[Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA syndrome) in adults].
The PFAPA syndrome is characterized by a regular appearance of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis and is associated with a distinctive poor general condition of the patients. Since its first description in 1987 the syndrome has usually been described in children. But we here report its diagnosis in three adult patients. At the Department of Otorhinolaryngology/Head and Neck Surgery of the University Medical Center Freiburg, data on 36 patients with PFAPA syndrome were collected between 2004 and 2010. Data analysis was based on structured questionnaires, medical files of patients and a systematic assessment of the relevant international literature up to April 2011. The average age of the initial occurrence of PFAPA syndrome in the three patients was in the first few months after birth (month 2, 6 and 7). A tonsillectomy had been performed on all three patients in early childhood. As a result two patients had remission of symptoms for several years (4.5 and 12 years) with recurrence of PFAPA attacks while the third patient had no changes in symptoms. The PFAPA syndrome is an illness that first manifests itself in children. However, it can persist until adulthood or reappear after phases of remission. A knowledge of this periodic fever syndrome and extensive and close cooperation of general practitioners, paediatricians, internists and ENT specialists will be helpful in early diagnosis of this disorder.


Binding of [3H]serotonin to lymphocytes in patients with neuropsychiatric disorders.
Based on recent studies of neuroimmune networks, the lymphocyte binding of serotonin neurotransmitter was studied in patients with Alzheimer's disease, idiopathic mental retardation, and autism. The specific binding to lymphocytes of [3H]serotonin, at a single concentration of 100 nM, was significantly reduced in Alzheimer's disease patients as compared to aged controls (group mean of 3.667 +/- 2.301 v 7.506 +/- 1.717 picomoles; p = 0.001), and in children with idiopathic mental retardation as compared to healthy children (group mean of 3.694 +/- 1.627 v 5.792 +/- 1.902 picomoles; p = 0.003). However, autistic children did not differ significantly from the healthy children (group mean of 5.287 +/- 1.987 v 5.792 +/- 1.902 picomoles; p = 0.475). Reduced lymphocyte binding of serotonin may be an indication of breakdown of an unknown neuroimmune pathway relevant to the pathophysiology of Alzheimer's disease and idiopathic mental retardation.


Treatment of telangiectasias with the 532-nm and the 532/940-nm diode laser.
Recently, a dual-wavelength 532/940-nm laser has become available for treatment of facial vascular lesions as an alternative to the flashlamp pumped-dye lasers. Most facial vascular lesions will respond to the 532-nm wavelength. However, some of the larger and deeper lesions are resistant to this laser. The 940-nm wavelength can be used to treat these resistant lesions. Sixteen patients with 532-nm laser-resistant vascular lesions were treated with the 940-nm laser. Fourteen of these 16 patients had improvement in their telangiectasia in response to these treatments. Most facial l telangiectasias respond well to treatment with the 532-nm laser. However, some of the larger and deeper lesions will not respond well to this laser. The 940-nm wavelength laser can be used to treat these 532-nm laser resistant lesions.


Recognition of a 10 base pair sequence of DNA and stereochemical control of the binding affinity of chiral hairpin polyamide-Hoechst 33258 conjugates.
Chiral hairpin polyamides linked to a Hoechst 33258 analogue at the alpha-position of the hairpin turn amino acid (1,2) were synthesized on solid phase by adopting Fmoc and ivDde techniques. The DNA-binding properties of enantiomeric conjugates 1 and 2, and N-terminal linked conjugate 3 for 8-14bp sequences were determined by spectrofluorometric and thermal melting studies. Conjugates 1 and 2 recognize a 10bp sequence, while conjugate 3 recognizes a 9bp sequence. Interestingly, R-enantiomer 1 exhibited 10- to 30-fold higher binding affinities than S-enantiomer 2 for the DNA sequences studied. These binding differences were accounted for by molecular modeling studies, which revealed that the amide proton nearest to the chiral center in R-conjugate 1 is better positioned to form hydrogen bonds to the DNA bases, while S-conjugate 2 does not.


A prospective comparison of central and peripheral vein access for parenteral nutrition in the newborn.
Central venous parenteral nutrition (PN) is frequently used in preterm infants. Although central venous catheters (CVC) permit reliable delivery of hypertonic solution, they may be associated with more serious complications than when a peripheral venous infusion is used. The aim of this randomised prospective study was to compare complications of central versus peripheral venous access using Silastic catheters identical expect for intravascular length. Eighty such devices were inserted, 38 central (CVC), 42 peripheral (PVC). Catheter life was not significantly different between groups: median (range) CVC 10d (2-25); PVC 7d (1-22) with no difference in overall complication rate. Although peripherally sited catheters tended not to function for as long as CVCs, they offer a useful alternative to central venous catheterisation.


Environmental niche separation between native and non-native benthic invertebrate species: Case study of the northern Baltic Sea.
Knowledge and understanding of geographic distributions of species is crucial for many aspects in ecology, conservation, policy making and management. In order to reach such an understanding, it is important to know abiotic variables that impact and drive distributions of native and non-native species. We used an existing long-term macrobenthos database for species presence-absence information and biomass estimates at different environmental gradients in the northern Baltic Sea. Region specific abiotic variables (e.g. salinity, depth) were derived from previously constructed bathymetric and hydrodynamic models. Multidimensional ordination techniques were then applied to investigate potential niche space separation between all native and non-native invertebrates in the northern Baltic Sea. Such an approach allowed to obtain data rich and robust estimates of the current native and non-native species distributions and outline important abiotic parameters influencing the observed pattern. The results showed clear niche space separation between native and non-native species. Non-native species were situated in an environmental space characterized by reduced salinity, high temperatures, high proportion of soft seabed and decreased depth and wave exposure whereas native species displayed an opposite pattern. Different placement of native and non-native species along the studied environmental niche space is likely to be explained by the differences in their evolutionary history, human mediated activities and geological youth of the Baltic Sea. The results of this study can provide early warnings and effectively outline coastal areas in the northern Baltic Sea that are prone to further range expansion of non-native species as climate change is expected to significantly reduce salinity and increase temperature in wide coastal areas, both supporting the disappearance of native and appearance of non-native species.


Renal Na(+)-phosphate cotransport in X-linked Hyp mice responds appropriately to Na+ gradient, membrane potential, and pH.
To investigate the mechanism for the 50% decrease in Vmax of the high-affinity phosphate transport system in the renal brush-border membrane of X-linked Hyp mice, we compared the effects of external Na+ concentration, membrane potential, pH, phosphonoformic acid (PFA), and arsenate on Na(+)-Pi cotransport in brush-border membrane vesicles prepared from normal mice and Hyp littermates. The affinity of the Na(+)-Pi cotransport system for Na+ (apparent Km = 60 +/- 7 and 64 +/- 2 mM for normal and Hyp mice, respectively) and the Na(+)-Pi stoichiometry estimated from Hill plots (2.5 +/- 0.2 and 2.9 +/- 0.6 for normal and Hyp mice, respectively) were similar in brush-border membranes of both strains. Inside-negative membrane potential, generated by anions of different permeabilities, stimulated Na(+)-Pi cotransport and inside-positive membrane potential generated by valinomycin, and a K+ gradient (outside greater than inside) inhibited Na(+)-Pi cotransport to the same extent in brush-border membranes derived from normal mice and Hyp littermates. The pH dependence of Na(+)-Pi cotransport was similar in brush-border membrane vesicles of normal and Hyp mice. The ratio of Na(+)-Pi cotransport measured at pH 7.5 relative to that at pH 6.5 was 2.9 +/- 0.6 in normal mice and 2.9 +/- 0.7 in Hyp mice. PFA was a competitive inhibitor of Na(+)-Pi cotransport in brush-border membranes of both normal and Hyp mice. However, the apparent Ki for PFA was significantly lower in Hyp mice (0.31 +/- 0.01 and 0.19 +/- 0.02 mM in normal and Hyp mice, respectively, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Quinone interactions with the chloroplast cytochrome b6-f complex.
The requirements for reconstitution of electron transfer activity with a plastoquinone (PQ)-depleted cytochrome b6-f complex from spinach have been considered. Full restoration of activity measured as plastocyanin reduction with either duroquinol in the dark or Photosystem II (PSII) in the light requires both PQ-9 and phospholipid. However, a substantial dark activity can be observed with duroquinol and phospholipid in the absence of any added PQ-9. PSII, with its associated PQ molecules, can also donate electrons in the light to the cytochrome complex which has been depleted of plastoquinone. Electron donation by duroquinol in the dark to the PQ-depleted cytochrome complex is stimulated by PSII, and this stimulation is dependent on the presence of the two PQ molecules in the PSII preparation. Measurements of proton translocation with the PQ-depleted complex indicate this quinone is not required for the observed H+/e- ratio of 2. Studies of cytochrome b6 kinetics with the free and liposome-incorporated PQ-depleted complex show this cytochrome undergoes redox reactions similar to those of a control complex which contains PQ. These results indicate the PQ that copurifies with the cytochrome complex is not essential for any of the measured activities. These findings are considered in relation to a quinone binding site(s) in the cytochrome complex which is not specific to PQ but can bind other quinones, such as duroquinol, in a lipid-dependent process.


Inhibition of mitochondrial remodeling by cyclosporine A preserves myocardial performance in a neonatal rabbit model of cardioplegic arrest.
Mitochondrial permeability transition pore opening is associated with apoptotic signaling and alterations in mitochondrial structure and function. We tested whether inhibition of mitochondrial permeability transition pore opening with cyclosporine A preserved mitochondrial structure and function after cardioplegic arrest and whether this preservation is associated with improved myocardial performance. Langendorff-perfused neonatal rabbit hearts were perfused for 30 minutes with Krebs-Henseleit buffer (CCP; n = 6) or Krebs-Henseleit buffer containing 2 mumol/L of cyclosporine A (CCP+CsA; n = 6) followed by 60 minutes of normothermic crystalloid cardioplegia (CCP) and 60 minutes of reperfusion. Control hearts (non-CCP; n = 6) were constantly perfused for 150 minutes without cardioplegic arrest. In comparison with non-CCP, CCP was associated with Bax translocation to the mitochondria, cytochrome c release, and greater frequency of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive myocytes These changes were also associated with deficits in isolated mitochondrial oxygen consumption at complex I. CsA pretreatment minimized or prevented all these findings. Myocardial performance (systolic pressure, maximum positive and negative dP/dt, and elevated left ventricular end-diastolic pressure) at 5, 15, 30, and 60 minutes after reperfusion was diminished in CCP hearts when compared with non-CPB, and these deficits could be minimized with cyclosporine A pretreatment. (P < .05 all comparisons) Cyclosporine A prevents apoptosis-related mitochondrial permeabilization and dysfunction after cardioplegic arrest. This protection is associated with improved myocardial performance. Prevention of mitochondrial permeability transition pore opening is a valuable target for mitochondrial (and myocardial) preservation after neonatal cardioplegic arrest.


