EMG indications and findings in a sub-Saharan African neurorehabilitation center.
This study aims to assess the frequency and indication for electrodiagnostic referrals as well as to summarize the findings from the procedure at a neurorehabilitation center in Ibadan, Nigeria. This is a retrospective cross-sectional study. Data from referrals to Blossom Medical Centre/World Federation for Neurorehabilitation (BMC/WFNR) center, Ibadan, Nigeria, from April 2014 to December 2016 were collated and analyzed. Sixty referrals were received during the period of evaluation. Neurologists referred most of the patients (47; 71.7%). Disorders of the peripheral nerves were the most frequent reasons for electromyography (EMG), and they were the most common electrodiagnosis with better classified into axonal and demyelinating types. The overall congruence between the suspected diagnosis and final diagnosis was 58.3%. Requests by neurologists were significantly more appropriate than those by other specialists (p value = 0.02). Polyneuropathy, entrapment neuropathy, and disorders of the motor nerve root and plexus were the most common reasons for electrodiagnostic requests, and the majority of the referrals were from neurologists. EMG has changed the approach towards the diagnosis and management of neuromuscular disorders in Nigeria. It is hoped that with more neurophysiology education in this environment, neurophysiological practice will become widely available.


[Mapping of lichen frequencies as a tool in evaluating intensity of pollution].
With the hitherto existing methods of mapping lichen distribution usually only a qualitative record of only relatively great differences in the intensity of pollution is possible. By the following method of evaluating the frequency of the lichen species on individual trunks even very small differences in intensity of pollution can be detected, and quantitative gradation is possible. The lichens growing on the trunks of isolated trees in the surroundings of factories or other pollutants have been investigated. A "ladder" enclosing ten panels is used to determine the frequency: the calculation is made electronically and permits statistical statements about the quantity of the lichens to be made. The numerical material evaluated consists of reproduceable data obtained by a standardized method that appears to be suitable for routine use.As an example the occurrence of some lichen species in the surroundings of a potassium chloride mine is shown. Zones can be recognized by changes in frequency of the variously sensitive species. The following species show increasing sensitivity to the pollution under consideration: Parmelia sulcata, Parmelia dubia, Hypogymnia physodes, Evernia prunastri, Pseudevernia furfuracea.


Overexpression of vascular endothelin-1 and endothelin-A receptors in a fructose-induced hypertensive rat model.
To examine the temporal relationship between hyperinsulinemia and hypertension in the fructose-hypertensive rat model and to study the function of endothelin-1 (ET-1) in fructose-induced hypertension. Since ET-1 induces insulin resistance in conscious rats, we tested the hypothesis that both hyperinsulinemia and hypertension developed in the fructose-hypertensive rat model might be the sequelae of an elevated tissue content of ET-1 and ET(A) receptors. Systolic hypertension was induced within 3 weeks in male Sprague-Dawley rats fed on a fructose-rich diet. After continual monitoring of blood pressure and plasma insulin concentrations, the animals were killed at the end of experiment to determine plasma levels of ET-1, the contractile response of aortic rings to ET-1, and ET-1 and ET(A) receptor gene expressions. In a separate experiment, BQ-610 was administered to lower the effect of ET-1 in rats with fructose-induced hypertension. Compared with control rats given normal chow, the fructose-fed rats developed systolic hypertension after 3 weeks of the diet (127+/-3.7 versus 110+/-5.5 mmHg, P < 0.01) and hyperinsulinemia both before (1 07.1+/-32.5 versus 48.5+/-14.3 pmol/l, P < 0.005) and after (96.6+/-63.7 versus 50.4+/-5.6 pmol/l, P< 0.05) they became hypertensive. Although plasma ET-1 levels did not differ between the rat groups, aortic ring contraction-concentration curves, indicating vessel contractility in response to ET-1, were significantly greater in these rats than in controls (F1,72 = 12.34, P< 0.00077). Messenger RNA extracted from the tail arteries and blotted with both ET-1 and ET(A) probes showed that fructose-fed rats had greater ET-1 and ET(A)-receptor gene expression than control rats. Concomitant administration of BQ-610 to rats fed on a fructose diet significantly reduced the hypertension. Conclusions These findings suggest that elevated vascular expression of ET-1 and ET(A) receptor genes may mediate the development of hypertension and hyperinsulinemia in rats fed a fructose-rich diet


Axonal transport of receptors: coexistence with neurotransmitter and recycling.
Receptor sites move along the axon of neurones by means of fast transport mechanisms. In rat sciatic nerves, the accumulation of muscarinic receptors above a ligature was linear up to 24 hr after the operation and exactly paralleled that of dopamine-beta-hydroxylase. After 6-hydroxydopamine treatment, there was a marked reduction of these receptor sites in the rat sciatic nerve and the spleen. Fractionation of dog splenic nerves by differential and isopycnic centrifugation enabled us to show that the muscarinic receptors in sympathetic nerves are associated with noradrenaline and dopamine-beta-hydroxylase in synaptic vesicles. Receptor and neurotransmitter may thus coexist in the same subcellular organelle. Opiate receptors measured in vitro and in vivo with 3H-lofentanil in the rat vagus nerve were found to accumulate on both sides of the ligature. After capsaicin treatment this accumulation was markedly reduced suggesting that the opiate receptors in the vagus are mainly associated with substance P neurones. Double ligature experiments suggest the existence of a recycling phenomenon in the perikaryon for vesicles containing muscarinic receptors and dopamine-beta-hydroxylase. This may represent a pathway to convey informational molecules from the extracellular to the intracellular compartment of a neurone.


Effects of haloperidol and SCH 23390 on acoustic startle and prepulse inhibition under basal and stimulated conditions.
1. Adult Sprague-Dawley rats underwent startle testing for assessment of baseline startle amplitude and prepulse inhibition (PPI) of the startle reflex. 2. Animals were tested after administration of either: saline, a selective D1 dopamine (DA) receptor antagonist, a relatively selective D2 DA antagonist, or combined low dose D1 and D2 antagonists. 3. Changes due to antagonists were assessed with and without administration of the D1/D2 agonist apomorphine. 4. Testing without apomorphine stimulation showed that both D1 and D2 antagonists reduce baseline startle and enhance PPI. Further, the two antagonists exhibited a synergistic interaction. 5. Testing with apomorphine showed that D1 and D2 antagonists reduce apomorphine-induced startle enhancement. Again, the two exhibited a synergistic interaction. 6. For PPI, the D2 but not D1 antagonist reduced the apomorphine effect. However, the D1 antagonist potentiated the effect of the D2 antagonist.


Size and growth characteristics of dispersing voles, Microtus townsendii.
In a peak population of Microtus townsendii, adults and subadults dispersed during the spring decline, and subadults and juveniles dispersed during the summer and fall. Voles born in the spring dispersed before the start of the next year's breeding season, whereas fall-born voles dispersed during the next year's breeding season. Voles under 50 g, when they dispersed, had faster growth rates than similar-sized residents, but voles over 59 g, when they dispersed, had slower growth rates than similar-sized residents. Dispersing and resident voles 50-59 g had no consistent trend in growth rates.


Retinal pigment epithelium lesions as a biomarker of disease in patients with familial adenomatous polyposis. A follow-up report.
The sensitivity of retinal pigment epithelium (RPE) lesions as a predictive congenital marker for the development of familial adenomatous polyposis (FAP) is evaluated. In a prospective study, 34 patients at 50% risk of inheriting FAP were examined. Based on the presence or absence of four or more RPE lesions, patients were categorized as those who had inherited or those who lacked the FAP genes. All patients received dilated fundus examinations with binocular indirect ophthalmoscopy and all RPE lesions were documented with fundus photography. All patients underwent annual sigmoidoscopy to determine the presence or absence of polyps. A 3-year follow-up analysis showed that 8 of 14 patients who were positive for RPE lesions later developed polyps. Of the 20 patients considered negative for FAP based on normal fundus examination, none has developed polyps. The authors urge all patient at risk of inheriting FAP to undergo dilated fundus examination with binocular indirect ophthalmoscopy and wide-angle fundus photography at the earliest age possible. All patients with 4 or more RPE lesions should undergo annual sigmoidoscopic examinations beginning before 10 years of age.


Propagation of Homeostatic Sleep Signals by Segregated Synaptic Microcircuits of the Drosophila Mushroom Body.
The Drosophila mushroom body (MB) is a key associative memory center that has also been implicated in the control of sleep. However, the identity of MB neurons underlying homeostatic sleep regulation, as well as the types of sleep signals generated by specific classes of MB neurons, has remained poorly understood. We recently identified two MB output neuron (MBON) classes whose axons convey sleep control signals from the MB to converge in the same downstream target region: a cholinergic sleep-promoting MBON class and a glutamatergic wake-promoting MBON class. Here, we deploy a combination of neurogenetic, behavioral, and physiological approaches to identify and mechanistically dissect sleep-controlling circuits of the MB. Our studies reveal the existence of two segregated excitatory synaptic microcircuits that propagate homeostatic sleep information from different populations of intrinsic MB "Kenyon cells" (KCs) to specific sleep-regulating MBONs: sleep-promoting KCs increase sleep by preferentially activating the cholinergic MBONs, while wake-promoting KCs decrease sleep by preferentially activating the glutamatergic MBONs. Importantly, activity of the sleep-promoting MB microcircuit is increased by sleep deprivation and is necessary for homeostatic rebound sleep (i.e., the increased sleep that occurs after, and in compensation for, sleep lost during deprivation). These studies reveal for the first time specific functional connections between subsets of KCs and particular MBONs and establish the identity of synaptic microcircuits underlying transmission of homeostatic sleep signals in the MB.


Reactive oxygen species produced by myeloid cells in psoriasis as a potential biofactor contributing to the development of vascular inflammation.
Psoriasis is an immune-mediated inflammatory skin disease driven by interleukin-17A (IL-17A) and associated with cardiovascular dysfunction. We used a severe psoriasis mouse model of keratinocyte IL-17A overexpression (K14-IL-17Aind/+ , IL-17Aind/+ control mice) to investigate the activity of neutrophils and a potential cellular interconnection between skin and vasculature. Levels of dermal reactive oxygen species (ROS) and their release by neutrophils were measured by lucigenin-/luminol-based assays, respectively. Quantitative RT-PCR determined neutrophilic activity and inflammation-related markers in skin and aorta. To track skin-derived immune cells, we used PhAM-K14-IL-17Aind/+ mice allowing us to mark all cells in the skin by photoconversion of a fluorescent protein to analyze their migration into spleen, aorta, and lymph nodes by flow cytometry. Compared to controls, K14-IL-17Aind/+ mice exhibited elevated ROS levels in the skin and a higher neutrophilic oxidative burst accompanied by the upregulation of several activation markers. In line with these results psoriatic mice displayed elevated expression of genes involved in neutrophil migration (e.g., Cxcl2 and S100a9) in skin and aorta. However, no direct immune cell migration from the psoriatic skin into the aortic vessel wall was observed. Neutrophils of psoriatic mice showed an activated phenotype, but no direct cellular migration from the skin to the vasculature was observed. This suggests that highly active vasculature-invading neutrophils must originate directly from the bone marrow. Hence, the skin-vasculature crosstalk in psoriasis is most likely based on the systemic effects of the autoimmune skin disease, emphasizing the importance of a systemic therapeutic approach for psoriasis patients.


