was produced and purified from transformed Escherichia coli cells. To this purpose, the novel CUG start codon present in human bFGF cDNA and responsible for the synthesis of 24-kD bFGF was mutagenized to the classic AUG start codon. Transient expression of the mutagenized cDNA in simian COS-1 cells, followed by immunolocalization and subcellular fractionation, resulted in the synthesis of high levels of 24-kD bFGF, which localizes in the cell nucleus as an intact protein. When the same 24-kD bFGF cDNA was expressed in E. coli, the recombinant protein was purified to homogeneity by heparin-Sepharose and ion-exchange chromatography. Recombinant 24-kD bFGF was similar to recombinant 18-kD bFGF in receptor-binding activity and in inducing cell proliferation, plasminogen activator production, and chemotactic movement in cultured endothelial cells. In agreement with the in vitro observations, 24-kD bFGF and 18-kD bFGF exerted a similar angiogenic response when assayed in vivo in the rabbit cornea. Experiments performed with the radiolabeled molecule demonstrated that 24-kD bFGF has an intrinsic ability to bind to high-affinity receptors when added to endothelial GM 7373 cell cultures. Receptor-bound 24-kD bFGF is internalized within the cell and associates with the nucleus with kinetics similar to 18-kD bFGF. Internalized 24-kD bFGF is first processed to the 18-kD form via a chloroquine-insensitive pathway and then to smaller fragments into the lysosomal compartment. At variance with the data obtained in transfected COS-1 cells, only limited amounts of exogenous internalized 24-kD bFGF associates with the nucleus in the intact form, mostly of the nuclear-bound molecule being represented by the processed 18-kD protein and by smaller degradation products. In conclusion, human recombinant 24-kD bFGF exerts a biological response in endothelial cells similar to 18-kD bFGF both in vitro and in vivo. Our data point to a different intracellular behavior of the high-molecular-weight bFGF isoform when added exogenously to cultured cells or when produced endogenously in transfected cells.


[Analysis of the nutrients contents and the blood glucose response of the mixed grains in Chinese people].
To evaluate the nutrients contents and the glycemic index (GI) of the mixed grains and analyze the relationship between the nutrients contents and biological effect. The nutrients contents of mixed grains and control food were determined according to the methods of Chinese national standards. Choose 10 volunteers to ingest 50 g glucose and ingest the steamed bread of mixed grains which imply 50 g carbohydrate the second day. Limosis blood glucose and blood glucose levels during the subsequent 3 hours were determined. Calculating the GI according to the Wolver's method. The results showed that 100 g of the mixed grains contained dietary fiber (crude fiber) 13.7 g, vitamin B1 0.40 mg, protein 13.5g, ash2.0g, vitamin B2 0.16 mg, calcium 54 mg, iron 7.1 mg and zinc3.00 mg respectively. The absolute increase of blood glucose and the areas increased under the glycemic curves of mixed grains were less than which of glucose (P < 0.05). The GI of the mixed grains bread was 52.6. It was concluded that the high contents of protein, minerals, dietary fiber, VB1, VB2 and the low GI of mixed grains might play an important role in nutritional intervention


Possible involvement of cerebral hypoperfusion as trigger of neurally-mediated vasovagal syncope.
It is well known that some patients with neurally mediated syncope have a feeling of aura before the onset of syncope. A case is reported in which cerebral dysfunction recorded by EEG was present before the onset of a vasovagal reaction. The vasovagal reaction, bradycardia and/or asystole, was preceded by abnormal EEG findings when the patient complained of feeling a headache, photophobia, and nausea. These findings suggest that cerebral hypoperfusion, such as with cerebral vasospasms, before the onset of bradycardia might be involved in the mechanism of neurally mediated syncope in patients with an aura.


