Effects of cortisol and aminophylline upon survival, pulmonary mechanics, and secreted phosphatidyl choline of prematurely delivered rabbits.
Rabbits delivered at 27.0 days of gestation were studied after administration of cortisol (2 mg/kg/day), aminophylline (6.25 mg/kg/day), or sterile saline to the does on days 24-26 of gestation. Survival at 60 min was 52.9% in the aminophylline-treated group and 22.2% in the control and cortisol-treated groups with all animals being in a warm, oxygen-enriched environment and receiving frequent tactile stimulation. Lung volume at 30 cm H2O was lower in the cortisol-treated group than in the controls or aminophylline-treated group in animals surviving for 60 min (Table 2). The aminophylline-treated group retained significantly more gas at low pressures on the deflation curve (Table 2) and had significantly more phosphatidylcholine recovered in lung lavage fluid (Table 3) than the other groups. Aminophylline appears to have enhanced lung maturation better than cortisol in this experimental model.


Detachment of secondary dendrite arm in a directionally solidified Sn-Ni peritectic alloy under deceleration growth condition.
In order to better understand the detachment mechanism of secondary dendrite arm during peritectic solidification, the detachment of secondary dendrite arm from the primary dendrite arms in directionally solidified Sn-36at.%Ni peritectic alloys is investigated at different deceleration rates. Extensive detachment of secondary dendrite arms from primary stem is observed below peritectic reaction temperature TP. And an analytical model is established to characterize the detachment process in terms of the secondary dendrite arm spacing λ2, the root radius of detached arms and the specific surface area (SV) of dendrites. It is found that the detachment mechanism is caused by not only curvature difference between the tips and roots of secondary branches, but also that between the thicker secondary branches and the thinner ones. Besides, this detachment process is significantly accelerated by the temperature gradient zone melting (TGZM) effect during peritectic solidification. It is demonstrated that the reaction constant (f) which is used to characterize the kinetics of peritectic reaction is crucial for the determination of the detachment process. The value of f not only changes with growth rate but also with solidification time at a given deceleration rate. In conclusion, these findings help the better understanding of the detachment mechanism.


Effect of tetracosahexaenoic acid on the content and release of histamine, and eicosanoid production in MC/9 mouse mast cell.
6,9,12,15,18,21-Tetracosahexaenoic acid (24:6n-3) was isolated from a brittle star, Ophiura sarsi Lütken, at >95% purity to evaluate its physiological functions. The effects of 24:6n-3 on the production of leukotriene (LT)-related compounds such as LTB4, LTC4 and 5-hydroxyeicosatetraenoic acid, and the accumulation and release of histamine in an MC/9 mouse mast cell line were studied. We found that 24:6n-3 could inhibit the antigen-stimulated production of LT-related compounds as well as other n-3 polyunsaturated fatty acids (PUFA) such as eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3), which are major n-3 PUFA in fish oils; 24:6n-3 was also shown to reduce the histamine content in MC/9 cells at 25 microM (27% reduction from the control), and the effect was diminished with increase of the fatty acid concentration (up to 100 microM). These two n-3 PUFA, 20:5n-3 and 22:6n-3, also reduced the histamine content (16 and 20% reduction at 25 microM, respectively), whereas arachidonic acid (20:4n-6) increased it (18% increase at 25 microM). Spontaneous- and antigen-induced release of histamine was not influenced with these PUFA (at 25 microM). Ionophore-stimulated release of histamine was suppressed by the PUFA (13, 9, 15, and 11% reduction with 20:4n-6, 20:5n-3, 22:6n-3, and 24:6n-3, respectively). The patterns of the effects of 24:6n-3 on the synthesis of eicosanoids and histamine content were more similar to those of 22:6n-3 than 20:5n-3. From these results, 24:6n-3 can be expected to have anti-inflammatory activity and antiallergic activities similar to those of 22:6n-3.


"Eczema" of the nape: A marker of pthiriasis capitis.
Pthirus pubis usually infests the pubis, inguinal folds, buttocks and perianal region. In hairy males or when the infestation is longstanding, this louse can also occur on the thighs, abdomen, chest, axillae and beard. Eyelashes may be involved in children. The involvement of the scalp is very rare. We describe four girls with P. pubis infestation located exclusively on the scalp which was characterized by a rash on the nape that can suggest a head and neck form of atopic dermatitis.


Association between phthalate exposure and obesity risk: A meta-analysis of observational studies.
According to epidemiological studies, phthalate exposure is associated with an increased risk of obesity in children and adults; however, these observations remain debatable. Therefore, we performed a systematic review and meta-analysis of the current literature to explore the effects of phthalate exposure on obesity. A systematic search was performed from inception to July 2022 in PubMed, EMBASE, Scopus, and Web of Science. Quality assessment was completed using criteria modified from Newcastle-Ottawa Scale (NOS) for the included studies. Meta-analysis showed that childhood exposure to MnBP, MBP, MEP, MiBP, and MECPP was positively correlated with obesity. In adults, MMP, MEP, and MiBP were positively correlated with adult abdominal obesity, while MEHHP, MECPP, and MCOP were positively correlated with adult general obesity. Subgroup analysis revealed that the positive correlation was particularly significant in women, as well as in Europe and the United States. Overall, a substantial association exists between phthalate exposure and obesity in children and adults. Sex and study site may provide limited sources of heterogeneity.


Oncological status is not a determinant of refraining from breast reconstruction among 490 candidates for mastectomy and post-mastectomy radiotherapy.
Although breast reconstruction in the setting of post-mastectomy radiotherapy (PMRT) is controversial, we offer nipple-sparing mastectomy and immediate implant-based breast reconstruction ([N]SSM/IIBR) to women needing primary mastectomy regardless of PMRT. Nevertheless, some of these women have no reconstruction. To assess the uptake of breast reconstruction in women who undergo PMRT and the patient characteristics associated with such uptake. Additionally, we assessed the determinants of forgoing breast reconstruction. Demographic, physical and oncological characteristics of women who underwent mastectomy, PMRT and breast reconstruction were compared to the characteristics of those who did not undergo breast reconstruction from 2013 through 2018. As determinants of delaying or refraining from breast reconstruction, we distinguished between an oncological reason, patient's preference, patient's co-morbidity, combined tobacco abuse and obesity and the need for PMRT. 490 women received PMRT. Of these, 396 women (81%) underwent combined [N]SSM/IIBR and PMRT or mastectomy and PMRT with delayed breast reconstruction. Ninety-four additional women (19%) did not undergo breast reconstruction. The latter group differed significantly from those who did in demographic and physical characteristics but not in terms of oncological diagnosis and history. Patient's preference was the single most frequent determinant of not performing either immediate or delayed breast reconstruction among these 94 women. Oncological status was not a major determinant in refraining from reconstruction. The significant difference in non-oncological characteristics between the reconstructed and non-reconstructed women confirms the importance of these characteristics in the preference for either reconstruction or non-reconstruction.


Functionalized cell-free scaffolds for bone defect repair inspired by self-healing of bone fractures: A review and new perspectives.
Studies have demonstrated that scaffolds, a component of bone tissue engineering, play an indispensable role in bone repair. However, these scaffolds involving ex-vivo cultivated cells seeded have disadvantages in clinical practice, such as limited autologous cells, time-consuming cell expansion procedures, low survival rate and immune-rejection issues. To overcome these disadvantages, recent focus has been placed on the design of functionalized cell-free scaffolds, instead of cell-seeded scaffolds, that can reduplicate the natural self-healing events of bone fractures, such as inflammation, cell recruitment, vascularization, and osteogenic differentiation. New approaches and applications in tissue engineering and regenerative medicine continue to drive the development of functionalized cell-free scaffolds for bone repair. In this review, the self-healing processes were highlighted, and approaches for the functionalization were summarized. Also, ongoing efforts and breakthroughs in the field of functionalization for bone defect repair were discussed. Finally, a brief summery and new perspectives for functionalization strategies were presented to provide guidelines for further efforts in the design of bioinspired cell-free scaffolds.


A spectrophotometric method for following initial rate kinetics of blood platelet aggregation.
A double-beam recording spectrophotometer was used to assay platelet aggregation. Agonist-induced turbidity changes, at 540 nm, in dilute suspensions of platelets (1 ml, 6-8 X 10(7) platelets) were recorded differentially against a reference cuvette, also containing platelets, as a function of time. The curves obtained showed downward pen deflections (decrease of turbidity) abolished by preincubation with the aggregation inhibitor, citrate. The turbidity decrease occurred simultaneously with microscopically determined single platelet recruitment into aggregates and its initial slope (r0) was a linear function of platelet concentration upto approximately 1.5 X 10(8) per ml. At a fixed platelet concentration the r0 values of ADP-induced aggregation of calf platelet-rich plasma varied as a hyperbolic function of ADP concentration at both 32 degrees C and 37 degrees C. The kinetic data at 37 degrees C were comparable to those, in the literature, obtained by following single platelet recruitment into aggregates. The increase in turbidity due to ADP-induced shape-change (6 +/- 1%, mean +/- S.E.M., n = 7) measured in the present study was substantially greater than that (3%) measured in the aggregometer.


Characterization of SAF-A, a novel nuclear DNA binding protein from HeLa cells with high affinity for nuclear matrix/scaffold attachment DNA elements.
We identified four proteins in nuclear extracts from HeLa cells which specifically bind to a scaffold attachment region (SAR) element from the human genome. Of these four proteins, SAF-A (scaffold attachment factor A), shows the highest affinity for several homologous and heterologous SAR elements from vertebrate cells. SAF-A is an abundant nuclear protein and a constituent of the nuclear matrix and scaffold. The homogeneously purified protein is a novel double stranded DNA binding protein with an apparent molecular weight of 120 kDa. SAF-A binds at multiple sites to the human SAR element; competition studies with synthetic polynucleotides indicate that these sites most probably reside in the multitude of A/T-stretches which are distributed throughout this element. In addition we show by electron microscopy that the protein forms large aggregates and mediates the formation of looped DNA structures.


