Time-dependent transition from H(2)O(2)-extracellular signal-regulated kinase- to O(2)-nitric oxide-dependent mechanisms in the stimulatory effect of leptin on renal Na+/K+/-ATPase in the rat.
1. Recent studies suggest that leptin, a peptide hormone secreted by white adipose tissue, is involved in the pathogenesis of arterial hypertension, in part by regulating renal sodium handling. Previously, we have demonstrated that in normal rats leptin has a time-dependent effect on renal Na(+)/K(+)-ATPase that drives tubular sodium reabsorption. Short-term leptin infusion results in a transient decrease in Na(+)/K(+)-ATPase activity, whereas prolonged administration stimulates the enzyme. 2. In the present study, we investigated whether these acute effects of leptin are preserved in rats with experimentally induced chronic hyperleptinaemia. 3. Hyperleptinaemia was induced by administration of exogenous leptin (0.25 mg/kg twice daily, s.c., for 7 days). Acute effects of leptin in anaesthetized control (normoleptinaemic) and hyperleptinaemic animals was investigated. Leptin was infused into the abdominal aorta proximally to the renal arteries for 0.5, 1, 2 or 3 h. 4. Leptin (1 microg/min per kg) had a time-dependent effect on renal Na(+)/K(+)-ATPase in both the control and hyperleptinaemic groups. The inhibitory effect observed after 0.5 h infusion was impaired in the hyperleptinaemic group. However, in both groups this effect was abolished by the Janus kinase inhibitor tyrphostin AG490 (100 nmol/min per kg), as well as by the phosphatidylinositol 3-kinase inhibitors wortmannin (10 nmol/min per kg) and LY294002 (1 micromol/min per kg). 5. The stimulatory effect of leptin on Na(+)/K(+)-ATPase activity was observed after 3 h of infusion and was of similar magnitude in control and hyperleptinaemic groups. In the control group, the stimulatory effect of leptin was abolished by the NADPH oxidase inhibitor apocynin (1 micromol/min per kg), the H(2)O(2) scavenger catalase (1 mg/min per kg) and the extracellular signal-regulated kinase (ERK) inhibitor PD98059 (100 nmol/min per kg). In contrast, in the hyperleptinaemic group, the stimulatory effect of leptin was abolished by the cGMP analogue 8-bromo-cGMP (100 nmol/min per kg) and by the superoxide dismutase mimetic tempol (100 micromol/min per kg) but was not affected by catalase or PD98059. 6. Leptin increased urinary H(2)O(2) excretion and ERK phosphorylation in the renal tissue only in the control group. 7. The results suggest that the acute stimulatory effect of leptin on renal Na(+)/K(+)-ATPase is mediated by divergent mechanisms depending on the chronic leptin level (i.e. by H(2)O(2)-dependent stimulation of ERK in normoleptinaemic animals and by superoxide-dependent impairment of the nitric oxide-cGMP pathway in hyperleptinaemic rats).


A sigma32 mutant with a single amino acid change in the highly conserved region 2.2 exhibits reduced core RNA polymerase affinity.
sigma32, the product of the rpoH gene in Escherichia coli, provides promoter specificity by interacting with core RNAP. Amino acid sequence alignment of sigma32 with other sigma factors in the sigma70 family has revealed regions of sequence homology. We have investigated the function of the most highly conserved region, 2.2, using purified products of various rpoH alleles. Core RNAP binding analysis by glycerol gradient sedimentation has revealed reduced core RNAP affinity for one of the mutant sigma32 proteins, Q80R. This reduced core interaction is exacerbated in the presence of sigma70, which competes with sigma32 for binding of core RNAP. When a different but more conserved amino acid was introduced at this position by site-directed mutagenesis (Q80N), this mutant sigma factor still displayed a significant reduction in its core RNAP affinity. Based on these results, we conclude that at least one specific amino acid in region 2.2 is involved in core RNAP interaction.


Facial Nerve Palsy with Total Ophthalmoplegia; a Novel Presentation of Fungal Invasion.
Mucormycosis is an expeditious invasion of a fungus of angioinvasive nature, predominant in immunocompromised individuals, often leading to organ malfunction and loss. Facial nerve involvement and total ophthalmoplegia are its rare presentations. Early detection and treatment can alter natural disease course and prevent potential catastrophic outcomes in diabetic patients. Facial nerve palsy is mostly attributed to peripheral neuropathy in patients with advanced diabetes mellitus. It rarely raises alarm about an invasive fungal infection. Here, we report the case of a 38-year-old male with type 2 diabetes mellitus, who presented to us with left lower motor neuron type facial palsy and left-sided total ophthalmoplegia due to invasive rhino-orbito-cerebral mucormycosis (ROCM). Despite aggressive measures, including antifungal therapy and repeated endoscopic debridement, he subsequently developed central retinal artery occlusion (CRAO) and underwent left eye exenteration.


Decreased sensitivity of (18)F-fluorodeoxyglucose imaging in infection and inflammation.
Nuclear medicine plays an important role in the evaluation of inflammation and infection. Although (99m)Tc-methylene diphosphonate, (67)Ga-citrate, and in vitro labeled autologous leukocyte imaging are useful procedures, there are limitations to each of them. (18)F-fluorodeoxyglucose-positron-emission tomography (PET) and PET/computed tomography offer several advantages over conventional single-photon-emitting tracers and has proved to be a valuable addition to the nuclear medicine infection imaging armamentarium. PET provides high-resolution 3-dimensional images of the whole body that facilitates precise localization of abnormalities. Localization is enhanced with PET/computed tomography. Fluorodeoxyglucose, for the most part, is exquisitely sensitive with a high negative predictive value. In general, the limiting factor of the test is specificity. However, there are some situations in which the limitation to the test is not low specificity but rather low sensitivity.


Three-Dimensional Speckle-Tracking Echocardiography-Derived Tricuspid Annular Dimensions and Right Atrial Strains in Healthy Adults-Is There a Relationship? (Insights from the MAGYAR-Healthy Study).
The tricuspid valve and its annulus (TA) are thought to be integrally related to right atrial (RA) size and function. The present study aimed to assess associations between TA dimensions and RA strains, and quantitative features of its contractility were determined by 3DSTE in healthy adults. The study comprised 145 healthy volunteers with a mean age of 34.4 ± 12.5 years (73 males). Electrocardiographic, two-dimensional Doppler echocardiographic and 3DSTE parameters were in normal reference ranges in all subjects. Enlarged TA areas, regardless of which phase of the cardiac cycle were measured, were not associated with the deterioration of peak RA strains in longitudinal (LS) and circumferential (CS) directions. Increased end-diastolic TA area was associated with reduced RA strain in the radial direction (RS). Dilation of end-diastolic and end-systolic TA areas was related to increased RA volumes. End-diastolic TA area was the smallest in case of increased peak global RA-RS, and other associations between increasing TA areas and peak global strains could not be detected. Peak global RA-CS and RA-LS were not related to TA areas. Increasing peak global RA-RS was not associated with peak global RA-LS and RA-CS, while increasing peak global RA-LS and RA-CS were not associated with peak global RA-RS. Increasing peak global RS did not show associations with RA volumes, Vmin was the smallest in the case of highest peak global RA-CS and RA-LS. Vmax increased with increasing peak global RA-LS. 3DSTE is suitable for simultaneous non-invasive determination of TA dimensions and RA volumes and strains using the same acquired 3D dataset, allowing physiologic studies. RA volumes are associated with end-diastolic and end-systolic TA areas. RA strains in radial direction (RS) show associations with end-diastolic TA area.


Micromelic dysplasia-like syndrome in a captive colony of common marmosets (Callithrix jacchus).
Over several years, 0% to 5% of adolescent animals in a captive colony of common marmosets (Callithrix jacchus) showed severely bended arms and legs over several years. The animals showed no pain, discomfort, or altered behavior but were unable to stretch their distal limbs to their full extent. To characterize the lesion morphologically, the bones of 4 affected marmosets were compared macroscopically and radiographically with those of 6 unaffected animals. The deformities were characterized by mid- to distal diaphyseal bending and pronounced shortening of long bones. The morphology and density of other bones including the skull and vertebrae were unaffected. Although vitamin D values were low in a fifth affected marmoset during 10 to 16 mo of age, lesions associated with rickets were not observed. To our knowledge, this report is the first to describe a micromelic dysplasia-like syndrome comprising severe, idiopathic bending and shortening of long bones in a colony of marmosets.


[Value of postoperative radiotherapy in T3 or N+ bronchial cancer. Apropos of 113 cases].
Post-operative radiotherapy was applied in a series of 113 patients with bronchial cancer (T3 or N+) between 1977 and 1983, lesions being classified T1 in 24 cases, T2 in 44, T3 in 45, N0 in 23, N1 in 51 and N2 in 39, one out of two T3 cases being N+. Pneumonectomy has been performed in 64 cases (58%) and limited surgery in 49 (42%). An incomplete exeresis was carried out in 21% of cases. Radiotherapy dose 45 Gy in cases with macroscopically complete resection and 65 Gy in other cases. Fractioning was conventional (CI) 72 times with 5 sessions of 1.8 Gy per week, and hypofractionated (HFI) 41 times as 5 Gy on D1 and D3 and 6.5 Gy on D15 and D17 for an equivalent dose at 45 Gy in CI and with, in addition, 5 Gy on D29 and D31 for an equivalent dose at 65 Gy in CI. Overall actuarial survival at 5 years was 38%, and 42% for N+, with 54% for N1 (pedicular N+) and 28% for N2 (mediastinal N+). The 3-year actuarial survival for T3 N0 was 53%. Frequency of local and regional recurrence was 18% and was equal for N1 and N2. In contrast, metastases occurred in 33% of N2 and only 12% of N1. No apparent difference was noted in incidence of local and regional recurrence or survival as a function of histopathologic type, operation performed, quality of surgical resection, or irradiation fractioning. No serious complication of radiotherapy was reported.(ABSTRACT TRUNCATED AT 250 WORDS)


Biosorption of Pb(II) by Bacillus badius AK strain originating from rotary drum compost of water hyacinth.
The presence of heavy metals in the environment due to industrial activities is of serious concern because of their toxic behaviour towards humans and other forms of life. Biosorption of Pb(II) using dry bacterial biomass of Bacillus badius AK, previously isolated from water hyacinth compost, has been undertaken in batch system. The optimum conditions of biosorption were determined by investigating the initial pH, contact time, initial biomass dosage at constant temperature of 40 °C, initial metal concentration of 100 mg/L and rotational speed of 150 rpm. The optimum pH was found to be 5 and equilibrium contact time was 2.5 h. The maximum biosorption capacity of Pb(II) on Bacillus badius AK was 138.8 mg/g at an initial concentration of 100 mg/L. A kinetics study revealed that the adsorption process followed pseudo second order rate kinetics. The experimental data were fitted to the Langmuir isotherm. Characterization of the biomass indicated the presence of several functional groups. The results indicated that the bacterium Bacillus badius AK is efficient for the removal of Pb(II).