Increased birth prevalence of isolated hypospadias in Hungary.
The birth prevalence of simple (isolated) hypospadias increased significantly in Hungary up to 1978. Since then, although fluctuating, it has remained at this higher level.


Yttrium Oxide Nanoparticles Attenuate L-Arginine Induced Chronic Pancreatitis.
In this work, we tested the efficacy of yttrium oxide nanoparticles (NY), a promising antioxidant and anti-inflammatory agent, in L-arginine (L-Arg) induced chronic pancreatitis (CP) model. The nanoparticles were characterized using multiple techniques including transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (pXRD), and Energy dispersive X-ray analysis (EDX). The rats were divided into three groups: normal control, L-Arg control, L-Arg + NY (1 mg/kg). We probed the mechanistic effects of the NY by ELISA, multiplex analysis of TGF-β pathway and inflammatory cytokines and immunoblotting. NY treatment significantly reduced pancreatic oxidative-nitrosative stress. In addition, NY intervention also reduced inflammatory cytokines and chemokines resulting in the inhibition of fibrosis signaling. Further, NY treatment suppressed the TGF-β signaling and epithelial-mesenchymal transition (EMT). We conclude that NY shows potential antioxidant, anti-inflammatory, and anti-fibrotic effects against CP and associated fibrosis.


Antioxidant effects of ginkgolides and bilobalide against cerebral ischemia injury by activating the Akt/Nrf2 pathway in vitro and in vivo.
Ginkgolide terpenoid lactones, including ginkgolides and bilobalide, are two crucial bioactive constituents of extract of Ginkgo biloba (EGb) which was used in the treatment of cardiovascular and cerebrovascular diseases. The aims of this study were to investigate the antioxidant effects and mechanism of ginkgolides (ginkgolide A (GA), ginkgolide B (GB), ginkgolide K (GK)) and bilobalide (BB) against oxidative stress induced by transient focal cerebral ischemia. In vitro, SH-SY5Y cells were exposed to oxygen-glucose deprivation (OGD) for 4 h followed by reoxygenation with ginkgolides and BB treatments for 6 h, and then cell viability, superoxide dismutase (SOD), and ROS were respectively detected using kit. Western blot was used to confirm the protein levels of hemeoxygenase-1 (HO-1), quinone oxidoreductase l (Nqo1), Akt, phosphorylated Akt (p-Akt), nuclear factor-E2-related factor2 (Nrf2), and phosphorylated Nrf2 (p-Nrf2). GB combined with different concentrations of LY294002 (PI3K inhibitor) were administrated to SH-SY5Y cells for 1 h after OGD, and then p-Akt and p-Nrf2 levels were detected by western blot. In vivo, 2 h of middle cerebral artery occlusion (MCAO) model was established, followed with reperfusion and GB treatments for 24 and 72 h. The infarct volume ratios were confirmed by TTC staining. The protein levels of HO-1, Nqo1, SOD1, Akt, p-Akt, Nrf2, and p-Nrf2 were detected using western blot and immunohistochemistry (IHC). Experimental data in vitro confirm that GA, GB, GK, and BB resulted in significant decrease of ROS and increase of SOD activities and protein levels of HO-1 and Nqo1; however, GB group had a significant advantage in comparison with the GA and GK groups. Moreover, after ginkgolides and BB treatments, p-Akt and p-Nrf2 were significantly upregulated, which could be inhibited by LY294002 in a dose-dependent manner, meanwhile, GB exhibited more effective than GA and GK. In vivo, TTC staining indicated that the infarct volume ratios in MCAO rats were dramatically decreased by GB in a dose-dependent manner. Furthermore, GB significantly upregulated the protein levels of HO-1, Nqo1, SOD, p-Akt, p-Nrf2, and Nrf2. In conclusion, GA, GB, GK, and BB significantly inhibited oxidative stress damage caused by cerebral ischemia reperfusion. Compared with GA, GK, and BB, GB exerts the strongest antioxidant stress effects against ischemic stroke. Moreover, ginkgolides and BB upregulated the levels of antioxidant proteins through mediating the Akt/Nrf2 signaling pathway to protect neurons from oxidative stress injury.


A randomised phase 2 study comparing different dose approaches of induction treatment of regorafenib in previously treated metastatic colorectal cancer patients (REARRANGE trial).
The purpose of this article is to evaluate the safety of two regorafenib dose-escalation approaches in refractory metastatic colorectal cancer (mCRC) patients. Patients with mCRC and progression during or within 3 months following their last standard chemotherapy regimen were randomised to receive the approved dose of regorafenib of 160 mg QD (arm A) or 120 mg QD (arm B) administered as 3 weeks of treatment followed by 1 week off, or 160 mg QD 1 week on/1 week off (arm C). The primary end-point was the percentage of patients with G3/G4 treatment-related adverse events (AEs) in each arm. There were 299 patients randomly assigned to arm A (n = 101), arm B (n = 99), or arm C (n = 99); 297 initiated treatments (arm A n = 100, arm B n = 98, arm C n = 99: population for safety analyses). G3/4 treatment-related AEs occurred in 60%, 55%, and 54% of patients in arms A, B, and C, respectively. The most common G3/4 AEs were hypertension (19, 12, and 20 patients), fatigue (20, 14, and 15 patients), hypokalemia (11, 7, and 10 patients), and hand-foot skin reaction (8, 7, and 3 patients). Median overall survival was 7.4 (IQR 4.0-13.7) months in arm A, 8.6 (IQR 3.8-13.4) in arm B, and 7.1 (IQR 4.4-12.4) in arm C. The alternative regorafenib dosing schedules were feasible and safe in patients with mCRC who had been previously treated with standard therapy. There was a higher numerical improvement on the most clinically relevant AEs in the intermittent dosing arm, particularly during the relevant first two cycles. NCT02835924.


High-glucose-induced miR-214-3p inhibits BMSCs osteogenic differentiation in type 1 diabetes mellitus.
Type 1 diabetes mellitus (T1DM) is an autoimmune insulin-dependent disease associated with destructive bone homeostasis. Accumulating evidence has proven that miRNAs are widely involved in the regulation of bone homeostasis. However, whether miRNAs also regulate osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in T1DM mice is under exploration. In this study, miRNA microarray was utilized to screen the differentially expressed miRNAs, which uncovered that miR-214-3p potentially inhibited BMSCs osteogenic differentiation in T1DM mice. We found that high glucose suppressed BMSCs osteogenic differentiation with significant elevation of the miR-214-3p expression. Further study found that the osteogenic differentiation of BMSCs was inhibited by AgomiR-214-3p while enhanced by AntagomiR-214-3p in BMSCs supplemented with high glucose. Moreover, we found that miR-214-3p knockout T1DM mice were resistant to high-glucose-induced bone loss. These results provide a novel insight into an inhibitory role of high-glucose-induced miR-214-3p in BMSCs osteogenic differentiation both in vitro and in vivo. Molecular studies revealed that miR-214-3p inhibits BMSCs osteogenic differentiation by targeting the 3'-UTR of β-catenin, which was further corroborated in human bone specimens and BMSCs of T1DM patients. Taken together, our study discovered that miR-214-3p is a pivotal regulator of BMSCs osteogenic differentiation in T1DM mice. Our findings also suggest that miR-214-3p could be a potential target in the treatment of bone disorders in patients with T1DM.


Iron sensing and regulation in Saccharomyces cerevisiae: Ironing out the mechanistic details.
Regulation of iron metabolism in Saccharomyces cerevisiae is achieved at the transcriptional level by low (Aft1 and Aft2) and high iron-sensing (Yap5) transcription factors, and at the post-transcriptional level by mRNA-binding proteins (Cth1 and Cth2). In this review we highlight recent studies unveiling the critical role that iron-sulfur clusters play in control of Aft1/2 and Yap5 activity, as well as the complex relationship between iron homeostasis and thiol redox metabolism. In addition, new insights into the localization and regulation of Cth1/Cth2 have added another layer of complexity to the cell's adaptation to iron deficiency. Finally, biophysical studies on subcellular iron speciation changes in response to environmental and genetic factors have further illuminated the elaborate control mechanisms required to manage iron bioavailability in the cell.


Heterologous Prime Boost Vaccination Induces Protective Melanoma-Specific CD8+ T Cell Responses.
Cancer vaccination aims at inducing an adaptive immune response against tumor-derived antigens. In this study, we utilize recombinant human adenovirus serotype 5 (rAd5) and recombinant lymphocytic choriomeningitis virus (rLCMV)-based vectors expressing the melanocyte differentiation antigen gp100. In contrast to single or homologous vaccination, a heterologous prime boost vaccination starting with a rAd5-gp100 prime immunization followed by a rLCMV-gp100 boost injection induces a high magnitude of polyfunctional gp100-specific CD8+ T cells. Our data indicate that an optimal T cell induction is dependent on the order and interval of the vaccinations. A prophylactic prime boost vaccination with rAd5- and rLCMV-gp100 protects mice from a B16.F10 melanoma challenge. In the therapeutic setting, combination of the vaccination with low-dose cyclophosphamide showed a synergistic effect and significantly delayed tumor growth. Our findings suggest that heterologous viral vector prime boost immunizations can mediate tumor control in a mouse melanoma model.


Conflict resolution patterns and longevity of adolescent romantic couples: a 2-year follow-up study.
This study examined the predictors of longevity among 40 late adolescent romantic couples (mean age males=17.71 years; mean age females=17.18 years). Subjects were given a revealed differences task where they were asked to solve their disagreements. The joint task was recorded, transcribed and analysed by two raters. At 3, 6, 9, 12, 18, and 24 months after this procedure, partners were contacted by telephone and asked whether their relationship was still intact. A cluster analysis was performed on couples' interaction indices and yielded three distinctive conflict resolution patterns. The Downplaying pattern was characterized by a high tendency to minimize the conflict. The relationships of the adolescents displaying this pattern stayed intact for a period of 9 months. Half of them were still together after 24 months. The adolescents displaying the Integrative pattern, which shows a good ability to negotiate differences tended to stay together over a period of 24 months. Those showing the Conflictive pattern, characterized by a confrontative interaction, were separated by the 3 months follow-up. Results are discussed within the context of developmental perspectives of conflict resolution tendencies and adolescent romance.


