Reduced number of glomeruli in kidneys with neonatally induced partial ureteropelvic obstruction in pigs.
We quantify the structural components of the nephron in adult pig kidneys with neonatally induced unilateral hydronephrosis in comparison with nonobstructed kidneys. The study included 11 pigs with unilateral partial ureteropelvic obstruction induced 2 days after birth and 8 sham operated control pigs. Obstructed kidney glomerular filtration rate was significantly reduced at age 4 weeks but did not differ from control kidneys after 24 weeks. At age 24 weeks the kidneys were perfusion fixed, and the number and volume of glomeruli and tubular lengths were measured using stereological methods. Mean obstructed kidney volume did not differ from that of control kidneys. Mean number plus or minus standard deviation of glomeruli in the obstructed kidneys was reduced by 28% compared to that of control kidneys (502 +/- 163 x 103 versus 697 +/- 161 x 103, p = 0.02), whereas no difference in mean glomerular volume was observed. Mean length of the proximal or distal tubules did not differ between obstructed and control kidneys. Mean number or volume of glomeruli in nonobstructed kidneys contralateral to obstructed kidneys did not differ from that of control kidneys. The individual number of glomeruli in the obstructed kidneys was not associated with function of these kidneys. Neonatally induced unilateral partial ureteropelvic obstruction causes impaired nephrogenesis with a significant reduction in the number of nephrons, which is not reflected in measurements of kidney function in this model. The reduction in the number of glomeruli suggests that congenital unilateral obstruction impairs nephrogenesis.


In Vivo Biocatalytic Cascades Featuring an Artificial-Enzyme-Catalysed New-to-Nature Reaction.
Artificial enzymes utilizing the genetically encoded non-proteinogenic amino acid p-aminophenylalanine (pAF) as a catalytic residue are able to react with carbonyl compounds through an iminium ion mechanism to promote reactions that have no equivalent in nature. Herein, we report an in vivo biocatalytic cascade that is augmented with such an artificial enzyme-catalysed new-to-nature reaction. The artificial enzyme in this study is a pAF-containing evolved variant of the lactococcal multidrug-resistance regulator, designated LmrR_V15pAF_RMH, which efficiently converts benzaldehyde derivatives produced in vivo into the corresponding hydrazone products inside E. coli cells. These in vivo biocatalytic cascades comprising an artificial-enzyme-catalysed reaction are an important step towards achieving a hybrid metabolism.


High Current Density Oxygen Evolution in Carbonate Buffered Solution Achieved by Active Site Densification and Electrolyte Engineering.
High current density reaching 1 A cm-2 for efficient oxygen evolution reaction (OER) was demonstrated by interactively optimizing electrolyte and electrode at non-extreme pH levels. Careful electrolyte assessment revealed that the state-of-the-art nickel-iron oxide electrocatalyst in alkaline solution maintained its high OER performance with a small Tafel slope in K-carbonate solution at pH 10.5 at 353 K. The OER performance was improved when Cu or Au was introduced into the FeOx -modified nanostructured Ni electrode as the third element during the preparation of electrode by electrodeposition. The resultant OER achieved 1 A cm-2 at 1.53 V vs. reversible hydrogen electrode (RHE) stably for 90 h, comparable to those in extreme alkaline conditions. Constant Tafel slopes, apparent activation energy, and the same signatures from operando X-ray absorption spectroscopy among these samples suggested that this improvement seems solely correlated with enhanced electrochemical surface area caused by adding the third element.


Subtemporal-infratemporal and basal subfrontal approach to extensive cranial base tumours.
A subtemporal-infratemporal and basal subfrontal approach for the removal of extensive, predominantly extradural cranial base neoplasms is described. This approach was used successfully in six of our patients. The advantages of this approach are extensive exposure of the anterior and mid-cranial base as well as the clivus, direct exposure and management of the ipsilateral petrous and cavernous internal carotid artery (ICA), and access to extracranial vessels for microvascular flap transfer. Disadvantages include prolonged operative time and less control of the contralateral petrous ICA. Six patients with extensive cranial base neoplasms had operations using this technique without any mortality or major permanent morbidity. The value of this approach to patients in terms of control or cure of extensive cranial base tumours has to be proven by long term follow-up.


Effectiveness of collagen-gentamicin implant for treatment of "dirty" abdominal wounds.
The purpose of this work was to compare the efficacy and safety of the collagen-gentamicin sponge with conventional treatment (wound open, maintaining a close observation, and cleaning it daily with antiseptics) for the prophylaxis of infection in "dirty" abdominal wounds. Seventy-three patients with dirty abdominal wounds caused by gastrointestinal tract surgery were studied. The patients were randomized in two groups: group A, open wounds, treated with local cleansing, metronidazole 20 to 40 mg/kg/day IV and gentamicin 5 mg/kg/day IV for 7 days. Group B, primary closure with collagen-gentamicin implant plus metronidazole 20 to 40 mg/kg/day IV for 7 days. Surgical wound infections were significantly reduced by the collagen-gentamicin implant. Polymicrobial infections were observed in group A, whereas the infections were caused only by a single organism in group B. In conclusion, the collagen-gentamicin implant is effective and well tolerated in the treatment of "dirty" surgical abdominal wounds because it significantly reduces the wound infection rate (p < 0.01) and shortens healing time (p < 0.001) and the period of disability.


Synthesis of Azoxy Compounds: from Copper Compounds to Mesoporous Silica-Encaged Ultrasmall Copper Catalysts.
Azoxy compounds have aroused extensive attention due to their unique biological activities, but the chemical synthesis of these compounds often suffers from limitations due to their requirement for stoichiometric oxidants, high costs, and restricted substrate range. Herein, a series of azoxy compounds were constructed via facile coupling reactions by using cost-effective N-methoxyformamide and nitroso compounds over Cu-based catalysts, affording high product yields with excellent tolerance of functional groups. Significantly, the mesoporous silica nanosphere-encapsulated ultrasmall Cu (Cu@MSN) catalyst was developed via a one-pot synthetic method and first used for the synthesis of azoxy compounds. As compared with copper salt catalysts, the Cu@MSN catalyst exhibited remarkably enhanced catalytic activity and superior recycling stability. Such a Cu@MSN catalyst overcame the inherent drawbacks of low activity, fast deactivation, and difficult recycling of traditional metal salt catalysts in organic reactions. This work provides a green and efficient method for the construction of azoxy compounds and also creates new prospects for the application of nanoporous materials confined metal catalysts in organic synthesis.


Predicting factors for relapse in patients with granulomatosis with polyangiitis: results from a long-term cohort.
To investigate the predictive factors and the best predictive model for relapse in granulomatosis with polyangiitis (GPA) patients. All patients referred to our tertiary university hospital with confirmed diagnosis of GPA based on 1990-ACR criteria and/or revised Chapel Hill nomenclature, who were followed more than 24 months between 2012 and 2021 were included. Patients were classified into relapsing and non-relapsing groups. Disease activity was assessed based on Birmingham Vasculitis Activity Score (BVAS) and BVAS for GPA (BVAS-GPA). All demographic, clinical, laboratory, and radiologic parameters were compared between two groups. Data of 133 patients (male = 52 (39.1%); mean age = 46.5 ± 14.5 years) with a mean follow-up period of 49.4 ± 24.1 months were evaluated. Of those, 91 (68.4%) experienced at least one relapse episode. The mean duration of relapse-free-survival (RFS) was 12.5 months with 1-year, 3-year, and 5-year RFS rates of 46.6%, 34.6%, and 31.6%, respectively. The risk of relapse was higher if patients had higher BVAS or BVAS-GPA score (P-values < 0.001), constitutional syndrome (P-value = 0.01), neutrophil-to-lymphocyte ratio (NLR) (P-value = 0.01), C-reactive-protein (P-value = 0.03), alanine transaminase > 40 units/L (P-value = 0.04), and microscopic hematuria (P-value = 0.001). In backward logistic regression analysis, baseline BVAS score ≥ 12 (Ex(B) = 4.21, P-value = 0.03), and NLR > 2.5 (Ex(B) = 12.00, P-value = 0.007) remained statistically significant at the last step of the model with 75.8% sensitivity, 76.9% specificity, and 76.3% accuracy in predicting the relapsing patients. The frequency of relapse episodes was significantly lower in treatment group of rituximab-rituximab (0.3 ± 0.6) compared to cyclophosphamide-methotrexate (1.2 ± 1.3) and cyclophosphamide-azathioprine (1.8 ± 1.5) treatment protocols (P-value = 0.002). High-risk patients according to proposed model should be prioritized for more intensive care, more aggressive treatment, and closer follow-ups. • During the mean follow-up period of 50 months, 68.4% experienced at least one relapse episode • Patients with baseline BVAS > 12, renal involvement, and elevated NLR are more vulnerable to relapsing disease • Patients on rituximab for induction and maintenance less experienced relapse episodes compared to other treatment regimens.


[The pretransfusion bedside agglutination test is not a "Gold Standard"].
ABO-incompatible transfusions remain frequent in Europe despite the technological progresses in relation with the potential number of human errors during the control procedures of the transfusion chain. The agglutination bedside-test is only one step of this chain and the amelioration of the security will be achieved by its replacement by an electronical check.


Modular Design of High-Brightness pH-Activatable Near-Infrared BODIPY Probes for Noninvasive Fluorescence Detection of Deep-Seated Early Breast Cancer Bone Metastasis: Remarkable Axial Substituent Effect on Performance.
We herein report a series of high-brightness pH-activatable near-infrared (NIR) BODIPY probes for high-contrast intravital imaging of deep-seated early breast cancer bone metastasis by harnessing the axial substituent effect. These probes exhibit tunable pK a, higher brightness, and antiquenching capabilities in aqueous solution, which can be simultaneously adjusted by axial steric substituents. The optimized probe BODO-3 bearing axial dimethyl substituents exhibited a higher pK a value of 5.6 and a brighter NIR fluorescence under tumor acidic pH, showing 10.3-fold and 6.5-fold enhanced brightness (εΦ) at pH 5.5 and 6.5, respectively. Due to the higher brightness, BODO-3 with a brilliant NIR emission at 700 nm allows for deep optical penetrations of 5 and 8 mm at pH 6.5 and 4.5, respectively. Meanwhile, covalent functionalization with glucose (BODO-3-Glu) could further enhance breast cancer and its soft tissue metastasis imaging in vivo. Notably, covalent functionalization with bisphosphonate (BODO-3-PO 3 H 2 ) allowed the successful targeting and visualization of deep-seated bone metastases of breast cancer with a high tumor to normal contrast of 8/1, outperforming X-rays in early detection. This strategy may provide insights for designing high-brightness activatable NIR probes for detecting deep-seated tumors and metastases.