Long-Term Oncologic Outcomes After Robotic Lobectomy for Early-stage Non-Small-cell Lung Cancer Versus Video-assisted Thoracoscopic and Open Thoracotomy Approach.
Although robotic-assisted lobectomy has been increasingly used for resection of non-small-cell lung cancer (NSCLC), the long-term oncologic outcomes compared with video-assisted thoracoscopic surgery (VATS) and the open thoracotomy approach have remained ill-defined. Society of Thoracic Surgeons outcomes data and surveillance records of patients with stage I-IIIa NSCLC who had undergone lobectomy by robotic-assisted, VATS, or the open approach at a single center from 2012 to 2017 were reviewed. Propensity score adjustment by inverse probability of treatment weighting was used to balance the baseline characteristics. Recurrence and survival were analyzed and compared by the operative approach. The inverse probability of treatment weighting-adjusted cohort included 514 patients with NSCLC who had undergone robotic-assisted (n = 245), VATS (n = 118), and open (n = 151) lobectomy, with similar patient and disease characteristics. The minimally invasive procedures were associated with a shorter median hospital length of stay (robotic, 5.2 days; VATS, 4.9 days; open, 7.3 days; P < .001) and 0-adjusted 30-day mortality rate. With a median follow-up period of 45 months, the incidence for locoregional recurrence (robotic, 7%; VATS, 6%; open, 8%; P = .9) and distant failure (robotic, 14%; VATS, 18%; open, 17%; P = .9) was similar. The 5-year overall survival for robotic-assisted, VATS, and open lobectomy was 63%, 55%, and 65%, respectively (P = .56). No difference was found in stage-specific survival for stage I, II, and IIIa. On multivariate analysis, the robotic approach was associated with no differences in overall survival and recurrence-free survival compared with VATS and open lobectomy. Robotic lobectomy was associated with durable freedom of recurrence and long-term survival equivalent to those achieved with VATS and the traditional open thoracotomy approach.


Ex Vivo Gene Therapy Using Human Mesenchymal Stem Cells to Deliver Growth Factors in the Skeletal Muscle of a Familial ALS Rat Model.
Therapeutic protein and molecule delivery to target sites by transplanted human stem cells holds great promise for ex vivo gene therapy. Our group has demonstrated the therapeutic benefits of ex vivo gene therapy targeting the skeletal muscles in a transgenic rat model of familial amyotrophic lateral sclerosis (ALS). We used human mesenchymal stem cells (hMSCs) and genetically modified them to release neuroprotective growth factors such as glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF). Intramuscular growth factor delivery via hMSCs can enhance neuromuscular innervation and motor neuron survival in a rat model of ALS (SOD1(G93A) transgenic rats). Here, we describe the protocol of ex vivo delivery of growth factors via lentiviral vector-mediated genetic modification of hMSCs and hMSC transplantation into the skeletal muscle of a familial ALS rat model.


Catheter ablation of atrial fibrillation in cardiac amyloidosis.
Cardiac amyloidosis is a progressive infiltrative disease involving deposition of amyloid fibrils in the myocardium and cardiac conduction system that frequently manifests with heart failure (HF) and arrhythmias, most frequently atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia (AT). We performed an observational retrospective study of patients with a diagnosis of cardiac amyloid who underwent catheter ablation at our institution between January 1, 2011 and December 1, 2018. Patient demographics, procedural characteristics, and outcomes were determined by manual chart review. A total of 13 catheter ablations were performed over the study period in patients with cardiac amyloidosis, including 10 AT/AF/AFL ablations and three atrioventricular nodal ablations. Left ventricular ejection fraction was lower at the time of AV node ablation than catheter ablation of AT/AF/AFL (23% vs 40%, P = .003). Cardiac amyloid was diagnosed based on the results of preablation cardiac MRI results in the majority of patients (n = 7, 70%). The HV interval was prolonged at 60 ± 15 ms and did not differ significantly between AV nodal ablation patients and AT/AF/AFL ablation patients (69 ± 18 ms vs 57 ± 14 ms, P = .36). The majority of patients undergoing AT/AF/AFL ablation had persistent AF (n = 7, 70%) and NYHA class II (n = 5, 50%) or III (n = 5, 50%) HF symptoms, whereas patients undergoing AV node ablation were more likely to have class IV HF (n = 2, 66%, P = .014). Arrhythmia-free survival in CA patients after catheter ablation of AT/AF/AFL was 40% at 1 year and 20% at 2 years. Catheter ablation of AT/AF/AFL may be a feasible strategy for appropriately selected patients with early to mid-stage CA, whereas AV node ablation may be more appropriate in patients with advanced-stage CA.


Assembly of the (Na+ + K+)-adenosine triphosphatase. Post-translational membrane integration of the alpha subunit.
Guinea pig kidney poly(A+) RNA was translated in reticulocyte lysates and wheat germ extracts. Antibodies to the holoenzyme (Na/K-ATPase) immunoprecipitated only a 96,000-dalton product which was identified as the alpha subunit with a molecular weight that was indistinguishable from that of mature alpha subunit. To explore the possibility that the primary translational product is integrated as such into membranes, guinea pig kidney poly(A+) RNA was translated in reticulocyte lysates in the presence of dog pancreas microsomes; two immunoprecipitated products were detected, the 96,000-dalton alpha subunit and a 135,000-dalton new component that was integrated into the microsomal membrane since it was completely resistant to extraction with alkali. Addition of purified alpha subunit inhibited the binding of antibody to the 135,000-dalton product and extraction with urea-sodium dodecyl sulfate recovered the 96,000-dalton product, implying that the 135,000-dalton product was an alpha-chi dimer. Translation of size-fractionated poly(A+) RNA yielded evidence that the 135,000-dalton product is encoded in two separate mRNAs. The integration in vitro of the alpha subunit is, therefore, dependent on the co-translational integration into the membranes of a smaller peptide (35,000 to 40,000 daltons) which is presumably the beta subunit. Evidence was also obtained that this mechanism is present in vivo by isolation of mRNA alpha from free polysomes, as well as detection of the cytosolic form of the alpha subunit in pulse-chase experiments in MDCK cells.


Antitumor activity of living or killed Brucella: modification of the non-specific cytotoxic effector cells.
At various times after injection of living or killed smooth (S) or rough (R) Brucella abortus mice received a graft of the semi-allogenic EL4 lymphoma and their survival was studied. In parallel, the NK activity of spleen and peritoneal cells, the level of serum interferon (IFN), and the cytotoxic activity of peritoneal macrophages were investigated. Protection against the lymphoma lasted longer after injection of R organisms than after S. The parallelism between the in vivo resistance to El4 lymphoma and the augmentation of NK and macrophage activity was satisfactory with R but not with S. IFN production did not seem to be correlated with R antitumor activity. The antitumor effect of Brucella cannot therefore be simply explained on the basis of modification of the non-specific cytotoxic effector mechanisms.


Use of cyclophosphamide in azathioprine failures in pemphigus.
Four patients with pemphigus vulgaris are presented in which diagnosis was confirmed histologically and immunopathologically. Although these patients responded to high-dose prednisone therapy during the initial stages of acute disease, the addition of azathioprine failed to allow lower steroid doses and did not result in prolonged, complete remission. Indeed, the disease was exacerbated during azathioprine therapy, and significant side effects from prolonged high-dose steroid therapy were observed. Both clinical and serologic remission resulted from the addition of cyclophosphamide and dapsone to prednisone therapy. Thus, when azathioprine fails to produce remission or a steroid-sparing effect, cyclophosphamide may be an effective alternative. During a prolonged follow-up period, no recurrences of pemphigus have been observed, and no significant side effects of cyclophosphamide (Cytoxan) have been encountered. The addition of dapsone produced enhanced anti-inflammatory effects without increasing the existing or potential side effects of steroid therapy. Dapsone was easily withdrawn at the onset of remission. Thus the anti-inflammatory effect of dapsone may prove valuable in patients for whom steroids are contraindicated, who develop significant side effects during long-term steroid therapy, or for whom increases of dose threaten to enhance the possibility of catastrophic side effects.


Intraoperative Ultrasonography in Pituitary Surgery Revisited: An Institutional Experience and Systematic Review on Applications and Considerations.
The primary objective of this systematic review is to evaluate the effectiveness of intraoperative ultrasound (IOUS) in improving outcomes in patients undergoing pituitary surgery. A systematic review was performed by searching MEDLINE (PubMed), Web of Science, Scopus, and Embase electronic bibliographic databases from conception to 2022. The included studies yielded a total of 660 patients, with 488 patients undergoing IOUS. Outcome were available for 341 patients treated with IOUS and 157 patients who were treated without the IOUS application, and the remission rates following surgery were 76% and 59%, respectively. Only 2 studies reported remission rates for both groups, and meta-analysis for these studies showed significant superiority of intraoperative ultrasonography (Random effect, odds ratio 4.99, P < 0.01). Regarding extent of resection, IOUS resulted in 71% gross total resection, while absence of IOUS yielded a gross total resection rate of 44%. Among studies with available follow-up on IOUS, the recurrence rate was 3%. Pituitary dysfunction (34%), cerebrospinal fluid leak (31%), and central nervous system infection (8%) were the most common complications in the IOUS group. The mean follow-up was 19.97 months in studies reporting follow-up time. The application of the IOUS is both safe and effective and could improve the outcome of pituitary surgeries. IOUS can assist surgeons in the identification of pituitary tumors and their surrounding anatomy and can help minimize the risk of complications associated with this complex surgical procedure.


Enhancement of clonidine-induced analgesia by lesions induced with spinal and intracerebroventricular administration of 5,7-dihydroxytryptamine.
The role of serotonin (5-HT) in analgesia induced by clonidine was examined by determining the effect of intraspinal (i.s.) and intracerebroventricular (i.c.v.) injections of 5,7-dihydroxytryptamine (5,7-DHT) on analgesia produced by clonidine in the tail-flick and hot plate tests. Depletion of amines was verified by high performance liquid chromatography analysis. Intraspinal injections of 5,7-DHT potentiated the action of clonidine in both tests for analgesia and caused depletion of 5-HT in the spinal cord. Intracerebroventricularly injected 5,7-DHT also increased the action of clonidine and depleted 5-HT in brain as well as in the spinal cord. In the groups given intracerebroventricular injections, there appeared to be a biphasic increase in the action of the clonidine. Significant hyperalgesia from pretreatment with neurotoxin was observed only on a limited number of occasions. The present results indicate that 5-HT mechanisms in the CNS are important mediators of the analgesic action of clonidine. Interactions between clonidine and 5-HT systems at both spinal and supraspinal sites are considered.