Telomerase as a universal tumor-associated antigen for cancer immunotherapy.
Although the search for pharmacologic inhibitors of telomerase activity represents a promising approach for telomerase-based anti-cancer therapy, the immunological properties of the telomerase reverse transcriptase hTERT suggest that the enzyme is also an attractive target for novel immunotherapies against cancer. Data from both human and murine systems demonstrate that cytotoxic T-lymphocytes (CTL) can recognize peptides derived from TERT and kill TERT-positive tumor cells of multiple histologies. Given the vast overexpression of hTERT in human tumors and its low-level expression in rare normal tissues, clinical trials have begun that test the credentials of hTERT as a broadly applicable target for immunotherapy of cancer.


What about the other kidney?
Sophisticated diagnostic techniques have made the isolation of renal lesions more accurate. However, it must be remembered that simultaneous bilateral kidney pathology can exist in any patient. The most obvious lesion may not be the most important. Four cases are presented to illustrate this point.


Surgical treatment of neuropathic urinary incontinence in 2005. When, what, and how?
We present our current opinions on the surgical treatment of urinary incontinence in children with spina bifida. The age of treatment, preferred treatment modalities and results are discussed. We emphasize the importance of initiating treatment for incontinence at an early age as well as the use of effective surgical techniques.


[Animal experiments on combined local immunization against influenza (author's transl)].
Mice in ether narcosis were immunized 10 times by means of an inhalation spray with Begrivacs S (Behring-Werke) and then infected nasally with the virulent A/PR8 virus 7 to 12 days after the last immunization. A significant protection was achieved as gauged from the mortality rate. Furthermore, mice were nasally immunized with the polyvalent bacterial lysate vaccine IRS 19 (Sarbach, Chatillon) and subsequently infected nasally with the virulent influenza virus. A significant degree of non-specific protection also developed under these conditions, but was less effective than that after specific immunization. The best protective effect can be gained by applying both vaccines (Begrivac S and IRS 19) in combination. In this case, the mortality rate of the test animals decreases from 68% in the control to 31% in the animals receiving combined vaccination.


Overview of renal osteodystrophy in Brazil: a cross-sectional study.
The epidemiologic profile of renal osteodystrophy (ROD) is changing over time and cross-sectional studies provide essential information to improve care and health policies. The Brazilian Registry of Bone Biopsy (REBRABO) is a prospective, nationalmulticenter cohort that includes patients with chronic kidney disease (CKD) undergoing bone biopsy. REBRABO aims to provide clinical information on ROD. The main objective of this subanalysis was to describe the profile of ROD, including clinically relevant associations. From Aug/2015 to Dec/2021, 511 patients with CKD who performed bone biopsy were included in the REBRABO platform. Patients with no bone biopsy report (N = 40), GFR > 90 mL/min (N = 28), without asigned consent (N = 24), bone fragments inadequate for diagnosis (N = 23), bone biopsy indicated by a specialty other than nephrology (N = 6), and < 18 years old (N = 4) were excluded. Clinical-demographic data (e.g., age, sex, ethnicity, CKD etiology, dialysis vintage, comorbidities, symptoms, and complications related to ROD), laboratory (e.g., serum levels of total calcium, phosphate, parathormone, alkaline phosphatase, 25-hydroxyvitamin D, and hemoglobin), and ROD (e.g., histological diagnosis) were analyzed. Data from 386 individuals were considered in this subanalysis of REBRABO. Mean age was 52 (42-60) years; 198 (51%) were male; 315 (82%) were on hemodialysis. Osteitis fibrosa (OF) [163 (42%)], adynamic bone disease (ABD) [96 (25%)] and mixed uremic osteodystrophy (MUO) [83 (21%)] were the most frequent diagnosis of ROD in our sample; 203 (54%) had the diagnosis of osteoporosis, 82 (56%) vascular calcification; 138 (36%) bone aluminum accumulation, and 137 (36%) iron intoxication; patients with high turnover were prone to present a higher frequency of symptoms. A high proportion of patients were diagnosed with OF and ABD, as well as osteoporosis, vascular calcification and clinical symptoms.


Protein corona mitigated the cytotoxicity of CdTe QDs to macrophages by targeting mitochondria.
Despite the potential of cadmium telluride quantum dots (CdTe QDs) in bioimaging and drug delivery, their toxic effects have been documented. It is known that the immunotoxicity of CdTe QDs targeting macrophages is one of their adverse effects, and the protein corona (PC) will affect the biological effects of QDs. In order to prove whether the PC-CdTe QDs complexes could alleviate the toxicity of CdTe QDs without weakening their luminescence, we investigated the impact of protein corona formed in fetal bovine serum (FBS) on the cytotoxicity of CdTe QDs to mitochondria. RAW264.7 cells were used as the model to compare the effects of CdTe QDs and PC-CdTe QDs complexes on the structure, function, quantity, morphology, and mitochondrial quality control of mitochondria. As result, the protein corona form in FBS alleviated the inhibition of CdTe QDs on mitochondrial activity, the damage to mitochondrial membrane, the increase of ROS, and the reduction of ATP content. Also, CdTe QDs increased the number of mitochondria in macrophages, while the complexes did not. In line with this, the morphology of mitochondrial network in macrophages which were exposed to CdTe QDs and PC-CdTe QDs complexes was different. CdTe QDs transformed the network into fragments, punctuations, and short rods, while PC-CdTe QDs complexes made the mitochondrial network highly branched, which was related to the imbalance of mitochondrial fission and fusion. Mechanically, CdTe QDs facilitated mitochondrial fission and inhibited mitochondrial fusion, while protein corona reversed the phenomenon caused by QDs. Besides mitochondrial dynamics, mitochondrial biogenesis and mitophagy were also affected. CdTe QDs increased the expression of mitochondrial biogenesis signaling molecules including PGC-1α, NRF-1 and TFAM, while PC-CdTe QDs complexes played the opposite role. With regard to mitophagy, they both showed promoting effect. In conclusion, the formation of protein corona alleviated the toxic effects of CdTe QDs on the mitochondria in macrophages and affected mitochondrial quality control. Under the premise of ensuring the fluorescence properties of CdTe QDs, these findings provided useful insight into reducing the toxicity of CdTe QDs from two perspectives: protein corona and mitochondria, and shared valuable information for the safe use of QDs.


Cross linking to tissue transglutaminase and collagen favours gliadin toxicity in coeliac disease.
Intestinal inflammation in coeliac disease is driven by the gluten fraction of wheat proteins. Deamidation or cross linking of gluten peptides by tissue transglutaminase (tTG), the coeliac disease autoantigen, creates potent T cell stimulatory peptides. Therefore, our aim was to identify the reaction patterns of gluten peptides, intestinal extracellular matrix proteins, and tTG. tTG activity was analysed by incorporation of monodansyl cadaverine into gliadins. Fluorescence labelled tTG reactive short gliadin peptides were used to demonstrate their deamidation and explore their cross linking patterns with tTG itself or extracellular matrix proteins. Patient sera and controls were checked for autoantibodies to matrix proteins. Gliadins alpha1-alpha11, gamma1-gamma6, omega1-omega3, and omega5 were substrates for tTG. tTG catalysed the cross linking of gliadin peptides with interstitial collagen types I, III, and VI. Coeliac patients showed increased antibody titres against the collagens I, III, V, and VI. tTG formed high molecular weight complexes with all tested gliadins. As all tested gliadins were substrates for tTG, the tTG catalysed modifications were not restricted to single gliadin types and epitopes. Furthermore, haptenisation and long term immobilisation of gliadin peptides by tTG catalysed binding to abundant extracellular matrix proteins could be instrumental in the perpetuation of intestinal inflammation and some associated autoimmune diseases in coeliac disease.


Biosynthesis of gallotannins: beta-glucogallin-dependent formation of 1,2,3,4,6-pentagalloylglucose by enzymatic galloylation of 1,2,3,6-tetragalloylglucose.
An acyltransferase was detected in young leaves of pedunculate oak (Quercus robur) that catalyzed the formation of 1,2,3,4,6-penta-O-galloyl-beta-D-glucose, the common precursor of gallotannins and the related ellagitannins. This enzyme depended on beta-glucogallin (1-O-galloyl-beta-D-glucose) as acyl donor; 1,2,3,6-tetra-O-galloyl-beta-D-glucose was specifically required as acceptor molecule, whereas no reaction occurred with the 1,2,4,6-isomer of this substrate. The partially purified enzyme (Mr 260,000) was stable between pH 5.0 and 6.5; highest activities were observed at pH 6.3 and 40 degrees C. Km values of 2.3 and 1.0 mM, respectively, were determined for the substrates beta-glucogallin and tetragalloylglucose. In accordance with stoichiometric studies, the systematic name "beta-glucogallin: 1,2,3,6-tetra-O-galloylglucose 4-O-galloyltransferase" is proposed for this new enzyme.


Enzymic potential for fructose 6-phosphate phosphorylation by guard cells and by palisade cells in leaves of the broad bean Vicia faba L.
Guard cells and palisade cells were dissected from freeze-dried leaflets of the broad bean, Vicia faba L. Individual cell samples (6-12 ng) were assayed for ATP-dependent and pyrophosphate-dependent phosphofructokinases. The assay indicator, NADH loss, was monitored in real time in oil droplets with a computer-driven microfluorometer. On a protein basis, both activities were 10-fold higher in guard cells than in palisade cells, indicating (i) elevated carbon metabolism in guard cells to meet demands for energy and carbon skeletons required during stomatal opening, and (ii) parallel glycolytic pathways in guard cells, one responsive to the potent regulatory metabolite fructose 2,6-bisphosphate and the other not. Future work will be devoted to clarifying the roles of the cytosolic and chloroplastic compartments in guard cells.


Lesions of the dopaminergic nigrostriatal system in neonatal rats: effects on the electrophysiological activity of striatal neurons recorded during adulthood.
The spontaneous activity of single striatal neurons was recorded extracellularly from 3-4-month-old adult rats that had been given dopamine (DA)-depleting brain lesions 3 days after birth. Behavioral observations made prior to recording indicated no gross sensorimotor deficits, yet subsequent biochemical analyses revealed that animals had sustained near-total DA depletions (greater than 99%). Electrophysiological results showed that the firing rates of type II striatal cells were greatly increased relative to control levels. This finding contrasts sharply with the effects of DA-depleting brain lesions given to adult animals, in which similarly high levels of striatal cell activity are invariably associated with akinesia.


Iliac arteriovenous fistula following lumbar disc surgery. A case report.
Iliac arteriovenous (AV) fistula after lumbar disc surgery are uncommon entities with limited reported cases. This report describes a 44-year-old man with history of L4-L5 spinal discectomy who complained of congestive heart failure symptoms four years later. Computed tomography angiography (CTA) revealed an AV fistula connecting the right common iliac artery and vein. AV closure with lateral suturing of common iliac artery and vein was performed through transperitoneal aorto-iliac approach. Postoperatively, the patient's symptoms of orthopnea resolved. Follow-up at six years was uneventful.