Platelet lysate loaded electrospun scaffolds: Effect of nanofiber types on wound healing.
In healthy individuals, wound healing is a highly efficient process. However, interruptions of normal healing give rise to chronic wounds, characterized by inflammation with impaired angiogenesis and re-epithelialization. The aim of this work was the design and the development of electrospun nanofibrous scaffolds based on sodium alginate (SA) and pullulan (PUL) and loaded with human platelet lysate (PL) intended for skin reparation, to take the advantage of nanofibrous scaffolds (with improved physical structure) and of SA as biopolymer. Two preparation approaches have been used to load PL in the scaffolds: as component of the PUL/SA matrix, to be electrospun, or as coating component, to cover the previously prepared electrospun PUL based membranes. A preformulation study to assess pullulan entanglement concentration and alginate or citric acid critical concentration, to obtain electrospun nanofibers, has been performed. The preparation process allowed to obtain insoluble systems starting from aqueous solutions and these were able to act as scaffolds for tissue engineering with suitable mechanical properties and PL release. PL loading in PUL/SA matrix nanofibers did not substantially modify the nanofiber morphology before crosslinking, while the crosslinking process, in presence of PL, determined less sharp nanofibers probably due to an increase in hydrophilicity caused by PL proteins. On the contrary, the coated nanofibers showed an increase in diameters due to PL loading. The two different approaches affected the fiber dimension and scaffold elasticity, especially for PL loaded systems. Anyhow, these differences were not crucial for fibroblast adhesion and proliferation which were mainly influenced by PL loading. In particular, fibroblasts presented different conformation and orientation mainly due to the presence of PL. This caused a cell random orientation compatible to a fibroblast-to-myofibroblast transition that could enhance wound healing.


Impact of zinc roofing on urban runoff pollutant loads: the case of Paris.
Previous research on the Marais catchment in Paris demonstrated the very high zinc and cadmium contamination of runoff from zinc roofing. Thus further investigations were aimed at evaluating the relative importance of this type of roofing in Paris and its potential contribution to zinc and cadmium loads in wet weather flows. According to these results, about 40% of the surface of roofs in Paris is covered with rolled zinc (1016 ha), and this proportion is not likely to vary significantly in the next years, due to architectural rules. The Zn and Cd concentrations measured in runoff from these roofs are in accordance with literature


Cycle stability of the electrochemical capacitors patterned with vertically aligned carbon nanotubes in an LiPF6-based electrolyte.
The miniature ultracapacitors, with interdigitated electrodes of vertically aligned carbon nanotubes (VACNTs) and an inter-electrode gap of 20 μm, have been prepared in the LiPF6 organic electrolyte with and without PVdF-HFP gel. PVdF-HFP between two opposing electrodes enhances the device reliability, but lessens its power performance because of the extra diffusion resistance. Also noteworthy are the gel influences on the cycle stability. When the applied voltage is 2.0 or 2.5 V, both the LiPF6 and the gel capacitors exhibit excellent stability, typified by a retention ratio of ≥95% after 10,000 cycles. Their coulombic efficiencies quickly rise up, and hold steady at 100%. Nonetheless, when the applied voltage is 3.5 or 4.0 V, the cycle stability deteriorates, since the negative electrode potential descends below 0.9 V (vs. Li), leading to electrolyte decomposition and SEI formation. For the LiPF6 capacitor, its retention ratio could be around 60% after 10,000 cycles and the coulombic efficiency of 100% is difficult to reach throughout its cycle life. On the other hand, the gel capacitor cycles energy with a much higher retention ratio, >80% after 10,000 cycles, and a better coulombic efficiency, even though electrolyte decomposition still occurs. We attribute the superior stability of the gel capacitor to its extra diffusion resistance which slows down the performance deterioration.


Human antithrombin III heterogeneity.
Crossed immunoelectrophoretic patterns were obtained on three patients with a congenital deficiency of anti-thrombin III (AT-III), and on normal single donor and "pooled" plasma controls. In the presence of heparin (incorporated into the agarose gel matrix), the AT-III of normal human plasma was separated into four components: two major, faster-moving components, and two minor, slower-moving components. The three patients with congenital deficiency of AT-III (levels approximately 50% of normal) appeared to possess only one of the faster-moving components, and one of the slower-moving components.