Intra-tumor flow index can predict the malignant potential of breast tumor: dependent on age and volume.
The aim of this study was to assess tumor vascularity through three dimensional (3D) power Doppler breast ultrasound (US) and propose a decision model for the classification of benign and malignant breast tumors. Patient recruitment for this study was performed consecutively during a 13-mo period (January 2003 to February 2004). A total of 102 benign and 93 malignant solid breast images were analyzed. Three-dimensional power Doppler US imaging was performed using a Voluson730 ultrasound system equipped with a relative stopping power index (RSP) 6 to 12 transducer. The Virtual Organ Computer-aided Analysis (VOCAL)-imaging program (version 2.1) was used to analyze the stored volume. Histogram indices of the vascularization index (VI), flow index (FI) and vascularization-flow index (VFI) for the intra-tumor and for shells with a thickness of 3 mm surrounding the breast lesion were calculated and showed that for both, malignancy had a higher VI, FI and VFI than benignancy, with statistical significance. Multivariate and stepwise logistic regression revealed the model (including patient age, volume and intra-tumor FI in 3D power Doppler vascularity) to be the best choice for malignant breast tumor characterization. The receiver operating characteristics (ROC) index for the performance of the model was 0.926. Histogram indices for the intra-tumor FI in the 3D power Doppler scan are a good choice of parameter for differentiating between malignant and benign tumors with respect to the power of sensitivity, no matter whether one index is suggested or the patients' age and volume are considered.


Glutathione synthesis and export in experimental liver cirrhosis induced by thioacetamide: relations to ultrastructural changes.
Micro-and macronodular experimental liver cirrhosis was induced in female rats by administration of 0.03% thioacetamide (TAA) in drinking water for 3 or 6 months, respectively. The glutathione (GSH) status (content, synthesis, export) and ultrastructural changes of liver were investigated 14 d after withdrawal of TAA. The hepatic level of GSH was increased after 6 months TAA treatment. The levels of oxidized glutathione (GSSG) were not changed after 3 months or 6 months TAA administration. The GSH synthesis was not disturbed in the cirrhotic livers; only the ratio between the 2 synthesizing enzymes was changed in macronodular liver cirrhosis. The plasma GSH content was reduced in both cases, independent of the stage of liver cirrhosis. The electron microscopic studies on cirrhotic rat livers revealed a series of characteristic structural changes, such as disorganization and total lack of the microvilli border, appearance of basement membrane-like deposits within the narrowed space of Disse, disappearance of the highly porous endothelial cell lining and partly an intensively detoriated blood supply within the pseudolobules. It is suggested that all these changes may contribute to a disturbance of the GSH export from the hepatocytes into the blood. It is very likely, however, that the alterations of the sinusoidal cell surface play the most important role. 1. The GSH/GSSG redox potential is shifted in favour of the reduced form in this cirrhosis model. This shift seems to be connected with later stages of cirrhogenesis. 2. A GSH export disturbance is responsible for the decreased plasma GSH level in liver cirrhosis.


Beckwith-Wiedemann syndrome: prenatal ultrasound diagnosis using standard kidney to abdominal circumference ratio.
Enlarged fetal kidneys are characteristic of more than one possible diagnosis. Though infantile polycystic kidney disease is probably the most well known entity and is associated with oligohydramnios, Beckwith-Wiedemann syndrome should be considered in the differential diagnosis especially if a normal or increased amount of amniotic fluid is present. The presence of an omphalocele with a normal karyotype should also arouse suspicion. This constellation of findings carries potential morbidity including macrosomia, fetal hypoglycemia, mental retardation, microcephaly, increased risk of subsequent neoplasia, and even neonatal death. Beckwith-Wiedemann syndrome may not be obvious in the newborn period.


The strong hydrophobic domain of the activated estrogen receptor of porcine uterus.
Basic estrogen receptor (ER) molecule (vero-ER) of porcine uterus, which was previously shown to be the activated ER necessary to translocate from the cytoplasm into the nucleus, possesses a strongly hydrophobic nature. The strong hydrophobicity of vero-ER was concealed through binding with ER-binding factors (ERBFs). Vero-ER lost its strong hydrophobicity and its capability to bind with ERBFs after limited proteolysis by endogenous protease. The strong hydrophobic domain of vero-ER, indispensable for the nuclear translocation, was assumed to be located near the binding site with ERBFs.


Ultrasound assisted synthesis of nano-sized lithium cobalt oxide.
Nano-sized HT-LiCoO(2) powders were prepared by sonochemical synthesis in an aqueous solution of lithium hydroxide containing cobalt hydroxide at approximately 80 degrees C without any further heat treatment at high temperature. The effects of the LiOH concentration, oxidation conditions, ultrasound irradiation time and temperature on the formation of the nano-sized HT-LiCoO(2) phase were investigated. The formation of the HT-LiCoO(2) phase was confirmed by X-ray diffraction and Raman spectroscopy. The TEM images showed the presence of HT-LiCoO(2) aggregates with a mean particle diameter of approximately 20 nm. The reaction mechanism of the ultrasound assisted synthesis of nano-sized LiCoO(2) was proposed on the basis of the XRD, X-ray absorption spectroscopy analysis and TEM observation of the reaction products taken during the course of the synthesis.


Low-molecular-weight trypsin inhibitors of microbial origin.
Three hundred actinomyces cultures newly isolated from the soil of different regions of the Soviet Union were tested for their ability to produce inhibitors of trypsin-like proteases. Seven previously not known to produce trypsin inhibitors (Streptomyces bikiniensis 17-5, S. sporoclivatus 28-1, S. filamentosus 32-11, S. diastatochromogenes 20-4, S. lavendulae 29-4, S. violacens 52-8, and Streptoverticillium cinnamoneum 36-8) were found to possess high antitrypsin activity. The morphological and cultural properties of the strains and the dynamics of inhibitor production were investigated. S. bikiniensis 17-5 was studied in greatest detail. Its culture filtrate contained several inhibitors for trypsin and one for chymotrypsin. A mixture of oligopeptides with Mr of 300-500 was obtained by the described procedure which included the adsorption of the culture fluid filtrate on charcoal followed by ion-exchange chromatography on CM-cellulose. Four trypsin inhibitors (Sb-IT1, Sb-IT2, Sb-IT3, and Sb-IT4) were isolated from the mixture in a highly purified state by reversed-phase high-performance liquid chromatography. Sb-IT2 has been recognized as formylhistidylvaline with an Mr of 282. No trypsin inhibitor of this structure has been described previously.


Effects of carbon monoxide on cochlear electrophysiology and blood flow.
The belief that the cochlea is particularly vulnerable to a reduction in oxygen availability comes predominantly from studies reporting the disruption of electrophysiological measures, such as the compound action potential, endocochlear potential, inner hair cell intracellular potentials or afferent nerve fiber responses by asphyxiation. Because hypoxia has frequently been suggested as an underlying mechanism by which many ototoxic agents produce injury, and because such agents are not likely to completely disrupt oxygen delivery, we investigated the effects of graded hypoxia (using doses of carbon monoxide) on cochlear blood flow, the compound action potential (CAP) and the cochlear microphonic (CM). High doses of carbon monoxide injected intra-peritoneally yielded reversible loss of the CAP sensitivity for high frequency tone bursts, the extent of which was dose dependent. The loss was observed first at the highest frequency tested (50 kHz) and as carboxyhemoglobin levels increased, contiguous lower frequencies were influenced. Recovery progressed from low to high frequencies as carboxyhemoglobin levels declined. Carbon monoxide administration also produced a dose dependent elevation in the cochlear blood flow measured by a laser Doppler flow monitor. The data suggest that carbon monoxide administration disrupts cochlear function only under extremely severe exposure conditions. An elevation in cochlear blood flow may well serve as a protective mechanism which maintains cochlear function in the face of declining blood oxygen carrying capacity and delivery. While the site of action of carbon monoxide in the cochlea is uncertain, the data clearly indicate that elements involved in the generation of the CAP for high frequency tones are particularly vulnerable.(ABSTRACT TRUNCATED AT 250 WORDS)


Aspects of the effects of NSAID's on renal function in congestive heart failure.
In summary the present study shows that sulindac does not interfere with the action of furosemide in contrast to naproxen. Therefore, treatment of arthritic disorders with sulindac might be of advantage in elderly patients with cardiac failure.


Randomized double-blind controlled trial on the effects on iron status in the first year between a no added iron and standard infant formula received for three months.
Recent research has not only questioned the necessity of iron supplementation in human milk substitutes prior to weaning, but also suggested some potential adverse effects. This study investigated the hypothesis that infant formula need not contain added iron in the first 3 mo. Healthy term infants were recruited into a double-blind controlled trial and randomized to receive either a new no added iron formula (New; <0.1 mg Fe 100 ml(-1)) or a standard formula (Standard; 0.5 mg Fe 100 ml(-1)) for the first 3 mo of life. A breastfed reference group was also studied. Iron status was assessed at 3 and 12 mo from heel-prick capillary blood samples evaluated by full blood-count analysis, including reticulocytes and serum ferritin. In total, 149 infants were entered (51 New, 49 Standard, 49 breastfed) with no differences between the groups in gender distribution, birthweight, gestation or numbers completing the study. There were no significant differences between the principal outcome measures: mean values for haemoglobin, mean cell volume and ferritin, between the two formula-fed groups, and the proportion with a haemoglobin level <11 g dl(-1) or ferritin <10 microg l(-1) did not differ. The use of a "no added iron" infant formula in place of an iron-fortified formula during the first 3 mo of life did not clinically affect iron status at 3 and 12 mo of age. The universal supplementation of formulae with iron during this initial period needs further consideration.


Acute in vivo interactions of Helicobacter equorum with its equine host.
A novel urease-negative Helicobacter species has been isolated from faecal samples of clinically healthy horses, but no information is available about the main sites of colonisation in the equine gastrointestinal tract nor is the pathogenic potential of this microorganism known. An experimental infection in horses was therefore carried out. Four horses were infected with H. equorum strain CCUG 52199T and subjected to euthanasia at 10 (n = 2) and 30 days (n = 2) post inoculation. A fifth animal was inoculated with phosphate buffered saline and used as control. Gastrointestinal samples were examined histologically and bacteriologically. These samples, as well as faecal material collected at regular intervals, were also subjected to PCR analysis. All horses remained clinically healthy and no specific macroscopic lesions were identified, nor were there any microscopic changes. H. equorum-DNA was detected in the faeces during the whole experiment in all infected animals but not in the negative control. Sites of colonisation were caecum, colon and rectum. H. equorum is able to colonise the equine lower bowel and is excreted in faeces without apparent pathology. No association between the presence of the organism and gastrointestinal disease was demonstrated.