Correlates of methadone client retention: a prospective cohort study in Guizhou province, China.
Methadone client retention levels and treatment doses of patients vary widely in methadone clinics across China. Because methadone clinics have been available in China only recently, this study explored the relationship between methadone dosage and client retention in methadone maintenance programmes in Guizhou province. The study used a prospective cohort study design. Injecting and non-injecting heroin-using clients who had been treated for no more than two and half months in one of eight methadone maintenance treatment clinics in Guizhou province were recruited into the cohort, beginning on 3 June 2006 and followed up until 1 June 2007. A total of 1003 participants were enrolled. Face-to-face interviews were conducted to collect baseline information, and clients' daily doses were recorded. The 14-month retention rate was 56.2%. Controlling for other covariates in the multivariate Cox model, a higher methadone dose was found to predict higher client retention. Retention was also associated with intention to remain in treatment for life and the clinic attended. Clients need to receive an adequate methadone dose to assure continued retention. Patients who expect to be treated for life have higher retention rates than patients who anticipate only short-term treatment. Key factors associated with successful clinics in China need to be elucidated.


Non-obstructive azoospermia and clinical varicocele: therapeutic options.
Ten to fifteen percent of infertile men are azoospermic, and sixty percent of these men have been classified as having non-obstructive azoospermia (NOA). NOA results from testicular failure, and one of the causes of this is the presence of varicocele. Varicocele is observed in 5-10 % of men with NOA. This review discusses the impact of varicocele repair on semen quality and pregnancy rate among men with NOA. Based on the best available evidence, varicocele repair of men with NOA is associated with an improvement in semen quality and pregnancy rate. Thus, it appears to be an effective therapeutic option for this group of men, particularly for those with a female partner who is younger than 35 years of age, before an assisted reproductive technique (ART) is initiated. Semen cryopreservation is recommended once the patient has spermatozoa in the ejaculate. In addition, varicocele repair seems to improve the rate of spermatozoa recovery in testicular sperm extraction for those who requested ART.


Intussusception: the paediatric radiologist's perspective.
The diagnosis and treatment of idiopathic intussusception of childhood have changed over the last 10 years. Current diagnostic techniques include plain radiographs and ultrasonography. The standard treatment in the absence of peritonitis or free intra-abdominal air is gas enema, followed by surgical intervention if the intussusception remains irreducible. This review, by radiologists for surgeons, describes the current role of imaging in the diagnosis and management of intussusception.


Dynamics of early stages of nose morphogenesis.
The formation of sensory organs is an important developmental and evolutionary question. In the context of regenerative medicine also, it is important to know as accurately as possible how sensory organs form. The formation of ears, eyes or nose stems presumably from tissue thickenings called placodes Graham and Shimeld (J Anat 222(1):32-40, 2013), Horie et al. (Nature 560:228-232, 2018) which become these organs after processes termed inductions. However, the origin of the placodes, the mechanism of induction and the overall face organization are not understood. Recently, it has been suggested that there is a physical principle to face organization. Indeed, it has been shown that there exists a pattern of rings and rays in the early blastula which defines the position of face landmarks, especially the ears and eyes Fleury et al. (Second order division in sectors as a prepattern for sensory organs in vertebrate development, 2021), Fleury and Abourachid (Eu Phys J E 45:31, 2022). Tensions in the sectors defined by the intersections of the said rings and rays create the actual face features. I report here that a similar situation exists for the nose. This explains the robustness of face formation in the chordates phylum. By studying nasal pit formation in the chicken embryo by time-lapse (T-L) video microscopy, I show that the nasal placode originates in a narrow sector deformed by tension forces following the biaxial pattern of rings and rays mentioned above. Cells align in the pattern and exert organized forces. Further contractions of the pattern contribute to inducing the nasal pit. The observation of the early pre-pattern of lines which locks the facial features explains readily a number of facts regarding sensory organs. Especially the existence of a lacrimal canal between the eye and the nose Lefevre and Freitag (Semin Ophthalmo l 27(5-6):175-86, 2012), or of a slit connecting the nose to the mouth, the correlation between nose, mouth and eye morphogenesis Dubourg et al. (J Rare Dis 2(8), 2007), the presence of shallow valleys on the nasal and optic vesicles, the medio-lateral asymmetry of nostrils with often a bent slit Liu et al. (PLoS ONE 12: e0181928, 2017), the uneven number of nostrils in many fish Cox (J R Soc Interf 5(23):575-593, 2008) and possibly the transition between agnatha and gnathostomes Gai and Zhu (Chinese Sci Bull 57(31), 2012): all appear under this light, geometrically straightforward. The nasal pit forms in a sector of tissue which was present on the blastodic (early embryonic stage), and which is projected onto the nasal vesicle during neurulation. The nasal pit forms along a hairpin of tissue. The top part of the hairpin forms the nares, and the bottom part a groove often visible in many animals.


The localization over time of exogenous aldosterone and angiotensin II in various organs.
Central nervous system effects have been demonstrated for angiotensin II and suggested for aldosterone. In order to determine whether either of these chemicals naturally crosses the blood-brain barrier, radioactive aldosterone and angiotensin II were introduced via intracardiac injections in rats. Samples of blood, liver, kidney, adrenals, cerebral cortex, and hypothalamus were collected at three, 15, and 60 minutes, frozen, dissolved, and counted. Blood levels for aldosterone and angiotensin II remained constant over 60 minutes. Aldosterone accumulated in the liver, kidney, adrenals and hypothalamus three minutes after injection, and levels diminished over time. Angiotensin II levels peaked in the adrenal, kidney, and liver after three minutes, and in the hypothalamus after 15 minutes. Cerebral cortex levels were lower than hypothalamic levels by 30% for aldosterone and 50% for angiotensin II. This suggests that both drugs may enter the central nervous system and selectively accumulate in the hypothalamus.


Use of the cryoballoon to ablate pulmonary vein-dependent left atrial flutter.
New atrial flutter (AFL) that arises after pulmonary vein isolation (PVI) by catheter or surgical ablation can originate from reconnection of a pulmonary vein (PV). Reisolation of PVs with cryoballoon ablation (CBA) for treatment of peri-PV AFL after Maze or PVI has not previously been reported. The present case series describes use of CBA to treat post-PVI and post-Maze PV-dependent AFL. In these cases, CBA was used to reisolate the PVs and terminate AFL without requiring additional lesion sets for treatment of AFL.


Phyllanthi Fructus: A modal medicinal and food homologous item in quality evaluation.
Phyllanthi Fructus is a highly unique medicine and food homologous item, which exhibits distinctive flavor, notable nutritional value, and abundant pharmacological activity. It has enormous potential in the creation of health products and pharmaceuticals. However, due to the unique laws of quality formation and transfer of Phyllanthi Fructus, its appearance, shape, chemical compositions, nutrients, and sensory flavors are frequently greatly influenced by botanical resources, the processing and storage conditions. As a result, the current quality evaluation model is difficult to meet the needs of Phyllanthi Fructus as a medicine and food homologous item in the development of diversified products. This paper constructs the hierarchical utilization mode of Phyllanthi Fructus based on its unique quality formation and transmission laws, explores the quality evaluation model for food-oriented use and medicinal-oriented use, respectively, and systematically describes the quality evaluation idea under diversified application scenarios. This paper aims to serve as a reference for the construction of a quality evaluation model suitable for the medicine and food homologous item of Phyllanthi Fructus.


Weight loss between glucagon-like peptide-1 receptor agonists and bariatric surgery in adults with obesity: A systematic review and meta-analysis.
Glucagon-like peptide-1 (GLP-1) receptor agonists recently demonstrated 15% to 20% weight loss in adults with obesity, a range which has previously been achieved only with bariatric surgery. This systematic review and meta-analysis compares weight loss between GLP-1 receptor agonists and bariatric surgery. The databases MEDLINE, MEDLINE In-Process, MEDLINE Epubs Ahead of Print, Embase Classic + Embase (OvidSP), and Cochrane (Wiley) were searched from inception to April 21, 2021, for randomized controlled trials and observational studies. Two independent reviewers extracted data, reported risk of bias, and graded certainty of evidence. Random-effects models were used to pool change in weight, BMI, and glycated hemoglobin. Six studies, encompassing 332 patients, were included. Among randomized controlled trials, mean difference in weight between all bariatric surgery types and GLP-1 receptor agonists was -22.68 kg (95% CI: -31.41 to -13.96), mean difference in BMI was -8.18 kg/m2 (95% CI: -11.59 to -4.77), and mean difference in glycated hemoglobin was -1.28% (95% CI: -1.94% to -0.61%). Among observational studies, mean difference in weight was -25.11 kg (95% CI: -40.61 to -9.60), and mean difference in BMI was -10.60 kg/m2 (95% CI: -17.22 to -3.98). Only one observational study reported glycemic outcomes. In adults with obesity, bariatric surgery still confers the highest reductions in weight and BMI but confers similar effects in glycemic control when compared with GLP-1 receptor agonists.


Pathologic Tumor Size versus Mammography, Sonography, and MRI in Breast Cancer Based on Pathologic Subtypes.
The standard of care for imaging of breast pathology has historically been mammography and sonography. MRI is a modern adjunct in the surgeon's toolkit. We looked to examine the differences in imaging modalities and their ability to predict the size in relation to the pathologic size after excision with focus on pathologic subtypes. We analyzed patient records across a 4-year period from 2017 to 2021 who were treated surgically for breast cancer at our facility. We used a retrospective chart review to collect measurements that were recorded of the tumors by the radiologist for available mammography, ultrasound, and MRI which were compared to pathology report measurements of the final specimens. We subdivided the results by pathologic subtypes including invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and ductal carcinoma in situ (DCIS). 658 total patients met criteria for analysis. Mammography overestimated specimens with DCIS by 1.93 mm (P = .15), US underestimated by .56 (.55), and MRI overestimated by 5.77 mm (P < .01). There was no statistically significant difference in any modalities with IDC. With specimens of ILC, all 3 imaging modalities underestimated tumor size, with only US being significant. Mammography and MRI consistently overestimated tumor size with the exception of ILC while US underestimated tumor size on all pathologic subtypes. MRI significantly overestimated tumor size in DCIS by 5.77 mm. Mammography was the most accurate imaging modality for all pathologic subtypes and never had a statistically significant difference from actual tumor size.