Novel functional atrial fibrillation risk genes and pathways identified from coexpression analyses in human left atria.
Genomewide association studies have associated >100 genetic loci with atrial fibrillation (AF), but establishing causal genes contributing to AF remains challenging. The purpose of this study was to determine candidate novel causal genes and mechanistic pathways associated with AF risk loci by incorporating gene expression and coexpression analyses and to provide a resource for functional studies and targeting of AF-associated genes. Cis-expression quantitative trait loci were identified for candidate genes near AF risk variants in human left atrial tissues. Coexpression partners were identified for each candidate gene. Weighted gene coexpression network analysis (WGCNA) identified modules and modules with overrepresentation of candidate AF genes. Ingenuity pathway analysis (IPA) was applied to the coexpression partners of each candidate gene. IPA and gene set over representation analysis were applied to each WGCNA module. One hundred sixty-six AF-risk single nucleotide polymorphisms were located in 135 loci. Eighty-one novel genes not previously annotated as putative AF risk genes were identified. IPA identified mitochondrial dysfunction, oxidative stress, epithelial adherens junction signaling, and sirtuin signaling as the most frequent significant pathways. WGCNA characterized 64 modules (candidate AF genes overrepresented in 8), represented by cell injury, death, stress, developmental, metabolic/mitochondrial, transcription/translation, and immune activation/inflammation regulatory pathways. Candidate gene coexpression analyses suggest significant roles for cellular stress and remodeling in AF, supporting a dual risk model for AF: Genetic susceptibility to AF may not manifest until later in life, when cellular stressors overwhelm adaptive responses. These analyses also provide a novel resource to guide functional studies on potential causal AF genes.


Embolization of a bleeding Dieulafoy lesion of the duodenum in a child. Case report and review of the literature.
We report an adolescent with chronic, recurrent upper gastrointestinal bleeding in whom extensive prior investigations failed to reveal the source of bleeding. Angiography accurately identified a bleeding Dieulafoy lesion of the duodenum which was successfully embolized. The clinical history, angiographic appearances and treatment of this rare lesion are presented.


Evaluation of haplotype-aware long-read error correction with hifieval.
The PacBio High-Fidelity (HiFi) sequencing technology produces long reads of >99% in accuracy. It has enabled the development of a new generation of de novo sequence assemblers, which all have sequencing error correction as the first step. As HiFi is a new data type, this critical step has not been evaluated before. Here, we introduced hifieval, a new command-line tool for measuring over- and under-corrections produced by error correction algorithms. We assessed the accuracy of the error correction components of existing HiFi assemblers on the CHM13 and the HG002 datasets and further investigated the performance of error correction methods in challenging regions such as homopolymer regions, centromeric regions, and segmental duplications. Hifieval will help HiFi assemblers to improve error correction and assembly quality in the long run.


Hybrid 5 S ribosomal RNA encoded by a multicopy plasmid is incorporated into ribosomes of Escherichia coli.
The recombinant plasmid pJR3 delta contains a tandem pair of promoters from rrnA followed by a hybrid 5 S rRNA gene, derived from the two 5 S rRNA genes of the rrnD transcription unit, and a terminator. Escherichia coli cells transformed with this plasmid produce 2-3-times more 5 S rRNA compared to untransformed cells. The growth of cells containing this plasmid is not affected significantly. Although the sequence and the secondary structure of the plasmid-specific 5 S rRNA differ from those of its counterparts (e.g., from 5 S rRNA species encoded by chromosomal genes), it is processed properly and is incorporated into ribosomes.


Eighteen-year follow-up cohort study on hepatitis B and C virus infections related long-term prognosis among hemodialysis patients in Hiroshima.
This study aimed to investigate the prevalence trend of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and their genotype distribution among hemodialysis patients, determining their long-term prognosis and the risk factors to the mortality. This cohort study used both the medical data and the blood samples of hemodialysis patients at nine dialysis centers in Hiroshima from 1999 to 2017. Hepatitis B surface antigen (HBsAg) and anti-HCV were screened and then amplification was done to positive sera by polymerase chain reaction for genotyping. Data were employed for multiple regressions to determine the associated risk factors. A total of 3968 patients were subdivided into three groups: who started hemodialysis before 1990, during 1991 to 2001, and after 2002. The periodic prevalence of HBsAg decreased from 2.8% to 1.3% and that of anti-HCV from 33.3% to 9.5% in the three groups. By multiple regressions, the adjusted hazard ratio of diabetes mellitus (DM) ranges from 1.59 to 2.12 and that of HCV RNA positivity ranges from 1.18 to 1.48 (P < .05). Heart failure is the primary cause of death in all groups. Genotype C2 is predominant for HBV and genotype 1b is predominant for HCV. The decreasing trend of both HBV and HCV was found in the cohort. DM and HCV RNA were the significant risk factors leading to poor prognosis among hemodialysis patients. The similar genotype distribution of both HBV and HCV was found as general population. This alarmed to provide early diagnosis, prompt, and adequate treatment to HCV infection among hemodialysis patients.


Reduction of cutaneous reaction time by directing eyes towards the source of stimulation.
Reaction time to expected lateral cutaneous stimulation was measured in Man when the eyes were directed (1) towards the stimulated area, (2) towards another point within the same hemispace and (3) towards the other hemispace. As performance was better in the first case, this suggests that compatible eye postural activity reinforces the effect of spatial attention.


Functional Fc-receptor defect of polymorphonuclear leukocytes in a patient with Sjögren's syndrome.
We investigated polymorphonuclear leukocyte (PMN) function in a 50-year-old woman with primary Sjögren's syndrome (SS). The respiratory burst of PMN was monitored by luminol-enhanced chemiluminescence using zymosan, opsonized zymosan, zymosan-activated serum, and phorbol-myristate-acetate, as well as serial dilutions of aggregated immunoglobulin (aggIg) as Fc-receptor (FcR) stimulus. The effects of serum on the chemiluminescent response as well as the binding of aggIg to PMN were also compared. We found the patient's PMN not to respond to stimulation by aggIg, only the highest concentration (greater than 180 micrograms/ml) induced a marginal chemiluminescent response in the patient. By contrast, incubation of the patient's PMN with other stimuli resulted in responses similar to those in a healthy control. Binding of aggIg to PMN was higher in the patient (3.6% vs 1.5% of the radioactivity added in the control). Sera of patient and control induced similar chemiluminescence on PMN as did that of another human serum. Our data indicate a selective functional FcR defect of PMN despite unimpaired binding of aggIg in a patient with SS.


B-cell chronic lymphocytic leukaemia: prognostic value of the immunophenotype and the clinico-haematological features.
Sixty-two previously untreated patients with B-cell chronic lymphocytic leukaemia were analysed to study the prognostic value of both the immunologic phenotype and the clinicobiologic characteristics. Univariate studies showed that none of the immunological markers analysed, sheep-rosette, mouse-rosette, slg, and HLA/DR, CD20, FMC7, CD5, and CD9 antigens, had a significant influence on survival. On the other hand, several clinical and haematological characteristics were identified as being associated with survival: 1) clinical features--presence of lymphadenopathies (P less than .05) and hepatomegaly and/or splenomegaly (P less than .04); 2) haematologic parameters--presence of anaemia and/or thrombopenia (P less than .05), the absolute peripheral blood lymphocyte count (P less than .03), and the presence of hypogammaglobulinemia (P less than .08); 3) biochemical parameters--serum uric acid (P less than .03); and 4) bone marrow histopathological features--biopsy pattern (P less than .04) and the percentage of lymphocytes in bone marrow aspirate (P less than .03). Both the Rai staging and the International Workshop on CLL staging systems were effective in identifying groups of patients with significantly different prognoses (P less than .05). Multivariate regression analysis demonstrated that the combination of three clinicopathologic characteristics (bone marrow histopathologic pattern, absolute peripheral blood lymphocyte count, and the presence or not of hypogammaglobulinaemia) had the strongest predictive relationship with survival time. In summary, our findings show that the clinicobiological and anatomopathologic parameters have much more prognostic relevance than the immunological markers analysed in the present study.


Prefrontal dysfunction in pediatric Tourette's disorder as measured by near-infrared spectroscopy.
Tourette's disorder (TD) is a chronic childhood-onset disorder characterized by the presence of multiple motor and vocal tics. Despite strong evidence that the pathophysiology of TD involves structural and functional disturbances of the basal ganglia and cortical frontal areas, in vivo imaging studies have produced conflicting results. Recent developments in near-infrared spectroscopy (NIRS) technology have enabled noninvasive assessment of brain function in people with psychiatric disorders. We asked 10 individuals with pediatric TD and 10 healthy controls who were age- and sex- matched to perform the Stroop color-word task during NIRS. We used prefrontal probes and a 24-channel NIRS machine to measure the relative concentrations of oxyhemoglobin (oxy-Hb) every 0.1 s during the task. We found that oxy-Hb changes in the prefrontal cortex were significantly smaller in the TD group compared with the control group, especially in the left dorsolateral prefrontal cortex. Our data suggest that individuals with pediatric TD have a reduced prefrontal hemodynamic response as measured by NIRS.


[Differences in the electrophysiological patterns in the distinct variations of the presentation of chronic inflammatory demyelinating polyneuropathy].
Chronic inflammatory demyelinating polyneuropathy (CIDP) is a mixed (predominantly motor) neuropathy, with an autoimmune aetiology and different forms of clinical presentation including the idiopathic form and one related to concurrent diseases. Neurophysiological studies play a decisive role in its diagnosis. To evaluate the differences in the electrophysiological patterns in the two forms of presentation of the disease, based on the variables that were analysed by studying nerve conduction and the F wave. The study involved 27 patients with a diagnosis of probable CIDP, according to American Academy of Neurology criteria from 1991. Of all the patients included in the study group, 17 presented primary CIDP and in 10 cases it was related to other diseases, such as diabetes mellitus, adenocarcinoma, multiple sclerosis and human immunodeficiency virus infection. Motor and sensory nerve conduction studies were performed, as well as F wave studies of the nerves in the four limbs. Statistical methods were applied to compare the neurophysiological variables in the two groups of patients. Significant differences were found to exist between the two groups. The sensory study was more affected in patients with primary CIDP, whereas the motor and F wave study were affected to a greater extent in patients with secondary CIDP; these cases displayed a predominantly axonomyelinic pattern, with greater involvement of the proximal motor segment. The different variant forms of presentation of CIDP display distinct electrophysiological behaviours.