Utilization of Techniques for Upper Extremity Amputation Neuroma Treatment and Prevention.
This study aimed to understand the current utilization of surgical approaches for nerve ending management in upper extremity amputation to prevent and treat nerve-related pain. We administered a survey to 190 of 1270 surgeons contacted by email (15% response rate) and analyzed their demographics, practice patterns, and perceptions regarding techniques for nerve ending management in upper extremity amputees. Although many surgical techniques were employed, most surgeons (54%) performed traction neurectomy during amputation and, alternatively, bury nerve into muscle if a neuroma subsequently develops (52%). Surgeons in practice less than 10 years were more likely to perform targeted muscle reinnervation (TMR) and regenerative peripheral nerve interfaces (RPNI) than surgeons in practice greater than 10 years (p<0.001). TMR and RPNI were performed more frequently for proximal amputations than distal amputations, but there is no consensus regarding the optimal timing to utilize these techniques. Surgeons commonly cited improved prosthetic control, pain, and phantom limb symptoms as reasons for performing TMR and RPNI. Increased physician compensation as a consideration was more commonly cited among TMR non-adopter than adopters (31% vs 14%, p=0.008). There is no consensus regarding techniques for the prevention or treatment of nerve ending pain in upper extremity amputees. TMR and RPNI are being utilized with increasing frequency and both patient and surgeon factors affect implementation in clinical practice.


Structurally stable and surface-textured polylactic acid/copolymer/poly (ε-caprolactone) blend-based electrospun constructs with tunable hydroxyapatite responsiveness.
Functionally-designed nanotextured and copolymer (COP) mediated PLA/PCL (70:30 w/w) blend-based interface-engineered electrospun mats (EMs) based constructs, with phase-specific interactions, have been successfully developed. The thermal stability of constructs remained up to ∼300-350 °C, while the crystallinity reduced to ∼12-23 %, indicating enhanced pliability. The tensile strength increased by ∼75 % without much compromise in the tensile modulus whereas the dynamic relaxation response of the constructs shifted to lower temperatures upon the incorporation of ≥ 2.5 phr (parts per hundred parts of resin) of COP. The zeta potential evaluated from radial surface exposure intensity could be manipulated by controlling the extent of COP content (-60 mV for ∼5 phr COP) which in turn led to the dynamics of site-specific charge neutralization driven attachment of Ca2+ ions (∼13 % for ∼5 phr COP) of the nano-hydroxyapatite (n-HA). Such uniformly dispersed, n-HA attached, and surface-decorated (COP ≤ 5 phr) EMs enabled the selective L929 fibroblast cell attachment (∼200 % cell viability for ∼2.5 phr COP). Thus, the approach may prove to augment the biomineralization of Ca and apatite-driven healing kinetics amongst implant-seeking and inflammation-prone sites and thereby, paving a new pathway for controlled and targeted healing of bone, cartilage, dental gums, and other sites demanding n-HA and/or calcium-phosphorus assisted healing mechanism.


Fine and coarse particulate air pollution and out-of-hospital cardiac arrest onset: a nationwide case-crossover study in China.
Out-of-hospital cardiac arrest (OHCA) is a global public health concern. Nationwide studies on the effects of short-term exposure to particulate matter (PM) on OHCA risk are rare in regions with high PM levels, and evidence for coarse PM (PM2.5-10) is limited and inconsistent. To evaluate the associations between fine PM (PM2.5) and PM2.5-10 and OHCA onset, a time-stratified case-crossover study was conducted on 77,261 patients with cardiac OHCA in 26 cities across China in 2020. Daily PM2.5 and PM2.5-10 concentrations were assessed with high-resolution and full-coverage PM estimations. Conditional logistic regression models were applied in analyses. Each interquartile range of PM increase in 3-day moving average was associated with an increased risk of cardiac OHCA onset of 2.37% (95% CI, 1.20-3.56%) for PM2.5 and 2.12% (95% CI, 0.70-3.56%) for PM2.5-10. Stratified analyses showed higher susceptibility in patients over 75 years for PM2.5 exposure and with diabetes for PM2.5-10. This first nationwide study in region with high PM levels and great PM variability found not only PM2.5 but also PM2.5-10 were associated with a higher risk of OHCA onset, which could add powerful epidemiological evidence to this field and provide new evidence for the formulation of air quality guidelines.


Association of elevated inflammatory markers and severe COVID-19: A meta-analysis.
Our study aimed to assess the existing evidence on whether severe coronavirus disease 2019 (COVID-19) is associated with elevated inflammatory markers.The PubMed, Embase, Web of Science, Scopus, Chinese National Knowledge Infrastructure, WanFang, and China Science and Technology Journal databases were searched to identify studies published between January 1 and April 21, 2020 that assayed inflammatory markers in COVID-19 patients. Three reviewers independently examined the literature, extracted relevant data, and assessed the risk of publication bias before including the meta-analysis studies.Fifty-six studies involving 8719 COVID-19 patients were identified. Meta-analysis showed that patients with severe disease showed elevated levels of white blood cell count (WMD: 1.15, 95% CI: 0.78-1.52), C-reactive protein (WMD: 38.85, 95% CI: 31.19-46.52), procalcitonin (WMD: 0.08, 95% CI: 0.06-0.11), erythrocyte sedimentation rate (WMD: 10.15, 95% CI: 5.03-15.46), interleukin-6 (WMD: 23.87, 95% CI: 15.95-31.78), and interleukin-10 (WMD: 2.12, 95% CI: 1.97-2.28). Similarly, COVID-19 patients who died during follow-up showed significantly higher levels of white blood cell count (WMD: 4.11, 95% CI: 3.25-4.97), C-reactive protein (WMD: 74.18, 95% CI: 56.63-91.73), procalcitonin (WMD: 0.26, 95% CI: 0.11-0.42), erythrocyte sedimentation rate (WMD: 10.94, 95% CI: 4.79-17.09), and interleukin-6 (WMD: 59.88, 95% CI: 19.46-100.30) than survivors.Severe COVID-19 is associated with higher levels of inflammatory markers than a mild disease, so tracking these markers may allow early identification or even prediction of disease progression.


The heat shock protein 70 gene as a new alternative molecular marker for the taxonomic identification of Streptomyces strains.
With the developments in taxonomy, the classically used highly conserved 16S rRNA molecular marker has shown some disadvantages among closely related species. For further taxonomic studies of the prokaryotes, specific PCR primers were designed from two conserved regions in the amino acid sequences of the 70-kDa heat shock protein sourced from 20 different genera in actinomycetes. These were used for the amplification of the hsp70 genes in 16 Streptomyces strains. Then, we investigated the phylogenetic relationships among these Streptomyces strains and compared the tree topology based on the hsp70 gene with those based on the previously used markers (16S rRNA and gyrB). To our knowledge, this is the first use of the hsp70 gene as a molecular marker for the taxonomic identification of Streptomyces.


Illness recognition and disruptiveness in psychotic illness.
A case control investigation was performed to examine the relatively high rate of unrecognized psychotic illness within an extended family with a high-density of psychotic illness and identify factors related to nonrecognition. The study was conducted within the catchment area of a Regional Mental Health Center in central Israel. Subjects were recruited using clinic records indicating multiple family members with mental illness. Additional subjects were recruited in the homes of the subjects through family members. A total of 247 subjects were recruited, 111 of whom were determined to suffer from a psychotic disorder based on criteria in standard use. Sixty-six subjects were members of a single extended family (clan) and 181 subjects were members of nonrelated families residing in the same geographic area. While the rate of unrecognized psychotic illness was insignificant among the members of the families not related to the clan, among clan members the rate of unrecognized psychotic illness was 45%. Among this clan, recognition of psychotic illness appeared to be directly related to disruptive behavior. Additionally, it was found that, overall, subjects were more likely to recognized by the mental health system if they had fewer ill family members and more education. We conclude that although nonrecognition of mental illness does not appear to be a problem among the families in the area who are not related to the particular clan, within the clan a particular subculture appears to have developed in which perceived need for psychiatric services is related to disruptive behavior. A high density of psychotic illness within a family and less education may create a family environment that becomes tolerant of psychotic symptoms that are not disruptive to others, resulting in nonrecognition of nondisruptive illness by the mental health system.


Role of seminal prostaglandins in male fertility. I. Relationship of prostaglandin E and 19-OH prostaglandin E with seminal parameters.
Prostaglandin (PG) E and 19-OH PGE, now considered to be the most important of the human seminal prostaglandins, were assayed in infertile and normal men. In the 15 volunteers PGE and 19-OH PGE levels were 23-89 microgram/ml, respectively. In the 4 groups of infertile patients in whom either PGE or 19-OH PGE levels were increased or decreased with respect to normal, sperm concentration and motility were significantly reduced. The negative effects of low levels of seminal prostaglandins on sperm concentration and motility might be correlated respectively with decreased adenylcyclase and testicular androgen activity. The negative effects of high levels of prostaglandins on the seminal fluid might be due either to an inhibition in testicular DNA synthesis or to a decreased sensitivity of the receptors to high titers of prostaglandins.


Action of cobra venom phospholipase A2 on the gel and liquid crystalline states of dimyristoyl and dipalmitoyl phosphatidylcholine vesicles.
The activity of phospholipase A2 from cobra venom toward phospholipid in single-walled, sonicated vesicles was analyzed, particularly with respect to its activity toward the saturated phosphatidylcholines in the gel and liquid crystalline states. When egg phosphatidylcholine vesicles are used as substrate, the phospholipase has an apparent Km of 4.4 mM, an apparent Vmax of 100 mumol min-1 mg-1 of protein, and a pH optimum of 5.0 at 40 degrees C. The phospholipase hydrolyzed the gel state of dimyristoyl phosphatidylcholine vesicles and dipalmitoyl phosphatidylcholine vesicles at a rate 2 to 3 times greater than the liquid crystalline state, taking into account temperature effects on the enzymatic reaction itself. The results suggest that, toward sonicated vesicles, there is no specific enhancement of the rate when the both liquid crystalline and gel states are present together, as has been suggested to occur for multibilayers studied with other phospholipases. An apparent stimulation of activity as the reaction proceeded was observed above the phase transition temperature. This might be attributed to an increase in the phase transition temperature caused by free fatty acids so that, in the presence of reaction products, the enzyme is actually hydrolyzing gel state phospholipid which was found to be the preferred lipid state for phospholipase activity.


Comparison of deep learning-based recurrence-free survival with random survival forest and Cox proportional hazard models in Stage-I NSCLC patients.
The curative treatment for Stage I non-small cell lung cancer (NSCLC) is surgical resection. Even for Stage I patients, the probability of recurrence after curative treatment is around 20%. In this retrospective study, we included 268 operated Stage I NSCLC patients between January 2008 and June 2018 to analyze the prognostic factors (pathological stage, histological type, number of sampled mediastinal lymph node stations, type of resection, SUVmax of the lesion) that may affect relapse with three different methods, Cox proportional hazard (CoxPH), random survival forest (RSF), DeepSurv, and to compare the performance of these methods with Harrell's C-index. The dataset was randomly split into two sets, training and test sets. In the training set, DeepSurv showed the best performance among the three models, the C-index of the training set was 0.832, followed by RSF (0.675) and CoxPH (0.672). In the test set, RSF showed the best performance among the three models, followed by DeepSurv with 0.677 and CoxPH methods with 0.625. In conclusion, machine-learning techniques can be useful in predicting recurrence for lung cancer and guide clinicians both in choosing the adjuvant treatment options and best follow-up programs.