Metabolic diagnostic work-up in chronic conditions.
Neurological symptoms are very frequent in inborn errors of metabolism. This chapter presents a general approach to investigate inborn errors of metabolism in chronic neurological conditions. A diagnostic work-up has been designed to evaluate progressive neurological conditions with motor, cognitive, and/or behavioral signs in early infancy, late infancy to early childhood, and late childhood to adolescence. Inborn errors of metabolism associated with peripheral neuropathies, microcephaly, or macrocephaly are also reviewed.


Failure of repeated blood patch in the treatment of spinal headache.
The management of a persistent, incapacitating postdural puncture headache that required four consecutive autologous epidural blood patches is presented. Inadequate blood volumes, early patching and steroid in the epidural space are considered as possible causes of failure. Other associated problems and interventions are briefly discussed.


Photosensitivity in South Africa. V. A comparative study of the pathology of the ovine hepatogenous photosensitivity diseases, facial eczema and geeldikkop (Tribulosis ovis), with special reference to their pathogenesis.
The subject of this study was the pathological and scanning electron microscopical changes in the biliary systems of sheep suffering from facial eczema or geeldikkop (Tribulosis ovis), or made photosensitive by ligation of the common bile duct. While an obliterative cholangitis is responsible for the retention of phylloerythrin in facial eczema, the occlusion of bile ducts with crystalloid material (microliths) appear to perform a similar function in geeldikkop. The similarities and differences between the 2 diseases are discussed in the light of their pathogenetic mechanisms.


Comparison of erythroid progenitor cell growth in vitro in polycythemia vera and chronic myelogenous leukemia: only polycythemia vera has endogenous colonies.
The ability of erythroid cultures to distinguish among myeloproliferative disorders was examined. We studied 14 patients with polycythemia vera (PV), 11 with chronic myelogenous leukemia (CML), four with non-PV erythrocytosis, two with agnogenic myeloid metaplasia, as well as three normal fetuses and greater than 25 normal adults. Endogenous, i.e. grew without added erythropoietin, bone marrow CFU-E-derived colonies were observed in all but one PV patient. However, endogenous blood BFU-E-derived bursts were observed in only eight of 14 PV patients. Endogenous erythroid colonies were not seen in cultures from any normal adults or fetuses, or patients with CML, erythrocytosis, or myeloid metaplasia. In PV, relative HbF synthesis was always greater in cultures without erythropoietin, while in cultures from all other patients relative HbF synthesis was similar to that observed in cultures from normal individuals. We conclude that PV and CML are distinguishable in culture since CML patients do not have endogenous growth. Most important, endogenous bone marrow CFU-E-derived colonies are the only consistently unique observation in patients with PV, and endogenous CFU-E- and BFU-E-derived colonies and bursts are not uniformly observed in PV blood cultures. In-vitro studies of erythropoiesis to confirm the diagnosis of PV, therefore, require marrow when endogenous colonies and bursts are absent from blood cultures.


Epithelial modulation of non-adrenergic, non-cholinergic and vasoactive intestinal peptide-induced responses: role of neutral endopeptidase.
Relaxation of guinea-pig trachea was induced by vasoactive intestinal peptide (VIP) or electrical field stimulation. Mechanical removal of airway epithelium potentiated responses to VIP and attenuated inhibitory non-adrenergic, non-cholinergic (i-NANC) responses to low stimulation frequencies. Phosphoramidon potentiated responses to VIP in intact but not de-epithelialised preparations, and had no effect on i-NANC responses. These findings suggest that neutral endopeptidase localised to the epithelium may modulate relaxation of guinea-pig trachea induced by VIP but not i-NANC nerve-stimulation.


Thioredoxin as a biomarker for oxidative stress in patients with rheumatoid arthritis.
There is no doubt that oxidative stress occurs in patients with rheumatoid arthritis (RA) and play an important role in both inflammation and destruction of RA joints. Thioredoxin (TRX) is a ubiquitous redox-active protein and is known to be induced in several cells against oxidative stress and to be secreted extracellularly. To clarify whether plasma thioredoxin levels could be a marker for oxidative stress in patients with RA, we measured plasma TRX levels in patients with RA using a sensitive sandwich enzyme-linked immunosorbent assay (ELISA) and investigated its relationship to TRX concentrations in the inflammatory joints. We have found that the plasma TRX levels of RA patients were significantly higher than those of normal subjects (86.8 +/-54.1 ng/ml versus 38.6 +/-18.5 ng/ml, P<0.0001). The plasma levels were correlated with the disease activity of RA and also with serum C-reactive protein (CRP) values (P<0.01). The concentration of TRX in synovial fluid (SF) from RA was 353.3 +/- 220.1 ng/ml (mean +/- S.D.) which was significantly higher than that in SF from osteoarthritis patients (70.6 +/- 31.0 ng/ml, P<0.0001). The SF TRX concentration was significantly correlated with the number of leukocytes infiltrating in SF and with the serum CRP levels. The serum TRX levels were significantly positively correlated with the SF TRX concentrations in RA patients (P<0.05). By the histological examination for synovial tissue of RA patients, TRX was shown to be present on the surface of synovial lining layer as well as in the leukocytes.Moreover, urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage by endogenously generated oxygen radicals, was significantly higher in RA patients than in healthy subjects (11.55 +/- 4.71 versus 7.76 +/- 2.26 ng/mg creatinine, P<0.0001). Plasma TRX levels were significantly correlated with urinary excretion of 8-OHdG (P<0.005). We concluded that plasma TRX level is a new biomarker for the disease activity of RA and may reflect higher levels of oxidative stress in RA patients.


Linear-array EUS improves detection of pancreatic lesions in high-risk individuals: a randomized tandem study.
Studies comparing linear and radial EUS for the detection of pancreatic lesions in an asymptomatic population with increased risk for pancreatic cancer are lacking. To compare pancreatic lesion detection rates between radial and linear EUS and to determine the incremental diagnostic yield of a second EUS examination. Randomized controlled tandem study. Five academic centers in the United States. Asymptomatic high-risk individuals (HRIs) for pancreatic cancer undergoing screening EUS. Linear and radial EUS performed in randomized order. Pancreatic lesion detection rate by type of EUS, miss rate of 1 EUS examination, and incremental diagnostic yield of a second EUS examination (second-pass effect). Two hundred seventy-eight HRIs were enrolled, mean age 56 years (43.2%), and 90% were familial pancreatic cancer relatives. Two hundred twenty-four HRIs underwent tandem radial and linear EUS. When we used per-patient analysis, the overall prevalence of any pancreatic lesion was 45%. Overall, 16 of 224 HRIs (7.1%) had lesions missed during the initial EUS that were detected by the second EUS examination. The per-patient lesion miss rate was significantly greater for radial followed by linear EUS (9.8%) than for linear followed by radial EUS (4.5%) (P = .03). When we used per-lesion analysis, 73 of 109 lesions (67%) were detected by radial EUS and 99 of 120 lesions (82%) were detected by linear EUS (P < .001) during the first examination. The overall miss rate for a pancreatic lesion after 1 EUS examination was 47 of 229 (25%). The miss rate was significantly lower for linear EUS compared with radial EUS (17.5% vs 33.0%, P = .007). Most detected pancreatic lesions were not confirmed by pathology. Linear EUS detects more pancreatic lesions than radial EUS. There was a "second-pass effect" with additional lesions detected with a second EUS examination. This effect was significantly greater when linear EUS was used after an initial radial EUS examination.


Predicting Student Engagement: The Role of Academic Belonging, Social Integration, and Resilience During COVID-19 Emergency Remote Teaching.
The COVID-19 pandemic has forced higher education (HE) to shift to emergency remote teaching (ERT), subsequently influencing academic belonging and social integration, as well as challenging students' engagement with their studies. This study investigated influences on student engagement during ERT, based on student resilience. Serial mediation analyses were used to test the predictive effects between resilience, academic belonging, social integration, and engagement. The Student Well-being Monitor (SWM 2021) was completed by 1332 HE students studying at Inholland University of Applied Sciences in the Netherlands. Predictive models were compared among students with low, normal, or high resilience using SPSS extension Macro PROCESS. A significant serial mediation model was found among all HE students, including positive mediating effects of academic belonging and social integration. More so, independent partial predictive effects of academic belonging and social integration on engagement were also present. Assessment of student resilience profiles revealed substantial differences between predictive models. For low resilience students, serial mediation was present and included the largest partial predictive effect from social integration compared to other groups. For highly resilient students, mediation via academic belonging was found, including the strongest partial and indirect effects compared to other groups. Overall, academic belonging and social integration positively mediate the effect of resilience on engagement in addition to demonstrating independent positive predictive effects. Inspection of resilience profiles reveals substantial model fit differences, suggesting use of different engagement strategies between student groups. Findings contribute to understanding of HE student engagement during ERT in the Netherlands and provide novel insight on the mechanisms between resilience and engagement. While ERT continues to be required, engagement may be enhanced by stimulating academic belonging for all students generally, but low resilience students could be best served by additionally targeting social integration and resilience.


Penile electrodiagnosis. Value of bulbocavernosus reflex latency versus nerve conduction velocity of the dorsal nerve of the penis in diagnosis of diabetic impotence.
The nerve conduction velocity of the dorsal nerve of the penis was evaluated with a direct measuring technique in impotent men with and without diabetes mellitus. The average nerve conduction velocity was 37 M. per second in impotent diabetics and 45 M. per second in nondiabetics. The latency of the bulbocavernosus reflex showed no significant difference between the groups and was within normal limits. The measurement of the nerve conduction velocity of the dorsal nerve of the penis is a valuable test for assessment of impotence in patients with diabetes mellitus.