Bronchial and nonbronchial systemic arteries in patients with hemoptysis: depiction on MDCT angiography.
In this pictorial essay, we show the usefulness of MDCT angiography for visualization of the bronchial and nonbronchial systemic feeder vessels responsible for hemoptysis. By providing thin-section transaxial, multiplanar reconstruction, and 3D images, CT angiography using MDCT allows comparable or better images than conventional angiography with respect to the depiction of bronchial or nonbronchial systemic arteries. CT angiography is particularly useful for visualizing the ectopic origin of bronchial arteries and nonbronchial systemic collateral arteries.


Monoclonal rheumatoid factor-IgG immune complexes. Poor fixation of opsonic C4 and C3 despite efficient complement activation.
Monoclonal IgM rheumatoid factor forms complexes with IgG in essential mixed cryoglobulinemia. We demonstrate that such complexes fix C3 and C4 poorly, although efficient fluid-phase C3 conversion can occur. Fixation of small amounts of C4 may be sufficient to generate a C3 convertase, but may prevent subsequent fixation of C3 by competing for binding sites on the complex. These complexes bind inefficiently to normal erythrocyte complement receptor type 1 (CR1) in vitro, and are undetectable on erythrocytes of patients with essential mixed cryoglobulinemia in vivo. Clearance of such phlogistic complexes from tissues by CR1-bearing cells may be inefficient.


Deletion of IL-18 receptor ameliorates renal injury in bovine serum albumin-induced glomerulonephritis.
Bovine serum albumin (BSA) glomerulonephritis is a type of immune complex glomerulonephritis that is characterized by a large number of leukocytes infiltrating the kidney. Interleukin (IL)-18, which has potent interferon (IFN)-gamma-inducing activities, may play an important role in lymphocyte-mediated inflammatory responses. To investigate the role of IL-18 in BSA glomerulonephritis, we used IL-18R-deficient C57BL/6 mice. Compared with control mice, IL-18R-deficient mice showed a significant reduction of proteinuria, renal pathological findings including glomerular IgG and C3 deposits, and leukocyte infiltrates. Transcripts encoding IFN-gamma and tumor necrosis factor (TNF)-alpha in the kidney were significantly reduced in IL-18R-deficient mice compared with those in control mice. On the other hand, serum anti-BSA Ab was not reduced in IL-18R-deficient mice. We conclude that the blockading of IL-18 signaling in BSA nephritis mice significantly alleviates immune complex renal disorder; this may thus represent a novel approach to the treatment of patients with immune complex nephritis.


Effect of torsemide and furosemide on clinical, laboratory, radiographic and quality of life variables in dogs with heart failure secondary to mitral valve disease.
Diuretic therapy reduces preload and relieves congestion secondary to cardiac dysfunction. Torsemide (torasemide) is a loop diuretic with longer duration of action, decreased susceptibility to diuretic resistance, and adjunctive aldosterone antagonist properties compared with furosemide. We hypothesized that torsemide would be well tolerated and no less effective than furosemide at diuresis, control of clinical signs, and maintenance of quality of life (QOL) in dogs with congestive heart failure (CHF). Seven client-owned dogs with stable CHF receiving twice daily oral furosemide and adjunctive medications. Utilizing a double-blinded, randomized, crossover design, dogs were administered either oral furosemide at their current dose or an equivalent oral dose of torsemide (1/10 of the daily furosemide dose divided into twice daily dosing) on day 0. Crossover occurred at day 7 and the study ended on day 14. Clinical, laboratory, radiographic, and QOL variables were evaluated on days 0, 7 and 14. No dogs developed recurrent CHF during the study. Mean furosemide dose on day 0 was 5.13 mg/kg/day (range 2.8-9.6). Following torsemide treatment, creatinine (P = 0.020), urea nitrogen (P = 0.013), phosphorus (P = 0.032), albumin (P = 0.019), carbon dioxide (P = 0.015) and anion gap (P = 0.005) were significantly increased, and urine specific gravity (P = 0.004) and chloride (P = 0.021) were significantly decreased compared with furosemide dosing. No differences in QOL were found. Results indicate that torsemide is equivalent to furosemide at controlling clinical signs of CHF in dogs and is likely to achieve greater diuresis vs. furosemide. Larger clinical trials evaluating torsemide as a first or second-line loop diuretic for congestive heart failure in dogs are warranted.


Effects of intrinsic and extrinsic noise can accelerate juxtacrine pattern formation.
Epithelial pattern formation is an important phenomenon that, for example, has roles in embryogenesis, development and wound-healing. The ligand Epithelial Growth Factor (EGF) and its receptor EGF-R, constitute a system that forms lateral induction patterns by juxtacrine signalling-binding of membrane-bound ligands to receptors on neighbouring cells. Owen et al. developed a generic ordinary differential equation model of juxtacrine lateral induction that exhibits stable patterning under some conditions. The model predicts relatively slow pattern formation. We examine here the effects of both intrinsic and extrinsic cellular noise arising from the stochastic treatment of this model, and show that this noise could have an accelerating effect on the patterning process.


A rotating iterative procedure (RIP) for estimating hybrid constants in multi-compartment analysis on desk computers.
The rotating iterative procedure (RIP) is a programming concept for non-linear least squares fitting of multiexponential equations to experimental data in pharmacokinetics. The method is economical in its use of program and active register capacity and can be employed in modern electronic desk-top computers. The algorithms necessary for obtaining primary estimates of various logarithmic components and their subsequent correction are presented, with as little higher mathematics as appeared permissible. The procedure is described in the sequence that would actually be followed in a pharmacokinetic analysis, and an example is included, as well as a skeleton version of a program written in BASIC. Some instructions for obtaining overall statistical parameters are given.


Shoulder complex and trunk coordination of individuals with severe hemiparesis following a constraint-induced movement therapy protocol: A case series.
Constraint Induced Movement Therapy (CIMT) has been shown to be an effective rehabilitation technique in individuals with mild and moderate upper limb (UL) hemiparesis. The aim was to evaluate the effect the CIMT for improving paretic UL use and interjoint coordination with individuals in severe hemiparesis. Six individuals with severe chronic hemiparesis (mean age = 55 ± 16 years) received a UL CIMT intervention for 2 weeks. UL clinical assessments were conducted five times: two assessments at pre-intervention and then, one assessment at post-intervention and 1- and 3-month follow-up using the Graded Motor Activity Log GMAL) and the Graded Wolf Motor Function Test (GWMFT). Scapula, humerus and trunk coordination variability were assessed using the 3-D kinematics during arm elevation, combing hair, turning on the switch and grasp a washcloth. A paired t-test was used to check differences between coordination variability and a one-way ANOVA repeated measures was used to check differences between GMAL and GWMFT scores. There were no differences in GMAL and GWMFT between the patient screening and the baseline data collection (p > 0.05). GMAL scores increased at post-intervention and at follow-ups (p < 0.02). GWMFT performance time score decreased at post-intervention and at 1-month follow-up (p < 0.04). Improvements in kinematic variability of the paretic UL at pre and post-intervention were observed in all tasks, except in the activity of turn on the light switch. Following the CIMT protocol, improvements in GMAL and GWMFT scores may reflect improvements in paretic UL performance, in real-life environment. Improvements in kinematic variability may reflect an improving of UL interjoint coordination for individuals with chronic severe hemiparesis.


Local microwave hyperthermia in treatment of advanced prostatic adenocarcinoma.
Fifteen patients with advanced (T3-4, Nx-2, M0-1) prostatic adenocarcinoma were treated with local microwave hyperthermia (LMwH) applied as the sole method of therapy (automatically controlled set generating 2,450 MHz microwaves with intrarectal applicator). All patients were monitored with a battery of tests, including USG image and volumetry of prostate, bone scintigraphy, serum alkaline phosphatase and serum level of PAP. LMwH sessions were well tolerated and did not cause pain except a moderate sensation of heating in the pelvic region. 8 of these 15 patients responded to the therapy (3x complete remission and 5x partial remission). Involution of the prostatic tumor in responders was accompanied by improvement of the general clinical and urological state. In two responders bone metastases, documented scintigraphically before therapy, disappeared. 7 patients did not respond to LMwH, mostly patients with very large primary tumors.


Weaknesses and capacities affecting the Prehospital emergency care for victims of road traffic incidents in the greater Kampala metropolitan area: a cross-sectional study.
Pre-hospital emergency care is a vital and integral component of health systems particularly in the resource constrained countries like Uganda. It can help to minimize deaths, injuries, morbidities, disabilities and trauma caused by the road traffic incidents (RTIs). This study identifies the weaknesses and capacities affecting the pre-hospital emergency care for the victims of RTIs in the Greater Kampala Metropolitan Area (GKMA). A cross-sectional study was conducted in the GKMA using a three-part structured questionnaire. Data related to the demographics, nature of RTIs and victims' pre-hospital experience and existing Emergency Medical Services (EMS) were collected from victims and EMS specialists in 3 hospitals and 5 EMS institutions respectively. Data was descriptively analyzed, and after the principal component analysis was employed to identify the most influential weaknesses and capacities affecting the pre-hospital emergency care for the victims of RTI in the GKMA. From 459 RTI victims (74.7% males and 25.3% females) and 23 EMS specialists (91.3% males and 8.7% females) who participated in the study between May and June 2016, 4 and 5 key weaknesses and capacities respectively were identified to affect the pre-hospital emergency care for RTI victims in the GKMA. Although some strengths exist like ambulance facilitation, EMS structuring, coordination and others), the key weaknesses affecting the pre-hospital care for victims were noted to relate to absence of predefined EMS systems particularly in the GKMA and Uganda as a whole. They were identified to involve poor quality first aid treatment; insufficient skills/training of the first responders; inadequate EMS resources; and avoidable delays to respond and transport RTI victims to medical facilities. Though some strengths exist, the weaknesses affecting prehospital care for RTI victims primarily emanate from the absence of predefined and well-organized EMS systems in the GKMA and Uganda as a whole.


Interplay between glutathione, Atx1 and copper. 1. Copper(I) glutathionate induced dimerization of Atx1.
Copper is both an essential element as a catalytic cofactor and a toxic element because of its redox properties. Once in the cell, Cu(I) binds to glutathione (GSH) and various thiol-rich proteins that sequester and/or exchange copper with other intracellular components. Among them, the Cu(I) chaperone Atx1 is known to deliver Cu(I) to Ccc2, the Golgi Cu-ATPase, in yeast. However, the mechanism for Cu(I) incorporation into Atx1 has not yet been unraveled. We investigated here a possible role of GSH in Cu(I) binding to Atx1. Yeast Atx1 was expressed in Escherichia coli and purified to study its ability to bind Cu(I). We found that with an excess of GSH [at least two GSH/Cu(I)], Atx1 formed a Cu(I)-bridged dimer of high affinity for Cu(I), containing two Cu(I) and two GSH, whereas no dimer was observed in the absence of GSH. The stability constants (log beta) of the Cu(I) complexes measured at pH 6 were 15-16 and 49-50 for CuAtx1 and Cu (2) (I) (GS(-))(2)(Atx1)(2), respectively. Hence, these results suggest that in vivo the high GSH concentration favors Atx1 dimerization and that Cu (2) (I) (GS(-))(2)(Atx1)(2) is the major conformation of Atx1 in the cytosol.