[Need for surgical ligation of patent ductus arteriosus among patients treated at the Neonatology Department of the University of Medical Sciences, Poznan, Poland].
Clinical assessment of newborns requiring surgical ligation of patent ductus arteriosus (PDA). 51 newborns operated on PDA in Department of Neonatology in Poznań in years 2000 and 2001. Newborns were classified for surgical ligation after echocardiographic examination (ACUSON 128 XP/10 or HDI 3500, sector scanhead 5MHz). Following data were analyzed: antenatal steroid therapy, gestational age, birth weight, Apgar score, the reason of respiratory insufficiency after birth, duration of mechanical ventilation and oxygen therapy, incidence of bronchopulmonary dysplasia (BPD), intraventricular haemorrhage (IVH) and deaths. 30 of 51 analyzed patients had very low birth weight (< or = 1000 g). Antenatal steroids were used in 21 cases, 20 newborns were delivered by caesarean section. The status of 22 newborns was assessed after birth as bad (0-3 points in Apgar scale). In 38 newborns respiratory distress syndrome was diagnosed and 32 required surfactant therapy. Surgical ligation of PDA was performed on 19.8 +/- 14.4 day of life in neonates born in our hospital and on 24.3 +/- 11.9 day of life in newborns admitted for ligation from other wards. Surgery of one patient was complicated by pneumothorax. 42 patients required mechanical ventilation before operation. Mean duration of mechanical ventilation was 33.4 +/- 26.9 days. 30 infants developed BPD and 15 infants IVH III or IV degree, 6 infants died. PDA is a serious clinical problem especially for very low birth weight newborns. Surgical ligation of a PDA, without transportation of a patient, is associated with a low incidence of complications.


The Role of Psychological Stress on Heart Autophagy in Mice With Heart Failure.
Psychological stress in chronic heart failure (CHF) is associated with systemic neurohormonal and immune system responses and increased mortality. Autophagy refers to the biological process of degradation and recycling of dysfunctional cellular components. We investigated the role of psychological stress on autophagy function in CHF mice. C57BL/6 mice underwent transverse aortic constriction, with or without combined acoustic and restraint stress, and cardiac function was assessed by echocardiography analysis. Serum corticosterone and angiotensin II (Ang II) were determined using enzyme-linked immunosorbent assay (ELISA). Autophagy and oxidative stress were measured with immunohistochemistry and quantitative polymerase chain reaction, and chloroquine and rapamycin were used to detect autophagy flux. In vivo, cardiomyocytes were cultured with or without Ang II or N-acetylcysteine, and autophagy and oxidative stress were also detected. A 1-week stress exposure significantly increased serum levels of corticosterone and Ang II (p = .000), increased levels of oxidative stress, induced overt heart failure, and increased mortality (p = .002). Furthermore, stress exposure unregulated messenger RNA expression of Bcl-2-interacting coiled-coil protein 1 (10.891 [3.029] versus 4.754 [1.713], p = .001), cysteine-rich domain containing beclin-1 interacting (6.403 [1.813] versus 3.653 [0.441], p = .006), and autophagy 7 (111.696 [4.049] versus 6.189 [1.931], p = .017), increased expression of autophagosomal, and decreased clearance of autophagosomes. In vitro, Ang II significantly increased autophagy flux in cultured cardiomyocytes, which could be partly inhibited by N-acetylcysteine. Psychological stress may contribute to the development of CHF by enhancing heart oxidative stress and impairing autophagy flux.


Ambient Air Exposure to PCBs: Regulation and Monitoring at Five Contaminated Sites in EPA Regions 1, 2, 4, and 5.
Existing regulations seek to protect the public from exposure to polychlorinated biphenyls (PCBs) in food, water, and soil. Exposure to PCBs in ambient air has recently been given explicit consideration in the human health risk assessments that form the basis of risk management decisions at contaminated sites. The objective of this paper is to examine how ambient air exposure to PCBs is regulated and monitored at five contaminated sites in the United States. We reviewed online accessible materials (including Environmental Protection Agency-site specific websites, data repositories, and other agency websites). Results indicate that the five sites vary in regard to the measured PCB concentrations in air, the sampling and monitoring methodologies, and the established site-specific guidelines/standards and their basis. We conclude that current practices may not adequately protect those living or working near these sites from airborne PCB exposure and that regulations should include recognition of exposure to indoor sources.


Investigating the relationship between iron and depression.
Lower levels of circulating iron have been associated with depression. Our objective was to investigate the phenotypic and genetic relationship between measures of circulating levels of iron (serum iron, transferrin, transferrin saturation, and ferritin) and depressive symptoms. Data were available from ongoing studies at QIMR Berghofer Medical Research Institute (QIMRB), including twin adolescents (mean age 15.1 years, standard deviation (SD) 3.2 years), and twin adults (mean age 23.2 years, SD 2.2 years). In the adolescent cohort, there were 3416 participants from 1688 families. In the adult cohort there were 9035 participants from 4533 families. We estimated heritabilities of, and phenotypic and genetic correlations between, traits. We conducted analyses that linked results from published large-scale genome-wide association studies (including iron and Major Depressive Disorder) with our study samples using single SNP and multi-SNP genetic risk score analyses, and LD score regression analyses. In both cohorts, measures of iron, transferrin, transferrin saturation, and log 10 of ferritin (L10Fer) were all highly heritable, while depressive measures were moderately heritable. In adolescents, depression measures were higher in those in the middle 10th versus top 10th percentile of transferrin saturation measures (p = 0.002). Genetic profile risk scores of the iron measures were not significantly associated with depression in study participants. LD score analyses showed no significant genetic relationship between iron and depression. Genetic factors strongly influence iron measures in adolescents and adults. Using several different strategies we find no evidence for a genetic contribution to the relationship between blood measures of iron and measures of depression.


Overlaps between Frailty and Sarcopenia Definitions.
Aging is characterized by the catabolism of muscles leading to sarcopenia and frailty. These are two geriatric syndromes with partly overlapping phenotypes. Primary sarcopenia, i.e. loss of muscle mass and function related to aging alone, usually precedes frailty. Thus, robustness passes from sarcopenia over frailty to disability leading eventually to a mortal outcome. Frailty (defined according to the phenotype model) encompasses states as exhaustion, weakness, and slowness, whereas sarcopenia, combining mass and function, is more strictly focused on muscles. Frailty is age related, whereas sarcopenia is also related to disease, starvation, and disuse. In general, the criteria for the two conditions overlap, but frailty requires weight loss, whereas sarcopenia requires muscle loss. Both gait speed and hand grip strength are suggested to be used as diagnostic measures for the two conditions since muscle function is crucial for any of the two syndromes. It is suggested that frailty screening should be part of the geriatric comprehensive assessment starting with measuring walking capacity and complemented by taking a history of fatigue and low activity. For younger adults (i.e. <70 years), sarcopenia screening could first register gait speed or hand grip strength and then body composition measurements. Simple questionnaires are feasible clinical alternatives. Treatment of frailty and sarcopenia overlaps, i.e. provide adequate protein and vitamin D supplementation, and encourage resistance exercise.


Effect of vitamin D replacement in primary hyperparathyroidism with concurrent vitamin D deficiency: a systematic review and meta-analysis.
We conducted a meta-analysis to assess the effects of vitamin D replacement on biochemical and skeletal parameters in subjects with mild primary hyperparathyroidism (PHPT) and coexistent vitamin D deficiency. A systematic search of all English-language medical literature published from 1980 till May 2016 using PubMed, Embase and Ovid was performed. Nine observational studies were evaluated after fulfilling the inclusion and exclusion criteria. A total of 547 patients were examined. All studies used vitamin D2/D3 or calcifediol (25-hydroxyvitamin D3), There was significant improvement of serum 25(OH)D with unchanged serum iPTH level after vitamin D replacement, with pooled d+: 3.10 (95% CI 2.25 to 3.95), P<0.01 and pooled d+: 0.82 (95% CI -0.35 to 1.98), P=0.16 respectively. There was neither worsening of the pre-existing hypercalcemia (pooled d+: -0.27 [95% CI -1.09 to 0.64, P=0.56]) nor hypercalciuria (pooled d+: 3.64 [95% CI -0.55 to 7.83, P=0.09]). Two studies assessed in this meta-analysis reported unchanged bone density with vitamin D replacement. Vitamin D replacement in subjects with mild PHPT and coexistent vitamin D deficiency improved serum 25(OH)D level without worsening of pre-existing hypercalcemia or hypercalciuria. Well-designed multicenter randomized controlled trials examining pre- and postoperative outcomes of vitamin D therapy in patients with different severities of PHPT and vitamin D inadequacy are warranted to elucidate the most appropriate vitamin D treatment protocol and determine the long-term safety concerns.


Value of one additional injection at the root of the limb in the lymphoscintigraphic evaluation and management of primary and secondary lower-limb lymphedemas.
The classical lymphoscintigraphic investigations of lower-limb lymphatic edema [LLLE] sometimes reveal either no or few lymph nodes [LNs] at the root of the limb[s] and/or in the abdomen. The aim of the present paper is to report the results of performing one additional injection at the root of the edematous limb[s] to force the visualization of the LNs and/or to demonstrate the collateral lymphatic pathways in such patients. We retrospectively reviewed our database and found 99 patients [44 primary LLLE with 47 limbs injected and 55 with LLLE secondary to treatments for cancer with 64 limbs injected] where such an additional injection had been performed. In the 43 LLLE patients where no LNs were seen at the end of the classical exam [15 primary LLLE and 28 secondary LLLE], the extra injection showed lymphatic drainage toward LN[s] in all except 3 and when at least one LN was seen, the injection showed lymphatic drainage in every case toward the same ipsilateral [inguinal and/or iliac] LNs [as shown by the classical injection] and/or toward additional LNs. In 40.7% of patients, we observed one or more additional lymphatic pathways: prepubic superficial lymphatic vessels [LV] crossing the midline anteriorly toward contralateral inguinal LNs in 21 [18.9%], "posterior" LV [toward contralateral inguinal LNs and/or ipsi- or contralateral lumbo-aortic and/or para-renal LNs] in 14 [12.6%], but deep LV toward the ipsilateral common iliac LNs passing between the gluteal muscles in 32 [28.8%]. Our work pinpoints one limitation of classical bipedal radionuclide lymphangiography. In patients with primary and secondary LLLE where inguinal and/or iliac LNs cannot be seen on bipedal radionuclide lymphangiography, this additional injection reveals the true lympho-nodal status and shows unexpected collateral lymphatic pathways in 40% of cases. Such information is of the utmost importance in LLLE management and its acquisition is consequently recommended in these patients.