A study protocol to evaluate the impact of a personal and domestic hygiene intervention on lead exposure in a community next to a mine dump.
Lead has been associated with adverse health effects, especially neurocognitive and behavioural effects, in children. Communities living close to mining land are at risk of elevated exposure to lead. This paper outlines a before and after intervention study protocol to evaluate the impact of a personal and domestic hygiene intervention on lead exposure in a community located adjacent to a mine dump. In each participating household, parents or guardians will be interviewed using a structured questionnaire to obtain information on socio-demographic characteristics, living conditions, domestic hygiene practices and potential alternative sources of exposure to lead. A registered nurse will collect hand wipe samples from children aged one to five years, for whom parental consent and where possible child assent has been obtained. Environmental dust samples will be collected from the floors and/or windowsills of children's dwellings for lead content analysis. Soil samples will be collected from yards to determine lead content. An educational intervention will then be applied to the intervention group, including the engagement of households or guardians in an educational discussion on the sources, pathways of exposure, health effects of lead exposure and protective measures, with the aid of a specially designed educational brochure. Data will be analysed for descriptive and inferential statistics using Stata version 16. The study will determine whether the intervention led to a reduction in indoor dust lead levels, and if shown to be effective, will inform the development of an awareness campaign to reduce lead exposure in communities located in close proximity to mine dumps. The study is retrospectively registered on ClinicalTrials.gov Protocol Registration and Results System with registration number NCT05265572 and first release date of 18th February 2022.


Sequential and structural homology between intracellular pathogenesis-related proteins and a group of latex proteins.
The intracellular pathogenesis-related proteins have been identified in a broad range of flowering plants. Some display quite different patterns of expression, in many cases unrelated to the pathogenic response. Nevertheless, these proteins are all very similar and in most cases share more than 35% sequence identity. In this report we investigate the significance of a rather weak similarity between the intracellular pathogenesis-related (IPR or PR-10) proteins and a group of proteins identified in the latex of opium poppy and in Arabidopsis, among others. A sequence analysis held together with the recently published three-dimensional structure of Bet v 1, an IPR protein from birch pollen, strongly suggests sequential and structural homology between the two protein families.


Peguero-Lo Presti criteria modified by body surface area for the electrocardiographic diagnosis of left ventricular hypertrophy in Thai patients.
Several electrocardiographic (ECG) criteria are used to diagnose left ventricular hypertrophy (LVH); however, they have low sensitivity. To assess the sensitivity of LVH diagnosis using Peguero-Lo Presti criteria modified by body surface area (BSA). This study used retrospective data from 9,438 patients who attended the Central Chest Institute of Thailand from January 2017 to December 2017 with available echocardiography, and who were categorized into those with and without LVH to determine diagnostic accuracy. We randomly selected 317 patients after excluding others based on various conditions. The left ventricular mass of the 317 patients was estimated using echocardiography. Peguero-Lo Presti criteria were modified by dividing original criteria by BSA. The accuracy of the modified criteria was compared with that of the original Peguero-Lo Presti, Sokolow-Lyon, and Cornell voltage criteria. A McNemar test was used to determine the agreement of all ECG criteria examined with LV mass index. The area under a receiver operating characteristic curve (AUC) was used to assess the performance of the criteria. LVH was diagnosed in 164 of the 317 patients using echocardiography. The sensitivity of modified Peguero-Lo Presti criteria was 50.6% (95% confidence interval [CI] 42.7% to 58.5%), and specificity was 88.2% (95% CI 82.0% to 92.9%), with an AUC of 0.67 (95% CI 0.61-0.73). Peguero-Lo Presti criteria modified by dividing them by BSA can improve sensitivity with acceptable specificity for the diagnosis of LVH compared with other ECG criteria examined, at least in selected Thai patients. The modified Peguero-Lo Presti criteria have accuracy similar to that for the original criteria.


Practical implications of postoperative adhesions for preoperative consent and operative technique.
Adhesions complicate most intra-peritoneal operations. Once adhesions have formed, patients are at life-long risk for complications that include small bowel obstruction, increased risks during subsequent operations and female infertility. This has two implications for the daily work of surgeons. On the one hand, surgeons need to include the risks from adhesions during pre-operative consent. On the other hand, surgeons need to use operative techniques that minimize adhesions. Therefore this review focuses on the practical implications of adhesions for preoperative consent and operative technique.


Enhanced shear protection and increased production of an anti-tumor polysaccharide by Agaricus blazei in xanthan-supplemented cultures.
Xanthan supplementation provided shear protection and stimulated polysaccharide production by Agaricus blazei. In xanthan-free cultures, the optimal cell yield, 0.63 g biomass g(-1) glucose, and product yield, 0.19 g polysaccharide g(-1) glucose, were, respectively, when the critical impeller tip speed was 50.3 cm s(-1) and 100.5 cm s(-1). Furthermore, the critical impeller tip speed of cell yield shifted from 50.3 cm s(-1) to 100.5 cm s(-1) with the supplementation of 1 g xanthan l(-1). Maximum specific product yield, namely 0.74 g polysaccharide g(-1) biomass, was achieved with inlet air supply of 3% O2 and impeller tip speed of 100.5 cm s(-1).


Correlation between changes of pelvic bone marrow fat content and hematological toxicity in concurrent chemoradiotherapy for cervical cancer.
To quantify the pelvic bone marrow (PBM) fat content changes receiving different radiation doses of concurrent chemoradiotherapy for cervical cancer and to determine association with peripheral blood cell counts. The data of 54 patients were prospectively collected. Patients underwent MRI iterative decomposition of water and fat with echo asymmetrical and least squares estimation (IDEAL IQ) scanning at RT-Pre, RT mid-point, RT end, and six months. The changes in proton density fat fraction (PDFF%) at 5-10 Gy, 10-15 Gy, 15-20 Gy, 20-30 Gy, 30-40 Gy, 40-50 Gy, and > 50 Gy doses were analyzed. Spearman's rank correlations were performed between peripheral blood cell counts versus the differences in PDFF% at different dose gradients before and after treatment. The lymphocytes (ALC) nadirs appeared at the midpoint of radiotherapy, which was only 27.6% of RT-Pre; the white blood cells (WBC), neutrophils (ANC), and platelets (PLT) nadirs appeared at the end of radiotherapy which was 52.4%, 65.1%, and 69.3% of RT-Pre, respectively. At RT mid-point and RT-end, PDFF% increased by 46.8% and 58.5%, respectively. Six months after radiotherapy, PDFF% decreased by 4.71% under 5-30 Gy compared to RT-end, while it still increased by 55.95% compared to RT-Pre. There was a significant positive correlation between PDFF% and ANC nadirs at 5-10 Gy (r = 0.62, P = 0.006), and correlation was observed between PDFF% and ALC nadirs at 5-10 Gy (r = 0.554, P = 0.017). MRI IDEAL IQ imaging is a non-invasive approach to evaluate and track the changes of PBM fat content with concurrent chemoradiotherapy for cervical cancer. The limitation of low-dose bone marrow irradiation volume in cervical cancer concurrent chemoradiotherapy should be paid more attention to.


SSEv: A New Small Samples Evaluator Based on Modified Survival Curves.
Rare diseases, either of genetic or epigenetic origin, either proliferative or degenerative, are hard to be studied credibly, because of sparse prevalence, thus, small sampling. In addition, biological or translational experimentation either with animal models, or in vitro studies share small sampling-often due to lack of financial support or due to mannered and costly techniques. Pilot or feasibility studies been performed, before expensive clinical trials are decided, focus on small samples. Small Samples Evaluator (SSEv) is a useful tool based on a modification of survival curves. The technique can be applied to repeated measures, as well as to case-control or cross-sectional designed studies. A web-based application of SSEv is created and presented herein. The application is freely accessible at: https://ssev.eu .


Overrepresentation of the proarrhythmic, sudden death predisposing sodium channel polymorphism S1103Y in a population-based cohort of African-American sudden infant death syndrome.
The S1103Y-SCN5A polymorphism has been implicated as a proarrhythmic, sudden death predisposing risk factor in African Americans, including one postmortem investigation of African-American infants with sudden infant death syndrome (SIDS). The purpose of this study was to assess whether the relatively African-American-specific common polymorphism S1103Y in the SCN5A-encoded cardiac sodium channel is overrepresented in SIDS among African Americans. Seventy-one cases from a population-based cohort of unexplained infant deaths among African Americans (37 females and 34 males, average age 3 +/- 2 months, age range birth to 11 months) were submitted to the Mayo Clinic Windland Smith Rice Sudden Death Genomics Laboratory for postmortem genetic testing. Polymerase chain reaction and a restriction digest assay were performed to genotype this cohort for S1103Y. Targeted mutational analysis of exon 18 in SCN5A of the African-American SIDS cohort (n = 71) revealed the S1103Y polymorphism in 16 (22.5%) of 71 African-American cases of SIDS compared to 135 (11.6%) of 1,161 ostensibly healthy adult African Americans (P = .01). This study provides an independent assessment of the prevalence of S1103Y-SCN5A among African-American infants with sudden, unexpected, unexplained death prior to their first birthday. Further scrutiny and quantification of the risk apparently associated with S1103Y appear warranted.


A mathematical approach to cognitive processes.
A mathematical formalization of cognitive processes based on concepts previously given in Experientia is presented. Cognitive processes are described as a set of exponentially decaying interaction probabilities determined by previous interactions between different elements and an association parameter, the inverse of the cognitive stability. The interactions occur in a 'cognitive string' surrounded by a 'cognitive plasma' which carries the contextual information. The 'complexity' of a cognitive process is proportional to time.


Tibial slope in the posterolateral quadrant with and without ACL injury.
An increased tibial slope is a risk factor for rupture of the anterior cruciate ligament. In addition, a tibial bone bruise or posterior lateral impression associated with slope changes also poses chronic ligamentous instability of the knee joint associated with an anterior cruciate ligament (ACL) injury. In the majority of cases, the slope is measured in one plane X-ray in the lateral view. However, this does not sufficient represent the complex anatomy of the tibial plateau and especially for the posterolateral quadrant. Normal values from a "healthy" population are necessary to understand if stability of the knee joint is negatively affected by an increasing slope in the posterolateral area. Until now there are no data about the physiological slope in the posterolateral quadrant of the tibial plateau. In 116 MRI scans of patients without ligamentous lesions and 116 MRI scans with an ACL rupture, tibial slope was retrospectively determined using the method described by Hudek et al. Measurements were made in the postero-latero-lateral (PLL) and postero-latero-central (PLC) segments using the 10-segment classification. In both segments, the osseous as well as the cartilaginous slope was measured. Measurements were performed by two independent surgeons. In the group without ligamentous injury the mean bony PLL slope was 5.8° ± 4.8° and the cartilaginous PLL slope was 6.7° ± 4.8°. In the PLC segment the mean bony slope was 6.6° ± 5.0° and the cartilaginous slope was 9.4° ± 5.7°. In the cohort with ACL rupture, the bony and cartilaginous slope in both PLL and PCL were significantly higher (P < 0.001) than in the group without ACL injury (bony PLL 9.8° ± 4.8°, cartilage PLL 10.4° ± 4.7°, bony PLC 10.3° ± 4.8°, cartilage PLL 12.8° ± 4.3°). Measurements were performed independently by two experienced surgeons. There were good inter- (CI 87-98.7%) and good intraobserver (CI 85.8-99.6%) reliability. The bony and the cartilaginous slope in the posterolateral quadrant of the tibial plateau are different but not independent. Patients with an anterior cruciate ligament injury have a significantly steeper slope in the posterolateral quadrant compared to a healthy group. Our data indicate that this anatomic feature might be a risk factor for a primary ACL injury which has not been described yet. III.