Comparison of the macroparasite communities of wild and stocked brown trout (Salmo trutta L.) in the west of Ireland.
The aim of the present study was to compare the helminth infra and component communities of wild and stocked brown trout in Lough Feeagh, in the west of Ireland, and also to examine the establishment and development of helminth communities in stocked brown trout. Fish were sampled in May, August and November 1997 and 1998 and an additional sample of wild brown trout was examined in April 1997. In total 217 wild trout and 122 stocked trout were examined. The acanthocephalans Acanthocephalus clavula and Pomphorhynchus laevis were the first parasite species to infect stocked trout in May 1997. In May 1998 both acanthocephalan species along with the trout specialists Eubothrium crassum and Crepidostomumfarionis were the first to infect trout. Mean species richness values for stocked trout increased from May to November, in 1997 and 1998. For wild trout, mean species richness values increased from April to November, in 1997 and decreased from May to November in 1998. The parasite communities of wild trout were richer than those of stocked trout in May of both years. In August the parasite communities recorded for wild and stocked trout were similar in terms of the number of species present but differed in terms of structure, and in November the parasite communities of stocked trout were richer than those of wild trout.


Determinants of microbial load in infected diabetic foot ulcers: a pilot study.
We examined the determinants of microbial load in infected diabetic foot ulcers in 62 patients (38 men and 24 women, mean age: 65.63 ± 12.71 years) with clinically infected diabetic foot ulcers. Tissue cultures were taken from ulcers by 4 mm punches. Ulcer grade (University of Texas classification), neuropathy disability score (NDS), neuropathy symptom score (NSS), ankle-brachial index (ABI), perfusion, extent, depth, infection, and sensation (PEDIS) grade of diabetic foot infection, and laboratory parameters were evaluated in all patients. Total microbial load was positively correlated with the number of isolates on tissue cultures (r s = 0.544, P < 0.001), white blood cell count (WBC) (r s = 0.273, P = 0.032), and platelet count (PLT) (r s = 0.306, P = 0.015). It also exhibited a borderline insignificant positive correlation with PEDIS infection grade (r s = 0.246, P = 0.053). In stepwise linear regression analysis, the number of isolates on tissue cultures and WBC were identified as the only two significant parameters accounting for 38% of the variation in the log of total microbial load (adjusted R (2) = 0.380, P < 0.001). In conclusion, patients with infected diabetic foot ulcer exhibit a positive correlation of total microbial load with the number of isolates on tissue cultures, WBC and PLT.


Mechanical Signaling in the Sensitive Plant Mimosa pudica L.
As sessile organisms, plants do not possess the nerves and muscles that facilitate movement in most animals. However, several plant species can move quickly in response to various stimuli (e.g., touch). One such plant species, Mimosa pudica L., possesses the motor organ pulvinus at the junction of the leaflet-rachilla, rachilla-petiole, and petiole-stem, and upon mechanical stimulation, this organ immediately closes the leaflets and moves the petiole. Previous electrophysiological studies have demonstrated that a long-distance and rapid electrical signal propagates through M. pudica in response to mechanical stimulation. Furthermore, the spatial and temporal patterns of the action potential in the pulvinar motor cells were found to be closely correlated with rapid movements. In this review, we summarize findings from past research and discuss the mechanisms underlying long-distance signal transduction in M. pudica. We also propose a model in which the action potential, followed by water flux (i.e., a loss of turgor pressure) in the pulvinar motor cells is a critical step to enable rapid movement.


Persistent pruritus after hydroxyethyl starch infusion therapy: a result of long-term storage in cutaneous nerves.
A high incidence of severe pruritus has been observed after the administration of hydroxyethyl starch (HES) on account of plasma volume substitution and improvement of the microcirculation. The aim of this study was to elucidate the possible pathomechanisms of HES-induced itching. Skin biopsies were taken from 93 patients, half of them presenting with pruritus, who received HES of various preparations and cumulative dosages. The samples were subjected to immunoelectron microscopical investigation using an antibody highly specific for HES. After infusion therapy with HES, formation of intracytoplasmic storage vacuoles in the skin could be demonstrated in all patients. A dose-dependent uptake of HES was first detectable in macrophages and, thereafter, in endothelial and epithelial cells. Consecutive control biopsies taken from single patients revealed a subsequent reduction of the vacuoles, in size and number, within 3 years, thus indicating a regular cutaneous metabolism of HES. Patients suffering from pruritus consistently showed additional deposition of HES in small peripheral nerves. HES-reactive vacuoles could be demonstrated in the Schwann cells of unmyelinated, as well as small myelinated, nerve fibres, and in endoneural and perineural cells. Neural devacuolization paralleled the clinical improvement in the symptoms. In conclusion, HES deposits in cutaneous nerves, as a consequence of a higher cumulative dosage, may account for the itching seen after HES infusion.