Production of catalytic cells for formaldehyde production and alcohol oxidase by a catabolite repression-insensitive mutant of a methanol yeast Candida boidinii A5.
A catabolite repression-insensitive mutant of Candida boidinii A5, strain ADU-15, was investigated as to alcohol oxidase production and the production of cells exhibiting the maximum catalytic activity for formaldehyde production. The mutant strain ADU-15 showed higher cell productivity and higher alcohol oxidase activity when grown on mixed substrates (glucose-methanol), especially with a high concentration of glucose in the medium. Thus, even under substrate (glucose-methanol)-limited chemostat conditions, where the glucose concentration was low, partial derepression of alcohol oxidase by glucose in mutant strain ADU-15 was detected. The chemostat culture conditions with the glucose-methanol medium were optimized for alcohol oxidase production and the production of cells exhibiting the maximum catalytic activity for formaldehyde production, respectively. By means of chemostat culturing on mixed substrates, we improved the alcohol oxidase productivity 5.0-fold and the productivity of cells exhibiting the maximum catalytic activity for formaldehyde production 3.8-fold, in comparison with the parent strain chemostat cultured with methanol as the single substrate.


Genetic and epigenetic stability of oligodendrogliomas at recurrence.
Among diffuse gliomas, oligodendrogliomas show relatively better prognosis, respond well to radiotherapy and chemotherapy, and seldom progress to very aggressive tumors. To elucidate the genetic and epigenetic background for such behavior and tumor evolution during tumor relapse, we comparatively analyzed 12 pairs of primary and recurrent oligodendrogliomas with 1p/19q-codeletion. Initial treatment for these patients was mostly chemotherapy alone. Temozolomide was used for 3, and procarbazine, nimustine and vincristine (PAV chemotherapy) were used for 7 patients. World Health Organization histological grade at recurrence was mostly stable; it was increased in 2, the same in 9, and decreased in 1 cases. Whole-exome sequencing demonstrated that the rate of shared mutation between the primary and recurrent tumors was relatively low, ranging from 3.2-57.9% (average, 33.3%), indicating a branched evolutionary pattern. The trunk alterations that existed throughout the course were restricted to IDH1 mutation, 1p/19q-codeletion, and TERT promoter mutation, and mutation of the known candidate tumor suppressor genes CIC and FUBP1 were not consistently observed between primary and recurrent tumors. Multiple sampling from different regions within a tumor showed marked intratumoral heterogeneity. Notably, in general, the number of mutations was not significantly different after recurrence, remaining under 100, and no hypermutator phenotype was observed. FUBP1 mutation, loss of chr. 9p21, and TCF12 mutation were among a few recurrent de novo alterations that were found at recurrence, indicating that these events were clonally selected at recurrence but were not enough to enhance malignancy. Genome-wide methylation status, measured by Illumina 450 K arrays, was stable between recurrence and the primary tumor. In summary, although oligodendroglioma displays marked mutational heterogeneity, histological malignant transformation accompanying events such as considerable increase in mutation number and epigenetic profile change were not observed at recurrence, indicating that noticeable temporal and spatial genetic heterogeneity in oligodendrogliomas does not result in rapid tumor progression.


Long-term efficacy and safety of carotid artery stenting versus endarterectomy: A meta-analysis of randomized controlled trials.
Many recent trials have investigated the long-term efficacy and safety of endarterectomy versus stenting in treating patients with carotid artery stenosis. We aimed to determine the long-term comparative efficacy and safety of both procedures by pooling this evidence in a meta-analysis. We searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials for studies published until May 6, 2016. Randomized controlled trials, which reported outcomes of interest with a median follow-up of at least 4-year, were included. Eight trials involving 7005 patients and 41824 patient-years of follow-up were included. In terms of the periprocedural outcomes, stenting was associated with a lower risk of myocardial infarction (OR: 0.51; 95% CI: 0.33 to 0.80; P = 0.003) but a higher risk of death or stroke (the composite endpoint, OR: 1.76; 95% CI: 1.38 to 2.25; P < 0.0001), a result that was primarily driven by minor stroke (OR: 2.19; 95% CI: 1.59 to 3.01; P < 0.0001), less so by periprocedural death (OR: 1.68; 95% CI: 0.82 to 3.44; P = 0.16) and major stroke (OR: 1.41; 95% CI: 0.95 to 2.09; P = 0.09). In terms of the long-term outcomes, stenting was associated with a higher risk of stroke (OR 1.45; 95% CI: 1.22 to 1.73; P < 0.0001) and the composite outcome of death or stroke (OR 1.25; 95% CI: 1.05 to 1.48; P = 0.01). No difference was found in long-term all-cause mortality between stenting and endarterectomy (OR: 1.09; 95% CI: 0.95 to 1.26; P = 0.21) and restenosis (OR: 1.48 (95% CI: 0.93 to 2.35; P = 0.10). No evidence of significant heterogeneity was found in any of the analyses. Carotid endarterectomy was found to be superior to stenting for short- and long-term outcomes, although endarterectomy was associated with a higher risk of periprocedural myocardial infarction. Carotid endarterectomy should be offered as the first choice for carotid stenosis at present, however, more evidence is needed because rapid progress in concurrent devices and medical treatments is being made.


Extracellular vesicles from medicated plasma of Buyang Huanwu decoction-preconditioned neural stem cells accelerate neurological recovery following ischemic stroke.
Introduction: The neurological impairment of survivors after ischemic stroke poses a serious risk to their quality of life and health. Effective therapeutic options are still lacking. Neural stem cells (NSCs) promote neurogenesis via secreted extracellular vesicles (NSC-EVs), which would be a potential therapeutic option, but the insufficient quantity of NSC-EVs in vivo restrains clinical application. Buyang Huanwu Decoction (BHD), a classic traditional Chinese medicine (TCM) decoction, is promising to alleviate neurological impairment after ischemic stroke. It was speculated that BHD might promote neurological recovery through the NSC-EVs. Methods: The medicated plasma of BHD (MP-BHD) was prepared to precondition NSCs and isolate EVs (BHD-NSC-EVs). Middle cerebral artery occlusion (MCAO) models and primary NSCs were administered to evaluate the therapeutic effect. Next-generation sequencing was performed to explore the mechanism. Results: The BHD-NSC-EVs more significantly accelerated neurological recovery after MCAO and promoted NSCs proliferation and differentiation than BHD and NSC-EVs alone. MP-BHD enhanced the largescale generation of BHD-NSC-EVs, which encapsulated functional miRNA and may play critical roles in neurogenesis. Discussion: In replacing BHD or NSCs, the preconditioned NSC-EVs present a more efficient therapeutic strategy for ischemic stroke. Based on the clinical efficacy of TCM, the preconditioning of NSC-derived EVs via the MP of TCM herbs would presents a newly promising therapeutic strategy for neurological diseases.


Assessment of conventional criteria for the early diagnosis of thrombophlebitis with the 125I-fibrinogen uptake test.
Analysis of 55 positive tests of a total of 300 tests by conventional criteria revealed that 125I-fibrinogen provides useful information early enough for clinical management. Of the tests which were ultimately interpreted as positive by conventional criteria, at least one was positive at 3-4 hours in 67% of the tests and 98% of the tests were positive at 24 hours after the administration of 125I-fibrinogen. A 20% difference between contralateral identical locations of the legs and a 20% difference between adjacent locations of the ipsilateral leg were found with almost equal frequency in the positive tests, whereas a 20% increase at the same location was less sensitive. The 125I-fibrogen uptake test is a simple and accurate technique for early diagnosis of active thrombophlebitis.


Local immune complexes and inflammatory response in patients with chronic interstitial pulmonary disorders associated with collagen vascular diseases.
Evidence is accumulating that the lung injury in collagen vascular diseases (CVD) is triggered by immune complexes (IC). These reactions are neutrophil- and complement-dependent. The direct, in vivo phagocytosis of IC by bronchoalveolar lavage polymorphonuclear leucocytes (BAL-PMN), was studied in 15 patients with CVD and chronic interstitial pulmonary disorders. A control group (NC) consisted of nine healthy, non-smoking volunteers. Concentrations of soluble IC were measured using a solid phase Clq ELISA assay, and an indirect, in vitro phagocytosis assay performed using healthy donor PMN. Local Ig and C3 concentrations were determined using laser nephelometry and Mancini techniques, respectively. In the patient group the total cell counts/ml recovered lavage fluid and the proportions of BAL-PMN were significantly increased (P less than 0.05 and P less than 0.001, respectively). The influxed PMN showed high scores of direct IC phagocytosis. Soluble IC concentrations were significantly increased compared with controls (all comparisons P less than 0.01), and in the BAL relatively higher than in the serum of the same patients. Concomitantly high local IgG concentrations were observed. Corticosteroid treatment gave rise to significantly decreased total cell counts (P less than 0.05), and proportions of BAL-PMN (P less than 0.001), a decrease in the in vivo IC phagocytosis (P less than 0.05), in the indirect, in vitro IC phagocytosis, in the Clq ELISA and in the local IgG concentrations (all comparisons P less than 0.001). We concluded that locally formed IC may induce an inflammatory response in the lungs of patients with CVD.


Neuropathic bone and joint disease.
The pathogenesis of the neuropathic joint has been a subject of controversy for many years. Two main theories of pathophysiologic pathways have evolved: (1) the neurotraumatic, which states that the changes result from mechanical trauma and repetitive injuries to an insensitive extremity or joint and (2) the neurovascular, which states that the changes result from a neurally initiated vascular reflex that leads to hyperemia, angiogenesis, and very active bone resorption by osteoclasts. Through clinical, radiographic, and pathologic observation, it appears evident that both pathways contribute to neuropathic bone and joint disease. Initially, the alteration of sympathetic control triggers a persistent hyperemia, leading to active bone resorption. There may or may not be associated pathologic fractures and subsequent repair. This depends upon the degree of joint insensitivity and whether or not it is subjected to continued weightbearing. If so, the neurotraumatic mechanisms come into play, but only secondarily.


Transcatheter Closure of Complex Post-Myocardial Infarction Left Ventricular Pseudoaneurysm and Unique Post-Traumatic Right Ventricular Pseudoaneurysm.
Ventricular pseudoaneurysm (PSA) is a rare, yet life-threatening complication of myocardial infarction, cardiac surgery, and transcatheter valve replacement. Although conventional surgery is the preferred treatment strategy, transcatheter closure has emerged as an effective alternative in selected candidates. In this report, we describe successful transcatheter closure of two unique cases of ventricular pseudoaneurysm (PSA): first, a complex post-myocardial infarction left ventricular PSA (LVPSA) with multi-communications, and second, a case of post-traumatic right ventricular PSA (RVPSA) following blunt chest injury caused by domestic violence.