Nucleosomes induce lymphocyte necrosis.
Nucleosomes are major autoantigens in systemic lupus erythematosus. These are found as circulating complexes in both lupus patients and lupus mice. The existence of a potential ubiquitous cell surface receptor specific for nucleosomes has been suggested. However, neither the nature nor the role of this receptor has been identified. Moreover, the consequence of receptor-nucleosome interaction on the target cell has not been studied in detail so far. We show here that purified nucleosomes induce cell death of normal and lupus lymphocytes ex vivo in a dose- and time-dependent manner whereas human dendritic cells were relatively resistant. Most importantly, nucleosome-induced cell death is primary necrosis. Moreover, necrosis could be abolished when nucleosomes were first treated with deoxyribonuclease I, proteinase K or with a specific monoclonal antibody. Finally, intravenous injections of purified nucleosomes result in a reduced spleen cell number compared to buffer-injected mice, indicating that circulating nucleosomes may behave similarly in vivo. Taken together, this is the first report indicating that nucleosomes are able to induce necrosis,which in turn could result in an amplification loop of the disease causing the inflammation observed in lupus patients.


[Sclerosing epithelioid fibrosarcoma. A case report].
Sclerosing epithelioid fibrosarcoma is a rare variant of fibrosarcomas, which was recently identified as a separate entity due to specific histologic and immunohistochemistry features and its poor prognosis. We report a case of sclerosing epithelioid fibrosarcoma of soft tissues, which developed in a 37-year-old woman who presented a tumor involving the posteromedial aspect of the left knee and which progressed in size for one year. Imaging revealed a well-delimited tumor process measuring 8 cm in its largest diameter and situated in the medial compartment of the left knee. Histology of the tumorectomy specimen and the immunohistochemistry study led to the diagnosis of sclerosing epithelioid fibrosarcoma of soft tissues. This new case illustrates the characteristic features of this tumor and recalls the difficult pathological diagnosis.


Cycling probe-based real-time PCR for the detection of Human herpesvirus 6A and B.
Human herpesvirus 6 (HHV-6) is classified as two distinct species: HHV-6A and B. HHV-6B infection can cause several clinical manifestations in transplant recipients including encephalitis, bone marrow suppression, and pneumonitis. In contrast to HHV-6B, the clinical features of HHV-6A infection remain largely undefined. Herein, we developed a multiplex cycling probe real-time PCR that discriminated between HHV-6A and HHV-6B. The assay was HHV-6-specific and no cross amplification was demonstrated for other herpesviruses. Moreover, the assay had a broad, linear dynamic range of detection between 1 and 10(6) copies of viral DNA. The quantification of HHV-6A DNA was suppressed by an excess amount of HHV-6B DNA (1 × 10(6) copies/tube) in the multiplex PCR assay; however, 1 × 10(6) copies/tube of HHV-6A DNA did not affect the quantification of 1 × 10(4) copies/tube of HHV-6B DNA. To determine the reliability of the assay for analysis of clinical specimens, DNAs extracted from the peripheral blood of hematopoietic stem cell transplant recipients were assayed using our multiplex real-time PCR versus the standard TaqMan PCR. Strong correlations were demonstrated between the two different assay systems for both HHV-6A (R(2) = 0.913) and HHV-6B (R(2) = 0.909). Therefore, our multiplex HHV-6 species-specific cycling probe real-time PCR is useful for evaluating the precise copy numbers of HHV-6A and B in transplant recipients. However, as HHV-6A copy numbers was affected by presence of high copies of HHV-6B DNA (1 × 10(6) copies/tube), it may be difficult to measure precise copy numbers of HHV-6A in inherited chromosomally integrated HHV-6B patient. J. Med. Virol. 88:1628-1635, 2016. © 2016 Wiley Periodicals, Inc.


["Handball shoulder" in the focus of diagnosis and treatment].
Handball is one of the most popular team sports in Germany. In the diagnosis and treatment of shoulder injuries and shoulder complaints, a distinction must be made between sports-specific adaptation over many years and supposed decompensation. In contrast to throwing sports such as baseball or javelin, intended movement sequences in handball are often disrupted suddenly and abruptly by simultaneous contact with an opponent. This can result in a potential for further injuries. There is usually a gradual transition from a physiologically adapted handball shoulder to a pathological throwing shoulder requiring therapy. A throwing shoulder is characterised by a limitation of performance caused by pain in the shoulder during repeated sports-specific stress. In addition to a thorough clinical examination, MRI is the preferred method of examination due to the fact that changes in a handball shoulder are reflected in muscular tissue, tendons and bone in the form of overstrain reactions (bone bruise). Patients should not only take a break from sports and receive adequate pain treatment, but also undergo a specific physiotherapy regimen. MRI results should always be interpreted in due consideration of symptoms and clinical examination results. Surgery is indicated if there is a lack of improvement after specific pain treatment and physiotherapy, or structural damage corresponding to the symptoms without a chance of recovery or with a higher probability of symptoms and function improving in response to surgery. After surgical treatment, the subsequent rehabilitation plays a major role. Depending on the injury, up to 90 % of the patients may be able to return to sports.


The N-Terminal Domain of cGAS Determines Preferential Association with Centromeric DNA and Innate Immune Activation in the Nucleus.
Cytosolic DNA activates cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS), an innate immune sensor pivotal in anti-microbial defense, senescence, auto-immunity, and cancer. cGAS is considered to be a sequence-independent DNA sensor with limited access to nuclear DNA because of compartmentalization. However, the nuclear envelope is a dynamic barrier, and cGAS is present in the nucleus. Here, we identify determinants of nuclear cGAS localization and activation. We show that nuclear-localized cGAS synthesizes cGAMP and induces innate immune activation of dendritic cells, although cGAMP levels are 200-fold lower than following transfection with exogenous DNA. Using cGAS ChIP-seq and a GFP-cGAS knockin mouse, we find nuclear cGAS enrichment on centromeric satellite DNA, confirmed by imaging, and to a lesser extent on LINE elements. The non-enzymatic N-terminal domain of cGAS determines nucleo-cytoplasmic localization, enrichment on centromeres, and activation of nuclear-localized cGAS. These results reveal a preferential functional association of nuclear cGAS with centromeres.


Crystal structure of bis-(1,3-di-amino-propane-κ(2) N,N')bis-[2-(4-nitro-phen-yl)acetato-κO]cadmium.
In the structure of the title compound, [Cd(C8H6NO4)2(C3H10N2)2], the Cd(II) atom is located on a center of symmetry with one independent Cd-O distance of 2.3547 (17) Å and two Cd-N distances of 2.3265 (18) and 2.3449 (19) Å. The Cd(II) atom has an overall octa-hedral coordination environment. Several types of hydrogen-bonding inter-actions are evident. Both intra- and inter-molecular inter-actions occur between the amino groups and the O atoms of the acetate group. These N-H⋯O hydrogen bonds lead to a layered structure extending parallel to the bc plane. In addition, weak inter-molecular C-H⋯O inter-actions involving the nitro groups exist, leading to the formation of a three-dimensional network structure.


Radiological routine examination of the stomach and duodenum by means of double contrast method.
The double contrast radiologic examination performed routinely allows us to improve the study of the mucosal relief, thus increasing the diagnosis of gastric ulcers, polyps and gastric cancer. In the operated stomach one can obtain better results with this technique than with the conventional examinations.


Alkhumra virus infection, a new viral hemorrhagic fever in Saudi Arabia.
Four patients with typical acute viral hemorrhagic fever were identified in the holy city of Makkah, Saudi Arabia, between 8 and 23 February 2001, the Hajj (pilgrimage) period of that year. Tests for Rift Valley fever (RVF), Crimean-Congo hemorrhagic fever (CCHF), and dengue were negative. Blood specimens were sent to the Centres for Disease Control and Prevention (CDC), Atlanta for viral culture and testing for other hemorrhagic fever viruses. A new flavivirus closely related to the tick-borne Kyasanur forest disease virus was isolated. This new flavivirus was originally isolated in 1995 from 6 patients with dengue-like hemorrhagic fever from Alkhumra district, south of Jeddah, Saudi Arabia. A case definition was formulated for surveillance of this new disease in Saudi Arabia. Blood specimens were collected from all patients with suspect 'Alkhumra' virus (ALKV) infection and tested for ALKV, RVF, CCHF, dengue, and West Nile encephalitis. Patients data were prospectively collected on standardized data collection forms. From 8 February 2001 through 9 February 2003, a total of 37 cases were identified in Makkah, 20 of them were laboratory confirmed. Acute febrile flu-like illness with hepatitis (100%), hemorrhagic manifestations (55%), and encephalitis (20%) were the main clinical features. The case fatality was 25%. The disease seemed to be transmitted from sheep or goat to humans by the mosquito bites or direct contact with these animals. ALKV infection is a novel serious zoonotic hemorrhagic fever virus discovered in Saudi Arabia. The role of arthropods such as ticks and mosquitoes, and animals such as sheep, goat, and rodents in the transmission and maintenance of the virus remains to be elucidated.


Evidence of tetraphenylporphyrin monoacids by ion-transfer voltammetry at polarized liquid|liquid interfaces.
We present a simple methodology to illustrate the existence of tetraphenylporphyrin monoacid based on ion-transfer voltammetry at a polarized water|1,2-dichloroethane interface and organic pK values are also estimated.


1H NMR studies of a 17-mer DNA duplex.
Transcription factor 1 (TF1), encoded by the Bacillus subtilis bacteriophage SPO1, is a DNA-binding protein of the HU family. In preparation for a determination of the structure of the DNA-TF1 complex, we have studied the conformation of one core 17-mer duplex d(5'-CACTACTCTTTGTAGTG-3')-d(5'-CACTACAAAGAGTAGTG-3'). NOESY, DQF-COSY and TOCSY spectroscopy provide resonance assignments of non-exchangeable and exchangeable protons, internucleotide and interstrand proton-proton distances, and dihedral angle constraints. Restrained molecular dynamics calculations yield a family of NMR solution structures for which the RMSD is 0.7 A (all atoms). The helical twist is 34.9 degrees for the central 15 bp. Bends toward the major groove are located between the second and fourth base pairs from each end. The G12 x C23 base pair, which is bounded on each side by consecutive A x T pairs, causes a local disturbance to the DNA helix that makes the conformations of the two end segments unsymmetrical. The pyrimidine rings at T9, T10 and T11 experience more extensive rotational movement than the rest of the structure.