Serum S100B levels in patients with epidural haematomas.
Protein S100B is today the most promising biomarker for cerebral injury. A welcomed area for the use of such a marker is in the early stages of head trauma and diagnosis of brain injury, in particular epidural haematomas. We report five consecutive cases of epidural haematoma where serum samples for S100B were drawn at admission. Three of the patients showed low levels of S100B (< or =0.2 microg/l). One patient with a large epidural haematoma with radiological signs of cerebral herniation displayed normal levels (0.14 microg/l) of S100B 3.5 h after the initial head trauma. Normal S100B levels in serum do not predict normal intracranial findings. S100B may be unreliable as a marker for epidural haematomas after closed head injury.


A prospective randomized trial of lafutidine vs rabeprazole on post-ESD gastric ulcers.
To compare the effects of rabeprazole and lafutidine on post-endoscopic submucosal dissection (ESD) gastric ulcers. Patients with gastric tumors indicated for ESD were prospectively studied. After ESD, all patients were treated with intravenous omeprazole for the first 3 d. Patients were then randomly assigned to oral lafutidine or rabeprazole. Ulcer size, ulcer size reduction rate, and ulcer stage were evaluated 4 wk later. Occurrence of complication was monitored throughout the 4-wk period. Sixty five patients were enrolled in the study, and 60 patients were subjected to the final analysis. In the lafutidine group (30 lesions in 29 patients), initial and 4-wk post-ESD ulcer sizes were 33.3 ± 9.2 and 10.5 ± 4.8 mm, respectively. In the rabeprazole group (34 lesions in 31 patients), the values were 34.7 ± 11.3 and 11.8 ± 6.7 mm, respectively. Ulcer size reduction rates in lafutidine and rabeprazole groups were 32.3% and 33.5%, respectively (P = 0.974). Ulcer stage 4 wk post-ESD did not differ significantly between the two groups (P = 0.868). Two cases in the rabeprazole group and no cases in the lafutidine group developed ulcer bleeding during the oral dose period, although the difference of bleeding rate between the two groups was not statistically significant (P = 0.157). Lafutidine and rabeprazole have equivalent therapeutic effects on post-ESD gastric ulcers.


[Permeability of the erythrocyte membrane to pentoxifylline and propentofylline. Research on their effects on some structural and functional properties of the membrane].
Contrarily to previous studies, we show that the red blood cell membrane is permeable to pentoxifylline and propentofylline. The kinetics of inward and outward flux are rapid. Both molecules do not transit via the pores for the water transport but instead seems to freely diffuse through the lipidic bilayer. It has not been possible to detect a significant compartimentation of the two drugs on the erythrocyte membrane. We have been searching for a possible modification of some of the structural and functional properties of the erythrocyte membrane in the presence of pentoxifylline and propentofylline. The experiments included measurement of the membrane fluidity, kinetics of water, glycerol and ethylene glycol transport, and studies on the stability of the membrane-cytoskeleton complex. No detectable differences were measured suggesting that the therapeutic action of pentoxifylline and propentofylline may result more from protective effect in the cases of pathological stresses occurring on the erythrocyte membrane than from their ability to repair the damaged membrane.


Innate, adaptive and regulatory responses in schistosomiasis: relationship to allergy.
Helminth infections have profound effects on the immune system. Here, recent insights in the molecular interactions between schistosomes and the host are described with respect to adaptive but also with respect to innate immune responses. Furthermore, the different mechanisms of immune hyporesponsiveness are depicted with emphasis on regulatory T cells. Finally, the relationship between downregulatory responses and allergy is discussed.


Temperature and Magnetic Field Dependence of the Internal and Lattice Structures of Skyrmions by Off-Axis Electron Holography.
The internal and lattice structures of magnetic Skyrmions in B20-type FeGe are investigated using off-axis electron holography. The temperature, magnetic field, and angular dependence of the magnetic moments of individual Skyrmions are analyzed. The internal Skyrmion shape is found to vary with applied magnetic field. In contrast, the inter-Skyrmion distance remains almost unchanged in the lattice phase over the studied range of applied field. The amplitude of the local magnetic moment is found to vary with temperature, while the Skyrmion shape does not change significantly. Deviations from a circular to a hexagonal Skyrmion structure are observed in the lattice phase, in agreement with the results of micromagnetic simulations.