Age, gender and refractive error association with intraocular pressure in healthy Saudi participants: A cross-sectional study.
To determine the distribution of intraocular pressure (IOP) and its association with age, gender and refractive error in non-glaucomatous Saudi participants. Hospital-based cross-sectional observational study during Vision Day Screening Program. 458 participants living in the Al-Khobar, Saudi Arabia. Recruited participants (aged 20 years or over) underwent a comprehensive questionnaire and ocular examination, including measurement of IOP with Perkins hand-held applanation tonometry and autorefraction. The distribution of IOP of either of the eyes (right or left eye by randomization) and associations with age, gender and refractive error. Median IOP was 15.0 (range: 6-28) mmHg in the total population. There is no significant difference between the overall IOP of male participants, median 15 (range: 6-28) mmHg and female participants, median 16 (range: 6-28) mmHg (p = 0.180). No statistically significant difference in IOP in relation to age comparing 20-45 years group to 46-69 years group was documented (p = 0.751). There was no statistically significant relationship between refractive error category and IOP (p = 0.405). Ocular hypertension with IOP > 21 mmHg was found in 8.7% of the participants. Variation in IOP by gender, age group and type of refractive error was not statistically significant. The observations need confirmation by study with larger sample representing Saudi population.


COPD updates: what's new in pathophysiology and management?
The historic perspective that used to define chronic obstructive pulmonary disease has changed. As reviewed in this article, it is based on a better understanding of the underlying inflammatory airflow obstruction and a multidimensional classification, which mostly targets a subgroup called 'frequent exacerbators'. Clinical and radioimaging predictors are the stamina for an aggressive therapeutic approach. A simplified explanation of the updated Global Initiative for Obstructive Lung Disease guidelines will ease the burden of treatment selection.


Multimodal multilayer network centrality relates to executive functioning.
Executive functioning (EF) is a higher order cognitive process that is thought to depend on a network organization facilitating integration across subnetworks, in the context of which the central role of the fronto-parietal network (FPN) has been described across imaging and neurophysiological modalities. However, the potentially complementary unimodal information on the relevance of the FPN for EF has not yet been integrated. We employ a multilayer framework to allow for integration of different modalities into one 'network of networks.' We used diffusion MRI, resting-state functional MRI, MEG, and neuropsychological data obtained from 33 healthy adults to construct modality-specific single-layer networks as well as a single multilayer network per participant. We computed single-layer and multilayer eigenvector centrality of the FPN as a measure of integration in this network and examined their associations with EF. We found that higher multilayer FPN centrality, but not single-layer FPN centrality, was related to better EF. We did not find a statistically significant change in explained variance in EF when using the multilayer approach as compared to the single-layer measures. Overall, our results show the importance of FPN integration for EF and underline the promise of the multilayer framework toward better understanding cognitive functioning.


An adiabatic approximation to the tissue homogeneity model for water exchange in the brain: II. Experimental validation.
A frequently reported limitation to using water as a tracer for measuring CBF has been the dependence of the CBF estimate on the experimental time (referred to as the falling flow phenomenon, FFP). To eliminate the FFP, we have developed the adiabatic solution of the tissue homogeneity model to replace the solution of the single-compartment Kety model. In Part I, the derivation of the adiabatic solution was presented. In this second part, the adiabatic solution was applied to measure CBF in rabbits using nuclear magnetic resonance spectroscopy and the tracer deuterium oxide. It was shown that the FFP, observable when the 2H clearance data were analyzed with the Kety equation, was significantly reduced when the same data were analyzed with the adiabatic solution of the tissue homogeneity model. By concurrently measuring CBF with radioactive microspheres, it was determined that the CBF estimates from the adiabatic solution were accurate for true blood flow values less than 60 mL x 100 g(-1) x min(-1). Above this value the CBF estimate was progressively underestimated, which was attributed to the diffusion limitation of water in the brain.


Acute fetal distress associated with percutaneous umbilical blood sampling.
Percutaneous umbilical blood sampling is emerging as an important procedure in the armamentarium of the obstetrician involved with prenatal diagnosis. It has apparent low morbidity and can be accomplished with relative ease by the experienced operator. We report a series of 42 successful percutaneous umbilical blood sampling procedures in 22 patients and describe the indications and gestational ages of the fetuses undergoing the blood-sampling procedures. Nine of the procedures involved intravascular transfusions. In one of our 42 cases, acute fetal distress developed in a manner similar to that of a previously reported case that was likewise associated with a compromised fetus and ended in death. Because of prompt and immediate delivery, the infant described in this series survived and, although this procedure appears to be relatively safe in experienced hands, it is imperative that the associated complications be duly recorded.


Autonomic dysfunction in polyneuropathies: a report on 106 cases.
Autonomic dysfunction is a common feature in various forms of polyradiculoneuropathy. This study investigated the kinds and frequency of of autonomic dysfunction in 106 cases. Denervation insufficiency of organs associated with supersensitivity of reflex mechanisms was found to be the best explanation of the pathophysiology. Early insertion of a transient cardiac pacemaker is recommended to counteract life-threatening cardiac failure.


Clinical dose assessment for scanned carbon-ion radiotherapy using linear energy transfer measurements and Monte Carlo simulations.
Objective. Dosimetric commissioning of treatment planning systems (TPS) focuses on validating the agreement of the physical dose with experimental data. For carbon-ion radiotherapy, the commissioning of the relative biological effectiveness (RBE) is necessary to predict the clinical outcome based on the radiation quality of the mixed radiation field. In this study, we proposed a approach for RBE commissioning using Monte Carlo (MC) simulations, which was further strengthen by RBE validation based on linear energy transfer (LET) measurements.Approach. First, we tuned the MC simulation based on the results of dosimetric experiments including the beam ranges, beam sizes, and MU calibrations. Furthermore, we compared simulated results to measured depth- and radial-LET distributions of the 430 MeV u-1carbon-ion spot beam with a 1.5 mm2, 36μm thick silicon detector. The measured dose-averaged LET (LETd) and RBE were compared with the simulated results. The RBE was calculated based on the mixed beam model with linear-quadratic parameters depending on the LET. Finally, TPS-calculated clinical dose profiles were validated through the tuned MC-based calculations.Main results. A 10 keVμm-1and 0.15 agreement for LETdand RBE, respectively, were found between simulation and measurement results obtained for a 2σlateral size of 430 MeV u-1carbon-ion spot beam in water. These results suggested that the tuned MC simulation can be used with acceptable precision for the RBE and LET calculations of carbon-ion spot beam within the clinical energy range. For physical and clinical doses, the TPS- and MC-based calculations showed good agreements within 1.0% at the centre of the spread-out Bragg peaks.Significance. The tuned MC simulation can accurately reproduce the actual carbon-ion beams, and it can be used to validate the physical and clinical dose distributions calculated by TPS. Moreover, the MC simulation can be used for dosimetric commissioning, including clinical doses, without LET measurements.


Longitudinal changes in the control mechanisms for blood pressure and cerebral blood flow in Alzheimer's disease: Secondary results of a randomized controlled trial.
Dynamic cerebral autoregulation (dCA) and baroreflex sensitivity (BRS) are key mechanisms involved in the homeostasis of blood pressure (BP) and cerebral blood flow. We assessed changes in these mechanisms in Alzheimer's disease (AD) during a 1.5 year follow-up. In this secondary analysis of a randomized controlled trial we measured beat-to-beat BP, heart rate, and cerebral blood flow velocity at baseline, 0.5 and 1.5 years, during: rest (spontaneous oscillations), repeated sit-stand maneuvers (induced oscillations), an orthostatic challenge, and hypo- and hypercapnia. dCA was estimated using transfer function analysis and the autoregulatory index on spontaneous and induced oscillations. BRS was estimated by calculating the heart rate response to BP changes during induced oscillations. Linear mixed models were used to assess changes over time. 56 patients were included (mean age:73 ± 6 years, 57% female). BRS did not change over time. dCA parameters showed small changes after 0.5 years, suggestive of a reduction in efficiency (e.g. higher gain [linear mixed effect model: B = 0.09, SE = 0.03, P = 0.008] and lower phase [B = -9.7, SE= 3.2, P = 0.004] in the very low frequency domain, and lower autoregulatory index during induced oscillations [B = -0.69, SE = 0.26, P = 0.010]). These changes did not show further progression after 1.5 years of follow-up. In this sample of patients with dementia due to AD we found no evidence that dCA or BRS become impaired during AD progression. This paves the way for further studies that investigate the safety and benefits of antihypertensive treatment in patients with AD.


The expression of hypoxia-inducible factor-1alpha in hepatitis B virus-related hepatocellular carcinoma: correlation with patients' prognosis and hepatitis B virus X protein.
Hypoxia inducible factor-1alpha (HIF-1alpha) was well correlated with carcinogenesis and tumor progression in many kinds of cancer. In this study, high expression of HIF-1alpha was found in 37 of the 72 (51.39%) tumor specimens, and significantly correlated with venous invasion and lymphonode invasion. Patients with high expression of HIF-1alpha had a significantly shorter overall survival rate and disease-free survival rate than those with low expression. Multivariate analysis showed high HIF-1alpha expression was a borderline independent factor of overall survival. HIF-1alpha expression was also found to be significantly correlated with the expression of hepatitis B virus X protein (HBx), and over-expressed HBx upregulated HIF-1alpha protein expression in vitro. These results suggested that HIF-1alpha, which was partially regulated by HBx, might be a prognostic marker of HBV-related HCC patients.


Cutaneous Rosai-Dorfman disease of the forearm: case report.
Sinus histiocytosis with massive lymphadenopathy, also known as Rosai-Dorfman disease (RDD), is a rare non-neoplastic pathologic condition that frequently pursues a prolonged clinical course marked by exacerbations and remissions. Cutaneous RDD is even less common than cases involving lymph nodes. We present the case of a patient with long-standing Crohn's disease who developed cutaneous RDD in the forearm.