Amylase synthesis as a simple model system for translation and hybrid arrest in Xenopus oocytes.
A human alpha-amylase-encoding cDNA has been cloned in a transcription vector. When messenger RNA (mRNA) made in vitro from this construct was injected into Xenopus oocytes, amylase (AMY) activity was detected both in oocyte homogenates and in the incubation medium, indicating that the oocyte machinery correctly translated and processed the protein. Because AMY activity is easy to detect with a blue-starch assay, this expression system was used to determine the parameters of antisense oligodeoxyribonucleotide (oligo) inhibition of translation in the oocytes. Unique oligos complementary to the AMY mRNA sequence were effective in arresting translation, at approximately stoichiometric levels. Mixed oligos also inhibited translation, at levels that suggest that some mismatches may be tolerated in the formation of DNA-RNA hybrids. The AMY system provides a convenient probe of oocyte protein synthesis and processing machinery and can serve as a control substrate in investigations of other mRNAs.


Capn4 is induced by and required for Epstein-Barr virus latent membrane protein 1 promotion of nasopharyngeal carcinoma metastasis through ERK/AP-1 signaling.
Capn4, also known as CapnS1, is a member of the calpain family, which plays a crucial role in maintaining the activity and function of calpain. We previously reported that Capn4 also plays an essential role in the migration of nasopharyngeal carcinoma (NPC) cells through regulation of (MMP-2) by nuclear factor-kappa B activation. Epstein-Barr virus latent membrane protein 1 (LMP1) is closely related to the malignant functions of NPC; however, the relationship between LMP1 and Capn4 in NPC remain unclear. Immunohistochemical studies showed that the level of LMP1 and Capn4 expression was high in both primary and metastatic NPC tissues, with a significantly positive correlation. We further found that LMP1 was able to upregulate the Capn4 promoter in a dose-dependent way through the C-terminal activation region (CTAR)1 and CTAR2 domains to activate AP-1. Moreover, we also found that LMP1 activated AP-1 through ERK/JNK phosphorylation. These findings indicate that Capn4 coordination with LMP1 promotes actin rearrangement and, ultimately, cellular migration. These results show that Capn4 coordination with LMP1 enhances NPC migration by increasing actin rearrangement involving ERK/JNK/AP-1 signaling. Therapeutically, additional and more specific LMP1 and Capn4 targeted inhibitors could be exploited to treat NPC.


Modulation of the mutagenic effects of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) in bacteria with rat-liver 9000 x g supernatant or monolayers of rat hepatocytes as an activation system.
An in vitro protocol was designed to separate the process of metabolic activation from the mutational events. Cultured rat hepatocytes were first incubated with the food mutagens 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) or 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ). After the incubation period the medium was removed and further incubated with Salmonella typhimurium TA98. A high direct mutagenic activity of the culture medium was then measured. The half-lives of the mutagenic metabolites formed from IQ and MeIQ were in the order of 45 min. The presence of the cytochrome P450 inhibitors alpha-naphthoflavone and metyrapone during the pre-incubation period reduced the accumulation of mutagenic metabolites. No effects of ascorbate on the mutagenic effects of IQ and MeIQ were seen. (+)-Catechin, another antioxidant and free-radical scavenger, markedly enhanced the number of IQ/MeIQ-induced revertants when added to the hepatocytes. In contrast, (+)-catechin clearly decreased the number of revertants when 9000 X g supernatant from rat liver (S9) was used as an activation system. No marked effect of pentachlorophenol, an inhibitor of hepatocyte sulfation and bacterial O-acetylation, was seen using hepatocytes as an activation system, while the mutagenic activity of both IQ and MeIQ was reduced by 90% in the S9/Salmonella system. The addition of an inhibitor of glucuronidation, galactosamine, or the nucleophile glutathione caused no or only minor decreases in the genotoxic effects of the IQ compounds. With both S9 and hepatocytes as activation systems the relative mutagenic effects observed in the S. typhimurium strains TA98 and TA98 NR were in the same order of magnitude, while a large decrease was seen with TA98/1,8-DNP6. The results show that this in vitro test protocol may be useful as a tool to study mechanisms involved in the formation of mutagenic metabolites.


The ribosomal subunit assembly line.
Recent proteomic studies in Saccharomyces cerevisiae have identified nearly 200 proteins, other than the structural ribosomal proteins, that participate in the assembly of ribosomal subunits and their transport from the nucleus. In a separate line of research, proteomic studies of mature plant ribosomes have revealed considerable variability in the protein composition of individual ribosomes.


Selection on the Fly: Short-Term Adaptation to an Altered Sexual Selection Regime in Drosophila pseudoobscura.
Experimental evolution studies are powerful approaches to examine the evolutionary history of lab populations. Such studies have shed light on how selection changes phenotypes and genotypes. Most of these studies have not examined the time course of adaptation under sexual selection manipulation, by resequencing the populations' genomes at multiple time points. Here, we analyze allele frequency trajectories in Drosophila pseudoobscura where we altered their sexual selection regime for 200 generations and sequenced pooled populations at 5 time points. The intensity of sexual selection was either relaxed in monogamous populations (M) or elevated in polyandrous lines (E). We present a comprehensive study of how selection alters population genetics parameters at the chromosome and gene level. We investigate differences in the effective population size-Ne-between the treatments, and perform a genome-wide scan to identify signatures of selection from the time-series data. We found genomic signatures of adaptation to both regimes in D. pseudoobscura. There are more significant variants in E lines as expected from stronger sexual selection. However, we found that the response on the X chromosome was substantial in both treatments, more pronounced in E and restricted to the more recently sex-linked chromosome arm XR in M. In the first generations of experimental evolution, we estimate Ne to be lower on the X in E lines, which might indicate a swift adaptive response at the onset of selection. Additionally, the third chromosome was affected by elevated polyandry whereby its distal end harbors a region showing a strong signal of adaptive evolution especially in E lines.


Characterization of specific and distinct patient types in clinical trials of acute schizophrenia using an uncorrelated PANSS score matrix transform (UPSM).
Understanding the specificity of symptom change in schizophrenia can facilitate the evaluation antipsychotic efficacy for different symptom domains. Previous work identified a transform of PANSS using an uncorrelated PANSS score matrix (UPSM) to reduce pseudospecificity among symptom domains during clinical trials of schizophrenia. Here we used UPSM-transformed factor scores to identify 5 distinct patient types, each having elevated and specific severity among each of 5 symptom domains. Subjects from placebo-controlled clinical trials of acute schizophrenia were clustered (baseline) and classified (post-baseline) by a machine-learning algorithm. At baseline, all 5 patient types were similar in PANSS total score. Post-baseline, subjects' memberships among the 5 UPSM patient types were relatively stable over treatment duration and were relatively insensitive to overall improvements in symptoms, in contrast to other methods based on untransformed PANSS items. Using UPSM-transformed PANSS, drug treatment effect sizes versus placebo were doubly-dissociated for specificity across symptom domains and within specific patient types. This approach illustrates how broader clinical trial populations can nevertheless be utilized to characterize the specificity of new mechanisms across the dimensions of schizophrenia psychopathology.


Wound infection under occlusive dressings.
It is often supposed that occlusive dressings potentiate wound infection. However, even though heavy colonization by skin and wound flora is often seen under certain types of occlusion, clinical infection is not a frequent occurrence. Commensal wound flora consists of a variety of Gram-positive and Gram-negative organisms and fungi which do not appear to be detrimental to healing. Certain aspects of wound healing may in fact be promoted by bacterial colonization, although clinical infection can lead to wound breakdown and systemic infection. Wounds compromised by devitalized tissue, drains or sutures are more susceptible than clean wounds to clinical infection. Occlusive dressings may help prevent infection by presenting a barrier to potential pathogens, and hydrocolloid occlusive dressings have been shown to prevent dissemination of methicillin-resistant Staphylococcus aureus. The rate of clinical infection as deduced from published trials of dressings is lower under occlusion than when non-occlusive dressings are used, and this is likely to be a result of normal activity of the host defences under occlusive dressings.


In Vivo Wound Healing Studies.
Wound healing has emerged as a major treatment issue which has provoked the development of drugs that can improve the healing process. Studies using plant drugs have revealed many interesting results about existing commercial drugs. Effective wound healing leads to the restoration of tissue integrity and occurs through a highly organized multistage. Use of plant-derived medicines against excision, incision, and dead space models accelerates the wound healing process, which is briefly discussed in a manner to be followed easily during experimental sessions.


Community structure and modularity in networks of correlated brain activity.
Functional connectivity patterns derived from neuroimaging data may be represented as graphs or networks, with individual image voxels or anatomically-defined structures representing the nodes, and a measure of correlation between the responses in each pair of nodes determining the edges. This explicit network representation allows network-analysis approaches to be applied to the characterization of functional connections within the brain. Much recent research in complex networks has focused on methods to identify community structure, i.e. cohesive clusters of strongly interconnected nodes. One class of such algorithms determines a partition of a network into 'sub-networks' based on the optimization of a modularity parameter, thus also providing a measure of the degree of segregation versus integration in the full network. Here, we demonstrate that a community structure algorithm based on the maximization of modularity, applied to a functional connectivity network calculated from the responses to acute fluoxetine challenge in the rat, can identify communities whose distributions correspond to anatomically meaningful structures and include compelling functional subdivisions in the brain. We also discuss the biological interpretation of the modularity parameter in terms of segregation and integration of brain function.


The molecular diagnostic yield of frame-based stereotactic biopsies in the age of precision neuro-oncology: a cross-sectional study.
With the increasing role of molecular genetics in the diagnostics of intracranial tumors, delivering sufficient representative tissue for such analyses is of paramount importance. This study explored the rate of successful diagnosis after frame-based stereotactic biopsies of intracranial lesions. Consecutive patients undergoing frame-based stereotactic biopsies in 2020 and 2021 were included in this retrospective analysis. Cases were classified into three groups: conclusive, diagnosis with missing molecular genetics (MG) data, and inconclusive neuropathological diagnosis. Of 145 patients, a conclusive diagnosis was possible in n = 137 cases (94.5%). For 3 cases (2.0%), diagnosis was established with missing MG data. In 5 cases (3.5%), an inconclusive (tumor) diagnosis was met. Diagnoses comprised mainly WHO 4 glioblastomas (n = 73, 56%), CNS lymphomas (n = 23, 16%), inflammatory diseases (n = 14, 10%), and metastases (n = 5, 3%). Methylomics were applied in 49% (n = 44) of tumor cases (panel sequencing in n = 28, 30% of tumors). The average number of specimens used for MG diagnostics was 5, while the average number of specimens provided was 15. In a univariate analysis, insufficient DNA was associated with an inconclusive diagnosis or a diagnosis with missing MG data (p < 0.001). Analyses of planned and implemented trajectories of cases with diagnosis with missing MG data or inconclusive diagnosis (n = 8) revealed that regions of interest were reached in almost all cases (n = 7). Although stereotactic frame-based biopsies deliver a limited amount of tissue, they bear high histopathological and molecular genetic diagnostic yields. Given the proven surgical precision of the planned biopsy trajectories, optimizing surveyed lesion regions could help improve the rate of conclusive diagnoses.