Solvents and color discrimination ability. Nonreplication of previous findings.
Previous research has shown exposure-related increases in the prevalence of acquired color vision deficits among printers. We administered the Lanthony D-15 desaturated test of color vision to 82 print shop workers. Two tests of cognitive function, Trails A and B and the Symbol Digit Modalities Test, were also administered. Personal air sampling indicated that current exposure to organic solvents was highest among printers and lowest among bindery workers. In contrast to previous studies, the age-adjusted quantitative Lanthony D-15 desaturated test error scores did not differ significantly between exposure groups, and the proportion of subjects with > or = 1 error was greater in the lower-exposure, rather than higher-exposure, groups (P = .03). Of note, the proportion of subjects with > or = 2 errors did not differ significantly between groups (P = .24). Cognitive tests showed no significant association with exposure. These results are discussed in the context of methodological issues related to lighting sources, reliability of test results, and establishment of criteria for identifying deficits.


Hijab pin inhalation.
Foreign body aspiration can be an acute life-threatening emergency and, if left untreated, can result in severe complications. Among Muslim women, the hijab pin can be accidentally aspirated. The article describes standard management with rigid bronchoscopy and a new technique involving magnets.


Ambulatory care for chronic conditions in an inner-city elderly population.
Factors affecting the extent to which individuals aged 65 and over living in inner-city households received health care for three chronic conditions (high blood pressure, heart trouble, arthritis) are examined. These factors are age, sex, living arrangements, and the presence of more than one chronic condition. Indicators of receiving care are having seen a health care provider within the previous six months and being on medication for the condition. A more detailed scrutiny of care received for high blood pressure is undertaken as well. This analysis is part of a larger study investigating health care of groups within East Baltimore who utilize different systems of care, focusing on a hospital outpatient department and a new HMO. Data were obtained from 1455 household interviews among three sample populations: enrolees in an HMO, public housing project residents, and the general community. The findings indicate that high proportions of the elderly who report having these conditions also report receiving care for them. For people with high blood pressure, the majority are receiving care and being given self-care instructions, and high proportions report compliance with instructions.


Histopathologic and histoenzymatic observations in carcinomas treated with human leukocyte interferon.
In this study histologic and histochemical examinations were performed on the bioptic material of 30 cases of head and neck tumors and 34 cases of uterocervical carcinomas after treatment with human leukocyte interferon (HLI). Particular attention was paid to the interaction between stromal and neoplastic cells as a possible host response to the treatment with interferon. In addition to tumor biopsies, regional lymph nodes were also examined microscopically. Stromal cells (macrophages, T and B lymphocytes, and granulocytes) were detected by enzyme-histochemical methods. Histologic and histochemical criteria for classification of tumor biopsies into five groups included the frequency, the cellular composition of peritumoral stroma, the grade of macrophage infiltration into the tumor (expressed quantitatively), and cytologic changes, followed by the regression of tumor. The overall appraisal of patients with cervical carcinoma based on histopathologic and chemical criteria showed the positive effect of HLI therapy in 70% of the cases; observations of head and neck carcinoma treated with HLI showed positive effects in 82% of the cases.


The nutritional knowledge scores of morbidly obese patients selected for gastric bypass surgery.
Repeated attempts at weight-reduction might be expected to coincide with an increase in nutritional knowledge. In this study a 30-item multiple choice test was used to compare the nutritional knowledge of 50 morbidly obese patients, selected for gastric bypass surgery, to that of 50 hospital control subjects prospectively matched for age, sex, educational experience, and socio-economic status. Morbidly obese patients knew less about general nutrition than subjects in the control group (P less than 0.005). In addition there was no significant correlation (rs = 0.10, n = 24) between the amount of weight lost one year after surgery and the nutritional knowledge scores. It seems that whilst morbidly obese patients have a relatively poor level of nutritional knowledge, this finding cannot be related to the extent of weight loss after gastric bypass surgery.


Sex for food: a transactional sex reaction to the COVID-19-induced rise in the prevalence of hunger among in-school female adolescents in Ogun State, Nigeria.
COVID-19 has doubled the proportion of people with acute hunger globally and Nigeria is categorized as having a "severe" form of hunger. Vulnerable groups responding more to hunger stressors include the female adolescents who transact sex for both survival and luxury purposes. This study assessed the engagement in transactional sex to obtain food among female adolescents in Ogun State, Nigeria. this descriptive cross-sectional research was conducted among 668 in-school female adolescents that were selected through a multistage sampling method. Data were collected with a structured interviewer-administered questionnaire. Food security was assessed using a standard tool while engagement in transactional sex was elicited through self-report. Data analysis was done using Statistical package for the social sciences (SPSS) version 25. Logistic regression was used to find factors associated with transactional sex. P< 0.05 was taken as statistically significant. the mean age of the respondents was 15.18±1.35 years. More than two-fifths (41.5%) were staying in households without food security. Less than one-fifth (15.3%) were engaging in transactional sex. Having emotional stress (OR = 4.33; 95 CI: 1.37-13.63), mother´s education (OR =0.163; 95% CI: 0.057- 0.461), having sexual partner (OR = 0.132; 95% CI: 0.047-0.370 and missing classes (OR 3.35, 95% CI: 1.084-10.331) were significant predictors of engaging in transactional sex among female adolescents. transactional sex is commoner among female adolescents who were missing classes, had sexual partners, and were emotionally stressed. There is a need for intervention programs to protect the female adolescent, delay sexual debut and improve academic performance among them.


Role of Semaphorins in Immunopathologies and Rheumatic Diseases.
Rheumatic diseases are disorders characterized by joint inflammation, in which other organs are also affected. There are more than two hundred rheumatic diseases, the most studied so far are rheumatoid arthritis, osteoarthritis, spondyloarthritis, systemic lupus erythematosus, and systemic sclerosis. The semaphorin family is a large group of proteins initially described as axon guidance molecules involved in nervous system development. Studies have demonstrated that semaphorins play a role in other processes such as the regulation of immunity, angiogenesis, bone remodeling, apoptosis, and cell migration and invasion. Moreover, semaphorins have been related to the pathogenesis of multiple sclerosis, asthma, Alzheimer, myocarditis, atherosclerosis, fibrotic diseases, osteopetrosis, and cancer. The aim of this review is to summarize current knowledge regarding the role of semaphorins in rheumatic diseases, and discuss their potential applications as therapeutic targets to treat these disorders.


Activated T cells express a novel gene on chromosome 8 that is closely related to the murine ecotropic retroviral receptor.
A novel cDNA clone (20.5) which is differentially expressed between two closely related T-lymphoma cell clones was isolated by subtraction-enriched differential screening. SL12.4 cells, from which the cDNA was isolated, have characteristics of thymocytes at an intermediate stage in development. A sister cell clone derived from the same tumor, SL12.3, does not express this mRNA, has a distinct phenotype, and expresses fewer genes required for mature T-cell function. The cDNA sequence predicts a highly hydrophobic protein (approximately 49.5 kilodaltons) which contains seven putative membrane spanning domains. The gene was expressed on concanavalin A-activated T lymphocytes and was designated Tea (T-cell early activation gene). The Tea gene mapped to chromosome 8 and appeared to be conserved among mammalian and avian species. The Tea gene is distinct from, but bears extensive amino acid and DNA sequence similarity with, the murine ecotropic retroviral receptor which is encoded by the Rec-1 gene. Neither gene product displayed significant homology with other known transmembrane-spanning proteins. Thus, the Tea and Rec-1 genes establish a new family encoding multiple membrane-spanning proteins.


Towards a general synthesis of 3-metal-substituted β-lactams.
Joining metals and antibiotics: Studies towards a general method for the synthesis of β-lactams that have a metal complex moiety attached to the C3-position are reported (see scheme). The cis/trans selectivity of the reactions ranges from low in complexes containing the alkyne moiety joined directly to the cyclopentadienyl ring to complete when the metal moiety is separated from the reactive alkyne by an alkynyl-aryl fragment.


C-terminal domains deliver the DNA replication factor Ciz1 to the nuclear matrix.
Cip1-interacting zinc finger protein 1 (Ciz1) stimulates DNA replication in vitro and is required for mammalian cells to enter S phase. Here, we show that a significant proportion of Ciz1 is retained in nuclear foci following extraction with nuclease and high salt. This suggests that Ciz1 is normally immobilized by interaction with non-chromatin nuclear structures, consistent with the nuclear matrix. Furthermore, matrix-associated Ciz1 foci strikingly colocalize with sites of newly synthesized DNA in S phase nuclei, suggesting that Ciz1 is present in DNA replication factories. Analysis of green fluorescent protein-tagged fragments indicates that nuclear immobilization of Ciz1 is mediated by sequences in its C-terminal third, encoded within amino acids 708-830. Immobilization occurs in a cell-cycle-dependent manner, most probably during late G1 or early S phase, to coincide with its reported point of action. Although C-terminal domains are sufficient for immobilization, N-terminal domains are also required to specify focal organization. Combined with previous work, which showed that the DNA replication activity of Ciz1 is encoded by N-terminal sequences, we suggest that Ciz1 is composed of two functionally distinct domains: an N-terminal replication domain and a C-terminal nuclear matrix anchor. This could contribute to the formation or function of DNA replication factories in mammalian cells.


Postnatal encephalitis: a diagnosis not to be missed.
Viral encephalitis is a common condition but only a few studies are available on occurrence of viral encephalitis in postnatal women. The objective of this study was to determine the frequency of postnatal encephalitis among patients presenting with cerebral neurological complications during puerperium and to determine a response to 10 day course of acyclovir therapy and final outcome of the patients. This cross-sectional descriptive study was conducted at Department of Medicine, Unit A, Ayub Teaching Hospital, Abbottabad from Jan to Dec 2011. All patients presenting with encephalitis in their postnatal period were enrolled. Eclampsia patients were excluded from study. The diagnosis of encephalitis was made on clinical assessment, CSF routine examination, CT scan and MRI. Among patients 16 (84.2%) presented with fever, 13 (68.42%) with headache, 8 (42.1%) with meningeal irritation, 7 (36.84%) with hemiparesis, 18 (94.7%) with altered sensorium, 13 (68.42%) with seizures, and 7 (36.84%) with coma. Cerebrospinal fluid of 16 (84.21%) patient had the changes consistent with viral encephalitis. It was normal in 2 (10.52%) patients and showed picture of pyogenic meningitis in 1 (5.26%) cases. On CT scan of brain, 3 (15.78%) had normal scans, 3 (15.78%) had cerebral oedema, 4 (21.05%) had ischemic infarct, 3 (15.78%) had meningo-encephalitis, 2 (10.52%) had infarct plus cerebral oedema, 1 (5.26%) had encephalitis and 3 (15.78%) had infarct plus haemorrhage. On MRI brain 15 out of 17 (88.2%) had lesions consistent with encephalitis. All 19 (100%) patients were treated with 10 days course of acyclovir and a broad spectrum third generation antibiotic. After hospitalisation 11 (57.8%) patients were discharged with complete recovery, 5 (26.31%) were discharged with partial recovery and 3 (15.78%) patients expired. Clinical presentation of the patient is most important in diagnosing viral encephalitis in postnatal women especially when patient presents with fever, altered sensorium and convulsions. Acyclovir therapy should be started without delay while awaiting other investigations.