Correction to: Mindray 3-directional NMT Module (a new generation "Tri-axial" neuromuscular monitor) versus the Relaxometer mechanomyograph and versus the TOF-Watch SX acceleromyograph.
In the original publication of the article, the article note "Ashraf A. Dahaba and Zhao Yang Xiao equally contributed to the study and are both first authors." was published incorrectly. The correct statement should read as "Ashraf A. Dahaba and Zhao Yang Xiao equally contributed to the study and are both first authors and are both co-corresponding authors."


Pharmacological management of pancreatitis.
Pancreatitis is a common disease with substantial morbidity and mortality. Pharmacological therapy for the prevention and treatment of pancreatitis is an intense subject of investigation. The use of proteinase inhibitors such as gabexate mesylate in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis (ERCP) has been disappointing. Initial studies using ulinastatin are promising but additional dose-response studies are needed. Somatostatin, but not octreotide, is likely to be effective in the prevention of post-ERCP pancreatitis. Rectal diclofenac might provide a simple, cheap alternative but large-scale studies are again needed. New insights into the role of proteinase-activated receptor-2 in the pancreas add to the complexity of the mechanisms involved in the pathophysiology of pancreatitis, and the development of specific agonists and antagonists of this receptor is necessary to assess their therapeutic potential in the prevention and management of pancreatitis.


Episodic stemflow inputs of magnesium and potassium to a tropical forest floor during heavy rainfall events.
Stemflow inputs of magnesium and potassium were measured from 57 canopy trees representing eight species under heavy rainfall conditions in two tropical forest sites in northeast Queensland, Australia. In the premontane tropical moist forest site on the Atherton Tableland, the stemflow input per unit trunk basal area of 51 canopy trees was found to be 0.46 g m-2 of Mg2+ and 4.22 g m-2 of K+ for an average wet season rainday of 99 mm. In the wetter montane tropical rainforest site on Mount Bellenden Ker, the stemflow input per unit trunk basal area of six canopy trees was 5.55 g m-2 of Mg2+ and 9.12 g m-2 of K+ for a wet season rainday of 38 mm. These stemflow inputs from single raindays are greater than the mean annual rainfall input and are almost of the same order of magnitude as the mean annual throughfall input of these cations to areas equal to the trunk basal area from which the stemflow was collected. Stemflow cation fluxes of this magnitude are mainly attributable to the funnelling of large quantities of rainwater down the trunks of these canopy trees by their thoroughly wetted, upwardly inclined branches.


A novel drug to reduce tumor perfusion: antitumor effect alone and with hyperthermia.
We have investigated the feasibility of enhancing damage induced by hyperthermia in SCK murine tumors by reducing tumor blood perfusion using a new agent, KB-R8498. Within several minutes of an i.v. injection, the tumor perfusion was reduced to less than 20% of the control value, and it recovered to 40-70% of the control value by 1 h after injection. The perfusion in normal tissues decreased or increased soon after drug administration depending on the tissue type. However, by 1 h after drug treatment, perfusion in five of the seven tissues examined had returned to the control level. The tumor pH was also reduced after i.v. drug administration. Control tumors grew to four times the initial volume in 6 days. Tumors that were heated at 42.5 degrees C for 60 min were delayed in growth by 4 days compared to control tumors. There was a growth delay of 14 days when an i.v. injection of KB-R8498 was given and the tumors were heated at 42.5 degrees C either immediately or 1 h later. In drug-alone studies, the tumor growth was delayed by 4 days when the drug was infused continuously at a rate of 30-50 mg/kg day(-1) for 7 days or about 2 days when mice were treated with five daily injections of 30 mg/kg KB-R8498.


Cytogenetic studies of epithelial ovarian carcinoma.
We performed cytogenetic studies of 36 human epithelial ovarian carcinomas using in situ culture and robotic harvest. We obtained analyzable metaphases of all 36 tumors (100%). One or more chromosomally abnormal clones were observed in 80% of tumors. Common clonal chromosome gains (each occurring in six or more cases) included +1, +2, +3, +6, +7, +9, and +12. Common clonal chromosome losses (occurring in 12 or more cases) included -X, -4, -8, -11, -13, -15, -17, and -22. Common clonal structural abnormalities (occurring in four or more cases) involved regions 1p36, 1q32, 1q42, 3p13-->p26, 3q26-->q29, 7p22, 9q34, 11p13-p15, 17q21-->q23, 19p13.3, and 19q13.3. Trisomy 12 was noted as the sole anomaly in three of five borderline and grade 1 tumors. Two grade 2 tumors contained i(1q), -14, -15 and -22. The results suggest that the pathogenesis of borderline and low-grade tumors may differ from that of higher grade tumors. Two high-grade tumors had an apparent translocation between 17q21 and 19p13.3, two chromosome regions believed to be critical to ovarian carcinogenesis.


Malignant fibrous histiocytoma of the vulva: a case report.
Primary sarcomas of the vulva are rare tumors that account for 1.8-3% of all vulvar malignancies. Malignant fibrous histiocytoma occurs infrequently on the vulva but nonetheless is the second most frequent sarcoma of this region. The purpose of this report is to review the diagnosis and therapy of this exceedingly rare tumor. A 72-year-old woman was presented with a vulvar mass that was ultimately found to be a vulvar malignant fibrous histiocytoma. After surgical excision and 9 months of initial diagnosis, she returned with rapid localized progression and pulmonary metastases. Malignant fibrous histiocytoma arising in the vulva represents an example of vulvar sarcomas. Since the diagnostic criteria and natural history of this tumor still remain poorly defined, further case studies may be helpful to elucidate these issues as well as the optimal therapeutic approach of this heterogeneous group of malignancies.


Single-port laparoscopic repair of an epigastric hernia using an epidural needle.
Epigastric hernia is a rare form of ventral hernia, occurring along the linea alba anywhere from the xiphoid process to the umbilicus. We present the case of a 19-month-old boy with an epigastric hernia who underwent a single-port laparoscopic repair using an epidural needle. A nonabsorbable suture was threaded through an epidural needle, with one end of the suture threaded back through the needle tip to make a loop. The loop-shaped suture was left in the abdominal cavity through the rectus muscle at the site of the defect. Another suture was inserted into the looped suture through the opposite rectus muscle. The loop was pulled taut and the defect was closed by tying the suture extracorporeally with a subcutaneous knot. In epigastric hernia, the surgical technique involves overlapping muscle layers, and currently laparoscopic surgery is introduced to repair the hernia defect. Laparoscopy is a minimally invasive method of repairing epigastric hernias. The epidural needle proved a simple and cosmetically acceptable device with which to close the epigastric hernia defect.


Using GNG to improve 3D feature extraction--application to 6DoF egomotion.
Several recent works deal with 3D data in mobile robotic problems, e.g. mapping or egomotion. Data comes from any kind of sensor such as stereo vision systems, time of flight cameras or 3D lasers, providing a huge amount of unorganized 3D data. In this paper, we describe an efficient method to build complete 3D models from a Growing Neural Gas (GNG). The GNG is applied to the 3D raw data and it reduces both the subjacent error and the number of points, keeping the topology of the 3D data. The GNG output is then used in a 3D feature extraction method. We have performed a deep study in which we quantitatively show that the use of GNG improves the 3D feature extraction method. We also show that our method can be applied to any kind of 3D data. The 3D features obtained are used as input in an Iterative Closest Point (ICP)-like method to compute the 6DoF movement performed by a mobile robot. A comparison with standard ICP is performed, showing that the use of GNG improves the results. Final results of 3D mapping from the egomotion calculated are also shown.


Characterization of flow and voltage profiles in planar electrochromatography.
Planar electrochromatography (PEC) is a new technology for thin layer chromatography (TLC) where the separation is driven by electroosmotic forces, not capillary action. This allows for much faster and more efficient chromatography in a planar format. Care needs to be taken when performing these experiments because voltage and flow characteristics can change through a single run, due to buffer gradients, temperature changes (Joule heating) and localized plate heterogeneity. We have designed a PEC instrument and cover grid to allow investigation of flow and voltage characteristics as solvent moves across a TLC plate. Our unique cover grid allows monitoring voltage at eight discrete points between the positive and negative reservoirs. A linear relationship between voltage and distance should be seen, giving a constant voltage drop across a plate, but this did not occur. This non-linear function changes over time, following the plate equilibration. Once a plate is equilibrated, voltage and flow characteristics remain fairly constant. Theoretical calculations support the physical observations. Larger plate widths (5 cm) were also briefly investigated and it is concluded that large width plates could be easily implemented to maintain multiple sample capability.


Effects on guinea pig cochlea from exposure to moderately intense broad-band noise.
Guinea pigs, which were either anesthetized (A) or conscious (U), were exposed to four 2 h sessions of broad-band noise of 96 dB SPL. Cochlear microphonics and N1 thresholds were measured prior to killing from 1 to 13 days later. The cochleas were examined by SEM and by section. The U series suffered less N1 threshold loss and recovered within 10-13 days, while the large initial loss in the A series did not completely reverse within the period of study. Initially, the IHC stereocilia in the basal half of the cochlea showed marked bending, the affected area being somewhat more extensive in the A group. These hairs gradually recovered, although not progressively. On the other hand, the disturbance to OHC stereocilia, which appeared to be less pronounced early on and was more apically centered, developed over time into marked permanent damage. The outermost row consistently showed the greatest effect with hairs becoming elongated or fused, and occasionally lost altogether. Susceptibility to noise varied between individuals of both groups. The recovery of N1 threshold was concomitant with the recovery of the erectness of the IHC hairs.


Copper-zinc superoxide dismutase in cerebrospinal fluid: implications for oxygen-radical stress in the central nervous system.
We determined the concentration of copper zinc superoxide dismutase (CuZnSOD) in cerebrospinal fluid (CSF) and plasma of 36 persons without neurological illness or with various central and peripheral nervous system disorders not supposed to generate abnormal radical formation. The CuZnSOD concentration in CSF was significantly higher compared with plasma, suggesting the presence of a high oxygen-radical load on the central nervous system. Our data may be considered to reflect normal values.