[Immediate and long-term results of endarterectomies in atherosclerotic occlusions of the abdominal aorta and iliac arteries].
An analysis of the clinical material evidences a sufficiently high efficiency of endarterectomy even in spread occlusions of the aorto-femoral segments of atherosclerotic etiology with the absence of atheromatosis and calcinosis of the arteries. Good and satisfactory immediate results were obtained in 89.4% of the patients, long-term results in 52.8% and with regard to reoperations--in 67.5% of the patients.


(+)-Catechin, epicatechin and epigallocatechin gallate are important inducible defensive compounds against Ectropis grisescens in tea plants.
The tea plant, Camellia sinensis (L.) O. Kuntze, is an economically important, perennial woody plant rich in catechins. Although catechins have been reported to play an important role in plant defences against microbes, their roles in the defence of tea plants against herbivores remain unknown. In this study, we allowed the larvae of Ectropis grisescens, a leaf-feeding pest, to feed on the plants, and alternatively, we wounded the plants and then treated them with E. grisescens oral secretions (WOS). Both approaches triggered jasmonic acid-, ethylene- and auxin-mediated signalling pathways; as a result, plants accumulated three catechin compounds: (+)-catechin, epicatechin and epigallocatechin. Not only was the mass of E. grisescens larvae fed on plants previously infested with E. grisescens or treated with WOS significantly lower than that of larvae fed on controls, but also artificial diet supplemented with epicatechin, (+)-catechin or epigallocatechin gallate reduced larval growth rates. In addition, the exogenous application of jasmonic acid, ethylene or auxin induced the biosynthesis of the three catechins, which, in turn, enhanced the resistance of tea plants to E. grisescens, leading to the coordination of the three signalling pathways. Our results suggest that the three catechins play an important role in the defences of tea plants against E. grisescens.


Erythrocyte heterogeneity in sickle cell disease: effect of deoxygenation on intracellular polymer formation and rheology of sub-populations.
Erythrocytes from 12 patients with homozygous sickle cell disease in the steady state were fractionated on a Percoll-Stractan density gradient. Erythrocyte deformability was measured by initial-flow-rate filtration through pores of 5 microns diameter and erythrocyte polymer content was calculated as a function of oxygen saturation. Density fractionated sub-populations of sickle cells showed distinct rheological characteristics, the filterability of dense cells being impaired by minimal oxygen desaturation with the apparent formation of little or no intracellular polymer. Lighter cell fractions required a greater degree of deoxygenation and polymer formation to impair deformability, although this occurred prior to morphological sickling. Dense cells therefore exert a disproportionate effect on blood rheology in sickle cell disease and are likely to have an adverse rheological effect in vivo at arterial oxygen tension.


Preparation and use of MitoPY1 for imaging hydrogen peroxide in mitochondria of live cells.
Mitochondria peroxy yellow 1 (MitoPY1) is a small-molecule fluorescent probe that selectively tracks to the mitochondria of live biological specimens and responds to local fluxes of hydrogen peroxide (H(2)O(2)) by a turn-on fluorescence enhancement. This bifunctional dye uses a triphenylphosphonium targeting group and a boronate-based molecular switch to selectively respond to H(2)O(2) over competing reactive oxygen species (ROS) within the mitochondria. MitoPY1 can be used to measure mitochondrial H(2)O(2) levels in both cell culture and tissue models. In this protocol, we describe the synthesis of MitoPY1 and how to use this chemical tool to visualize mitochondrial H(2)O(2) in live cells. The preparation of MitoPY1 is anticipated to take 7-10 d, and assays involving microscopy of cultured mammalian cells can be performed in 1-2 d.


Chitosan-based nerve guidance conduit with microchannels and nanofibers promotes schwann cells migration and neurite growth.
Peripheral nerve injury (PNI) is the leading cause of permanent dysfunction in movement and sensation. Despite the rapid development of tissue engineering in peripheral nerve regeneration, autograft remains the gold standard for treating PNI. Synthesized nerve guidance conduits (NGCs) were reported as a potential alternative treatment that could replace autograft. However, most current NGCs are hollow tubular structured, or NGCs with macro or microstructures, but not both. These simple structures could not meet the need for neurite and Schwann cell guidance and accelerate peripheral nerve regeneration. In the current study, we combine unidirectional freezing with electrospinning to produce a unique NGC with longitudinal microchannels and parallel nanofibers. The in vitro study showed the importance of having both features in promoting Schwann cell growth, migration, and PC-12 cells neurite elongation. The novel NGCs could provide desirable physical support and guidance for peripheral nerve regeneration. From the current study, we found both the micro feature and the nano feature are helpful in terms of helping cell migrating through the NGCs, and the combination of both features will have a syngeneic effect.


Lack of effect of nitroglycerin on the diameter response of larger retinal arterioles in normal persons during hypoxia.
Retinal hypoxia with consequent changes in blood flow play a role in a number of vision-threatening diseases, such as diabetic retinopathy. Previous studies have shown that the inhibition of nitric oxide synthase (NOS) and cyclooxygenase (COX) products are involved in the diameter regulation of the retinal vessels during hypoxia. Therefore, the aim of the present study was to examine the effects of an NO donor combined with COX inhibition on the diameter regulation of retinal vessels during hypoxia in normal persons. Twenty normal persons aged 21-47 years were examined. The Dynamic Vessel Analyzer (DVA) was used to measure retinal vessel diameters at rest, during isometric exercise, and during flicker stimulation. The measurements were performed during normoxia and hypoxia before and after sublingual administration of the NO donor nitroglycerin, and were repeated on a second study day after topical administration of the COX-inhibitor diclofenac. The resting diameter of arterioles and venules increased significantly during hypoxia (p < 0.0001). Hypoxia also significantly reduced the arteriolar constriction during isometric exercise, and the dilatation of the arterioles and venules during flicker stimulation (p < 0.0001). Diclofenac further reduced the arteriolar constriction induced by isometric exercise during hypoxia (p = 0.005). However, the NO-donor nitroglycerin had no effect on vascular diameters. Diameter regulation of retinal vessels during hypoxia in normal persons can be influenced by the inhibition of COX products, but not by increasing the NO concentration. The findings suggest that the vasoactive effects of NO on retinal arterioles during hypoxia are saturated in normal persons.


Serial assessment of left ventricular remodeling by measurement of left ventricular torsion using speckle tracking echocardiography in patients with acute myocardial infarction.
The relation between remodeling and left ventricular (LV) torsion has not yet been fully investigated. The aim of this study was to determine whether LV torsion assessed by speckle tracking imaging can predict progressive LV dilation after acute myocardial infarction (AMI). From January 2006 through June 2008, 91 patients with AMI who were successfully treated with primary coronary intervention underwent conventional and speckle tracking echocardiographies at initial presentation and 3 days and 6 months after first AMI. Patients were divided into 2 groups based on presence of LV remodeling (increase of LV end-diastolic volume >20%) at 6-month follow-up. LV remodeling developed in 23 patients. At initial presentation, LV end-diastolic volume was not significantly different between the no-remodeling and remodeling groups (91.27 ± 35.68 vs 85.74 ± 28.89 ml, p = 0.51), but LV torsion (2.23 ± 0.67 vs 1.70 ± 0.58°/cm, p <0.05) was significantly decreased in the remodeling group. At 6-month follow-up speckle tracking echocardiography, apical rotation and global torsion in patients with remodeling were 6.7 ± 2.6 (p <0.05) and 1.7 ± 0.7°/cm (p = 0.76 from baseline), respectively, and in patients without remodeling, 8.8 ± 3.4 (p <0.01) and 2.5 ± 0.7°/cm (p <0.01 from baseline), respectively. According to receiver operating characteristic analysis, LV torsion of 1.9°/cm (area under curve 0.79, sensitivity 75%, specificity 78%) at initial presentation was selected as a significant predictor of remodeling. In conclusion, decreased LV torsion assessed by speckle tracking echocardiography may predict late LV remodeling after reperfusion therapy after AMI.


The application of an improved solid phase synthetic technique to the delineation of an antigenic site of apolipoprotein A-II.
Previous studies have shown that the antigenic sites of human plasma high-density apolipoprotein A-II (apoA-II) are separate from their lipid-binding determinants in human high density lipoproteins (HDL). A specific radioimmunoassay has shown that three distinct antigenic sites are located in residues 4-23, 31-46, and 56-77; these studies suggested that an antigenic site might be restricted to residues 60-77 in the 56-77 fragment. To further delineate this site, we have developed a solid phase radioimmunoassay technique using an improved solid support on which selected sequences of peptides were synthesized, deprotected with HF, and the resulting peptidyl-resins tested for their capability of binding purified 125I-anti-apoA-II antibodies. Amino acid analyses and solid phase sequence analyses were performed to verify the sequence of the synthetic peptide on the solid support. Using this technique, 125I-anti-apoA-II antibodies had achieved 50% of maximal binding when residues 61-77 were attached to the solid support. The maximal binding was achieved by the addition of one more residue, Leu60, thus confirming our suggestion that a major antigenic site is located in residues 60-77. The binding to the peptidyl-resin was inhibited by a synthetic fragment corresponding to residues 60-77 indicating that the antibodies were specifically bound to the resin.


Graft-free surgical retroperitoneal vascular access as bail-out technique for failed percutaneous approach to transcatheter aortic valve replacement.
Surgical retroperitoneal access to the iliac artery may provide an alternative route for transcatheter aortic valve replacement (TAVR) in patients with aortic stenosis and prohibitively small common femoral arteries. Consecutive patients undergoing TAVR via the femoral approach were divided into two groups; standard percutaneous access (n=103) and surgical retroperitoneal access (n=15) for patients in whom dilators could not be advanced without resistance. For retroperitoneal access, proximal groin vessels were exposed surgically and direct puncture was performed. The sheath was tunneled from the level of the initial inguinal puncture site in order to achieve coaxial entry of the sheath into the vessel. Baseline characteristics were similar in both groups. Procedural characteristics were insignificantly different between groups; although, procedure time was longer (34 min), while fluoroscopy time and contrast utilization were lower in the retroperitoneal access group. There was no outcome difference between groups. Surgical retroperitoneal access is a reasonable alternative for transcatheter aortic valve replacement in high-risk patients with aortic stenosis who have poor percutaneous access options due to peripheral vascular disease.