Size Attenuated Copper Doped Zirconia Nanoparticles Enhances In Vitro Antimicrobial Properties.
Biofilm formation hinders the activity of antimicrobial drugs at the site of infections and any agent that can act on both Gram-positive and Gram-negative bacteria by inhibiting the bacterial growth and rupturing the biofilm is needed to manage infection. In the present study, we have synthesized zirconia nanoparticles (ZrO2 NPs) and copper doped zirconia nanoparticles (Cu-ZrO2 NPs) and characterized them using dynamic light scattering, X-ray diffractometry, and scanning electron microscopy (SEM). The size of the Cu-ZrO2 NPs drastically reduced compared to ZrO2 NPs, and the antimicrobial activity was studied against Gram-positive bacteria (Lactobacillus sp.) and Gram-negative bacteria (Pseudomonas aeruginosa), respectively. The synthesized Cu-ZrO2 NPs showed superior inhibitory action against Lactobacillus sp. compared to ZrO2 NPs, due to the negatively charged cell wall of Lactobacillus sp., which could attract readily the positively charged Cu-ZrO2 NPs, thereby inhibiting its activity. The biocompatibility was tested using XTT assay in FL cells, and the results demonstrated that Cu-ZrO2 NPs were nontoxic to mammalian cells. Hence, it could be proposed that the synthesized Cu-ZrO2 NPs possess possible biomedical applications and can be used as antibacterial agents without causing toxicity in mammalian cells.


[Immunization against tick-borne encephalitis].
Tick-borne encephalitis (TBE) is a viral infection that may cause irreversible damage to the brain and even result in death. No specific therapy exists. Active immunization is of major importance in controlling the infection. Vaccination is recommended to all adults and children > 6 years who live in endemic areas. Two inactivated vaccines are available in Switzerland. The vaccination schedule includes a basic immunization composed of 3 injections followed by boosting every 10 years. The efficacy of the vaccines has never been investigated in controlled studies, however, from indirect evidence, the vaccines are thought to cause good protection and to be safe. Local reactions at the injections site may occur in one third and mild systemic side effects in one fifth of vaccinees. Anaphylactic reactions and severe central nervous side effects are very rare.


The silica mineralisation properties of synthetic Silaffin-1A1 (synSil-1A1).
The synthetic monodisperse pentadecapeptide synSil-1A1 is a representative of the microdisperse mixture of the native silaffin natSil-1A1 produced by the diatom Cylindrotheca fusiformis. The octaphosphorylated zwitterionic synSil-1A1 is able to mineralise silica under slightly acidic conditions at pH 5.5, which is the physiologically relevant pH range assumed. Like the posttranslational modifications of the native silaffins, synSil-1A1 is functionalised on all four lysine and phosphorylated on all seven serine residues. We describe the synthesis of a trimethyl-δ-hydroxy-L-lysine building block, the incorporation of this choline-type amino acid in peptide synthesis and its phosphorylation, together with all further posttranslational modifications observed in the native silaffins. Quantitative structure-activity relationships from silicification experiments at high dilution reveal the unique mineralisation properties of the hyperphosphorylated peptide as a single substance and in interaction with long-chain polyamines (LCPA). Diffusion-ordered spectroscopy (DOSY) experiments reveal the formation of polyelectrolyte complexes (PEC) between synSil-1A1 and long-chain polyamines, which promotes the silicification process. The microdroplets have an overall balanced ratio of 100-150 cationic and the same number of anionic charges. The unique zwitterionic synSil-1A1 confirms the prevailing molecular model of biosilicification and validates it with quantitative data based on a single phosphopeptide species, avoiding the usual unphysiologically high concentrations of phosphate of many previous in vitro silicification experiments.


Refractory anemia with ringed sideroblasts and thrombocytosis without JAK2 V617F mutation: report of three cases.
In the WHO classification, there is a provisional entity called Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable (MDS/MPN, U). Refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T) was included in this category. Recently published studies report a small percentage of patients with RARS-T. Sixty percent of these have JAK2 V617F mutation, which can suggest the coexistence of two pathological conditions (MDS and MPN). In this paper, we analyzed three patients diagnosed with RARS-T in the Department of Hematology, "Fundeni" Clinical Institute, Bucharest, Romania, during the period 2005-2011. The patients were investigated with cytogenetic exam and molecular biology. In these three cases were identified morphological features of multilineage dysplasia (two-lineage dysplasia in two cases and three-lineage dysplasia in one case). In two cases, thrombocytosis was under 1000×10(3)/μL and clinical evolution was similar to the myelodysplastic syndrome (transfusion dependent anemia with response to administration of erythropoietin). In the third case, the platelets were over 1000×10(3)/μL and with response to the treatment with Hydrea, which improved anemia. JAK2 V617F mutation was not identified in any case. RARS-T remains a provisional entity and requires a complex investigation of patients for the correct diagnosis of these patients. Therapeutic options should be personalized to each case in part because there is not yet a standardized treatment of these patients.


Design of molecular scaffolds based on unusual geometries for magnetic modulation of spin-diverse complexes with selective redox response.
A weakly coupled heterometallic [CuFe] complex has been prepared in which the metal centers are coordinated to a new electroactive ligand. The spin-diverse system delivers distinct ground states upon application of selective redox potentials. Ligand oxidation fosters radical generation, and the initial ground state associated with a weakly coupled [CuFe] core switches to a ground state associated with the [Fe-radical] coupling; the Cu(II) ion remains uncoupled. A third state is obtained upon reduction of the cupric center and in absence of the radical. The possibilities and limitations of these systems are discussed.


MOLECULAR EVOLUTIONARY DIVERGENCE AMONG NORTH AMERICAN CAVE CRICKETS. II. DNA-DNA HYBRIDIZATION.
Single-copy DNA divergence among 23 populations of cave crickets belonging to two genera (Euhadenoecus and Hadenoecus) has been determined by DNA-DNA hybridization employing the TEACL method. These same populations have been studied for allozyme variation (Caccone and Sbordoni, 1987). In addition, a European relative (Dolichopoda laetitiae) has been included as an outgroup for rooting the phylogeny. One of the most remarkable findings is the large degree of DNA divergence among these species and populations. A ΔTm of up to 5°C has been found between populations of the same species; even further divergence is indicated by a lowered normalized percentage of reassociation. A phylogeny was constructed and tested for synchrony of rates, i.e., a molecular clock. Statistically, we could not reject the clock hypothesis. Attempts to calibrate the clock led to the conclusion that these insects are among the fastest evolving (with respect to single-copy DNA) groups yet studied-at least as fast as Drosophila and sea urchins-where a ΔTm of 1°C indicates 0.5 to 1.5 MY since the last common ancestor. In general, the phylogeny derived from the DNA data agrees with that derived from isozymes. Nei's D and ΔTm are correlated; in this group a D of 0.1 corresponds to a ΔTm of about 1.5°C. This indicates that, relative to total single-copy DNA, the protein-coding regions of the genome are slowly evolving.


Comparative outcomes of physician-modified fenestrated/branched endovascular aortic aneurysm repair in the setting of prior failed endovascular aneurysm repair.
Endovascular treatment of aortic aneurysms involving renal-mesenteric arteries, especially in the setting of prior failed endovascular aneurysm repair (EVAR) typically requires fenestrated/branched endovascular aneurysm repair (F/BEVAR) with a custom-made device (CMD). CMDs are limited to select centers, and physician-modified endografts are an alternative treatment platform. Currently, there is no data on the outcomes of physician-modified F/BEVAR (PM-F/BEVAR) in the setting of failed prior EVAR. The purpose of this study was to evaluate the use of PM-F/BEVAR in patients with prior failed EVAR. A prospective database of consecutive patients treated at a single center with PM-F/BEVAR between March 2021 and November 2022 was retrospectively reviewed. The cohort was stratified by presence of a failed EVAR (type Ia endoleak or aneurysm development proximal to a prior EVAR) prior to PM-F/BEVAR. Demographics, operative details, and postoperative complications were compared between the groups using univariate analysis. One-year survival and freedom from reintervention were compared using the Kaplan-Meier method. A total of 103 patients underwent PM-F/BEVAR during the study period; 27 (26%) were in the setting of prior EVAR. Patients with prior failed EVAR had similar age (75.2 ± 7.7 vs 71.5 ± 8.8 years; P = .058), male gender (n = 24 ; 89% vs n = 57 ; 75%; P = .130), and comorbid conditions except higher incidence of moderate-to-severe chronic obstructive pulmonary disease (n = 7 ; 26% vs n = 7 ; 9%; P = .047). Overall, aneurysm diameter was 65.5 ± 13.9 mm with aneurysms categorized as juxta-/pararenal in 43% and thoracoabdominal in 57%, with no differences between the groups. Twelve patients (14%) presented with symptomatic/ruptured aneurysms. The average number of target arteries incorporated per patient was 3.8. Four different aortic devices were modified with a greater proportion of Terumo TREO devices used in the failed EVAR group (P = .03). There was no difference in procedure time, radiation dose, or iodinated contrast use between groups. Overall technical success was 99%. Rates of 30-day mortality (n = 0 ; 0% vs n = 3 ; 4%; P = .565) and major adverse events (n = 6 ; 22% vs n = 16 ; 21%; P = 1.0) were similar between groups. For the overall cohort, rates of type 1 or 3 endoleak, branch vessel stenosis/occlusion, and reintervention were 2%, 1%, and 8%, respectively, with no difference between groups. One-year survival (failed EVAR 94% vs no EVAR 82%; P = .756) was similar between groups. PM-F/BEVAR is a safe and effective treatment for patients with aneurysms involving the renal-mesenteric arteries in the setting of prior failed EVAR where additional technical challenges may be present. Additional follow-up is warranted to demonstrate long-term efficacy, but early results are encouraging and similar to those using CMDs.