Customized birthweight centiles predict SGA pregnancies with perinatal morbidity.
To determine the following: (1) the proportion of babies reclassified as small or appropriately grown using customized and population centiles; and (2) the relative risks of perinatal morbidity, including abnormal umbilical Doppler studies, in babies classified as small for gestational age (SGA) and appropriate for gestational age (non-SGA) using the two centile calculations. Cohort study in SGA and general hospital populations. National Women's Hospital, Auckland, NZ. A cohort of SGA pregnancies (n= 374) and a general obstetric population (n= 12,879). Pregnancy outcomes were compared between 'non-SGA both' (> or =10th% by population and customized centiles) and those who were 'SGA both' (<10th% by population and customized centiles), 'SGA customized only' (SGA by customized but non-SGA by population centiles) and 'SGA population only' (SGA by population but non-SGA by customized centiles). Maternal and newborn morbidity and perinatal death. In the SGA cohort 271 (72%) babies were 'SGA both', 27 (7%) were 'SGA customized only', 32 (9%) were 'population SGA only' and 44 (12%) were 'non-SGA both'. In the general obstetric population 863 (6.7%) babies were 'SGA both', 445 (3.5%) were 'customized SGA only', 285 (2.2%) were 'population SGA only' and 11,286 (88%) were 'non-SGA both'. Perinatal death and newborn morbidity including nursery admission and long hospital stay were increased and comparable between 'SGA both' and 'customized SGA only' in both study populations. Newborn morbidity was low and comparable between 'population SGA only' and 'non-SGA both'. No perinatal deaths occurred in 'population SGA only' babies. Abnormal Doppler studies were more common in 'SGA both' or 'customized SGA only' but not in 'population SGA only' groups compared with 'non-SGA both'. Customized birthweight centiles identified small babies at risk of morbidity and mortality. Use of customized centiles is likely to detect more babies at risk of perinatal morbidity and mortality than would be detected by population centiles.


DTI parameters of axonal integrity and demyelination of the optic radiation correlate with glaucoma indices.
In glaucoma, damage of retinal ganglion cells may continue to the linked optic radiations. This study investigates the correlation of glaucoma severity indicators with parameters of axonal and myelin integrity of the optic radiations. In this observational case-control study, 13 patients with normal-tension glaucoma, 13 patients with primary open-angle glaucoma, and seven control subjects (mean age, 57.6 ± 12.5 years) were randomly selected for diffusion tensor imaging (DTI) of the optic radiations. The results of the frequency doubling test (FDT) and the HRT-based linear discriminant functions of Burk (BLDF) and Mikelberg (MLDF) were correlated with the mean of the fractional anisotropy (FA), apparent diffusion coefficient (ADC), and radial diffusivity (RD) of the optic radiations. Multiple correlation analysis, corrected for age, stage of cerebral microangiopathy, diagnosis group, and gender was conducted at increasing thresholds of linear anisotropy (C(L)) to reduce mismeasurements because of complex fiber situations. The best correlations were found for BLDF with FA at C(L) threshold 0.3 (0.594, p = 0.001), with ADC at C(L) 0.4 (-0.511, p = 0.005), and with RD at C(L) 0.4 (-0.585, p = 0.001). MLDF correlated with FA at C(L) 0.4 (0.393, p = 0.035). The FDT score correlated with FA at C(L) 0 (-0.491, p = 0.007) and with RD at C(L) 0 (-0.375, p = 0.045). In glaucoma, DTI-derived parameters of the axonal integrity (FA, ADC) and demyelination (RD) of the optic radiation are linked to HRT-based indices of glaucoma severity and to impairment of the spatial-temporal contrast sensitivity.


Cu/Zn-superoxide dismutase (GLY93-->ALA) mutation alters AMPA receptor subunit expression and function and potentiates kainate-mediated toxicity in motor neurons in culture.
The cause of the selective degeneration of motor neurons in amyotrophic lateral sclerosis (ALS) remains a mystery. One potential pathogenic mechanism is excitotoxicity due to disturbances of glutamatergic neurotransmission, particularly via AMPA-sensitive glutamate receptors. We report here that motor neurons from a familial ALS-linked superoxide dismutase (SOD1) mutant G93A mouse show an higher susceptibility to kainate-induced excitotoxicity. Moreover, they expressed GluR(3) and GluR(4) mRNA at detectable levels more frequently, with a modified electrophysiology when compared with control and wild-type SOD1 motor neurons. Thus, the SOD1 G93A mutation causes changes in the AMPA-receptor expression and function, as well as a susceptibility to kainate-mediated excitotoxicity, which may promote the motor neuron degeneration seen in ALS.


The status quo of systematic reviews published in high-impact journals in Korea: a study focused on protocol registration and GRADE use.
This study investigated the status quo of systematic reviews published in major journals in Korea from the perspective of protocol registration and adopting the grading of recommendation, assessment, development and evaluation (GRADE) system. We examined systematic reviews published in Korea's top 15 medical journals from 2018 to 2021. Teams of 2 reviewers assessed the studies' eligibility criteria and extracted data independently and in duplicate. We collected information on study characteristics, protocol registration, and GRADE use of the included reviews, and reviewed the "Instructions for Authors" of the selected journals to assess any guidance related to systematic reviews. Out of the 126 identified reviews, 18 (14.3%) reported that they registered or published their protocol. Only 5 (4.0%) rated the certainty of evidence; and all 5 used the GRADE system. Only 6 of 15 journals mentioned systematic reviews in their "Instructions for Authors." Six journals endorsed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework for systematic review reporting (2 mandatory, 3 recommended, and 1 unclear). None of the journals included mentioned protocol registration or certainty of evidence in their authors' guidelines. Overall, the proportion of systematic reviews that had prior protocol registration or used the GRADE approach to rate the certainty of evidence was very low. Our study highlights the need for adherence to systematic review standards in medical journals in Korea, including prior protocol registration and certainty of evidence assessment. Our review will help improve the quality of systematic reviews in Korea.


[Do we live in an ageist society? Results from an empirical study].
It is the starting-point of this contribution that--on the precondition that requirements for development and usage of older people's potentials for creativity are adequately met--population ageing does not necessarily imply a loss in society's capability for innovation. Following a brief sketch of central perspectives in public discourse on demographic change cognitive representations of ageing are described as an important factor in the realisation of potentials in old age. This realisation might not only threatened by an exaggeration of negative aspects of ageing but also by an exaggeration of positive aspects. By contrast, only a society which takes note of the magnitude of different abilities, needs, and lifestyles in older people is able to meet the challenges of demographic change and to increase productivity in old age. Results from an empirical study suggest that cognitive representations of ageing are less salient, more differentiated and more optimistic than might be expected from the popular notion of ageist western societies. Similarly, policy makers show an increasing consciousness for the potentials of old age. The latter point is illustrated by the leading perspectives of the German government's fifth report on old age and older people.


The course of intracranial pressure and volume-pressure relationships following extirpation of meningiomas and astrocytomas.
Thirty-five patients with meningiomas were compared with 37 patients with astrocytomas with respect to the postoperative course of their ICP and elastance. In the case of the meningioma patients, the ICP increased on average over a longer period and achieved higher values than in the astrocytoma patients. In the first group, the elastance attained values that were three times as high as in the second group. There was no fixed relationship between pressure and elastance in the two groups of patients.


Altering therapy of type II diabetes mellitus from insulin to tolazamide increases blood pressure in spite of weight loss.
In a retrospective study we investigated the effects of altering treatment of type II diabetes mellitus from insulin to tolazamide on weight and blood pressure. In 17 patients, weight decreased from 136 +/- 6 to 131 +/- 6% of ideal body weight (P = .01). Even though weight loss occurred, mean systolic blood pressure increased from 133 +/- 3 mm Hg to 142 +/- 4 mm Hg (P = .025). There was no difference in diastolic blood pressure on the two treatments (79 +/- 3 v 78 +/- 4 mm Hg). In an additional 10 patients whose treatment was changed from tolazamide to insulin, mean systolic blood pressure decreased from 136 +/- 1 to 124 +/- 2 mm Hg (P < .01). In spite of the potential benefits of reversal of insulin resistance and weight reduction, altering therapy of type II diabetes mellitus from insulin to tolazamide may increase blood pressure, thereby increasing cardiovascular risk.


[A case of familial hypercholesterolemia caused by a novel mutation p. FsS65:D129X of human low density lipoprotein receptor gene].
Novel mutation p. FsS65:D129X in human low density lipoprotein receptor gene in a female patient with typical clinical symptoms of familial hypercholesterolemia is described in this paper. Segregation of this mutation with hypercholesterolemia in the family of the patient from Petrozavodsk is demonstrated.


Hypercholesterolemia and atherosclerosis: present and future therapy including LDL-apheresis.
Atherosclerosis-induced coronary heart disease remains the major cause of death and disability in industrialized countries. Hypercholesterolemia is recognized as a causative factor in the development of atherosclerosis. While the lowering of cholesterol levels as a treatment goal has met with general agreement and acceptance, the preferred methods for doing so are still open to conjecture. This literature review discusses various factors in the hypercholesterolemia-atherosclerosis link and surveys a variety of treatment protocols including diet modification, drug therapy, surgical intervention, and plasmapheresis. Evidence is accumulating to prove that the ideal hypercholesterolemia therapy is one that reduces LDL levels while maintaining or increasing HDL levels. Because LDL-apheresis has this potential, this paper also reviews the various LDL-apheresis methods, including immunoadsorption, chemical affinity, and double-membrane filtration.


intER-ACTINg: The structure and dynamics of ER and actin are interlinked.
The actin cytoskeleton is the driver of gross ER remodelling and the movement and positioning of other membrane-bound organelles such as Golgi bodies. Rapid ER membrane remodelling is a feature of most plant cells and is important for normal cellular processes, including targeted secretion, immunity and signalling. Modifications to the actin cytoskeleton through pharmacological agents such as Latrunculin B and phalloidin, or disruption of normal myosin function also affect ER structure and/or dynamics. Here, we investigate the impact of changes in the actin cytoskeleton on structure and dynamics on the ER as well as in return the impact of modified ER structure on the architecture of the actin cytoskeleton. By expressing actin markers that affect actin dynamics, or expressing of ER-shaping proteins that influence ER architecture, we found that the structure of ER-actin networks is closely inter-related; affecting one component is likely to have a direct effect on the other. Therefore, our results indicate that a complicated regulatory machinery and cross-talk between these two structures must exist in plants to co-ordinate the function of ER-actin network during multiple subcellular processes. In addition, when considering organelle structure and dynamics, the choice of actin marker is essential in preventing off-target organelle structure and dynamics modifications.