Postoperative Clostridium septicum dermatitis simulating toxic epidermal necrolysis.
Widespread detachment of the epidermis as a result of Clostridium septicum infection after a laparotomy for intestinal obstruction is described. A clinicopathological picture, hitherto undescribed, is outlined.


Specific regulation of the gene expression of some pancreatic enzymes during postnatal development and weaning in the calf.
The construction of cDNA library from calf pancreas allowed us to examine the mRNA levels of four pancreatic hydrolases (chymotrypsin, lipase, trypsin and amylase) during postnatal development in preruminant and ruminant animals. The lack of parallel variations in the levels of the enzyme specific activities suggested that protein synthesis was not coordinately regulated. In preruminant calves, the change in chymotrypsin and lipase mRNA concentrations (0-28 day period) and in trypsin mRNA concentrations (0-119 day period) was opposite to that in the corresponding specific activities. In contrast, both the activity and mRNA profiles of amylase during the latter period, on the one hand, and those of chymotrypsin and lipase during the 28-119 day period, on the other hand, were comparable. However, the extent to which the specific activity and mRNA concentration of each enzyme were increased did not necessarily coincide. The observed changes in mRNA levels probably resulted from some transcriptional control of the gene expression and/or variation in mRNA stability. Moreover, a translational regulation of the messengers could explain the existence of non-parallel mRNA and specific activity profiles. In sharp contrast with the multiple control of protein synthesis during postnatal development in preruminant calves, weaning was found to induce the same increase in enzyme activity and corresponding mRNA for each of the four pancreatic enzymes, suggesting that pretranslational modulation of gene expression was mainly, if not exclusively, concerned.


Attractiveness bias: A cognitive explanation.
According to cognitive averaging theory, preferences for attractive faces result from their similarity to facial prototypes, the categorical central tendencies of a population of faces. Prototypical faces are processed more fluently, resulting in increased positive affect in the viewer.


Influence of local radiotherapy of breast cancer patients on the frequency of cytotoxic T lymphocyte precursor cells.
Alloantigen-specific cytotoxic T lymphocyte precursor (CTL-p) frequencies were analyzed in ten patients with histologically proven breast cancer receiving prophylactic RT. The frequency of CTL-p was assessed by limiting dilution (LD) analyses before, immediately after discontinuation of treatment and at various times following RT. The number of pbmnc, adherent cells and T cells was determined in parallel. Local RT led to a minor and transient reduction of CTL-p frequencies lasting approximately three months: on average a 25% decrease of CTL-p numbers was seen immediately after RT. Three months following treatment, a 20% reduction was still evident. Values subsequently returned to pretreatment levels. Moreover, these changes in the frequency of antigen-specific CTL were accompanied by a 25% to 39% decrease in the blood T cell counts lasting for more than 12 months. The reductions following local RT were less pronounced than those induced by immunosuppressive drugs in allograft recipients.


The endothelin axis in cancer.
The endothelin axis, comprising endothelins and their receptors, has recently emerged as relevant player in tumor growth and metastasis by regulating mitogenesis, cell survival, angiogenesis, bone remodeling, stimulation of nociceptor receptor, tumor-infiltrating immune cells, epithelial-to-mesenchymal transition, invasion and metastatic dissemination. Endothelin-1 participates in the growth and progression of a variety of tumors such as prostatic, ovarian, renal, pulmonary, colorectal, cervical, breast, bladder, endometrial carcinomas, Kaposi's sarcoma, brain tumors, melanoma, and bone metastases. This review highlights key signaling pathways activated by endothelin-1 axis in cancer, since the understanding the full spectrum activated by endothelin-1 is critical for the optimal design of targeted therapies. Preliminary experimental and clinical data demonstrate that interfering with endothelin receptor by using endothelin-1 receptor antagonists alone and in combination with cytotoxic drugs or molecular inhibitors could represent a new mechanism-based antitumor strategy.


Stellate ganglion block does not change the tympanic membrane temperatures of either block or unblock sides in male volunteers.
To test the effect of stellate ganglion block on tympanic membrane temperatures. Prospective, observational study. Department of Anesthesia, Yamanashi Medical University, Yamanashi, Japan. 7 healthy male volunteers. Stellate ganglion block, 6 ml of 1% mepivacaine hydrochloride, was administered. Application of temperature probes (right and left tympanic membranes, eight adhesive right skin-surface temperatures at the chest, upper arm, digital fingertip, lateral calf, thigh, and great toe) was followed by a 30-minute control period. Temperatures were recorded every 15 minutes for 30 minutes before stellate ganglion block and every 5 minutes for 40 minutes after the block. The right tympanic membrane temperature increased slightly but not significantly compared with the left tympanic membrane temperature 10 minutes after stellate ganglion block and subsequently. Right skin-surface temperature gradients at the upper limb decreased slightly but not significantly after stellate ganglion block. Similarly, right skin-surface temperature gradients at the lower limb decreased slightly but not significantly after stellate ganglion block. Stellate ganglion block does not change the tympanic membrane temperatures of either block or unblock sides.


Barring progress: The influence of paternal incarceration on families' neighborhood attainment.
A growing body of literature has recognized that incarceration has implications beyond the offender, with detrimental effects reverberating onto families. In this study, we use the Fragile Families and Child Wellbeing Study (N = 3288) to investigate the relationships between paternal incarceration and the neighborhood outcomes of the children of incarcerated fathers and their mothers. Specifically, we examine whether children whose fathers are currently and/or have recently been incarcerated experience more residential instability, live in more socioeconomically disadvantaged neighborhoods, and/or live in less socially cohesive neighborhoods. We find that paternal incarceration is associated with moving more frequently, greater socioeconomic neighborhood disadvantage, and lower social cohesion for the children of incarcerated fathers and their mothers, though some of these relationships depend on the timing of paternal incarceration. Our findings have important implications for understanding the societal costs of incarceration, the nature of neighborhood attainment and inequality for families facing paternal incarceration, and the processes through which some families are sorted into their neighborhood contexts.


Two-body wear of occlusal splint materials against different antagonists.
This study aimed to demonstrate that the material of the occlusal splint can be chosen according to the needs of individual patients and contribute to the knowledge of the wear rate of these materials. In this study, four occlusal splint materials (Sr Ivocap Heat Cured, Valplast, SR Ivocap Elastomer and Eclipse) and three antagonists (natural tooth enamel, inCoris TZI and IPS e.max Press ceramic materials) were used. Each wear test was performed using a chewing simulator (n = 16; test load: 50 N; number of cycles: 10,000, 20,000 and 30,000; continuous rinsing with water at 30 °C for the wet condition). The Shapiro Wilk test was used for normal distribution suitability. Antagonist on average wear quantities both main effects and interactions of material, cycle and condition factors were investigated by Univariate variance analysis. Multiple comparisons were examined using the Games-Howell test. There was a statistically significant effect of the difference in materials on the amount of wear (p < 0.001). Furthermore, there was a statistically significant difference among the mean values of all materials (p > 0.001). The highest mean value was obtained with Eclipse (0,318 μm3), and the lowest mean value was obtained with Valplast (0,134 μm3). Our study found differences in the in vitro wear rate among various occlusal splint materials.


Sulfate radical-based oxidation of antibiotics sulfamethazine, sulfapyridine, sulfadiazine, sulfadimethoxine, and sulfachloropyridazine: Formation of SO2 extrusion products and effects of natural organic matter.
The widespread occurrence of sulfonamide antibiotics in the environment has raised great concerns about their potential to proliferate antibacterial resistance. Sulfate radical (SO4•-) based advanced oxidation processes (SR-AOPs) are promising in-situ chemical oxidation (ISCO) technologies for remediation of soil and groundwater contaminated by antibiotics. The present study reported that thermally activated persulfate oxidation of sulfonamides (SAs) bearing six-membered heterocyclic rings, e.g., sulfamethazine (SMZ), sulfapyridine (SPD), sulfadiazine (SDZ), sulfadimethoxine (SDM), and sulfachloropyridazine (SCP), all produced SO2 extrusion products (SEPs), a phenomenon that is of potential importance, but not systematically studied. As an electrophilic oxidant, SO4•- tends to attack the aniline moiety, the reactive site of SAs, via electro-transfer mechanism. The resulting anilinyl radical cations are subjected to further intermolecular Smiles-type rearrangement to produce SEPs. Formation of SEPs is expected to occur in other SR-AOPs as well. The temperature-dependent evolution pattern of SEP of SMZ, 4-(2-imino-4,6-dimethylpyrimidin-1(2H)-yl)aniline, can be well fitted by kinetic modeling concerning sequential formation and transformation of intermediate product. The presence of natural organic matter (NOM) influenced the evolution patterns of 4-(2-imino-4,6-dimethylpyrimidin-1(2H)-yl)aniline significantly. Toxicological effects of SEPs on ecosystem and human health remain largely unknown, thus, further monitoring studies are highly desirable.


Mental health stigma and mental health knowledge in Chinese population: a cross-sectional study.
Little is known about the public stigma on mental illness and mental health knowledge (MHK) in China, public stigma and low MHK can negatively affect patients' health and increase the burden of mental disorders on society. This study aimed at investigating the rates of stigma and MHK, the correlates of stigma and MHK, and the association between MHK and stigma among a Chinese population. The data is from the Tianjin Mental Health Survey (TJMHS), which involved a large and a representative sample of adult community residents in the Chinese municipality of Tianjin (n = 11,748). In a 12% random subsample (n = 1775) the Perceived Discrimination and Devaluation scale (PDD) and a Mental Health Knowledge Questionnaire (MHKQ) were administered. First, percentages of the responses to the individual items of the PDD and MHKQ were investigated. Second, sociodemographic correlates of PDD and MHK, and the association between stigma and MHK were investigated. We found that a sizable proportion of participants responded that others would hold a negative attitude towards (former) mental patients, especially with regard to engaging in closer personal relationships. Most people were not familiar about the causes, treatments and prevention of mental illness. Resident area, age, education level, Per capita family income and employment status were related to devaluation score and MHKQ score. MHK was negatively associated with public stigma. There is room for improvement with regard to levels of public stigma and MHK in China. Providing psychoeducation to improve public MHK could also contribute to reduction of public stigma.