Trajectory of smoking and early bladder cancer risk among Korean young adult men.
The aim of this study was to examine the risk of bladder cancer according to the trajectory pattern of amount of smoking among Korean young adult men. Smoking status was assessed with a standardized questionnaire in the Korean Life Course Health Study (KLCHS). Trajectory analyses were performed among young adult men using seven repeated surveys of cigarette per day (CPD) every two years from 1992 to 2005. The occurrence of bladder cancer was tracked from 2006 to 2016. The Cox proportional models were used to calculate the hazard ratio (HR) (95% confidence interval) of smoking patterns on bladder cancer. The mean (standard deviation) age of the 161,069 participants was 34.0 (3.9) years, and 2,280,143 person-years (PY) were examined during the follow-up period of 14.2 (median 14.3) years. During this period, 263 new cases of bladder cancer occurred (11.5/100,000 PY). Among the six trajectory groups (low steady, lowering, rise and fall, high steady, rise and sharp fall, and very high steady), there was a higher risk of developing bladder cancer in the all the other groups compared to the low steady group. The highest risk group was the very high steady group, with HR 2.83 (95% CI 1.79-4.49). In addition, the risk of bladder cancer was 2.61 (95% CI 1.50-4.54) in the rise and sharp fall group. The risk of bladder cancer did not show much difference according to trajectories, except for low steady group. Thus quitting smoking should be the priority to lower the risk of bladder cancer in smokers.


Prognostic value of amino acid metabolism-related gene expression in invasive breast carcinoma.
An increasing number of studies indicated that metabolic reprogramming of amino acid metabolism may either promote or inhibit tumor progression. The purpose of this study was to investigate the ability of a gene risk signature associated with amino acid metabolism to predict the prognosis and immune characteristics of invasive breast carcinoma. LASSO Cox regression analysis was performed to construct and validate the prognostic risk signature based on the expression of 9 amino acid metabolism-related genes. The predictive value of the signature, immune characteristics, and chemotherapeutic drugs was also predicted. Finally, 9 significant genes were examined in MDA-MB-231 and MCF-7 cells, and the predicted chemotherapeutic drugs were also verified. The prognosis of the low-risk group was better than that of the high-risk group. The areas under the curve (AUCs) at 1, 2, and 3 years were 0.852, 0.790, and 0.736, respectively. In addition, the GSEA results for KEGG and GO revealed that samples with a high-risk score exhibited a variety of highly malignant manifestations. The high-risk group was characterized by an increased number of M2 macrophages, a high level of tumor purity, low levels of APC co-stimulation, cytolytic activity, HLA, para-inflammation, and type I IFN response. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) confirmed that MDA-MB-231 and MCF-7 cells express 9 amino acid metabolism-related genes differently. In addition, cell experiments were conducted to examine the effect of cephaeline-induced on cell viability, migration ability, and protein expression of the PI3K/AKT signaling pathway and HIF-1α. We established a risk signature based on 9 amino acid metabolism-related genes for invasive breast carcinoma. Further analyses revealed that this risk signature is superior to other clinical indexes in survival prediction and that the subgroups identified by the risk signature exhibit distinct immune characteristics. Cephaeline was determined to be a superior option for patients in high-risk groups.


Comparative bioavailability study with two chlorpropamide tablet formulations in healthy volunteers.
The aim of this study was the assessment of the bioequivalence of two formulations (250 mg tablet) of chlorpropamide (CAS 94-20-2) in 36 healthy volunteers of both sexes. The study was conducted using an open, randomized, two-period crossover design with a 3-week washout interval. Plasma samples were obtained over a 72-h period. Plasma chlorpropamide concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using multiple reaction monitoring (MRM). From the chlorpropamide plasma concentration vs time curves, the following pharmacokinetic parameters were obtained: AUC(0-72h), AUC(inf) and C(max). The limit of quantification was 0.1 microg/mL for plasma chlorpropamide analysis. The geometric mean and respective 90 % confidence interval (CI) of Test/ Reference percent ratios were 93.99% (87.11%-101.41%) for C(max), 92.45% (85.96%-99.44%) for AUC(0-72h) and 90.30% (83.35%-97.82%) for AUC(0-inf). Since the 90 % CI for AUC(0-72h), AUC(0-inf) and C(max) ratios were within the 80-125%interval proposed by the US FDA, it was concluded that chlorpropamide 250 mg tablet (test formulation) was bioequivalent to the reference 250 mg tablet for of both the rate and extent of absorption.


A study of the influence of arrangement of upper posterior artificial teeth on pronunciation: Japanese sounds articulated on the posterior palate.
To clarify the standard of bucco-lingual tooth arrangement in complete denture construction, the influence of the bucco-lingual position of upper posterior artificial teeth on pronunciation was investigated. Wearing 7 kinds of experimental artificial teeth with the upper posterior ones arranged in 7 different positions, patients pronounced 5 test sounds: "ka", "ki", "kw", "ke" and "ko". Resultant sounds were evaluated in terms of how the bucco-lingual position of posterior artificial teeth influenced pronunciation as determined with by aural pronunciation judgment test and frequency analysis using a 1/3 octave-band real-time analyzer. Pronunciation disorders caused by the arrangement of the upper posterior artificial teeth in complete dentures occur when the lingual surfaces of the upper molars is located more than 1/4 inward of the distance between the right and left denture border from the buccal denture border or less than 1/10 of that distance outward from the buccal denture border. Results of the aural pronunciation judgment test indicated that the influence of the arrangement of the upper posterior artificial teeth on pronunciation depends on the vowel following the consonant of the sound. When the vowel following the consonant is a back vowel, as in "ka", "kw" and "ko" the sound was barely influenced, but when the vowel is a front vowel. as in "ke" and "ki", the sound was markedly influenced. We established the frequency spectrum of the consonant of the normally pronounced 5 test sounds as the standard frequency spectral range and compared distorted and misheard sounds with it.(ABSTRACT TRUNCATED AT 250 WORDS)


[Radiation therapy for glial tumors: technical aspects and clinical indications].
Radiotherapy of glial tumors is rapidly evolving with the recent technical and therapeutic progress. About technical aspects, progress in technical imaging and development of non-coplanar conformal and IMRT techniques provide new possibilities for sparing healthy tissue while increasing dose in tumoral volume. Furthermore, functional and molecular imaging are helpful for delineation and for prediction of relapse. Even modest, the actual improvement of survival with radiochemotherapy leads now to new and important developments for clinical research according to clinical data (age, general status), biological data (MGMT promotor methylation and cytogenetic modifications) and technical data (quality of surgery and radiotherapy). Understanding of molecular mechanisms allows for rational targeting or specific pathways of repair, signaling angiogenesis associated with surgery and radiotherapy in a multidisciplinary approach.


Complications and Comorbidities in Foals Undergoing Surgical Repair for Uroperitoneum.
Surgical repair is frequently effective at resolving uroperitoneum in foals, though complications occur. Despite their occurrence, management strategies used to address these complications, and their impact on survival are not clearly defined. To better describe the complications following surgical correction of uroperitoneum and to document treatment strategies and outcomes after intervention, a multi-center retrospective case series was performed. Medical record data of foals undergoing surgical treatment for uroperitoneum were retrieved from three surgical centers, and cases identified with complications or comorbidities were reviewed. Long-term follow-up was obtained through owner contact. Of 45 foals with uroperitoneum, 13 (29%) had complications or comorbidities following surgical repair. Uroperitoneum recurred in 9 (20%) foals 12-264 hours after surgery. Foals with recurrence were managed medically with an indwelling urinary catheter, repeat celiotomy, or were euthanized. Other comorbidities following repair included sepsis and persistent azotemia. One horse developed cystic calculi 14 months later. Urinary catheters maintained for 3-7 days in combination with medical and surgical interventions successfully resolved uroperitoneum. The decision to debride bladder tear edges or the selection of suture material or pattern did not impact recurrence or survival. Six (67%) foals with recurrent uroperitoneum survived to hospital discharge; 86% survived if treatment was attempted. Four (80%) of cases treated for recurrent uroperitoneum were alive without active medical problems >2 years later. Despite recurrence, medical or surgical treatment of recurrent uroperitoneum enables short-term survival, and maintenance of long-term health. Indwelling urinary catheters should be considered in select cases with recurrent uroperitoneum.


Simulation of sound field in a tissue medium generated by a concave spherically annular transducer.
The concave spherically annular transducer is regarded as a negative and a positive concave spherical transducer, and the spheroidal beam equation is used to simulate the linear and nonlinear sound field in a tissue medium generated by this transducer. It is found that the acoustic focus of the ring does not coincide with the acoustic focus of its central part. If the width of the ring increases, its acoustic focus will move toward the geometric focus and the amplitudes of nonlinear harmonics will increase obviously. If there are several coaxial rings placed on the concave spherical surface, more than one peak will appear along the axial direction for the fundamental, and high harmonics focus better. The distribution of sound field will change with the number and the excited signals of rings, so it maybe is a potential approach to treat locally big tumors.


Pure laparoscopic donor hepatectomy: Experience of 556 cases at Seoul National University Hospital.
Pure laparoscopic donor hepatectomy (PLDH) has become a routine procedure at Seoul National University Hospital, and the pure laparoscopic method is now being applied to liver recipients as well. This study aimed to review the procedure and outcomes of PLDH to identify any areas that required improvement. Data from 556 donors who underwent PLDH between November 2015 and December 2021 and their recipients were retrospectively reviewed. Among these, 541 patients underwent pure laparoscopic donor right hepatectomy (PLDRH). The mean hospital stay of the donor was 7.2 days, and the rate of grade I, II, IIIa, and IIIb complications was 2.2%, 2.7%, 1.3%, and 0.9%, respectively, without any irreversible disabilities or mortalities. The most common early and late major complications in the recipient were intraabdominal bleeding (n = 47, 8.5%) and biliary problems (n = 198, 35.6%), respectively. Analysis of the PLDRH procedure showed that operative time, liver removal time, warm ischemic time, Δhemoglobin%, Δtotal bilirubin%, and postoperative hospital stay decreased significantly as the number of cases accumulated. In conclusion, the operative outcomes of PLDRH improved as the number of cases increased. However, continuous caution is needed because major complications still occur in donors and recipients even after hundreds of cases.