A New Contact Lens Sensor System for Continuous Intraocular Pressure Monitoring: Evaluation of Safety and Tolerability.
To assess the safety and tolerability of a new contact lens sensor (CLS) system for continuous 3- and 24-hr intraocular pressure (IOP) monitoring in human eyes. Twenty-five subjects were recruited for 3-hr IOP measurement by CLS. Corneal fluorescein staining (CFS) scores were evaluated before and after measurement. Then, 30 participants (10 normal subjects and 20 glaucoma patients) were recruited for 24-hr IOP monitoring. Ocular surface disease index (OSDI) was assessed before and one day after measurement. Contact lens dry eye questionnaire-8 was assessed immediately after measurement. Visual analog scale of discomfort was measured before, immediately after, and one day after measurement. Best-corrected visual acuity (BCVA), tear break-up time (TBUT), and CFS were assessed before, immediately after, and 1 day after measurement. All participants completed 3- or 24-hr IOP measurement by CLS. Corneal fluorescein staining increased from 0.6±0.7 to 2.4±1.5 after 3-hr IOP measurement ( P <0.001). For participants undergoing 24-hr IOP monitoring, OSDI increased from 9.1±9.7 to 18.0±12.4 ( P =0.001). CLDEQ-8 score was 11.6±5.8. Visual analog scale increased from 11.1±14.2 to 35.2±21.8 after measurement ( P <0.001) and decreased to 26.7±18.4 one day later ( P <0.001 compared with baseline). BCVA decreased from 1.0±0.01 to 0.8±0.1 ( P <0.001) and returned to 0.9±0.1 after one day ( P <0.001 compared with baseline). TBUT decreased from 5.1±3.9 to 2.6±1.5 s ( P =0.001) and returned to 4.8±2.5 s ( P =0.465 compared with baseline). Corneal fluorescein staining increased from 0.7±0.9 to 4.3±0.8 ( P <0.001) and dropped to 0.8±0.7 ( P =0.599 compared with baseline). No significant difference was found for all variations of indicators between normal subjects and glaucoma patients ( P >0.1 for all comparisons). The CLS shows a great potential for a safe and tolerable 24-hr IOP monitoring in normal subjects and glaucoma patients. Clinical attention to the worsening signs and symptoms after measurement is required.


Integrative analysis of lncRNAs, miRNAs, and mRNAs-associated ceRNA network in a neonatal mouse model of bronchopulmonary dysplasia.
To elucidate the potential roles of the lncRNA-mediated competitive endogenous RNA (ceRNA) network in the pathogenesis of bronchopulmonary dysplasia (BPD), we performed an integrated bioinformatics analysis based on miRNA and mRNA microarray datasets between BPD and normal samples. The mRNA and miRNA expression profiles of BPD were downloaded from the Gene Expression Omnibus (GEO) database to perform an integrated analysis. The limma package was used to identify differentially expressed genes (DEGs) and differentially expressed miRNA (DEmiRs), followed by functional enrichment analysis of DEGs. DEmiR-DEG and DEmiRNA-lncRNA interactions were predicted. Subsequently, the lncRNA-related ceRNA network was structured. Finally, a newborn BPD mouse model was established, and quantitative real-time PCR (qPCR) was used to validate the expression of the selected mRNAs, miRNAs, and lncRNAs. A total of 445 DEGs and 155 DEmiRs were obtained by comparing BPD samples and normal samples. Functional enrichment analysis showed that DEGs were primarily enriched in GO terms such as cell division and inflammatory response; and DEGs were mainly involved in the p53 signaling pathway. The miR17hg-miR-130b-3p-roundabout guidance receptor 2 (Robo2) and GM20455-miR-34a-5p-BMP/retinoic acid-inducible neural specific 1 (Brinp1) ceRNA axes were obtained by constructing the ceRNA network. In addition, the upregulation of Robo2 and miR17hg while the downregulation of miR-130b-3p; as well as the upregulation of Brinp1 and GM20455 but the downregulation of miR-34a-5p were validated by qPCR. The miR17hg-miR-130b-3p-Robo2 and GM20455-miR-34a-5p-Brinp1 axes may serve important role in the development of BPD. These findings might provide novel insight for a comprehensive understanding of molecular mechanisms in BPD, and genes in the ceRNA network might be considered as potential biomarkers and therapeutic targets against BPD.


Arbor Clinical Nutrition Updates: evidence-based clinical nutrition education using the Internet.
The Arbor Clinical Nutrition Updates (ACNU) is a weekly electronic nutrition journal for health professionals. Each issue summarises several recent clinical research papers appearing in the general medical and nutrition literature and which deal with a common nutrition topic. A commentary is added on how this research fits in with previous work, and what it all means for the practising clinician. ACNU is the world's most widely read electronic nutrition publication, with over 100,000 largely health-professional readers in 186 countries. It is published in nine languages and distributed by email without charge in both plain text and Acrobat formats. ACNU utilises a number of the Internet's unique characteristics to facilitate broad reach, currency and active reader feedback. This, together with its brevity and summarising format, helps to maintain its relevance to the nutrition education needs of health professionals, particularly those in clinical practice, and to overcome the factors most commonly reported by health professionals as obstacles to their greater adoption of evidence-based medicine. ACNU is intended to be a collaboration with the primary research journals to extend the reach of new nutrition research findings to a wider community of researchers, academics and clinicians than each journal might otherwise reach individually. As such, ACNU utilises the Internet to promote the goals of open-access publishing and evidence-based medicine.


Prostate-specific antigen levels in the United States: implications of various definitions for abnormal.
The finding that some men with a normal prostate-specific antigen (PSA) level (i.e., less than 4 ng/mL) nonetheless have microscopic evidence of prostate cancer has led to some suggestions that the threshold defining abnormal should be lowered to 2.5 ng/mL. We examined the effect of this lower threshold on the number of American men who would be labeled abnormal by a single PSA test. We obtained PSA data on a nationally representative sample of American men 40 years of age and older with no history of prostate cancer and no current inflammation or infection of the prostate gland (n = 1308) from the 2001-2002 National Health and Nutrition Examination Survey. We obtained data on the 10-year risk of prostate cancer death in the pre-PSA era from DevCan, the National Cancer Institute's software to calculate the probability of dying of cancer. Based on NHANES data, approximately 1.5 million American men aged 40 to 69 years have a PSA level over 4.0 ng/mL. Lowering the threshold to 2.5 ng/mL would label an additional 1.8 million men as abnormal, if all men were screened. For men aged 70 years or older, the corresponding numbers are 1.5 and 1.2 million. The proportion of the population affected by different thresholds would vary with age. Among men in their 60s, for example, 17% have a PSA level over 2.5 ng/mL, 5.7% have a PSA level over 4.0 ng/mL, and 1.7% have a PSA level over 10.0 ng/mL. For context, only 0.9% of men in their 60s are expected to die from prostate cancer in the next 10 years. Lowering the PSA threshold to 2.5 ng/mL would double the number of men defined as abnormal, to up to 6 million. Until there is evidence that screening is effective, increasing the number of men recommended for prostate biopsy--and the number potentially diagnosed and treated unnecessarily--would be a mistake.


Stress across the life course and depression in a rapidly developing population: the Guangzhou Biobank Cohort Study.
The objective of this study was to examine the role of stress across the life course in the development of depression among older adults in a non-Western developing setting. Multivariable linear and multinomial logistic regression were used in cross-sectional analyses of 9729 Chinese participants (mean age 60.2 years) from phase 3 of the Guangzhou Biobank Cohort Study (2006-2008) to investigate the association of childhood adversities and adulthood stressors with depression. Childhood adversities were associated with mild depression (odds ratio (OR) 1.78, 95% confidence interval (CI) 1.58, 2.02) and moderate-to-severe depression (OR 2.30, 95% CI 1.68, 3.15), adjusted for age, sex, education and childhood socio-economic status. Past-year adulthood stressors were also associated with mild depression (OR 1.96, 95% CI 1.54, 2.02) and moderate-to-severe depression (OR 3.55, 95% CI 2.21, 5.68), adjusting additionally for occupation and income. Adulthood stressors were more strongly associated with depressive symptoms among individuals with a history of childhood adversities. Childhood adversities and adulthood stressors were independently associated with an increased risk of depression among older ambulatory adults, although adulthood stressors were more strongly associated with depression following exposure to childhood adversities. This is consistent with evidence from Western settings in which the social context of risk and protective factors for depression may differ and implies that the role of stress in the aetiology of depression is not context specific.


Microhabitat selection and coexistence in feather mites (Acari: Analgoidea) on Alaskan seabirds.
Two species of feather mites, Alloptes (A.) sp. and Laronyssus martini, coexisted on the flight feathers of kittiwakes, while Alloptes (C.) sp. occurred alone on murres. All three species were found mostly on the ventral surface of mid-wing regions. On individual feathers, the mites were attached to the distal sides of barbs on the trailing vanes. The two species coexisted on kittiwakes but occupied different portions of feathers. The results suggest that the two species compete for the attachment site on the feather and Alloptes (A.) sp. is excluded by L. martini from the preferred microhabitat.


Oxygen-releasing biomaterials for chronic wounds breathing: From theoretical mechanism to application prospect.
Chronic wounds have always been considered as "gordian knots" in medicine, in which hypoxia plays a key role in blocking healing. To address this challenge, although tissue reoxygenation therapy based on hyperbaric oxygen therapy (HBOT) has been performed clinically for several years, the bench to bedside still urges the evolution of oxygen-loading and -releasing strategies with explicit benefits and consistent outcome. The combination of various oxygen carriers with biomaterials has gained momentum as an emerging therapeutic strategy in this field, exhibiting considerable application potential. This review gives an overview of the essential relationship between hypoxia and delayed wound healing. Further, detailed characteristics, preparation methods and applications of various oxygen-releasing biomaterials (ORBMs) will be elaborated, including hemoglobin, perfluorocarbon, peroxide, and oxygen-generating microorganisms, those biomaterials are applied to load, release or generate a vast of oxygen to relieve the hypoxemia and bring the subsequent cascade effect. The pioneering papers regarding to the ORBMs practice are presented and trends toward hybrid and more precise manipulation are summarized.


Biological characterization of a tumour-growth-promoting factor from ascitic fluid of tumour-bearing mice.
Tumour-growth-promoting activity has been observed in ascitic fluids of mice with progressively growing SV40- and chemically induced tumours. Administration of ascitic fluid to animals together with a normally non-tumorigenic dose of SV40- transformed tissue culture cells (TU-5) will cause these cells to grow progressively and eventually kill the animals. Also, the mKSA-specfic, immunologically non-responsive state (the eclipse phase) of mice bearing large mKSA tumours can be maintained by administration of ascitic fluid or serum from tumour-bearing animals after the tumours have been surgically removed. Normally, complete immunity to a secondary tumour cell challenge is re-established approximately 10 days after removal of the primary tumour, but daily injections of ascitic fluid or serum will maintain sclipse so that a secondary challenge of tumour cells will grow progressively. The active component apparently acts non-specifically, since ascitic fluid from an unrelated tumour also is able to maintain the mKSA-specific eclipse phase. Thascitic fluid has no apparent immunosuppressive activity in vivo.