The role of the right temporo-parietal junction in maintaining a coherent sense of one's body.
We constantly feel, see and move our body, and have no doubt that it is our own. The brain possesses a distinction between the body and the objects in the outside world. This distinction may be based on a process that monitors whether sensations, events and objects should be attributed to one's body or not. We controlled whether an external object was represented as part of the body or not, by experimentally inducing a bodily illusion using correlated visual and tactile stimulation. We then studied the role of right temporo-parietal junction (rTPJ) in the processing of multisensory events that may or may not be attributed to one's body. Disruption of rTPJ using transcranial magnetic stimulation (TMS) made the distinction between what may or may not be part of one's body on the basis of multisensory evidence more ambiguous, suggesting that the rTPJ is actively involved in maintaining a coherent sense of one's body, distinct from external, non-corporeal, objects.


Alcohol use among college students: a comparison of athletes and nonathletes.
This study examines alcohol use among college students, focusing on variation in binge drinking based on involvement in athletics. Prior research indicates that college students who participate in athletics are more likely to report binge drinking than are students who are not involved in athletics. However, existing research has not offered an explanation why college athletes are at a greater risk for binge drinking. Using data from the 1999 Harvard School of Public Health College Alcohol Study, a national study examining substance use and other health risk behaviors of college students in the United States, the current research examines social norms as a possible source of the elevated levels of binge drinking among college athletes. Findings indicate that athletes are more likely to report binge drinking, in part, because they view alcohol use as being more normative. The limitations of the study are noted.


Imaging of abdominal abscesses.
The aim of the study is presenting own experiences in using different diagnostic modalities in evaluating abdominal abscesses. Material comprises a group of nine patients with diagnosed abdominal abscess aged between 22 and 78 years. The plain abdominal radiograms, ultrasound examinations and computed tomography were performed in those patients. The CT examination was performed in 10-mm thick axial sections, before and after administering contrast agent. The perirenal abscesses were found in two patients. In US have showed various, inhomogeneous echogenicity, depending on the stage of the abscess. The contrast CT reveals enhancing septa, thick walls and oval, central area of lower density. The plane radiograms revealed abscesses in three cases. In two of them abscesses were complications of previouscholecystectomy. The large abscesses dislocated intestinal loops. CT was necessary to assess the extent, depth and shape of retroperitoneal fluid collections. Abdominal abscess is life threatening condition requiring quick diagnosis and proper management. The imaging methods are especially important in diagnosis of abscesses. Abscesses may by recognized on plain abdominal radiograms, but US and especially CT are much more sensitive and accurate. CT is imaging modality of choice in revealing abdominal abscess. CT and US are very useful in nonoperative therapies, including US and CT guided drainage.


Diabetic foot examination.
The 60-second tool (2012)(©) uses a cost-effective, simple, standardized approach to identifying, in a timely fashion, which individuals are at high risk for diabetic foot complications. Using this tool, occupational health nurses can screen for diabetic foot complications in varied clinical settings.


Overseas nurses--effective therapeutic agents?
Factors affecting the effectiveness of overseas people employed as psychiatric nurses are discussed. Basic cultural influences, especially different value systems between the immigrant and the host population, are seen as unlikely to be greatly altered by the environment in which the immigrant nurses find themselves. In fact a greater divergence would seem more likely to occur. The different experiences of immigrant nurses compared with nurses recruited in Britain are considered under the following headings: expectations of the immigrants on entering nursing, their contact with the host culture, the reaction of the indigenous population to the immigrant, language difficulties, and the insecurity of employment. The conclusion drawn is that the cultural differences, recruitment methods, the immigrants' experiences in employment and lack of contact with the culture of the indigenous population (apart from their deviant members) are likely to adversely affect his/her ability to function as a therapeutic agent. This is particularly important where the form of treatment is based on the social model.


Barley Seedling Extracts Inhibit RANKL-Induced Differentiation, Fusion, and Maturation of Osteoclasts in the Early-to-Late Stages of Osteoclastogenesis.
The number of patients with osteoporosis is increasing worldwide, and a decrease in bone mass is a main risk factor for fracture. The prevention of bone loss is critical for improving the quality of life for patients. However, the long-term use of antiosteoporotic agents is limited due to their side effects. Barley has been traditionally ingested for thousands of years as a safe, natural food with pharmaceutical properties, and its seedling can enhance the biological activity of the medicinal components found in food. This study aimed to clarify the antiresorptive activity of barley seedling and its mode of action. Barley seedling extracts (BSE) dose-dependently inhibited RANKL-induced osteoclast differentiation with alteration of IκB degradation, c-Fos, and NFATc1 molecules in the early-to-middle stages of osteoclastogenesis. In the late phase of osteoclastogenesis, BSE also prevented DC-STAMP and cathepsin K, which are required for cell fusion and bone degradation, such as osteoclast function. In conclusion, barley seedling from natural foods may provide long-term safety and be useful for the prevention or treatment of osteoclast-mediated bone metabolic diseases, including osteoporosis.


Mechanical properties of human oral mucosa tissues are site dependent: A combined biomechanical, histological and ultrastructural approach.
To investigate load-deformation properties of Thiel-embalmed human oral mucosa tissues and to compare three different anatomical regions in terms of mechanical, histological and ultrastructural characteristic with focus on the extracellular matrix. Thirty specimens from three different regions of the oral cavity: attached gingiva, buccal mucosa and the hard palate were harvested from two Thiel-embalmed cadavers. Mechanical properties were obtained, combining strain evaluation and digital image correlation in a standardised approach. Elastic modulus, tensile strength, strain at maximum load and strain to failure were computed and analysed statistically. Subsamples were also analysed using scanning electron microscopy (SEM) and histological analysis. The highest elastic modulus of 37.36 ± 17.4 MPa was found in the attached gingiva group, followed by the hard palate and buccal mucosa. The elastic moduli of attached gingiva differed significantly to the buccal mucosa (p = .01) and hard palate (p = .021). However, there was no difference in the elastic moduli between the buccal mucosa and hard palate (p > .22). The tensile strength of the tissue samples ranged from 1.54 ± 0.5MPa to 3.81 ± 0.9 MPa, with a significant difference between gingiva group and buccal mucosa or hard palate (p = .001). No difference was found in the mean tensile strength between the buccal mucosa and hard palate (p = .92). Ultrastructural imaging yielded a morphological basis for the various mechanical properties found intraorally; the attached gingiva showed unidirectional collagen fibre network whereas the buccal mucosa and hard palate showed multi-directional network, which was more prone to tension failure and less elasticity. This is the first study assessing the various morphological-mechanical relationships of intraoral soft tissues, utilising Thiel-embalmed tissues. The findings of this study suggest that the tissues from different intraoral regions showed various morphological-mechanical behaviour which was also confirmed under the SEM and in the histological analysis.


Evaluation and comparison of silorane resin composite to glass ionomer in occluso-proximal restorations of primary molars: A randomized controlled trial.
In general, proximal restorations of primary molars fracture, so it is vital to study the new materials that could solve this problem. Hence, the present trial assessed the success of occluso-proximal atraumatic restorative treatment (ART) restorations using silorane and glass ionomer cement (GIC) in carious primary molars for a period of 2 years. One hundred and ninety-two children between the age group of 4 and 9 years were randomly allocated to GIC or silorane. In the clinical set up, they were treated by a pediatric dentist, and their restorations were evaluated at 3, 6, 12, 18, and 24 months. The primary outcome was the survival of restoration, which was analyzed using the Kaplan-Meier and superior Cox regression models. As a sensitivity analysis, intention-to-treat (ITT) was executed. Sex, age, molar, jaw, cavity volume, and caries incidence were the independent variables. The restoration survival after 24 months for GIC and silorane was 82.75% and 88.88%, respectively, whereas ITT analysis showed a success of 84.37% and 89.58% for GIC and silorane, respectively. With regard to longevity, there was no statistically significant difference between silorane and GIC in primary molar occlusoproximal ART restorations.


Polycystin-1 affects cancer cell behaviour and interacts with mTOR and Jak signalling pathways in cancer cell lines.
Polycystic Kidney Disease (PKD), which is attributable to mutations in the PKD1 and PKD2 genes encoding polycystin-1 (PC1) and polycystin-2 (PC2) respectively, shares common cellular defects with cancer, such as uncontrolled cell proliferation, abnormal differentiation and increased apoptosis. Interestingly, PC1 regulates many signalling pathways including Jak/STAT, mTOR, Wnt, AP-1 and calcineurin-NFAT which are also used by cancer cells for sending signals that will allow them to acquire and maintain malignant phenotypes. Nevertheless, the molecular relationship between polycystins and cancer is unknown. In this study, we investigated the role of PC1 in cancer biology using glioblastoma (GOS3), prostate (PC3), breast (MCF7), lung (A549) and colorectal (HT29) cancer cell lines. Our in vitro results propose that PC1 promotes cell migration in GOS3 cells and suppresses cell migration in A549 cells. In addition, PC1 enhances cell proliferation in GOS3 cells but inhibits it in MCF7, A549 and HT29 cells. We also found that PC1 up-regulates mTOR signalling and down-regulates Jak signalling in GOS3 cells, while it up-regulates mTOR signalling in PC3 and HT29 cells. Together, our study suggests that PC1 modulates cell proliferation and migration and interacts with mTOR and Jak signalling pathways in different cancer cell lines. Understanding the molecular details of how polycystins are associated with cancer may lead to the identification of new players in this devastating disease.


A systematic review of quantitative research on traumatic brain injury in India.
Over a quarter of the world's trauma deaths occur in India, with traumatic brain injury (TBI) as the leading cause of death and disability within trauma. With little known about TBI in India, we set out to do a systematic review to characterize the quantitative literature on TBI in India. The following databases were searched from their inception to December 31, 2015: PubMed, Cochrane, Web of Science, and the World Health Organization's Global Health Library, using the keywords: neurotrauma, brain injury, traumatic brain injury, TBI, head injury, and India. Articles were screened by two independent reviewers, with disagreements arbitrated by discussion or a third reviewer. A total of 72 manuscripts were included, encapsulating 19962 patients over 27 years in 14 states of India. The sample-size-weighted mean age was 31.3 years, male-to-female ratio was 3.8:1, and sample-size-weighted mean in-hospital mortality was 24.6%. Age and mortality did not change significantly over time. Road traffic accidents (55.5%) and falls (29.2%) were the most commonly reported mechanisms of injury for TBI in India. The mean quality of reporting on TBI in India was 65.7%, according to the appropriate EQUATOR guideline score. The quality of reporting of quantitative studies published on TBI in India is low, and future methodological excellence should be ensured. The demographics and outcomes identified can be used as an epidemiological baseline for future research on TBI in India. Future research can build upon this platform to develop and refine context-appropriate policy recommendations and treatment protocols.