Primary skeletal muscle lymphoma: A case report.
Primary lymphomas of the bone or skeletal muscle are rare. Three mechanisms of lymphomatous involvement of the muscle have been described, namely direct invasion from adjacent involved lymph nodes or bone, metastatic spread and, least commonly, primary muscle lymphoma. We herein present a rare case of primary mucle non-Hodgkin lymphoma with a description if the associated clinicopathological findings and a review of the relevant literature. A 41-year-old female patient was referred to our hospital with a painful mass in the right lower extremity. Following resection and histopathological examination, a diffuse large B-cell lymphoma originating from the muscle with cutaneous and subcutanenous infiltration was diagnosed. The patient received chemotherapy with six cycles of cyclophosphamide, hydroxydaunomycin, oncovin and prednisone (CHOP regimen) and a complete radiological response was achieved after six cycles of treatment.


Imidazolium ionic liquids containing selenium: synthesis and antimicrobial activity.
The synthesis and antimicrobial profile of imidazolium ionic liquids containing selenium are described herein. Minimum inhibitory concentration revealed that these compounds are especially active against algae, and their activity is modulated by substituents attached to the selenium moiety as well as by the counterion.


[Complication with paraaortic lymphadenectomy in gynecological cancer patients].
Although paraaortic lymphadenectomy is one of the standard treatments for gynecological cancer in Japan, it is very invasive so one must examine its safety for patients. Paraaortic lymphadenectomy was performed in 215. Two hundred and fifteen gynecologic cancer patients at our hospital between January 1991 and August 2005. We evaluated operation time, estimated blood loss and the incidence of operative injury, wound complication, and postoperative ileus. It was revealed that the mean operation time was 364 minutes and the estimated blood loss was increased at the operation around the vena cava or renal vein. After we adopted Kocher's technique, the mean blood loss was decreased. The incidence of postoperative ileus was 13.3%, but almost all of the patients were cured within seven days without surgical treatment. The incidence of wound complication was within 10%.


Empowering the Girl Child, Improving Global Health.
The health and productivity of a global society is dependent upon the elimination of gender inequities that prevent girls from achieving their full potential. Although some progress has been made in reducing social, economic, and health disparities between men and women, gender equality continues to be an elusive goal. The Millennium Development Goals (2000-2015) and the Sustainable Development Goals (2015-2030) include intergovernmental aspirations to empower women and stress that change must begin with the girl child.


Carrageenan nasal spray in virus confirmed common cold: individual patient data analysis of two randomized controlled trials.
Clinical trials applying iota-carrageenan nasal spray have previously shown to reduce duration of virus-confirmed common cold. The present study pooled data of two similar clinical trials to provide further evidence for the antiviral effectiveness of carrageenan. Individual patient data were analyzed from two randomized double blind placebo controlled trials assessing the therapeutic effectiveness of carrageenan nasal spray in acute common cold. Patients with virus-confirmed common cold (n = 254, verum 126, placebo 128) were included and the following parameters were appraised: duration of disease, number of patients with relapses, number of respiratory viruses and viral titers at inclusion (visit 1) compared to days 3-5 (visit 2). Carrageenan treated patients showed a significant reduction in duration of disease of almost 2 days (p < 0.05) as well as significantly fewer relapses during 21 days of observation period (p < 0.05). The virus clearance between visit 1 and visit 2 was significantly more pronounced in the carrageenan group (p < 0.05). In both studies, virus-confirmed common cold was caused by three main virus subtypes: human rhinovirus (46%), human coronavirus (25%) and influenza A (14%) virus. Carrageenan nasal spray showed significant antiviral efficacy in all three virus subgroups, the highest effectiveness was observed in human corona virus-infected patients. The reduced duration of disease was 3 days (p < 0.01) and the number of relapses was three times less (p < 0.01) in carrageenan treated corona-virus-infected patients compared to control patients. Administration of carrageenan nasal spray in children as well as in adults suffering from virus-confirmed common cold reduced duration of disease, increased viral clearance and reduced relapses of symptoms. Carrageenan nasal spray appeared as an effective treatment of common cold in children and adults. Pooled data from ISRCTN52519535 and ISRCTN80148028.