Analysis of SAA1 gene polymorphisms in the Greek population: rheumatoid arthritis and FMF patients relative to normal controls. Homogeneous distribution and low incidence of AA amyloidosis.
To address whether or not the rarity of amyloidosis in Greek patients with rheumatoid arthritis (RA) is related to specific alleles of single nucleotide polymorphisms (SNPs) in the 5'-flanking region and the exon 3 of the SSA1 gene. The genotypes of the -13T/C SNP in the 5'-flanking region of the SAA1 gene and the two SNPs within exon 3 of SAA1 (2995C/T and 3010C/T polymorphisms) were determined in 88 Greek patients with RA, 14 patients with familial Mediterranean fever (FMF) and 110 healthy controls. Linkage disequilibrium and haplotype frequencies involving -13T/C, 2995C/T and 3010C/T in these populations were tested and estimated, respectively. The genotypic distribution and allelic frequencies were similar in all groups tested. SNPs 2995 and 3010 were in linkage disequilibrium for all study populations (p < 0.05), whereas SNP -13 was not in linkage disequilibrium with either 2995 or 3010 (p > or = 0.05). Two major haplotypes presented in all patients with RA and FMF and controls: -13C; 2995T; 3010C (-13C; alpha) and -13C; 2995C; 3010T (-13C; beta). The -13T allele was linked with the gamma haplotype in Greek patients with RA and controls. The frequency of the -13T allele was found to be very rare in all groups tested. In conclusion, the rarity of the putative amyloidogenic -13T allele in Greek populations may be related to low prevalence of AA amyloidosis development in Greek RA patients.


Better early outcome with enhanced recovery total hip arthroplasty (ERAS-THA) versus conventional setup in randomized clinical trial (RCT).
Numbers of total hip arthroplasty (THA) are steadily rising and patients expect faster mobility without pain postoperatively. The aim of enhanced recovery after Surgery (ERAS) programs in a multidisciplinary setup was to keep pace with the needs of quality and quantity of surgical THA-interventions and patients' expectations. 194 patients undergoing THA procedures were investigated after single-blinded randomization to ERAS (98) or conventional setup group (96). Primary outcome variable was mobilization measured with the Timed Up and Go Test (TUG) in seconds. Secondary outcome variables were floor count and walking distance in meters as well as rest, mobilization and night pain on a numerous rating scale (NRS). All variables were recorded preoperatively and daily until the sixth postoperative day. To assess and compare clinical outcome and patient satisfaction, the PPP33-Score and PROMs were used. No complications such as thromboembolic complications, fractures or revisions were recorded within the first week postoperatively in either study group. Compared to the conventional group, the ERAS group showed significantly better TUG (p < 0.050) and walking distance results after surgery up to the sixth, and floor count up to the third postoperative day. On the first and second postoperative day, ERAS patients showed superior results (p < 0.001) in all independent activity subitems. Regarding the evaluation of pain (NRS), PPP33 and PROMS, no significant difference was shown (p > 0.050). This prospective single-blinded randomized controlled clinical trial was able to demonstrate excellent outcome with comparable pain after ERAS THA versus a conventional setup. Therefore, ERAS could be used in daily clinical practice.


Microarray analysis of gene expression in proliferating Schwann cells: synergistic response of a specific subset of genes to the mitogenic action of heregulin plus forskolin.
Cultured Schwann cells treated with heregulin growth factor require costimulation with a cyclic adenosine monophosphate-elevating agent to produce maximal cell proliferation. Gene chip expression analysis was used to identify genes that are induced or repressed when Schwann cells are treated with heregulin and/or forskolin. By utilizing arrays that contained 8799 probes, the expression of over 1000 genes was found to be significantly changed after 30 hr of treatment with heregulin, forskolin, or heregulin plus forskolin. Hierarchical clustering revealed groups of genes with distinct expression patterns. Of particular interest was a cluster of 140 genes that were up-regulated by heregulin plus forskolin but not by heregulin or forskolin alone. Many of the genes in this group have roles in cell division, such as cyclin B, cyclin D3, E2F-5, cdc 25B, polo-like kinase, and protein kinase C type III. These findings identify a profile of gene expression for Schwann cell proliferation.


Laparoscopic total extraperitoneal (TEP) mesh repair for femoral hernia in a patient of child B liver cirrhosis with ascites. A case report.
Femoral hernia is infrequently encountered in surgical practice and is even rare in patients with liver cirrhosis. Recurrent pain adds to the existing morbidity and affects the quality of life of these patients. Management of such cases had rather high rates of morbidity and mortality owing to hepatic decompensation. However, more recent studies have shown a significant improvement of the quality of life and improved rates of morbidity in cirrhotic patients with inguinal hernias post repair. These studies all included open hernia repair with preperitoneal approach with improved results in terms of morbidity and lower rates of recurrence postoperatively. However, when compared to laparoscopic repairs these have more postoperative complications, complication related re-operations, pain and recurrence rates. Keeping these in mind, the laparoscopic approach was considered in our patient which has not been described yet in literature for femoral hernia. The report is in line with the SCARE criteria. (Agha et al. (2018) [1]) The case report is registered with research registry (UID researchregistry5467). A 40 year old female patient with Child B cirrhosis of liver with ascites was operated for a symptomatic left uncomplicated femoral hernia using standard three port laparoscopic total extraperitoneal repair with prolene mesh. She was discharged on postoperative day 2. She developed ascitic leak from the hypogastric port site in the late postoperative period which was managed conservatively. The patient has remained stable without recurrence at one year follow up. Laparoscopic TEP may be a safe option with no major adverse events in symptomatic femoral hernias. Further studies are needed to ascertain its role.


Failure of oral atenolol and verapamil to increase the capacity and duration of exercise in patients in sinus rhythm with mitral stenosis.
The efficacy of oral atenolol in increasing the capacity and duration of exercise in 43 patients in sinus rhythm with mitral stenosis was evaluated and compared with that of oral verapamil in an open-label cross-over design. It was observed that although oral atenolol (100 mg per day) caused significant reductions in heart rate while resting and during exercise (P less than 0.001), the increases in capacity and duration of exercise were not significant. Oral verapamil (80 mg three times per day) also caused significant reductions in the heart rates at rest and during exercise (P less than 0.05) but the increases observed, although greater than that with atenolol, failed to reach the level of statistical significance. Occasional side effects occurred with both the drugs. Subjective symptoms of dyspnoea at rest and on exertion were relieved with both the drugs. We conclude that, although both drugs reduce the symptoms of dyspnoea, they cause only minor increases in the objective parameters. They do not, therefore, provide an alternative to surgery and have only a temporary place in the management of patients in sinus rhythm with mitral stenosis who are awaiting surgery.


Annoyance due to residential road traffic and aircraft noise: Empirical evidence from two European cities.
Based on a study in two European cities, Mainz in Germany and Zurich in Switzerland, the article investigates both acoustical and non-acoustical factors affecting indoor annoyance due to residential road traffic and aircraft noise. We specifically focus on three factors: (1) the role of windows as a feature of the building where people live; (2) the role of individual environmental concern as a general attitude; and (3) the role of household income as an indicator of socioeconomic resources. Empirical results show that closed windows in general and closed high-quality windows in particular are an important barrier against outdoor road traffic and aircraft noise, as well as a helpful subjective coping tool against corresponding annoyances. Environmental concern, too, proves to be a significant predictor of noise annoyance. Environmentally highly concerned people articulate feelings of annoyance more often than environmentally less concerned ones. As expected income is negatively related to road traffic noise annoyance. However, we find a positive association of income with annoyance from aircraft noise. Although objective exposure to aircraft noise is lower for high-income households, they feel stronger annoyed by noise from airplanes. Income shows various indirect effects on noise annoyance. A comparative analysis of road traffic and aircraft noise annoyance yields similarities, but also remarkable differences in terms of their influence factors.


The influence of environmental efficiency on PM2.5 pollution: Evidence from 283 Chinese prefecture-level cities.
Environmental inefficiency caused by the extensive economic growth pattern is considered a critical driver of the unprecedented PM2.5 (fine particulate matter) pollution in China. However, the nexus between environmental efficiency and PM2.5 concentrations has rarely been examined. We used a recently developed data envelopment analysis method to measure environmental efficiency, environmental total factor productivity, and their compositions in China at the prefecture level from 2003 to 2013 and examined the effects of environmental efficiency on PM2.5 pollution. The results indicated that improvements in environmental efficiency significantly ameliorated PM2.5 pollution. The effect of technological progress on PM2.5 reduction is limited, but the pure efficiency and scale efficiency promoted by enhanced management level and optimized production scale strongly contribute to PM2.5 mitigation. The significant spatial spillover of environmental efficiency and PM2.5 pollution introduces challenges and opportunities for lowering PM2.5 emissions. The impact of environmental efficiency on PM2.5 pollution exhibits significant spatiotemporal heterogeneity, and the strength of influence tends to increase with PM2.5 concentration and become more pronounced over time. Furthermore, several socioeconomic factors are related to PM2.5 pollution, which implies that PM2.5 control is a complex system and requires a comprehensive policy mix.


Outdoor environmental exposome and the burden of tuberculosis: Findings from nearly two million adults in northwestern China.
We simultaneously assessed the associations for a range of outdoor environmental exposures with prevalent tuberculosis (TB) cases in a population-based health program with 1940,622 participants ≥ 15 years of age. TB status was confirmed through bacteriological and clinical assessment. We measured 14 outdoor environmental exposures at residential addresses. An exposome-wide association study (ExWAS) approach was used to estimate cross-sectional associations between environmental exposures and prevalent TB, an adaptive elastic net model (AENET) was implemented to select important exposure(s), and the Extreme Gradient Boosting algorithm was subsequently applied to assess their relative importance. In ExWAS analysis, 12 exposures were significantly associated with prevalent TB. Eight of the exposures were selected as predictors by the AENET model: particulate matter ≤ 2.5 µm (odds ratio [OR]=1.01, p = 0.3295), nitrogen dioxide (OR=1.09, p < 0.0001), carbon monoxide (OR=1.19, p < 0.0001), and wind speed (OR=1.08, p < 0.0001) were positively associated with the odds of prevalent TB while sulfur dioxide (OR=0.95, p = 0.0017), altitude (OR=0.97, p < 0.0001), artificial light at night (OR=0.98, p = 0.0001), and proportion of forests, shrublands, and grasslands (OR=0.95, p < 0.0001) were negatively associated with the odds of prevalent TB. Air pollutants had higher relative importance than meteorological and geographical factors, and the outdoor environment collectively explained 11% of TB prevalence.