Incorporating tick feeding behaviour into R0 for tick-borne pathogens.
Tick-borne pathogens pose a considerable disease burden in Europe and North America, where increasing numbers of human cases and the emergence of new tick-borne pathogens has renewed interest in resolving the mechanisms underpinning their geographical distribution and abundance. For Borrelia burgdorferi and tick-borne encephalitis (TBE) virus, transmission of infection from one generation of ticks to another occurs when older nymphal ticks infect younger larval ticks feeding on the same host, either indirectly via systemic infection of the vertebrate host or directly when feeding in close proximity. Here, expressions for the basic reproduction number, R0, and the related tick type-reproduction number, T, are derived that account for the observation that larval and nymphal ticks tend to aggregate on the same minority of hosts, a tick feeding behaviour known as co-aggregation. The pattern of tick blood meals is represented as a directed, acyclic, bipartite contact network, with individual vertebrate hosts having in-degree, kin, and out-degree, kout, that respectively represent cumulative counts of nymphal and larval ticks fed over the lifetime of the host. The in- and out-degree are not independent when co-aggregation occurs such that [Formula: see text] where 〈.〉 indicates expected value. When systemic infection in the vertebrate host is the dominant transmission route R02=T, whereas when direct transmission between ticks co-feeding on the same host is dominant then R0=T and the effect of co-aggregation on R0 is more pronounced. Simulations of B. burgdorferi and TBE virus transmission on theoretical tick-mouse contact networks revealed that aggregation and co-aggregation have a synergistic effect on R0 and T, that co-aggregation always increases R0 and T, and that aggregation only increases R0 and T when larvae and nymphs also co-aggregate. Co-aggregation has the greatest absolute effect on R0 and T when the mean larval burden of hosts is high, and the largest relative effect on R0 for pathogens sustained by co-feeding transmission, e.g. TBE virus in Europe, compared with those predominantly spread by systemic infection, e.g. B. burgdorferi. For both pathogens, though, co-aggregation increases the mean number of ticks infected per infectious tick, T, and so too the likelihood of pathogen persistence.


Engaging men in HIV programmes: a qualitative study of male engagement in community-based antiretroviral refill groups in Zimbabwe.
Suboptimal male engagement in HIV programmes is a persistent challenge, leading to lower coverage of HIV testing, prevention and treatment services, and to worse outcomes for men. Differentiated service delivery models, such as peer-led community antiretroviral refill groups (CARGs), offer the opportunity to enhance patient satisfaction, retention and treatment outcomes. We conducted an exploratory qualitative study to identify facilitators and barriers to CARG participation by HIV-positive men, with inputs from recipients of HIV care, community members, healthcare workers (HCWs), donors and policymakers. Between July and October 2017, we conducted 20 focus group discussions (FGDs) with 147 adults living with HIV, including men and women enrolled in CARGs and men not enrolled in CARGs, and 46 key informant interviews (KIIs) with policymakers, donors, HCWs and community members. FGDs and KIIs were recorded, transcribed and translated. A constant comparison approach was used to triangulate findings and identify themes related to male engagement in CARGs in rural Zimbabwe. CARG participants, policymakers, donors, HCWs, and community members noted many advantages to CARG participation, including convenience, efficiency, solidarity and mutual psychosocial support. Although those familiar with CARGs reported that these groups decreased HIV-related stigma, concerns about stigma and privacy were perceived to be the primary reason for men's non-participation. Other important barriers to male enrolment included lack of awareness of CARGs, misunderstanding of how CARGs operate, few perceived benefits and lack of flexibility in CARG implementation. More effective educational and awareness campaigns, community-based anti-stigma campaigns, more flexible CARG designs, and provision of financial and/or in-kind support to CARG members could mitigate many of the barriers to male enrolment in CARGs. Men may also prefer alternative differentiated service delivery models that are facility-based and/or do not require group participation.


Secretion and assembly of functional mini-cellulosomes from synthetic chromosomal operons in Clostridium acetobutylicum ATCC 824.
Consolidated bioprocessing (CBP) is reliant on the simultaneous enzyme production, saccharification of biomass, and fermentation of released sugars into valuable products such as butanol. Clostridial species that produce butanol are, however, unable to grow on crystalline cellulose. In contrast, those saccharolytic species that produce predominantly ethanol, such as Clostridium thermocellum and Clostridium cellulolyticum, degrade crystalline cellulose with high efficiency due to their possession of a multienzyme complex termed the cellulosome. This has led to studies directed at endowing butanol-producing species with the genetic potential to produce a cellulosome, albeit by localising the necessary transgenes to unstable autonomous plasmids. Here we have explored the potential of our previously described Allele-Coupled Exchange (ACE) technology for creating strains of the butanol producing species Clostridium acetobutylicum in which the genes encoding the various cellulosome components are stably integrated into the genome. We used BioBrick2 (BB2) standardised parts to assemble a range of synthetic genes encoding C. thermocellum cellulosomal scaffoldin proteins (CipA variants) and glycoside hydrolases (GHs, Cel8A, Cel9B, Cel48S and Cel9K) as well as synthetic cellulosomal operons that direct the synthesis of Cel8A, Cel9B and a truncated form of CipA. All synthetic genes and operons were integrated into the C. acetobutylicum genome using the recently developed ACE technology. Heterologous protein expression levels and mini-cellulosome self-assembly were assayed by western blot and native PAGE analysis. We demonstrate the successful expression, secretion and self-assembly of cellulosomal subunits by the recombinant C. acetobutylicum strains, providing a platform for the construction of novel cellulosomes.


Axillary web syndrome following secondary breast-conserving surgery: a case report.
Axillary web syndrome is a cause of significant morbidity in the early postoperative period after axillary surgery. A patient developed axillary web syndrome after secondary breast surgery and recovered in 3 weeks through physical therapy and using Aescuven Forte. The pathogenesis of axillary web syndrome is not clear. It is reported that axillary surgery is the main cause. The presented case indicates that tissue injury might be an important cause of axillary web syndrome. Though axillary web syndrome is self-limiting, special physical therapy and Aescuven Forte can shorten the natural duration. Secondary breast surgery could cause axillary web syndrome. Physical therapy and Aescuven Forte could shorten the duration of the self-limited morbidity.


Influences of age and pubertal status on number and intensity of perineuronal nets in the rat medial prefrontal cortex.
The prefrontal cortex (PFC) is a late developing region of the cortex, and its protracted maturation during adolescence may confer a period of plasticity. Closure of critical, or sensitive, periods in sensory cortices coincides with perineuronal net (PNN) expression, leading to enhanced inhibitory function and synaptic stabilization. PNN density has been found to increase across adolescence in the male rat medial PFC (mPFC). Here, we examined both male and female rats at four time points spanning adolescent development to stereologically quantify the number and intensity of PNNs in the mPFC. Additionally, because puberty coincides with broad behavioral and neuroanatomical changes, we collected tissue from age-matched pre- and post-pubertal siblings within a litter. Results indicate that both males and females show an increase in the total number and intensity of mPFC PNNs between postnatal day (P) 30 and P60. As we have previously found, white matter under the mPFC also increased at the same time. Male puberty did not affect PNNs, while female pubertal onset led to an abrupt decrease in the total number of PNNs that persisted through mid-adolescence before increasing at P60. Despite the change in PNN number, the intensity of female PNNs was not affected by puberty. Thus, though males and females show increases in mPFC PNNs during adolescence, the pubertal decrease in the number of PNNs in female rats may indicate a difference in the pattern of maximal plasticity between the sexes during adolescence.


Some pharmacokinetic parameters of R-(-)- and S-(+)-ketoprofen: the influence of age and differing physiological status in dairy cattle.
The pharmacokinetic parameters of ketoprofen have previously been studied in cattle, but no studies have been performed on differing ages and metabolic situations in these animals. The aim of this work was to study the possible modifictions of the pharmacokinetics of ketoprofen enantiomers that may result from age, lactation or gestation in dairy cattle. Three groups of Holando Argentino cattle contained, respectively, 8 cows in early lactation, 8 pregnant cows and 8 newborn calves. Four animals from each group received the enantiomer R-(-)-ketoprofen, the other four animals received the S-(+) enantiomer, all by intravenous injection at a dose of 0.5 mg/kg. Significant differences between the three categories of animals were obtained in elimination half-life (t1/2) (1.52, 0.87 and 0.31 and 1.71, 0.69 and 0.26 in newborn calves, cows in early lactation and cows in gestation, respectively), mean residence time (MRT) (0.45, 1.25, 2.20 and 0.38, 0.99, 2.47 h, in cows in gestation, cows in early lactation and newborn calves, respectively) and area under the plasma concentration-time curve (AUC) (0.87, 2.93, 3.24, and 0.67, 2.78, 5.13 (microg/h)/ml in cows in gestation, cows in early lactation and newborn calves, respectively, for the R-(-) and S-(+) enantiomer, respectively. In calves, there was a significant difference in AUC (3.24 vs 5.13 (microg/h)/ml between R-(-)- and S-(+)-ketoprofen. In view of the differences between calves and adult cattle in the pharmacokinetic results for ketoprofen, the effects of age and physiological status (lactation, gestation) should be taken into account for therapeutic regimens.


Elite control of HIV Infection: implications for vaccines and treatment.
Spontaneous and sustained ("elite," or aviremic) control of HIV infection (ie, maintaining HIV RNA to less than 50 copies/mL in the absence of therapy) appears to occur in approximately 1 in 300 HIV-infected persons, and represents a distinct phenotype among HIV-infected individuals. Through a recently established international collaboration called the HIV Controller Consortium, over 300 elite controllers have been identified and blood samples collected. These ongoing studies will not only examine the immune responses to HIV that elite controllers generate, but will also make use of a newly available approach to defining the genetic basis of disease. Specifically, the consortium is attempting to determine the genetic basis underlying spontaneous control by performing whole genome analysis scans together with functional immunology studies in a large population of elite controllers. The goal of these studies is to provide insights that will help define the crucial parameters present in persons who are able to control HIV infection, similar to the control most people have with Epstein-Barr virus and varicella, namely by holding the virus in check. These findings could assist in the development of vaccines and new therapies. This article summarizes a presentation on spontaneous control of HIV infection and its implications for vaccine development made by Bruce D. Walker, MD, at an International AIDS Society-USA Continuing Medical Education course in New York in March 2007. The original presentation is available as a Webcast at www.iasusa.org.