Limited proteolysis of rat brain tyrosine hydroxylase defines an N-terminal region required for regulation of cofactor binding and directing substrate specificity.
Trypsin proteolysis of tyrosine hydroxylase (TH) produces a 34-kDa fragment that is catalytically active but does not contain the regulatory phosphorylation sites. In this report, activation of TH by proteolysis was characterized further. Proteolysis results in a decrease in Kms for both substrate and cofactor. The increase in affinity for cofactor was identical to that produced by phosphorylation with cAMP-dependent protein kinase. Additionally, proteolysis of an N-terminal region containing the regulatory phosphorylation sites was sufficient to produce a decrease in Km for cofactor. Activation of substrate binding required more extensive proteolysis but also corresponded to N-terminal digestion. Moreover, this activation was coincident with a broadened substrate specificity. In combination, these data indicate that the N-terminus of tyrosine hydroxylase regulates cofactor binding and directs substrate specificity.


A density-based cellular automaton model for studying the clustering of noninvasive cells.
We investigated whether cluster formation by noninvasive cells can be explained by a global attractive potential. Indices quantifying the persistence of migration in experimental conditions were compared to the same indexes computed from simulations with a density-based cellular automaton. The results indicate that the attractive potential hypothesis must be rejected.


Development of a multilayered in vitro model for studying events associated with wound healing.
Simplified in vitro models such as cellular monolayer cultures have only limited usefulness in the study of cutaneous wound repair processes. This has stimulated the investigation of three-dimensional tissue equivalent systems such as the dermal and skin equivalent models. With the use of a wound system constructed of rat tail type I collagen and human dermal fibroblasts, experimental wounding was accompanied by problems with mechanical scoring of the plastic substratum which prevented cell migration. These problems were overcome with the use of a multilayered model in which a punch biopsy-wounded dermal equivalent (bilayered model) or skin equivalent (tri-layered model) was placed onto an acellular collagen lattice and fixed in place with polymerizing collagen. This model permitted observation of the process of cellular repopulation of the "wound space," into which both fibroblast and keratinocyte migration commenced within 1 day. The number of fibroblasts in this space increased dramatically over a period of 9 days, the cells appearing to migrate both over and through the acellular lower collagen layer. Keratinocyte reepithelialization of the "wound space" was completed after 5 days. With the model it was shown that platelet-derived growth factor--AB and epidermal growth factor had positive effects in increasing fibroblast number within the wound space. In conclusion, the model described here should facilitate the study of fibroblast and keratinocyte responses to a wound stimulus in vitro and be a plausible in vitro system for evaluating agents which may have a potential stimulatory or inhibitory effect on numerous cellular responses associated with wound healing.


Abdominal muscle training can enhance cough after spinal cord injury.
Respiratory complications in people with high-level spinal cord injury (SCI) are a major cause of morbidity and mortality, particularly because of a reduced ability to cough as a result of abdominal muscle paralysis. . We investigated the effect of cough training combined with functional electrical stimulation (FES) over the abdominal muscles for 6 weeks to observe whether training could improve cough strength. Fifteen SCI subjects (C4-T5) trained for 6 weeks, 5 days per week (5 sets of 10 coughs per day) in a randomized crossover design study. Subjects coughed voluntarily at the same time as a train of electrical stimulation was delivered over the abdominal muscles via posterolaterally positioned electrodes (50 Hz, 3 seconds). Measurements were made of esophageal (Pes) and gastric (Pga) expiratory pressures and the peak expiratory flow (PEFcough) produced at the 3 time points of before, during, and after the training. During voluntary coughs, FES cough stimulation improved Pga, Pes, and PEFcough acutely, 20-fold, 4-fold, and 50%, respectively. Six weeks of cough training significantly increased Pga (37.1 ± 2.0 to 46.5 ± 2.9 cm H2O), Pes (35.4 ± 2.7 to 48.1 ± 2.9 cm H2O), and PEFcough (3.1 ± 0.1 to 3.6 ± 0.1 L/s). Cough training also improved pressures and flow during voluntary unstimulated coughs. FES of abdominal muscles acutely increases mechanical output in coughing in high-level SCI subjects. Six weeks of cough training further increases gastric and esophageal cough pressures and expiratory cough flow during stimulated cough maneuvers.


Maternal Transfer and Apical and Physiological Effects of Dietary Hexabromocyclododecane Exposure in Parental Fathead Minnows (Pimephales promelas).
Hexabromocyclododecane (HBCD) is a persistent organic pollutant that has been characterized as an endocrine disruptor, undergoes maternal transfer, and hinders development and growth in oviparous organisms. The present study examined the apical effects of dietary HBCD (11.5, 36.4, 106 mg/kg, wet wt) on adult fathead minnow exposed for 49 days and the subsequent accumulation and maternal transfer kinetics in adult tissue and eggs, respectively. Exposed adults displayed a significant increase in egg production in the medium treatment group, but no other significant effects were noted. Maternal transfer of dietary HBCD had a similar egg-to-muscle ratios (EMR) in the low and medium treatment groups (1.65 and 1.27 [wet wt], respectively). However, the high treatment group deviated from other treatments with an EMR of 4.2 (wet wt), potentially due to differences in total lipid content in food and/or reaching diffusion/lipid saturation limits in adult tissue, resulting in lower accumulation in the adult muscle tissue. A positive correlation was observed between egg HBCD concentration and time of exposure, which indicates that maternal transfer of HBCD is of concern in fish, and further studies should be conducted to fully elucidate the potential adverse effects that may be observed in the early life stage of oviparous organisms. Environ Toxicol Chem 2023;42:143-153. © 2022 SETAC.


Mesenchymal properties of SJL mice-stem cells and their efficacy as autologous therapy in a relapsing-remitting multiple sclerosis model.
Mesenchymal stem cells (MSCs) are a multipotent population of adult stem cells, which may represent a promising therapeutic approach for neurological autoimmune diseases such as multiple sclerosis. The mouse is the most used species for obtaining and studying the characteristics of MSC and their potential as autologous transplants in pre-clinical models. However, conflicting data have been published disclosing intraspecies variations. The choice of the mouse strain and the tissue source appear, among others, as important factors in the experimental application of MSCs. Adipose tissue-derived MSCs obtained from the SJL/JCrl mouse strain (SJL-AdMSC) have been cultured for a long time (from passage 0 up to 15) under controlled experimental conditions, and their growth rate, morphology, stromal and haematopoietic marker expression profiles and differentiation capacity towards adipocytes, osteocytes and chondrocytes have been determined. Moreover, their preclinical efficacy has been assessed by autologous transplant in relapsing-remitting experimental autoimmune encephalomielitis (RR-EAE)-induced SJL mice (a well established mice model for the study of RR-multiple sclerosis). We demonstrate that SJL-AdMSCs show the same fibroblastic shape, growth rate, profile of markers expression and multipotency described for MSCs in every passage evaluated (up to passage 15). Additionally, SJL-AdMSCs ameliorate the RR-EAE course, suggesting that they could modulate disease progression. Moreover, their features studied are fully comparable with the standardized Ad-MSCs obtained from the C57BL/6 mouse strain, which strengthens their use in cell therapy. SJL-AdMSCs might be a suitable source of Ad-MSCs for studies related to the properties of MSCs and their application as promising therapeutic tools in autologous transplants in experimental medicine.


Lactate dehydrogenase activity in laryngeal carcinoma and surrounding mucosa.
The total lactate dehydrogenase (LDH) activity and LDH isoenzyme pattern were measured in tissue taken from laryngeal cancers and from the laryngeal mucosa both close to and distant from the tumour margin. An increase in the total LDH activity and a cathodic shift in the isoenzyme pattern were found in tumour tissue compared to the close and distant mucosa. However, significant LDH alterations in the mucosa close to the tumour were shown in comparison to the distant mucosa and to the laryngeal mucosa of controls. Histochemical studies showed the LDH activity to be located in the basal and parabasal layers of the epithelium and in the cancer foci.


Classifying Types of Visual Loss Linked With Function to Inform Referral to Vision Rehabilitation for Older Adults in Singapore.
Objective: Visual impairment restricts performance in activities of daily living. The aim of this study was to classify types of visual loss associated with function in older adults based on clinical data and World Health Organization (WHO) acuity and visual field criteria. Methods: Seven hundred retrospective medical records of older adults seen at the outpatient ophthalmology clinics of a Singapore hospital were reviewed. Extracted data was mapped to the WHO low vision criteria. A flow chart was developed to classify the main types of visual loss aligned with function. Results: The flow chart developed describes four major types of visual loss: (1) full visual field with decreased visual acuity, (2) any visual field loss with greater than ten degrees of available field, (3) peripheral field loss with less than 10° of available field, and (4) any visual field loss due to a cortical event. Within each major type, sub-categories were identified reflecting the complexity of the visual impact of the eye conditions. Conclusion: The flow chart can be applied to outpatient records to identify older adults with different types of visual loss to inform targeted rehabilitation linked with function.


Comparative effectiveness of dual antiplatelet therapy versus monotherapy in patients with ischemic stroke.
To compare the effectiveness of aspirin-clopidogrel dual antiplatelet therapy (DAPT) with aspirin or clopidogrel antiplatelet monotherapy (AM) in patients with ischemic stroke. It was a single-center, retrospective cross-sectional study of medical records of ischemic stroke patients admitted at King Abdulaziz University Hospital between January 2015 and October 2019. The primary endpoints were ischemic stroke recurrence, rehospitalization, and all-cause mortality between DAPT and AM. Kaplan-Meier and Cox proportional hazard analyses were employed in univariate and multivariate time-to-event analyses. The median time to recurrence of ischemic stroke was 15.0 months (95% confidence interval [CI], 8.586-23.01) for DAPT and 20.4 months (95% CI, 9.872-30.928) for the AM. The median survival time until all-cause mortality was 8.0 months (95% CI, 2.893-13.107) for DAPT and 14.1 months (95% CI, 8.173-19.97) for the AM. No statistically significant reductions in the instantaneous risks of recurrence (hazard ratio [HR], 1.27; 95% CI, 0.59-2.72; p=0.54), re-hospitalization (HR, 0.95; 95% CI, 0.59-1.48; p= 0.77), and mortality (HR, 1.04; 95% CI, 0.48-2.26; p=0.92) were found between the DAPT and AM groups. The DAPT was not superior to AM in reducing recurrence and mortality events in patients with ischemic stroke. Rehospitalization due to the sequelae of the composite of stroke, angina, and myocardial infarction was higher in the DAPT group.