Interstimulus contingency facilitates saccadic responses in a bimodal go/no-go task.
The saccadic response to a suddenly appearing visual target stimulus is faster when an accessory auditory stimulus is presented in its spatiotemporal proximity. This multisensory facilitation of reaction time is usually considered a mandatory bottom-up process. Here, we report that it can be modulated by the predictability of the target location provided by an accessory stimulus, thereby indicating a form of top-down processing. Subjects were asked to make a saccade in the direction of a visual target randomly appearing left or right from fixation. An accessory auditory stimulus was presented either at the same location or opposite to the target, with the probability varying over blocks of presentation. Thus, the auditory stimulus contained probabilistic information about the target location (interstimulus contingency). A certain percentage of the trials were catch trials in which the auditory accompanying stimulus (Experiment 1) or the visual target (Experiment 2) was presented alone and the subjects were asked to withhold their response. In particular with visual catch trials, varying the predictability of target location resulted in reaction time facilitation in the bimodal trials, with both high (80%) and low predictability (20%), but only when both stimuli were presented within a small time window (40 ms). As subjects could not possibly follow the task instructions in this short period explicitly, we conclude that they utilized the interstimulus contingency information implicitly, thus revealing an extremely fast involuntary top-down control on saccadic eye movements.


Response of the cubital vein to occlusion and calcification of the abdominal aorta in patients with chronic renal failure on maintenance hemodialysis.
Dysfunction of vascular endothelial cells and accelerated calcification of the abdominal aorta were found in patients on maintenance hemodialysis. Indicators of vascular wall function, expressed as the amount of plasminogen activator and von Willebrand factor released during venous occlusion, suggested that the cubital venous wall in patients has normo- or hyper-responsiveness to occlusion. Calcification of the abdominal aorta on CT scan image was observed in most of patients including those of the ages of twenties years. The mean aortic calcification index (ACI), as an indicator of organic changes in vascular wall, was significantly higher in dialysis patients than in the nondialysis subjects. However, the mean values of indicators for vascular wall function decreased and ACI increased, as the period of treatment with hemodialysis became longer. A significant negative correlation was found between the mean ACI and most indicators of vascular wall function. The function of cubital vein was suggested to decrease in association with the progress in mural calcification of the abdominal aorta. We conclude that the alteration of the coagulation-fibrinolysis system induced by repeated hemodialysis may result from and continue to exacerbate endothelial damage, the consequence of which may be atherosclerosis.


Effects of hydralazine on in vivo tumor energy metabolism, hematopoietic radiation sensitivity, and cardiovascular parameters.
Energy metabolism of murine FSaII foot tumors was studied by in vivo 31P-MRS in C3Hf/Sed mice. Spectroscopy was performed following exposure to escalating doses of hydralazine (HYD) ip. At 0.25 mg/kg, HYD caused a 20% increase in PCr/Pi and had no significant effect on mean arterial blood pressure. HYD doses greater than or equal to 2 mg/kg lead to hypotension which was associated with a decrease in PCr, NTP, pH, and an increase in Pi (p less than 0.01 for control vs 10 mg/kg HYD). When mice were given ip injections of HYD (0.25, 1, 2 and 10 mg/kg) 10 min prior to whole body irradiation, spleen stem cell survival after 6 Gy was increased (2.19 colonies in control animals vs 6.74 colonies per spleen in animals treated with greater than or equal to 2 mg/kg HYD), as was the LD50/30 dose (6.49 Gy [control] vs 9.00 Gy [10 mg/kg HYD]). The data provide evidence that PCr/Pi is a useful indicator of perfusion efficiency (and indirectly of hypoxic cell fraction) in FSaII tumors. These observations suggest that HYD may be a useful adjuvant for hyperthermic treatment of tumors and for potentiation of agents specifically toxic to hypoxic or nutrient-deprived cancer cells. HYD should be used with care in patients receiving radiation treatments or other therapies for which hypoxia can unfavorably affect treatment outcome.


Structure-activity relationships for the anticholinoceptor action of tricyclic antidepressants.
1 The anticholinoceptor action of 15 tricyclic antidepressants and derivatives has been studied on the guinea-pig ileum. At the muscarinic receptors the compounds were found to exert antagonism which was reversible and apparently competitive up to dose-ratios of around 100 but non-competitive above this level. 2 Log affinity constants were derived from log dose-response curves at dose-ratios less than 100, where parallel curves were obtained. Amitriptyline, the most potent compound, had 214 X the potency of the weakest, hydroxyimipramine, but was itself 20 X weaker than atropine. 3 Structure-activity studies showed that dibenzocycloheptane derivatives were more potent than dibenzazepines and that S or O substitution for C-11 or other major changes in the central ring of the tricyclic nucleus greatly reduced activity. Side-chain N-methylation increased potency markedly. This and other findings indicate that both tricyclic nucleus and side-chain receptor attachments are largely non-polar in type.


Patients' and health care providers' perspectives on quality of hemophilia care in the Netherlands: a questionnaire and interview study.
Hemophilia care has improved greatly because of advances in treatment options and comprehensive care. In-depth insight into the perspectives of persons with hemophilia and health care providers on their care may provide targets for further improvements. To assess satisfaction of the hemophilia population with their care, to explore factors determining care satisfaction, and to identify areas for potential health care improvements, including digital health tools. First, to assess care satisfaction and factors determining satisfaction and health care improvements, data from a nationwide, cross-sectional questionnaire among 867 adult and pediatric Dutch persons with hemophilia A or B were analyzed. This included the Hemophilia Patient Satisfaction Scale questionnaire, Canadian Hemophilia Outcomes Kids' Life Assessment Tool satisfaction questions, a visual analog scale satisfaction score, and open questions. Second, to further explore factors determining satisfaction and health care improvements, semistructured interviews were conducted with 19 persons with hemophilia or their parents and 18 health care providers. High care satisfaction was found, with an overall median Hemophilia Patient Satisfaction Scale score of 12 (IQR, 6-21). Participants in the interviews reported that patient-professional interactions, availability of care, and coordination of care were major factors determining satisfaction. Suggested health care improvements included improved information provision and coordination of care, especially shared care with professionals not working within comprehensive care centers. Participants suggested that digital health tools could aid in this. Satisfaction with hemophilia care is high among persons with hemophilia in the Netherlands, although several potential improvements have been identified. Accentuating these is especially relevant in the current era of treatment innovations, in which we might focus less on other aspects of care.


Epidural analgesia for labour pain in nulliparous women in Norway in relation to maternal country of birth and migration related factors.
To investigate associations between maternal country of birth and other migration related factors (length of residence, reason for migration, paternal origin) and epidural analgesia for labour pain in nulliparous women in Norway. Population-based register study including nulliparous migrant women (n = 75,922) and non-migrant women (n = 444,496) with spontaneous or induced labour. Data were retrieved from the Medical Birth Registry and Statistics Norway, 1990-2013. Odds ratios (OR) with 95% confidence intervals (CI) were estimated by logistic regression, and adjusted for maternal age, marital status, maternal education, gross income, birth year, hospital size and health region. Epidural analgesia for labour pain. Epidural analgesia was administered to 38% of migrant women and 31% of non-migrant women. Compared with non-migrants, the odds of having epidural analgesia were lowest in women from Vietnam (adjOR 0.54; CI 0.50-0.59) and Somalia (adjOR 0.63; CI 0.58-0.68) and highest in women from Iran (adjOR 1.32; CI 1.19-1.46) and India (adjOR 1.19; CI 1.06-1.33). Refugees (adjOR 0.83; CI 0.79-0.87) and newly arrived migrants (adjOR 0.92; CI 0.89-0.94) had lower odds of epidural analgesia. Migrant women with a non-migrant partner (adjOR 1.14; CI 1.11-1.17) and those with length of residence ≥10 years (adjOR 1.06; CI 1.02-1.10) had higher odds. The use of epidural analgesia varied by maternal country of birth, reason for migration, paternal origin and length of residence. Midwives and obstetricians should pay extra attention to the provision of adequate information about pain relief options for refugees and newly arrived migrants, who had the lowest use.


Stability of intravenous famotidine stored in polyvinyl chloride syringes.
The stability of intravenous famotidine in dextrose 5% injection (D5W), NaCl 0.9% injection (NS), and sterile water for injection stored in polyvinyl chloride (PVC) syringes at 4 degrees C for 14 days was studied. The concentration of famotidine samples was determined at time 0, 7 days, and 14 days by reverse-phase high-performance liquid chromatography. Samples were inspected for visual changes and tested for changes in pH. Results of the HPLC analysis indicated that the famotidine samples remained within 94-100 percent and 99-103 percent of the time 0 concentrations at 7 and 14 days, respectively. Repeated measures analysis of variance demonstrated a significant time effect on famotidine concentration as concentrations changed over time (p less than 0.01). This change was small in magnitude, however, and concentrations decreased at 7 days and increased at 14 days. Famotidine is stable at a concentration of 2 mg/mL in D5W, NS, and sterile water for injection stored in PVC syringes at 4 degrees C for 14 days.


Mycotoxins from mould infested building materials.
Only limited documentation of non-allergenic, especially toxic reactions after inhalation of microfungal spores in water damaged buildings exists. Recently attention has been drawn to the mycotoxins as causal compounds, as some the dominating genera found in buildings are well known mycotoxin producers.Penicillium chrysogenum and A. ustus do not seem to produce any known mycotoxins when growing on building materials, whereasP. brevicompactum produces mycophenolic acid, someP. polonicum produces verrucosidin and verrucofortine,A. versicolor produces sterigmatocystins,A. niger produces nigragillin, orlandin, naphtho-γ-pyrones and tetracyclic compounds, someA. ochraceus produces ochratoxin A,Alternaria spp. produce alternariol and alternariol monomethyl ether,Chaetomium globosum produce chaetoglobosins, and finally 30-40% ofStachybotrys chartarum isolates from buildings produce macrocyclic trichothecenes and a number of other biologically active compounds.


Novel mutations in TUBB8 and ZP3 cause human oocyte maturation arrest and female infertility.
Variations in many genes may lead to the occurrence of oocyte maturation defectsand female infertility. The objective was to describe newly discovered mutations in TUBB8 and ZP3, and to characterise the accompanying spectrum of phenotypes and modes of inheritance. TUBB8 and ZP3 were sequenced from genomic DNA samples extracted from peripheral blood of patients and their family members by the whole-exome sequencing. The TUBB8 and ZP3 sequences are then aligned with cryptographic software to identify rare variations. Sanger sequencing and mass spectrometry were used to validate mutations. ExAC database was used to retrieve the frequency of corresponding mutations. PolyPhen-2 and PROVEAN were analyzed for mutations using silicon. We identified Three novel mutations and two known variant in TUBB8 and ZP3 associated with maturation in five families, and fertilization and developmental arrest are in these patients. These mutations include four heterozygous mutations in TUBB8 (c.730G > A, p.Gly244Ser, c.124C > G, p.Leu42Val, c.1172G > T, p.Arg391Leu and c.178G > A, p.Val60Met), and a heterozygous mutation in ZP3 (c.400G > A, p.Ala134Thr). Among them, these variants of TUBB8 were highly conserved among primates. As far as we know, the TUBB8 mutations detected in our study at four sites have not been reported before, and the variant of ZP3 has been published as pathogenic. Our findings extend the known mutant spectrum of TUBB8 and ZP3, and provide insights into the etiology of infertility in human women. The exact molecular mechanism has not been analyzed and should be further investigated in the future.