Dupuytren Disease Infiltrating a Full-Thickness Skin Graft.
Although the role of the skin in the development and propagation of Dupuytren disease remains unclear, dermofasciectomy and full-thickness skin grafting (FTSG) appears to delay recurrence. In 2011, a 71-year-old, left-handed man presented with recurrent Dupuytren disease in the dominant hand. In 1991, he originally underwent a primary dermofasciectomy and FTSG for Dupuytren disease involving the palmar skin. Twenty years later, the left middle finger was drawn into flexion by a recurrent cord, and the old graft and adjacent palmar skin were clinically involved by fibromatosis. We performed a revision dermofasciectomy and FTSG. Microscopic analysis of the excised graft demonstrated dense infiltration of the entire skin graft by Dupuytren disease, with areas of active and burnt-out fibromatosis distinct from hypertrophic scarring. This report of Dupuytren fibromatosis infiltrating a skin graft raises questions about the pathophysiology of Dupuytren disease.


Type 1 conventional dendritic cells: ontogeny, function, and emerging roles in cancer immunotherapy.
Dendritic cells (DCs) are key immune sentinels that orchestrate protective immune responses against pathogens or cancers. DCs have evolved into multiple phenotypically, anatomically, and functionally distinct cell types. One of these DC types, Type 1 conventional DCs (cDC1s), are uniquely equipped to promote cytotoxic CD8+ T cell differentiation and, therefore, represent a promising target for harnessing antitumor immunity. Indeed, recent studies have highlighted the importance of cDC1s in tumor immunotherapy using immune checkpoint inhibitors. Here, we review the progress in defining the key developmental and functional attributes of cDC1s and the approaches to optimizing the potency of cDC1s for anticancer immunity.


Expected day of delivery from ultrasound dating versus last menstrual period--obstetric outcome when dates mismatch.
To analyse the association between fetal size at time of dating ultrasound and risk for preterm delivery and small-for-gestational-age (SGA) birth and to evaluate if timing of ultrasound, that is before 14 weeks of gestation or after 16 weeks affects this association. Retrospective cohort study. Ultrasound departments of Ultragyn, Stockholm, Sweden. A total of 28,776 singleton pregnancies dated between 1998 and 2004. Obstetric outcome was assessed through linkage of the cohort to the Swedish Medical Birth Register. Risks of preterm delivery, low birthweight for gestational age, pre-eclampsia, asphyxia, respiratory distress, instrumental delivery, caesarean section, and postterm birth were calculated for the groups dated early and late. When the expected date of delivery was postponed after ultrasound dating by 7 days or more, there was an increased risk for preterm delivery and pre-eclampsia in the late dating group (OR 1.49, 95% CI 1.27-1.73 and OR 1.27, 95% CI 1.02-1.60, respectively) but not in the early dating group. In both dating groups, there was an increased risk for SGA birth (OR 1.77, 95% CI 1.13-2.78 and OR 2.09, 95% CI 1.59-2.73, respectively) There was no increased risk for any of the other diagnoses. Our study gives further support to the notion that intrauterine growth restriction may be present as early as the first trimester. Accordingly, our study also suggests that surveillance of pregnancies with postponed estimated date of delivery may provide means for increased detection of fetal growth restriction.


[A case of pain from bone metastases of a sigmoid tumor treated with a Lazorthes reservoir for continuous subarachnoid analgesia].
An observed case of metastasized carcinoma of the large intestine with very severe pain is presented. Pain disappeared after continuous subarachnoid analgesia using a Lazorthes reservoir.


The effects of chronic trichloroethylene exposure on neurobehavioral functioning in the rat.
Groups of rats were exposed by inhalation to either clean air (Controls) or trichloroethylene at 500, 1000 or 1500 ppm TCE for 16 hr/day, 5 days/week for 18 weeks. At preselected intervals, animals were evaluated for changes in: spontaneous activity, gripstrength, coordinated hindlimb movement, performance of a discrete-trial operant two-choice visual discrimination task, and peripheral nerve conduction velocity. Compared to Controls, TCE-treated rats showed no significant differences in open field behavior, fore- and hindlimb gripstrength or coordinated movement throughout the exposure period. Peripheral nerve conduction time was also unaffected. In contrast, TCE produced progressively marked changes in the speed and patterning of responding in the two-choice visual discrimination task. Two-choice response latency, for example, demonstrated an approximately four-fold increase (p less than 0.001) in the highest dose group. In addition, a recurrent within-week functional tolerance developed for all TCE-exposed groups. However, tolerance was lost in the TCE 1500 group as exposure became chronic. Finally, following the termination of exposure, there was no carry-over of TCE-related effects on any of the measures and performance quickly returned to baseline levels. This profile of effects argues for a primary involvement of the CNS with chronic TCE exposure and is quite unlike that seen with, e.g., n-hexane and carbon disulfide. Such findings underscore the differences in the effects which can be produced by long-term exposure to organic solvents and emphasize the need for a battery of tests in the evaluation of neurotoxicant-induced changes in nervous system functioning.


Retrieval of the protection filter with a soft coaxial catheter after carotid stenting.
The purpose of this study was to shorten and simplify the procedure of filter retrieval after carotid stenting with cerebral protecting devices. We propose a retrieval method with a soft-tip guiding catheter, which eliminates the step of balloon exchange and introduction of a retriever catheter for the protection filter. The technique was successfully used in our last 60 consecutive patients. One transient deficit occurred. In conclusion, retrieval of the filter with a soft coaxial catheter after carotid stenting is a feasible and safe method and may simplify cerebrovascular protection during stenting.


Lewy body dementia: case report and discussion.
Lewy body dementia is a common but frequently underdiagnosed cause of dementia often mistaken for the more familiar entity of Alzheimer disease. Clinically the distinction is important, because it can have profound implications for management. The medical literature was searched using the keywords "Lewy bodies," "Lewy body dementia," "Alzheimer dementia," and "parkinsonian disorders." A case of Lewy body dementia is described. An elderly man had long-standing diagnoses of Alzheimer disease and Parkinson disease. After he was evaluated thoroughly, the diagnosis was revised to Lewy body dementia, leading to changes in treatment that were associated with dramatic improvement in the patient's mental status. Evidence from the literature suggests that Lewy body dementia can be diagnosed in primary care settings based on clinical criteria. The physician should be alert to this diagnosis, and special attention should be paid to dementia patients who exhibit parkinsonism, hallucinations, fluctuating cognition, or prominent visuosperceptual deficits. The diagnosis of Lewy body dementia has important implications. It is associated with a high incidence of neuroleptic sensitivity, necessitating great caution in the use of these common antipsychotic agents. Early studies indicate cholinesterase inhibitors can be beneficial for treating the hallucinations and behavior disturbances that afflict these patients and might also improve cognition.


Effect of frequent or extended hemodialysis on cardiovascular parameters: a meta-analysis.
Increased left ventricular (LV) mass is a risk factor for cardiovascular mortality in patients with chronic kidney failure. More frequent or extended hemodialysis (HD) has been hypothesized to have a beneficial effect on LV mass. Meta-analysis. MEDLINE literature search (inception to April 2011), Cochrane Central Register of Controlled Trials and ClinicalTrials.gov using the search terms "short daily HD," "daily HD," "quotidian HD," "frequent HD," "intensive HD," "nocturnal HD," and "home HD." Single-arm cohort studies (with pre- and post-study evaluations) and trials examining the effect of frequent or extended HD on cardiac morphology and function and blood pressure parameters. Studies of hemofiltration, hemodiafiltration, and peritoneal dialysis were excluded. Frequent (2-8 hours, >3 times weekly) or extended (>4 hours, 3 times weekly) HD compared with conventional (≤4 hours, 3 times weekly) HD. Absolute changes in cardiac morphology and function, including LV mass index (LVMI; primary) and blood pressure parameters (secondary). We identified 38 single-arm studies, 5 crossover trials, and 3 randomized controlled trials. By meta-analysis of 23 study arms, frequent or extended HD significantly reduced LVMI from baseline (-31.2 g/m(2), 95% CI, -39.8 to -22.5; P < 0.001). The 3 randomized trials found a less pronounced net reduction in LVMI (-7.0 g/m(2); 95% CI, -10.2 to -3.7; P < 0.001). LV ejection fraction improved by 6.7% (95% CI, 1.6% to 11.9%; P = 0.01). Other cardiac morphologic parameters showed similar improvements. There also were significant decreases in systolic, diastolic, and mean blood pressure and mean number of antihypertensive medications. Paucity of randomized controlled trials. Conversion from conventional to frequent or extended HD is associated with improvements in cardiac morphology and function, including LVMI and LV ejection fraction, respectively, and several blood pressure parameters, which collectively might confer long-term cardiovascular benefit. Trials with long-term clinical outcomes are needed.


Management of large coronary dissection after STAR.
The guided-STAR technique is an alternative anterograde approach for treatment of coronary chronic total occlusion (CTO) and it is usually followed by implantation of multiple stents. We describe a case of residual long coronary dissection left unstented after guided-STAR, with good results at 2months follow-up. This case emphasizes the fact that sometimes even the longest coronary dissections can be left unstented especially in the contest of a CTO.


Potential global loss of life expected due to COVID-19 disruptions to organised colorectal cancer screening.
Screening for colorectal cancer (CRC) decreases cancer burden through removal of precancerous lesions and early detection of cancer. The COVID-19 pandemic has disrupted organised CRC screening programs worldwide, with some programs completely suspending screening and others experiencing significant decreases in participation and diagnostic follow-up. This study estimated the global impact of screening disruptions on CRC outcomes, and potential effects of catch-up screening. Organised screening programs were identified in 29 countries, and data on participation rates and COVID-related changes to screening in 2020 were extracted where available. Four independent microsimulation models (ASCCA, MISCAN-Colon, OncoSim, and Policy1-Bowel) were used to estimate the long-term impact on CRC cases and deaths, based on decreases to screening participation in 2020. For countries where 2020 participation data were not available, changes to screening were approximated based on excess mortality rates. Catch-up strategies involving additional screening in 2021 were also simulated. In countries for which direct data were available, organised CRC screening volumes at a country level decreased by an estimated 1.3-40.5% in 2020. Globally, it is estimated that COVID-related screening decreases led to a deficit of 7.4 million fewer faecal screens performed in 2020. In the absence of any organised catch-up screening, this would lead to an estimated 13,000 additional CRC cases and 7,900 deaths globally from 2020 to 2050; 79% of the additional cases and 85% of additional deaths could have been prevented with catch-up screening, respectively. COVID-19-related disruptions to screening will cause excess CRC cases and deaths, but appropriately implemented catch-up screening could have reduced the burden by over 80%. Careful management of any disruption is key to improving the resilience of colorectal cancer screening programs. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Cancer Council New South Wales, Health Canada, and Dutch National Institute for Public Health and Environment.