Antigenicity of adult Schistosoma mansoni alkaline phosphatase.
Antibodies to the alkaline phosphatase (AP) of Schistosoma mansoni in infected human and mice sera were evaluated by a direct solid-phase AP immunoadsorption assay (APIA) and by Western blot and immunostaining. APIA consisted of (a) solid-phase capture of immunoglobulins from infected human or mice, (b) immunoadsorption of the enzyme antigen by the antibodies, and (c) detection of the enzymatic activity. By this procedure the appearance of the anti-AP response in mice was detected around 50 days post-infection; this response was not specific for an AP of a given schistosome strain and it was not induced by an autoimmunity phenomenon. Fourteen out of 15 sera from infected people tested by APIA showed a clear antibody response against this enzyme. Immunoblots in non-reducing conditions supported APIA results indicating that the parasite AP was specifically recognized by the antibodies present in infected human and mice sera. These results suggest the possible usefulness of the schistosome AP as a marker for S. mansoni infection.


Pulmonary hypoplasia and anasarca syndrome in Cika cattle.
Hydrops foetalis is defined as excessive fluid accumulation within the foetal extravascular compartments and body cavities. It has been described in human and veterinary medicine, but despite several descriptive studies its aetiology is still not fully clarified. Pulmonary hypoplasia and anasarca (PHA) syndrome is a rare congenital abnormality in cattle that is characterised by hydrops foetalis including extreme subcutaneous oedema (anasarca) and undeveloped or poorly formed lungs (pulmonary hypoplasia). Until now, sporadic cases of PHA were reported in cattle breeds like Australian Dexter, Belted Galloway, Maine-Anjou, and Shorthorn. This report describes the first known cases of PHA syndrome in Slovenian Cika cattle. A 13-year-old cow aborted a male calf in the seventh month of pregnancy, while a male calf was delivered by caesarean section on the due date from a 14-year-old cow. The pedigree analysis showed that the calves were sired by the same bull, the dams were paternal half-sisters and the second calf was the product of a dam-son mating. Gross lesions were similar in both cases and characterized by severe anasarca, hydrothorax, hydropericardium, ascites, hypoplastic lungs, absence of lymph nodes, and an enlarged heart. The first calf was also athymic. Histopathology of the second affected calf confirmed severe oedema of the subcutis and interstitium of the organs, and pulmonary hypoplasia. The lymph vessels in the subcutis and other organs were severely dilated. Histopathology of the second calf revealed also lack of bronchus associated lymphoid tissue and adrenal gland hypoplasia. The findings were consistent with known forms of the bovine PHA syndrome. This is the first report of the PHA syndrome occurring in the local endangered breed of Cika cattle. Observed inbreeding practice supports that this lethal defect most likely follows an autosomal recessive mode of inheritance. In the light of the disease phenotype it is assumed that a mutation causing an impaired development of lymph vessels is responsible for the hydrops foetalis associated malformations in bovine PHA.


Determination of heptaminol in human plasma and urine by high-performance liquid chromatography.
Heptaminol was measured in plasma and urine following pre-column derivatisation with o-phthalaldehyde and reversed-phase high-performance liquid chromatography employing fluorescence detection. The limits of detection were sufficient for pharmacokinetic studies of the drug after clinically-used doses. Plasma concentrations of heptaminol reached peak levels (2.19 micrograms/ml) at 0.75 h after single oral doses (0.47 g of heptaminol) and declined with a half-life of 2.1 h (+/- 0.5 S.D.). Heptaminol was well absorbed and excreted rapidly, mainly unchanged in urine, 82% dose (+/- 10 S.D.).


Training and function of a women's health-care specialist, a physician's assistant, or nurse practitioner in obstetrics and gynecology.
Serious manpower shortages exist in the United States. Proposed corrective measures indicate the need for nonphysicians to provide medical care for well or worried well patients. We have tested this proposed solution in the field of obstetrics and gynecology using allied health personnel to provide health maintenance services to well women, and feel that the experiment has been a success. Using principles of pattern recognition allied health workers recognize normal and abnormal findings. Patients with abnormalities are referred to the supervising physician for diagnosis and therapy. Allied health workers can also perform technical health-maintenance tasks such as inserting intrauterine devices and obtaining Pap smears. This article describes the historical evolution of our allied health personnel workers, called women's health-care specialists (WHCS), the selection and training of students, functions and levels of performance of the specialists, and the future role of such individuals in obstetrics and gynecology. We feel that with appropriate preparation of the physician, co-workers, and patients, the integration of the WHCS into the health-care system is both desirable and appropriate and will offer significant advantages to the patient and the practicing obstetrician-gynecologist in either the clinic or private practice setting.


The Skin Microbiome: A New Actor in Inflammatory Acne.
Our understanding of the role of Cutibacterium acnes in the pathophysiology of acne has recently undergone a paradigm shift: rather than C. acnes hyperproliferation, it is the loss of balance between the different C. acnes phylotypes, together with a dysbiosis of the skin microbiome, which results in acne development. The loss of diversity of C. acnes phylotypes acts as a trigger for innate immune system activation, leading to cutaneous inflammation. A predominance of C. acnes phylotype IA1 has been observed, with a more virulent profile in acne than in normal skin. Other bacteria, mainly Staphylococcus epidermis, are also implicated in acne. S. epidermidis and C. acnes interact and are critical for the regulation of skin homeostasis. Recent studies also showed that the gut microbiome is involved in acne, through interactions with the skin microbiome. As commonly used topical and systemic antibiotics induce cutaneous dysbiosis, our new understanding of acne pathophysiology has prompted a change in direction for acne treatment. In the future, the development of individualized acne therapies will allow targeting of the pathogenic strains, leaving the commensal strains intact. Such alternative treatments, involving modifications of the microbiome, will form the next generation of 'ecobiological' anti-inflammatory treatments.


Characterization of anthropogenic materials on yellow-legged gull (Larus michahellis) nests breeding in natural and urban sites along the coast of Portugal.
Anthropogenic materials are a persistent pressure on ecosystems, affecting many species. Seabirds can collect these materials to construct their nests, which may modify nest characteristics and cause entanglement of chicks and adults, with possible consequences on breeding success. The incorporation of anthropogenic materials in nests of seabird species that breed in both natural and urban environments, such as gulls, is poorly known. Here, we characterize and compare anthropogenic materials incorporated in yellow-legged gull (Larus michahellis) nests from two natural and two urban breeding sites across their Portuguese breeding range and during 2 consecutive years. Anthropogenic materials were found in 2.6% and 15.4% of gull nests from natural locations and in 47.6% and 95.7% of nests from urban breeding sites. No differences were found on hatching success between urban and natural breeding colonies. A significantly higher number of anthropogenic materials were found in the largest and more populated urban breeding colony, which on average included items of a greater mass but smaller size than items from the other three colonies. The higher incorporation of anthropogenic materials in urban locations could be a consequence of a lower access to natural nest construction materials and higher availability of anthropogenic debris. The quantity and diversity of anthropogenic materials incorporated in gull nests from urban locations indicate a need for improved debris management in urban settlements.


Chronology of endocrine differentiation and beta-cell neogenesis.
Diabetes is a chronic and incurable disease, which results from absolute or relative insulin insufficiency. Therefore, pancreatic beta cells, which are the only type of cell that expresses insulin, is considered to be a potential target for the cure of diabetes. Although the findings regarding beta-cell neogenesis during pancreas development have been exploited to induce insulin-producing cells from non-beta cells, there are still many hurdles towards generating fully functional beta cells that can produce high levels of insulin and respond to physiological signals. To overcome these problems, a solid understanding of pancreas development and beta-cell formation is required, and several mouse models have been developed to reveal the unique features of each endocrine cell type at distinct developmental time points. Here I review our understanding of pancreas development and endocrine differentiation focusing on recent progresses in improving temporal cell labeling in vivo.


Assignment of 22 loci in the rat by somatic hybrid and linkage analysis.
Twenty structural genes and two unique anonymous DNA fragments have been mapped in the rat (Rattus norvegicus) with a panel of mouse x rat hybrids and linkage analysis. Ten of the 20 autosomes are represented by at least one of these markers. A new syntenic relationship among rat Chromosome (Chr) 16, mouse Chr 14, and human Chr 10q was established. Results of this study further support the extensive conservation of synteny between the rat and mouse and, to a lesser degree, between rat and human.


Global Nurse Involvement in ethical decision-making during pandemics: a concept analysis.
During pandemics, there are considerable ethical dilemmas. It is imperative that nurses are involved in ethical decision-making bringing nursing theory, practice and perspectives to better advocate for patients. In order to prepare nurses to be partners in ethical dilemma decision-making during pandemics, it is vital to understand the extent that nurses are involved in such decision-making during the COVID-19 pandemic. The purpose of this concept analysis is to identify nurse involvement in ethical decision-making during pandemics. Concept analysis methodology based on literature searches used bibliographic databases: PubMed - 20 papers; Google Scholar - 8120 papers; EMBASE - 25 papers; Science Direct - 246 papers and hand searches. Nurse involvement in ethical decision-making during pandemics focused on nurses' physical and emotional stress, communication challenges, saturation and collapse of limited resources and allocation of scarce resources. Additional dilemmas included, changing nature of nurses' relationships with patients and families, questionable ethical equipoise preforming COVID-19 research, triage patient decisions receiving scarce resources, partner participation during labour and delivery and end-of-life decisions. In order to protect and sustain nurses' well-being and competency, nurses should establish a framework for nurses' involvement in ethical policy development in emergencies, pandemics, education and preparedness and decision-making to be able to deal with public health emergencies.


Hydroxamate-based inhibitors of low affinity IgE receptor (CD23) processing.
A series of hydroxamic acids related to the non-selective matrix metalloprotease inhibitor Batimastat is described, which inhibits the proteolytic cleavage of the low affinity IgE receptor from cell membrane preparations. Limited SAR studies suggest that the structural requirements for effective inhibition are distinct from those required for the inhibition of collagenase.


Response to reactive nitrogen intermediates in Mycobacterium tuberculosis: induction of the 16-kilodalton alpha-crystallin homolog by exposure to nitric oxide donors.
In contrast to the apparent paucity of Mycobacterium tuberculosis response to reactive oxygen intermediates, this organism has evolved a specific response to nitric oxide challenge. Exposure of M. tuberculosis to NO donors induces the synthesis of a set of polypeptides that have been collectively termed Nox. In this work, the most prominent Nox polypeptide, Nox16, was identified by immunoblotting and by N-terminal sequencing as the alpha-crystallin-related, 16-kDa small heat shock protein, sHsp16. A panel of chemically diverse donors of nitric oxide, with the exception of nitroprusside, induced sHsp16 (Nox16). Nitroprusside, a coordination complex of Fe2+ with a nitrosonium (NO+) ion, induced a 19-kDa polypeptide (Nox19) homologous to the nonheme bacterial ferritins. We conclude that the NO response in M. tuberculosis is dominated by increased synthesis of the alpha-crystallin homolog sHsp16, previously implicated in stationary-phase processes and found in this study to be a major M. tuberculosis protein induced upon exposure to reactive nitrogen intermediates.