Influence of long-term treatment with hydrazinophthalazines on the activity of lysosomal exoglycosidases in rat tissues.
Serum antinuclear antibodies were induced in rats by treatment with hydralazine or todralazine, given in daily dose of 25 mg/kg of body wt. for 12 months. An increased activity of alpha-glucosidase, beta-glucosidase, beta-galactosidase, alpha-fucosidase, beta-xylosidase was found in heart muscle, liver, kidney and lung. Hydralazine produced a more significant increase in the enzyme activity than todralazine. The obtained results suggest drug-induced connective tissue damage, probably of an inflammatory type. The mechanism of this phenomenon and its relationship to immunological alterations remain unclear.


C-terminal Pro-Gly-Pro tripeptide in contrast to full-length neuropeptide semax exhibits no neuroprotective effect in experimental cerebral ischemia.
The C-terminal fragment Pro-Gly-Pro of semax does not modulate the development of symptoms of neurological deficiency and mortality in rats with incomplete global cerebral ischemia. Hence, previously revealed neuroprotective effects of semax are mainly determined by corticotropin ACTH4-7 fragment.


MXene/wood-derived hierarchical cellulose scaffold composite with superior electromagnetic shielding.
Electromagnetic-interference (EMI) shielding materials that are green, lightweight, and with high mechanical properties need to be urgently developed to address increasingly severe radiation pollution. However, limited EMI shielding materials are successfully used in practical applications, due to the intensive energy consumption or the absence of sufficient strength. Herein, an environmentally friendly and effective method was proved to fabricate wood-based composites with high mechanical robustness and EMI shielding performance by a MXene/cellulose scaffold assembly strategy. The lignocellulose composites with a millimeter-thick mimic the "mortar-brick" layered structure, resulting in excellent mechanical properties that can achieve the compressive strength of 288 MPa and EMI shielding effectiveness of 39.3 dB. This "top-down" method provides an alternative for the efficient production of robust and sustainable EMI shielding materials that can be used in the fields of structural materials for next-generation communications and electronic devices.


Heme oxygenase-1 modulates the expression of adhesion molecules associated with endothelial cell activation.
Heme oxygenase-1 (HO-1) cleaves the porphyrin ring of heme into carbon monoxide, Fe2+, and biliverdin, which is then converted into bilirubin. Heme-derived Fe2+ induces the expression of the iron-sequestering protein ferritin and activates the ATPase Fe2+-secreting pump, which decrease intracellular free Fe2+ content. Based on the antioxidant effect of bilirubin and that of decreased free cellular Fe2+, we questioned whether HO-1 would modulate the expression of proinflammatory genes associated with endothelial cell (EC) activation. We tested this hypothesis specifically for the genes E-selectin (CD62), ICAM-1 (CD54), and VCAM-1 (CD106). We found that HO-1 overexpression in EC inhibited TNF-alpha-mediated E-selectin and VCAM-1, but not ICAM-1 expression, as tested at the RNA and protein level. Heme-driven HO-1 expression had similar effects to those of overexpressed HO-1. In addition, HO-1 inhibited the activation of NF-kappaB, a transcription factor required for TNF-alpha-mediated up-regulation of these genes in EC. Bilirubin and/or Fe2+ chelation mimicked the effects of HO-1, whereas biliverdin or carbon monoxide did not. In conclusion, HO-1 inhibits the expression of proinflammatory genes associated with EC activation via a mechanism that is associated with the inhibition of NF-kappaB activation. This effect of HO-1 is mediated by bilirubin and/or by a decrease of free intracellular Fe2+ but probably not by biliverdin or carbon monoxide.


Glutathione synthetase homologs encode alpha-L-glutamate ligases for methanogenic coenzyme F420 and tetrahydrosarcinapterin biosyntheses.
Proteins in the ATP-grasp superfamily of amide bond-forming ligases have evolved to function in a number of unrelated biosynthetic pathways. Previously identified homologs encoding glutathione synthetase, d-alanine:d-alanine ligase and the bacterial ribosomal protein S6:glutamate ligase have been vertically inherited within certain organismal lineages. Although members of this specificity-diverse superfamily share a common reaction mechanism, the nonoverlapping set of amino acid and peptide substrates recognized by each family provided few clues as to their evolutionary history. Two members of this family have been identified in the hyperthermophilic marine archaeon Methanococcus jannaschii and shown to catalyze the final reactions in two coenzyme biosynthetic pathways. The MJ0620 (mptN) locus encodes a tetrahydromethanopterin:alpha-l-glutamate ligase that forms tetrahydrosarcinapterin, a single carbon-carrying coenzyme. The MJ1001 (cofF) locus encodes a gamma-F420-2:alpha-l-glutamate ligase, which caps the gamma-glutamyl tail of the hydride carrier coenzyme F420. These two genes share a common ancestor with the ribosomal protein S6:glutamate ligase and a putative alpha-aminoadipate ligase, defining the first group of ATP-grasp enzymes with a shared amino acid substrate specificity. As in glutathione biosynthesis, two unrelated amino acid ligases catalyze sequential reactions in coenzyme F420 polyglutamate formation: a gamma-glutamyl ligase adds 1-3 l-glutamate residues and the ATP-grasp-type ligase described here caps the chain with a single alpha-linked l-glutamate residue. The analogous pathways for glutathione, F420, folate, and murein peptide biosyntheses illustrate convergent evolution of nonribosomal peptide biosynthesis through the recruitment of single-step amino acid ligases.


Effect of fractionation on treatment outcome in local dual-frequency sonication and Dox-encapsulated nanomicelles.
The goal of this study was to localize drug release from nanomicelles using dual-frequency sonication at low levels of acoustic intensity. In this study, the antitumor effect of simultaneous dual-frequency sonication (28 kHz and 3 MHz) at low levels of acoustic intensity in combination with doxorubicin and micellar doxorubicin injection was assessed in a spontaneous model of breast adenocarcinoma in female Balb/c mice. Sixty-three tumor-bearing mice were randomly grouped into control, sham, dual-frequency sonication, doxorubicin injection with and without dual-frequency sonication, and micellar doxorubicin injection with and without dual-frequency sonication groups. The results of volume change relative to initial volume showed that in the micellar doxorubicin injection with sonication group, this parameter was significantly different from that of the control, sham, sonication, and doxorubicin injection groups (P < 0.05). In addition, the volume began to increase on the 15th day after the start of treatment, which is a good indication to repeat treatment; therefore, another group received an extra treatment on day 15. The animal life span in the micellar doxorubicin with sonication and repeated treatment groups was significantly higher than that in all the other experimental groups except for the micellar doxorubicin injection group (P < 0.05). It was concluded that dual-frequency sonication with micellar doxorubicin injection extends the life span relative to doxorubicin injection or dual-frequency sonication alone, and that repeating this treatment on day 15 decreases the rate of tumor growth significantly.


Characteristics of patients with juvenile onset systemic sclerosis in an adult single-center cohort.
Systemic sclerosis (SSc) is a rare connective tissue disease in childhood. We compared the characteristics of adult patients with juvenile-onset SSc (jSSc) from a single-center cohort to an adult-onset group. Patients with disease onset before the age of 17 years were included in the jSSc cohort, while subjects with SSc onset after age 17 formed the adult-onset cohort. We identified 52 adult subjects with jSSc and compared them to 954 patients with adult-onset SSc. The mean ± SD age at disease onset of the patients with jSSc was 14 ± 2 years, 39 (75%) of them were women, and 24 (46%) had the diffuse cutaneous subset of SSc (dcSSc). There were no differences between the 2 cohorts in terms of sex and disease subset. Overlaps were significantly more frequent among the jSSc cohort (37%) compared to the adult-onset group (18%; p = 0.002). Autoantibody analysis demonstrated significantly more antitopoisomerase I antibody-positive subjects (33% vs 20%; p = 0.034) and significantly fewer anticentromere antibody-positive subjects (2% vs 25%; p < 0.001) in the jSSc cohort. Compared to the adult-onset group at 10 years from disease onset, survival was significantly higher among the subjects with jSSc (98% vs 75%; p = 0.001), pulmonary arterial hypertension had a significantly lower incidence (2% vs 14%; p = 0.032), and there was no difference in terms of pulmonary fibrosis (22% vs 21%) and cardiac scleroderma (3% vs 2%) between the 2 groups. The high survival rates and lower proportion of dcSSc in the adult jSSc cohort may represent a survival bias.


Circadian Effects on Attention and Working Memory in College Students With Attention Deficit and Hyperactivity Symptoms.
Individuals with an evening chronotype prefer to sleep later at night, wake up later in the day and perform best later in the day as compared to individuals with morning chronotype. Thus, college students without ADHD symptoms with evening chronotypes show reduced cognitive performance in the morning relative to nighttime (i.e., desynchrony effect). In combination with symptoms presented in attention deficit hyperactivity disorder (ADHD), we predicted that having evening chronotype renders impairment in attention during the morning, when students require optimal performance, amplifying desynchrony. Four hundred college students were surveyed for evening chronotype and symptoms of ADHD. Of those surveyed, 43 students with evening chronotype (19 with ADHD symptoms) performed laboratory attention tasks and were queried about fatigue during morning and evening sessions. Students with ADHD symptoms demonstrated a greater decrement in sustained attentional vigilance when abstaining from stimulants and asked to perform cognitive tests at times misaligned with natural circadian rhythms in arousal compared to their non-ADHD counterparts with the same chronotype. While individuals with ADHD symptoms had slower reaction-times during sustained attention tasks in the morning session compared to those without symptoms, there was no significant group difference in working memory performance, even though both groups made more errors in the morning session compared to the evening session. These findings suggest that evening chronotype students with ADHD symptoms are at a greater disadvantage when having to perform sustained attention tasks at times that are not aligned to their circadian rhythm compared to their neuro-typical peers. The implications of this finding may be useful for the provision of disability accommodations to college age students with ADHD when they are expected to perform tasks requiring sustained attention at times misaligned with their circadian rhythms.