Role of phosphorus and nitrogen in photosynthetic and whole plant carbon gain and nutrient use efficiency in eastern white pine.
In white pine (Pinus strobus) seedlings grown in five forest soils from New York State, net photosynthetic capacity (Amax) plant-1 was correlated with total foliar N plant-1 (r 2=0.57), but was more highly correlated with total foliar P plant-1 (r 2=0.82). There was no relationship (r 2<0.01) between Amax [g leaf]-1 and foliar N [g leaf]-1 for the pooled data set, but there was a significant (P<0.001), but weak (r 2=0.20) positive relationship between Amax [g leaf]-1 and foliar P [g leaf]-1 across all soils. However, within two of the five soils leaf N concentration was a significant (P<0.05) determinant of photosynthetic capacity. Due to differences in soil nutrient availabilities a large range in foliar P:N ratio (0.02-0.15) was observed, and the proportion of leaf P:N appeared to control Amax [g leaf N]-1. Whole plant nitrogen (NUE) and phosphorus (PUE) use efficiencies were well correlated with whole plant P:N ratio. In addition, NUE was well correlated with Amax [g leaf N]-1 and PUE was well correlated with Amax [g leaf P]-1. However, NUE was not well correlated with PUE, and Amax [g leaf N]-1 was not well correlated with Amax [g leaf P]-1. These results indicated that P and/or N limitations were important components of photosynthetic nutrient relations in white pine grown in these five soils and suggest that both P and N and their proportions should be considered in analyses of photosynthesis-nutrient relations.


Discharge planning for acute coronary syndrome patients in a tertiary hospital: a best practice implementation project.
Acute coronary syndromes threaten the lives of patients, and pose a high risk for morbidity and mortality despite advances in treatment. Evidence highlights that effective discharge planning is associated with long-term prognosis of patients. The aim of this project was to improve local practice in discharge planning for acute coronary syndrome patients in Huadong Hospital, Shanghai. Five criteria identified by the Joanna Briggs Institute were used to conduct an audit in the Cardiovascular Ward and Coronary Care Unit of Huadong Hospital, Shanghai. Forty-two nurses and 65 patients were involved. The Joanna Briggs Institute Practical Application of Clinical Evidence System and Getting Research into Practice audit tools for promoting change in health practice were used to ascertain compliance with the criteria before and after the implementation of best practice. The program included three phases and was conducted over five months. The project showed that the compliance rates of in-house education, advice on lifestyle changes, education on discharge medication and left ventricular assessment reached 100%. Psychological screening also attained 97% compliance. There were improvements in the compliance rates of four criteria from 38% to 100%, excluding in-house education which was already 100% compliant. The project achieved significant improvements in establishing evidence-based practice of discharge planning for acute coronary syndrome patients in the Cardiovascular Ward and Coronary Care Unit. Strategies for sustaining best practice will continue to be developed in the future.


Fatigue fracture of a femoral sliding compression screw-plate device after bone union.
A failure of a femoral screw compression plate is described, the first such case to be reported after bone union. A fatigue fracture had started from an internal screw thread, near a keyway. Design improvements, such as lengthening the barrel around the lag screw, are suggested. The question as to whether keyways are necessary for the function of such devices is discussed. The morbidity of removal operations in elderly patients means that fatigue life improvements are needed, to avoid increasing numbers of failed implants in the continuing epidemic of fractures of the proximal femur.


Evaluation of the effect on patient parameters of not monitoring gastric residual volume in intensive care patients on a mechanical ventilator receiving enteral feeding: A randomized clinical trial.
This study aimed to evaluate the effects of not measuring gastric residual volume (GRV) in intensive care patients on a mechanical ventilator and receiving enteral feeding on the feeding intolerance, gastroesophageal reflux (GER) risk, and nutritional adequacy. This randomized clinical study was performed in 2 medical intensive care units of 2 university hospitals in Ankara, Turkey. The patients were randomized into 2 groups. In the group with GRV monitoring, GRV was measured 3 times a day, and the GRV threshold was accepted as 250 mL. In addition, 24-hour pH monitoring was used in this group to assess the risk of GER. In the group without GRV monitoring, GRV was not measured. The patients were followed-up for 5 days. The feeding targets were reached more quickly in the group without GRV monitoring (n = 26) with no increase in the complication rate (P < .05). No significant relationship was found between GRV and GER in the group with GRV monitoring (n = 25) (P > .05). The discrepancies in GRV measurement make it unreliable for monitoring feeding intolerance and GER. The use of GRV measurements may therefore be discontinued as part of the standard care protocol in medical intensive care units.


Cefepime dosing regimens in critically ill patients receiving continuous renal replacement therapy: a Monte Carlo simulation study.
Cefepime can be removed by continuous renal replacement therapy (CRRT) due to its pharmacokinetics. The purpose of this study is to define the optimal cefepime dosing regimens for critically ill patients receiving CRRT using Monte Carlo simulations (MCS). The CRRT models of cefepime disposition during 48 h with different effluent rates were developed using published pharmacokinetic parameters, patient demographic data, and CRRT settings. Pharmacodynamic target was the cumulative percentage of a 48-h period of at least 70% that free cefepime concentration exceeds the four times susceptible breakpoint of Pseudomonas aeruginosa (minimum inhibitory concentration, MIC of 8). All recommended dosing regimens from available clinical resources were evaluated for the probability of target attainment (PTA) using MCS to generate drug disposition in a group of 5000 virtual patients for each dose. The optimal doses were defined as achieving the PTA at least 90% of virtual patients with lowest daily doses and the acceptable risk of neurotoxicity. Optimal cefepime doses in critically ill patients receiving CRRT with Kidney Disease: Improving Global Outcomes (KDIGO) recommended effluent rates were a regimen of 2 g loading dose followed by 1.5-1.75 g every 8 h for Gram-negative infections with a neurotoxicity risk of < 17%. Cefepime dosing regimens from this study were considerably higher than the recommended doses from clinical resources. All recommended dosing regimens for patients receiving CRRT from available clinical resources failed to achieve the PTA target. The optimal dosing regimens were suggested based on CRRT modalities, MIC values, and different effluent rates. Clinical validation is warranted.


Extensive labelling of injured insect neurons with seven different heme peptides.
Seven different heme peptides were used in neuronal uptake and labelling experiments in flies. The peptides were: catalase, lactoperoxidase, hemoglobin, horseradish peroxidase (HRP), myoglobin, cytochrome c and microperoxidase. All of these peroxidase active peptides were taken up by lesioned neurons and the markers spread throughout the entire cells resulting in a detailed labelling of their processes and cell bodies. Only HRP was taken up by intact neurons. Attempts were made to block axonal transport of HRP with colchicine, vinblastine and 2,4-dinitrophenol. These attempts were unsuccessful and it is proposed that HRP and the other six heme peptides testes are non-selectively diffusing through lesioned or damaged nerve cells in flies.


A checklist of the mosquitoes of Indiana with notes on the cryptic species complexes Anopheles quadrimaculatus s.l. and Anopheles punctipennis.
The checklist of the mosquito species reported to occur in the state of Indiana is updated to include a number of new records and new classifications. Specimens of the cryptic species complex Anopheles quadrimaculatus s.1. are identified as An. quadrimaculatus s.s., and specimens of An. punctipennis are identified as the Eastern form of the species.


Qualitative evidence for expression of Klebsiella pneumoniae nif in Pseudomonas putida.
Pseudomonas putida MT20-3 carrying the Klebsiella pneumoniae nif plasmids pRD1 or pMF250 showed highly O2-sensitive aerobic acetylene reduction on low-N pyruvate or glucose agar. This finding confirms unequivocally that K. pneumoniae nif can be expressed in an obligate aerobe.


Plasma-renin response to isotonic volume contraction in young salt-sensitive normotensive men.
Salt-sensitive persons have lower plasma renin activity than salt-resistant persons and their plasma renin activity increases less with a low sodium diet or volume depletion, compared to salt-resistant individuals. However, the time course of the renin response to acute volume contraction has not been studied in humans. Therefore, we designed an acute study in salt-sensitive and salt-resistant normotensive volunteers, in which we examined the renin response to isotonic volume contraction. Twenty-four previously characterized salt-resistant (n = 13) and salt-sensitive (n = 11) persons were placed on a high salt diet containing 280 mmol NaCl/day for 3 days. After an overnight stay, volume depletion (total, 300 mmol Na) was induced by furosemide infusion. Free water deficits were replaced by 5% isotonic glucose infusion. Blood was obtained for electrolytes, plasma renin activity, and plasma aldosterone concentration. Blood pressure (BP) and heart rate were monitored during the experiment. Intravascular volume depletion resulted in a progressive increase in plasma renin activity that was both steeper and higher in salt-resistant than in the salt-sensitive subjects (P < .001). There was a slight increase in BP in response to volume contraction in both groups. Although heart rate did not change in salt-sensitive persons, it increased significantly (P < .001) in the salt-resistant group. These findings point to an intrinsic difference in the regulation of renin release between salt-sensitive and salt-resistant subjects that may account for the different BP responses to changes in dietary sodium intake.


The use of theory in everyday practice: an exploratory study.
This exploratory study, using a phenomenological framework with ethnographic methodology investigated the use of theory in everyday practice as described by three registered occupational therapists. Semi-structured interviews were conducted with three practicing occupational therapists. Ethnographic observations and field notes supplemented the data collection. Data were analyzed using qualitative techniques. Six major themes emerged from the interview data and were supported by the observational data: (1)"This is where I kind of get confused."(2)"I remember hearing about theory."(3)"It helps me."(4)"I don't think there's a particular reason."(5)"We rarely use the terminology." (6)"It's kind of hard to incorporate that." The lack of the use of theory is paradoxical since all three therapists valued its use and saw it as a way to distinguish occupational therapy from other professions. The lack of use may be due to inadequate educational preparation, pragmatic issues prevalent in clinical sites, and lack of role models. An alternative learning strategy is provided.