Optical and electronic coupling of the redox copper Azurin on ITO-coated quartz substrate.
We have investigated the hybrid system constituted by the redox copper protein Azurin integrated with the semiconductor indium tin oxide (ITO) coated on quartz substrate. The system appears to be a good candidate for bio-sensing and bio-optoelectronics applications, especially due to the coupling between the optical and electron transfer features of Azurin with the conductive properties and optical transparency of ITO. The optical, morphological and electrical properties of the system have been investigated by combining optical absorption and transmission, steady-state fluorescence, resonance Raman spectroscopy and scanning probe microscopies. We found that Azurin molecules are firmly anchored on ITO and retain their structural and optical features underlying the physiological electron transfer activity. Scanning tunnelling spectroscopy evidenced a good electric coupling between the protein molecules and the substrate and a concomitant modulation of the ITO semiconductor properties upon deposition of Azurin. Some interplay between the conduction and valence bands of ITO and the electronic levels of Azurin is therefore suggested. These results are of a significant relevance in the perspective of developing bio-nanodevices able to process both optical and electrical signals, in conjugation also with the biorecognition capability of the protein molecules.


Nonischemic cardiomyopathy substrate and ventricular tachycardia in the setting of coronary artery disease.
Patients with coronary artery disease (CAD) may have ventricular tachycardia (VT) from a separate nonischemic process. Catheter ablation in these patients can be misguided by abnormalities of coronary arteries. To identify (1) the prevalence of unanticipated nonischemic VT in patients with known CAD presenting with VT and (2) the substrate and VT characteristics of this unique subset of patients. We examined consecutive patients referred for VT catheter ablation who had a history of myocardial infarction and angiography documented CAD with presumed ischemic VT. Patients with low-voltage zones and/or VT origin inconsistent with CAD distribution were included for further analysis. Of 732 patients, 9 (1.2%) (7 men; median age 74 years; ejection fraction 30%) fulfilled inclusion criteria. Endocardial left ventricular scar inconsistent with CAD distribution was found in 8 patients. In 1 patient, only epicardial left ventricular scar was found. The distribution of low voltage (<1.5 mV) was predominantly around the aortic and mitral valves. Thirty-one VTs were induced in 8 patients. Most VTs had right bundle branch block (68%); of these VTs, 67% had an R/S transition zone later than lead V4 consistent with basal VT origin. Epicardial ablation was necessary in 2 patients. During follow-up (30 [25-39] months), 7 of 9 patients (78%) were free of recurrent VT. A small but important subgroup of patients with CAD and VT has a nonischemic substrate/etiology for VT. The presence of multiple VTs with basal origin suggests a potential nonischemic perivalvular substrate and possible need for epicardial VT ablation.


Effects of impaired membrane interactions on α-synuclein aggregation and neurotoxicity.
The post-mortem brains of individuals with Parkinson's disease (PD) and other synucleinopathy disorders are characterized by the presence of aggregated forms of the presynaptic protein α-synuclein (aSyn). Understanding the molecular mechanism of aSyn aggregation is essential for the development of neuroprotective strategies to treat these diseases. In this study, we examined how interactions between aSyn and phospholipid vesicles influence the protein's aggregation and toxicity to dopaminergic neurons. Two-dimensional NMR data revealed that two familial aSyn mutants, A30P and G51D, populated an exposed, membrane-bound conformer in which the central hydrophobic region was dissociated from the bilayer to a greater extent than in the case of wild-type aSyn. A30P and G51D had a greater propensity to undergo membrane-induced aggregation and elicited greater toxicity to primary dopaminergic neurons compared to the wild-type protein. In contrast, the non-familial aSyn mutant A29E exhibited a weak propensity to aggregate in the presence of phospholipid vesicles or to elicit neurotoxicity, despite adopting a relatively exposed membrane-bound conformation. Our findings suggest that the aggregation of exposed, membrane-bound aSyn conformers plays a key role in the protein's neurotoxicity in PD and other synucleinopathy disorders.


Small incision surgical iridotomy and iridectomy.
To describe a minimally invasive method to create a full-thickness surgical iridectomy. An interventional case series. Surgical iridectomies were performed through a 1-mm clear corneal incision. The anterior chamber was prepared with acetylcholine chloride 10 mg/ml and sodium hyaluronate 1%. A 25-gauge aspiration-cutter "probe" was introduced through the corneal incision such that the aspiration portal was occluded by the iris stroma. Then aspiration (600 mm/Hg) cutting (300 cpm) was used to create a surgical iridotomy in 2 cases. Then the probe was removed. Full-thickness iridotomies were created. None of the patients were noted to have a secondary increase in intraocular pressure, hyphema, infection, cataract or vision loss. The clear-corneal wounds were self-sealing. Small incision surgical iridectomy can be minimally invasive and effective. Use of a 25-gauge aspiration-cutting probe allowed for small incision surgery, rapid rehabilitation and no significant complications.


Oligoclonal immunoglobulins in patients with the acquired immunodeficiency syndrome.
Analysis of serum samples from patients with the acquired immunodeficiency syndrome (AIDS) was performed by high-resolution zone electrophoresis. A high incidence of monoclonal and oligoclonal immunoglobulins was detected in the sera of 24/27 patients with Kaposi's sarcoma and in 2/15 patients with opportunistic infections. The presence of monoclonal bands was independent of whether or not the patients had experienced an opportunistic infection. These findings indicate a monoclonal or oligoclonal B-cell activation occurring in a much higher frequency in AIDS patients with Kaposi's sarcoma, thus suggesting that similar mechanisms may be operative in the malignant or pseudomalignant proliferation of B-cells and endothelial cells in patients with AIDS.


[The "sacrificial electrode" : A safe option for the management of pacemaker infections in pacemaker-dependent patients].
As the number of cardiac implantable electronic devices (CIEDs) increases, so does the need to revise such systems. Pacemaker-dependent patients with a CIED infection are particulary challenging for the attending physician. Here, the CIED cannot simply be removed without replacement. Gold standard therapy is a sufficient, prolonged antibiosis, the complete removal of the CIED, and the installation of a temporary pacemaker system - usually by means of a transvenous probe or epimyocardial probe via thoracotomy. The disadvantages of these therapies are the insecure positioning of the unfixed transvenous or the invasiveness of the epimyocardial probes. Alternatively, we have since 2015 established a concept with the so-called "sacrificial" electrode. For this purpose - during the explantation of the infected CIED - a conventional, transvenous screw electrode is anchored via the subclavian vein in the right ventricle and is then connected cutaneously to an aggregate. If the anti-infective therapy is successful, a new CIED is implanted whenever possible over the contralateral side in the usual way. Stimulation via the sacrificial electrode can be stopped and the probe removed. This method is technically easy to perform and offers great advantages: no dislocation of the probe and maintained patient mobility.


Retention of clinical trial participants in a study of nongonococcal urethritis (NGU), a sexually transmitted infection in men.
Nongonococcal urethritis (NGU), an inflammation of the urethra not caused by gonorrhea, is the most common urethritis syndrome seen in men in the United States. It is a sexually transmitted infection commonly caused by Chlamydia trachomatis, a pathogen which occurs more frequently in African-American men compared to white men. The purpose of this study was to investigate factors related to retention of study participants in a randomized, double-blinded clinical trial that evaluated four treatment regimens for the treatment of NGU. After the one-week treatment period, follow-up visits were scheduled during days 15-19 and days 35-45. Participants were phoned prior to scheduled appointments to encourage attendance, and contacted after missed appointments to reschedule their clinic visits. Of the 305 male study participants, 298 (98%) were African-American, 164 (54%) were 25 years of age or younger, and 80 (31%) had a post-secondary school education. The overall retention rate was 75%. Factors associated with study completion were educational level attained and clinical center. Participants with higher levels of education were more likely to complete the study. Clinical centers with the highest retention rates also provided the highest monetary incentives for participation. The retention rate for this study suggests that strategies are needed for improving the proportion of study participants that complete a clinical trial among young men with a sexually transmitted disease. These strategies may include increasing contacts with study participants to remind them of scheduled study visits using text messaging or social media and the use of financial incentives.


Selective alterations of NMDAR function and plasticity in D1 and D2 medium spiny neurons in the nucleus accumbens shell following chronic intermittent ethanol exposure.
A major mouse model widely adopted in recent years to induce pronounced ethanol intake is the ethanol vapor model known as "CIE" or "Chronic Intermittent Ethanol." One critical question concerning this model is whether the rapid induction of high blood ethanol levels for such short time periods is sufficient to induce alterations in N-methyl-d-aspartate receptor (NMDAR) function which may contribute to excessive ethanol intake. In this study, we determined whether such short term intermittent ethanol exposure modulates NMDAR function as well as other prominent electrophysiological properties and the expression of plasticity in both D1 (D1+) and D2 (D1-) dopamine receptor expressing medium spiny neurons (MSNs) in the nucleus accumbens (NAc) shell. To distinguish between the two subtypes of MSNs in the NAc we treated Drd1a-TdTomato transgenic mice with CIE vapor and electrophysiological recordings were conducted 24 h after the last vapor exposure. To investigate CIE induced alterations in plasticity, long-term depression (LTD) was induced by pairing low frequency stimulation (LFS) with post synaptic depolarization. In ethanol naïve mice, LFS induced synaptic depression (LTD) was apparent exclusively in D1+ MSNs. Whereas in slices prepared from CIE treated mice, LFS induced synaptic potentiation (LTP) in D1+ MSNs. Furthermore, following CIE exposure, LFS now produced LTD in D1- MSNs. We found that CIE exposure induced an increase in excitability in D1+ MSNs with no change in D1- MSNs. After CIE, we found a significant increase in spontaneous EPSCs (sEPSCs) frequency in D1+ but not D1- MSNs suggesting alterations in baseline α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) mediated signaling. CIE induced changes in NMDAR function were measured using the NMDA/AMPA ratio and input-output curves of isolated NMDAR currents. We observed a significant increase in NMDAR function in D1+ MSNs and a decrease in D1- MSNs after ethanol vapor exposure. The reversal of NMDAR function may account for the CIE induced alterations in the expression of plasticity. The cell type specific alterations in excitatory signaling in the NAc shell may constitute an important neuroadaptation necessary for the expression of increased ethanol consumption induced by intermittent ethanol vapor exposure. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'.