Regional bond strengths and failure analysis of fiber posts bonded to root canal dentin.
This study evaluated the regional bond strengths of fiber posts to root canal dentin luted with dual-cure resin composite. Twelve extracted human premolars were decoronated and post spaces prepared to a depth of 8 mm. The root canal dentin was treated with Clearfil SE Bond and light-cured for 20 seconds. Three posts from each of the following four types of fiber posts-Snowlight, FibreKor, DT Light-Post and GC Fiber Post-were surface-treated with a mixture of Porcelain Bond Activator and Photobond, then luted into the post spaces with Clearfil DC Core Automix and light-cured for 60 seconds. After 24-hour water storage, each specimen was serially sliced into eight 0.6 x 0.6 mm-thick beams for the microtensile bond strength (microTBS) test. Failure modes were observed using SEM. The microTBS data were divided into coronal and apical regions and statistically analyzed. The highest bond strengths were obtained from FibreKor posts. Regional factors had no effect on bond strength. FibreKor and DT Light-Post specimens primarily failed at the post-resin composite interface, whereas Snowlight and GC Post cohesively failed within the post.


Edema and brain trauma.
Brain edema leading to an expansion of brain volume has a crucial impact on morbidity and mortality following traumatic brain injury (TBI) as it increases intracranial pressure, impairs cerebral perfusion and oxygenation, and contributes to additional ischemic injuries. Classically, two major types of traumatic brain edema exist: "vasogenic" due to blood-brain barrier (BBB) disruption resulting in extracellular water accumulation and "cytotoxic/cellular" due to sustained intracellular water collection. A third type, "osmotic" brain edema is caused by osmotic imbalances between blood and tissue. Rarely after TBI do we encounter a "hydrocephalic edema/interstitial" brain edema related to an obstruction of cerebrospinal fluid outflow. Following TBI, various mediators are released which enhance vasogenic and/or cytotoxic brain edema. These include glutamate, lactate, H(+), K(+), Ca(2+), nitric oxide, arachidonic acid and its metabolites, free oxygen radicals, histamine, and kinins. Thus, avoiding cerebral anaerobic metabolism and acidosis is beneficial to control lactate and H(+), but no compound inhibiting mediators/mediator channels showed beneficial results in conducted clinical trials, despite successful experimental studies. Hence, anti-edematous therapy in TBI patients is still symptomatic and rather non-specific (e.g. mannitol infusion, controlled hyperventilation). For many years, vasogenic brain edema was accepted as the prevalent edema type following TBI. The development of mechanical TBI models ("weight drop," "fluid percussion injury," and "controlled cortical impact injury") and the use of magnetic resonance imaging, however, revealed that "cytotoxic" edema is of decisive pathophysiological importance following TBI as it develops early and persists while BBB integrity is gradually restored. These findings suggest that cytotoxic and vasogenic brain edema are two entities which can be targeted simultaneously or according to their temporal prevalence.


Epidemiology and outcome of acute kidney injury in children, a single center study.
Information on the epidemiology of Acute Kidney Injury (AKI) in children is scarce. We performed a single center retrospective cohort study to analyze the incidence of AKI, the male/female ratio, the underlying etiology, and age at presentation. We also aimed to assess outcome measured by mortality, duration of PICU stay, and development of Chronic Kidney Disease (CKD). Records were searched for children presenting with or developing AKI between 1st January 2008 and 1st January 2015. AKI was classified according to the pediatric Rifle criteria while the cause of AKI was defined as the major underlying disease. Of the 28,295 children admitted, 167 episodes of AKI were identified, equaling 5.9 cases per 1000 children. Patients classified as Failure at presentation according to pRifle criteria where significantly more likely to need dialysis (27/50, 54%) compared to those presenting with Injury (12/57, 21.1%) or Risk (6/60, 10 %). Diarrhea-associated Hemolytic Uremic Syndrome (D+HUS) was the most frequent cause (20.3 %) peaking during the summer months, followed by cardiac surgery (13.7%), medication-related nephrotoxicity (13.2%), and acute Glomerulonephritis (12%). The median age of children admitted with AKI was 6.1 years (range 0.1-17) and 50.8% of cases were male. Twenty five (15%) children died while 27 (16.1%) developed CKD. Pediatric AKI poses a significant problem and strategies aimed at prevention, early detection, treatment, and adequate follow-up are needed. D+HUS is the most common underlying cause and effective surveillance of Enterohemorrhagic E. coli infections in association with additional measures is highly recommended.


Association of the Elevated Red Blood Cell Distribution Width with the Risk of Developing Diabetes Mellitus.
Objective The aim of this study was to determine whether elevated levels of RDW-coefficient of variation (CV) are associated with the development of diabetes mellitus (DM) in a population of healthy middle- and old-aged individuals. Method We conducted a retrospective cohort study. A total of 2,688 individuals (aged 49-66 years) without a DM diagnosis, impaired fasting glucose, or anemia at baseline were grouped according to the RDW-CV quartile, and the onset of DM during a 4-year period was recorded for each group. Results The correlation coefficients for the RDW-CV and waist circumference and for the RDW-CV and HbA1c were 0.114 and 0.133, respectively. The relative risks of future DM in RDW-CV quartiles II, III, and IV (high) compared with RDW-CV quartile I (low) were 1.9 [95% confidence interval (CI) 1.0-3.6, p=0.057], 1.6 (95% CI 0.8-3.0, p=0.157), and 2.2 (95% CI 1.2-4.0, p=0.015), respectively. After adjusting for sex, age, waist circumference, hemoglobin A1c, triglycerides, high density lipoprotein-cholesterol (HDL-C), and high-sensitivity C-reactive protein, the multivariate relative risk for the highest vs. the lowest RDW-CV quartile was 1.8 (95% CI, 1.1-3.4, p=0.046). Conclusion These data indicate that an elevated RDW-CV is associated with an increased incidence of DM.


Chronic subdural haematomas: a single-centre experience developing an integrated care pathway.
To improve quality of care for patients presenting with chronic subdural haematoma (CSDH) by introducing a multi-disciplinary integrated care pathway. CSDH is a common neurological condition. Incidence rises with age and currently affects around 58/100 000 people over 70 years. Six-month mortality is high (26%), however integrated care pathways have been shown to improve patient outcomes in other surgical subspecialties. A baseline retrospective audit completed in 2012 identified areas for improvement in patient management. Stakeholder meetings were held with subsequent development and implementation of a patient care pathway. A post-implementation prospective audit was completed between January and October 2015. patient demographics, medical co-morbidities, use of anti-platelet and anti-coagulant medication, timing of surgery, length of hospital stay, morbidity and mortality data, and reaccumulation rate. Patient groups were similar with a high incidence of multi-morbidity. The key areas targeted for improvement included enhanced pre-operative optimisation and time to surgery. Implementation of the patient care pathway significantly increased the number of patients undergoing surgery within 24 hours of admission (43% vs. 75%, p = 0.0006) but length of hospital stay did not change. Operative morbidity and mortality remained similar and there was no significant difference in CSDH reaccumulation rate. Our patient care pathway appears to have improved pre-operative care and significantly increased the proportion of patients undergoing surgery within 24 hours of admission. Difficulties were encountered with changing existing practice. Prospective research is required to demonstrate the full benefits, which may include a reduction in health and social care costs.


[Anesthesia and analgesia in intravenous drug dependent patients with injection abscesses of the upper extremity. Case report].
The morbidity and mortality rate of drug addicts is characteristically higher than in a normal population. Especially abscesses of the hand and the forearm region are frequent consequences of unsterile injection techniques. Pre-, intra-, and postoperative anaesthetic management has to take into consideration that the choice of the anaesthetic procedure should not interfere with the very special conditions of the drug addicts. In our experience, continuous axillary brachial plexus block offers a number of advantages in pain management in drug addicts as well as in former drug addicts.


An infestation of the mite Sancassania berlesei (Acari: Acaridae) in the external auditory canal of a Korean man.
We here report the case of a storage mite, Sancassania berlesei, infestation in the external auditory canal of a 46-yr-old male. He complained of feeling a foreign body and itching in the left external auditory canal for 1 mo, with accompanying otalgia for 3 days. Considering the duration of the patient's complaint and the 8-9-day life cycle of the mite, the mites are believed to have lived in the patient's ear for more than 3 generations.


Delivery of adipose-derived growth factors from heparinized adipose acellular matrix accelerates wound healing.
Dermal white adipocytes are closely associated with skin homeostasis and wound healing. However, it has not been fully investigated whether adipose-derived products improve wound healing. Here, we obtained adipose acellular matrix (AAM) and adipose-derived growth factors (ADGFs) from human adipose tissue and fabricated an ADGF-loaded AAM via surface modification with heparin. The product, HEP-ADGF-AAM, contained an adipose-derived scaffold and released ADGFs in a controlled fashion. To test its efficacy in promoting wound healing, mice with full thickness wound received three different treatments: HEP-ADGF-AAM, AAM and ADM. Control mice received no further treatments. Among these treatments, HEP-ADGF-AAM best improved wound healing. It induced adipogenesis in situ after in vivo implantation and provided an adipogenic microenvironment for wounds by releasing ADGFs. HEP-ADGF-AAM not only induced adipocyte regeneration, but also enhanced fibroblast migration, promoted vessel formation, accelerated wound closure, and enhanced wound epithelialization. Moreover, there was a close interaction between HEP-ADGF-AAM and the wound bed, and collagen was turned over in HEP-ADGF-AAM. These results show that HEP-ADGF-AAM might substantially improve re-epithelialization, angiogenesis, and skin appendage regeneration, and is thus a promising therapeutic biomaterial for skin wound healing.


Capillary electrochromatographic separation of proteins on a column coated with titanium dioxide nanoparticles.
A TiO2 nanoparticle (TiO2 NP)-coated open-tubular column for the capillary electrochromatographic separation of proteins is described. The surface chemistry of the TiO2 NPs on the inner wall of the fused silica was significantly affected by the running buffer. By varying of the phosphate buffer pH, only cathodic EOF was indicated. The results showed that TiO2 NPs are existed as a complexed form with the buffer ligand. Good separation of conalbumin (ConA), apo-transferrin (apoTf), ovalbumin (OVA), and BSA could be achieved with phosphate buffer (40 mM, pH 8.0) and an applied voltage of 15 kV. Five peaks of glycoisoforms of OVA were observed under these conditions. In comparison with the retention behavior of the analytes on the bare fused-silica column, the new column's high resolving power seems to be predominantly derived from the ligand exchange of the analytes with the phosphate adsorbed onto the TiO2 NPs. The method was also used to separate egg-white proteins. Both acidic and basic proteins in egg white were separated in a single run. The microheterogeneities of OVA could also be found in it. The separation efficiency for the main peak of OVA in egg white was around 10,000 plates/m.