Multi-criteria assignment problems for optimising the emergency medical services (EMS), considering non-homogeneous speciality of the emergency departments and EMS crews.
Dispatching of the EMS crews (ambulances) to awaiting patients and then directing the patients, that are already onboard, to appropriate Emergency Departments (ED), is a nontrivial decision problem. In many emergency medical systems it is handled by the Medical Dispatcher using various strategies-sometimes preferring the closest unit. However, applying a wrong strategy may result in transferring acute-state patients, who require very specialised medical aid, to low-speciality EDs with insufficient treatment capabilities. Then, they would need to be re-transferred to referential units, prolonging substantially the time to receive treatment. In some cases such a delay might make the treatment less effective or even impossible. In this work we propose two multi-criteria mathematical optimisation problems-the first one allows us to calculate the ambulance-to-patient assignment, the second one-to establish the patient-to-hospital assignment. These problems not only take the time-to-support criterion into consideration but also optimise for the speciality of care received by each patient. The ED dispatching problem proposed allows both for direct transfers of patients to referential units and for re-transferring them from non-referential EDs. The performance of the proposed approach is tested in simulations with real-life emergency cases from the NEMSIS data set and compared with classic assignment strategies. The tests showed the proposed approach is able to produce better and more fit-for-purpose dispatching results than other strategies tested. Additionally, we propose a framework for embedding the proposed optimisation problems in the current EMS/ED dispatching process.


Effect of recombinant human growth hormone on the intestinal structure of rats receiving bowel resection and parenteral nutrition.
Recombinant human growth hormone (rHGH) can improve nitrogen balance and promotecell proliferation. Little is known about the relationship between rHGH and gastrointestinal mucosal structure and function after bowel resection and parenteral nutrition (PN). The aim of this study was to determine the effect of rHGH on bowel mucosal structure and barrier function in rats receiving 50% small intestinal resection and PN. Thirty Wistar rats with central vein catheterization plus 50% small bowel resection were divided into three groups: chow (chow), standard (STD) and rHGH (rHGH). The chow group received chow food; the STD group was given standard PN; the rHGH group received standard PN plus rHGH (4.8 mg/kg/day, subcutaneously). The groups were maintained on their respective diets for 8 days and then killed. Body weight, small intestinal mucosal thickness, villus height and Goblet cells in the villus were measured. Body weight loss in the STD group was significantly greater than that in the chow and rHGH groups (P< 0.01). The mucosal thickness and villus height of rHGH group were significantly greater than the STD and chow groups (mucosal thickness: 806 +/- 5.5 vs. 533 +/- 6.0 and 593 +/- 6.0 microm; Villus height: 506 +/- 6.0 vs. 295 +/- 5.5 gm and 400 +/- 6.7 lam, respectively) (P< 0.05). The number of Goblet cells in the STD group was significantly greater than the rHGH and chow groups (9.06 +/- 1.07 vs. 5.35 +/- 1.48 and 6.10 +/- 1.51/per villus) (P < 0.01). rHGH can maintain body weight and promote bowel mucosal cell growth and might improve the barrier function of the bowel in rats after 50% small intestinal resection and PN.


Trace lead analysis based on carbon-screen-printed-electrodes modified via 4-carboxy-phenyl diazonium salt electroreduction.
This paper describes the use of 4-carboxyphenyl-grafted screen-printed carbon electrodes (4-CP-SPEs) for trace lead analysis. These novel and simple use of electrodes were easily prepared by the electrochemical reduction of the corresponding diazonium salt. Pb detection was then performed by a three-steps method in order to avoid oxygen interference: (i) immersion of the grafted screen-printed electrode (SPE) in the sample and adsorption of Pb(II), (ii) reduction of adsorbed Pb(II) by chronoamperometry (CA), and (iii) oxidation of Pb by Anodic Square Wave Voltammetry (SWV). The reoxidation response was exploited for lead detection and quantification. In order to optimize the analytical responses, the influence of the adsorption medium pH and the adsorption time were investigated. Moreover, an interference study was carried out with Cu(II), Hg(II), Al(III), Mn(II), Zn(II), Cd(II) and no major interference can be expected to quantify Pb(II). The described method provided a limit of detection and a limit of quantification of 1.2 × 10(-9)M and 4.1 × 10(-9)M, respectively. These performances indicate that the 4-CP-SPE could be considered as an efficient tool for environmental analysis.


Computer-aided classifying and characterizing of methamphetamine use disorder using resting-state EEG.
Methamphetamine (meth) is potently addictive and is closely linked to high crime rates in the world. Since meth withdrawal is very painful and difficult, most abusers relapse to abuse in traditional treatments. Therefore, developing accurate data-driven methods based on brain functional connectivity could be helpful in classifying and characterizing the neural features of meth dependence to optimize the treatments. Accordingly, in this study, computation of functional connectivity using resting-state EEG was used to classify meth dependence. Firstly, brain functional connectivity networks (FCNs) of 36 meth dependent individuals and 24 normal controls were constructed by weighted phase lag index, in six frequency bands: delta (1-4 Hz), theta (4-8 Hz), alpha (8-15 Hz), beta (15-30 Hz), gamma (30-45 Hz) and wideband (1-45 Hz).Then, significant differences in graph metrics and connectivity values of the FCNs were used to distinguish the two groups. Support vector machine classifier had the best performance with 93% accuracy, 100% sensitivity, 83% specificity and 0.94 F-score for differentiating between MDIs and NCs. The best performance yielded when selected features were the combination of connectivity values and graph metrics in the beta frequency band.


Clinical and Prognostic Implications of Cardiopulmonary Exercise Stress Echocardiography in Asymptomatic Degenerative Mitral Regurgitation.
The current guidelines recommend intervention in severe degenerative mitral regurgitation (MR) in symptomatic patients or asymptomatic patients with left ventricular dilatation or dysfunction. The insidious onset of symptoms may mean that patients do not report their symptoms. The role of systematic exercise testing for symptoms in MR is not clearly defined. A total of 97 patients with moderate to severe asymptomatic MR underwent exercise echocardiography combined with cardiopulmonary exercise testing. The predictors of exercise-induced dyspnea, symptom-free survival, and mitral valve intervention were identified. A total of 18 patients (19%) developed limiting dyspnea on exercise. Spontaneous symptom-free survival at 24 months was significantly higher in those without exercise-induced symptoms than those with exercise-induced symptoms, p <0.0001. The only independent predictors of spontaneous symptoms at 2 years were effective regurgitant orifice area (odds ratio 27.45, 95% confidence interval [CI] 1.43 to 528.40, p = 0.03) and exercise-induced symptoms (odds ratio 11.56, 95% CI 1.71 to 78.09, p = 0.01). The only independent predictor of surgery was indexed left ventricular systolic volumes (odds ratio 1.17, 95% CI 1.04 to 1.30, p = 0.006). Where only the patients who underwent surgery due to symptoms were included, the only independent predictor was exercise-induced symptoms (odds ratio 13.94, 95% CI 1.39 to 140.27, p = 0.025). In conclusion, in patients with primary asymptomatic degenerative MR, 1/5 develop revealed symptoms during exercise. This predicts a subsequent development of spontaneous symptoms and mitral valve intervention due to symptoms.


Emotions in the Time of COVID-19: Affections and Impacts among the Spanish Primary Care Workforce.
The literature review shows that most studies on the psychological impact of COVID-19 on healthcare professionals have focused on hospital staff, with few specifically addressing the primary care workforce. This study aims to explore primary care workers' verbal accounts of the emotions they experienced. This is a qualitative study carried out between July and December 2020 in Spain. Semi-structured interviews and focus groups were conducted with primary care workers. Data were analysed through thematic content analysis. Participants were selected using purposive sampling. A total of 53 primary care workers participated in the study, of whom 38 were individually interviewed, and 15 participated in three focus groups. Our analysis revealed themes in two categories: (1) from infection to affection; and (2) affected, but not patients-a discourse based on the acceptance of their experience as part of their work in primary care, creating an ideological construct or "shield" based on emotional self-management. Self-reflection on the emotional impact of COVID-19 is scarce. Examples of emotional affections include an obsessive focus on hygiene, the inability to establish clear boundaries between the personal and the professional spheres, and experiencing-and having to self-manage-emotional strain.


Synergestic interplay of uronic acid and sulfation composition of heparan sulfate on molecular recognition to activity.
Heparan sulfate (HS) is ubiquitous polysaccharide on the surface of all mammalian cells and extracellular matrices. The incredible structural complexity of HS arises from its sulfation patterns and disaccharide compositions, which orchestrate a wide range of biological activities. Researchers have developed elegant synthetic methods to obtain well-defined HS oligosaccharides to understand the structure-activity relationship. These studies revealed that specific sulfation codes and uronic acid variants could synergistically modulate HS-protein interactions (HSPI). Additionally, the conformational flexibility of l-Iduronic acid, a uronic acid unit has emerged as a critical factor in fine-tuning the microenvironment to modulate HSPI. This review delineates how uronic acid composition in HS modulates protein binding affinity, selectivity, and biological activity. Finally, the significance of sulfated homo-oligo uronic acid as heparin mimics in drug development is also discussed.


The role of vaginal brachytherapy in the treatment of surgical stage I papillary serous or clear cell endometrial cancer.
The optimal adjuvant therapy for International Federation of Gynecology and Obstetrics (FIGO) stage I papillary serous (UPSC) or clear cell (CC) endometrial cancer is unknown. We report on the largest single-institution experience using adjuvant high-dose-rate vaginal brachytherapy (VBT) for surgically staged women with FIGO stage I UPSC or CC endometrial cancer. From 1998-2011, 103 women with FIGO 2009 stage I UPSC (n=74), CC (n=21), or mixed UPSC/CC (n=8) endometrial cancer underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy followed by adjuvant high-dose-rate VBT. Nearly all patients (n=98, 95%) also underwent extended lymph node dissection of pelvic and paraortic lymph nodes. All VBT was performed with a vaginal cylinder, treating to a dose of 2100 cGy in 3 fractions. Thirty-five patients (34%) also received adjuvant chemotherapy. At a median follow-up time of 36 months (range, 1-146 months), 2 patients had experienced vaginal recurrence, and the 5-year Kaplan Meier estimate of vaginal recurrence was 3%. The rates of isolated pelvic recurrence, locoregional recurrence (vaginal+pelvic), and extrapelvic recurrence (including intraabdominal) were similarly low, with 5-year Kaplan-Meier estimates of 4%, 7%, and 10%, respectively. The estimated 5-year overall survival was 84%. On univariate analysis, delivery of chemotherapy did not affect recurrence or survival. VBT is effective at preventing vaginal relapse in women with surgical stage I UPSC or CC endometrial cancer. In this cohort of patients who underwent comprehensive surgical staging, the risk of isolated pelvic or extrapelvic relapse was low, implying that more extensive adjuvant radiation therapy is likely unnecessary.