Microwave-assisted generation of standard gas mixtures.
Microwave heating was employed for preparation of the standard gas of volatile organic compounds (VOCs) and semivolatile organic compounds (semi-VOCs) by using a 1000 W commercial domestic microwave oven and 1 L gas-sampling bulbs. The VOCs investigated were benzene, chloroform, 1,3-dichlorobenzene, tetrachloroethylene, toluene, and 1,1,2-trichloroethane, and the semi-VOCs used were the polychlorinated biphenyls (PCBs) PCB 1016 and PCB 1248. Since these weakly or nonpolar molecules are very poor absorbers of microwave energy, an appropriate amount of water was introduced to accept microwave radiation and act as the thermal source to accelerate their evaporation. The glass bulb may also contribute thermal energy to the VOCs/semi-VOCs by accepting microwave energy to a small degree. For 0.5 microL of liquid VOCs on 10 mg of glass wool, it was shown that 15 microL of H2O and 60 s of microwave heating yielded a very efficient evaporation [97.2-106.4%, compared with a classic method (Muller, L; Gorecki, T.; Pawliszyn, J. Fresenius' J. Anal. Chem. 1999, 364, 610-616)]. For 1 microL of PCB solution (1000 microg/mL in hexane), 15 microL of H2O and 90 s of microwave heating also provided a complete evaporation. The addition of water was particularly significant for microwave-assisted evaporation of PCBs because semi-VOCs are much more difficult to evaporate than VOCs. This developed microwave technique proved to be quite simple, powerful, rapid, accurate, and safe for the preparation of VOC/semi-VOC standard gas. Solid- phase microextraction combined with gas chromatography was used for the gas analysis.


Organisation of B-cell receptors on the cell membrane.
B-cell receptors (BCRs) have been reported to organise into oligomeric clusters on the B-cell surface, and mutations, that are likely to interfere with such clustering, result in B-cell unresponsiveness. This has led to the suggestion that pre-formed BCR clusters may be crucial for B-cell signalling. However, neither the size nor the fraction of BCRs organised in such clusters have yet been determined in experiments. Hence, the authors use a statistical approach to predict the membrane organisation of BCRs, based on available experimental data. For physiological parameters, most BCRs will organise into supramolecular polymers that comprise about five receptors where the non-covalent interactions are mediated by the IgH transmembrane helix. A reduction in the density of IgM to 2-5% of the normal density, a characteristic of anergic MD4 B cells, strongly reduces IgM polymerisation, and it is suggested that impaired BCR clustering may be responsible for the unresponsiveness of anergic B cells.


High-dose cytosine arabinoside in non-Hodgkin's lymphoma.
Thirty-two patients with refractory non-Hodgkin's lymphoma were treated with high-dose cytosine arabinoside (ara-C) given at 2 g/m2 IV over three hours every 12 hours for 4-8 g/m2/course repeated at three to four week intervals. There were eight partial responses (29%) and two minor responses among 28 evaluable patients. The median response duration was 10 weeks (range, 6-33 weeks). The median survival was significantly prolonged in responders compared to nonresponders (28 versus 15 weeks; p = 0.03). Two additional patients treated with 12 g/m2/course died of sepsis and myelosuppression. The dose-limiting toxicity was myelosuppression, which was more pronounced in patients with prior extensive radiation therapy and bone marrow involvement. In vivo measurements of intracellular concentrations of ara-CTP, the active metabolite of ara-C, showed significantly higher values in bone marrows with lymphomatous involvement compared to normal bone marrows (210 versus 95 microM; p = 0.05), probably indicating a preferential formation and retention of ara-CTP in malignant cells compared to normal hemopoietic cells. In addition, higher ara-CTP levels were found in bone marrows that had higher percentages of cells in S phase.


Influence of vanadate on glycolysis, intracellular sodium, and pH in perfused rat hearts.
Vanadium compounds have been shown to cause a variety of biological and metabolic effects including inhibition of certain enzymes, alteration of contractile function, and as an insulin like regulator of glucose metabolism. However, the influence of vanadium on metabolic and ionic changes in hearts remains to be understood. In this study we have examined the influence of vanadate on glucose metabolism and sodium transport in isolated perfused rat hearts. Hearts were perfused with 10 mM glucose and varying vanadate concentrations (0.7-100 microM) while changes in high energy phosphates (ATP and phosphocreatine (PCr)), intracellular pH, and intracellular sodium were monitored using 31P and 23Na NMR spectroscopy. Tissue lactate, glycogen, and (Na+, K+)-ATPase activity were also measured using biochemical assays. Under baseline conditions, vanadate increased tissue glycogen levels two fold and reduced (Na+, K+)-ATPase activity. Significant decreases in ATP and PCr were observed in the presence of vanadate, with little change in intracellular pH. These changes under baseline conditions were less severe when the hearts were perfused with glucose, palmitate and beta-hydroxybutyrate. During ischemia vanadate did not limit the rise in intracellular sodium, but slowed sodium recovery on reperfusion. The presence of vanadate during ischemia resulted in attenuation of acidosis, and reduced lactate accumulation. Reperfusion in the presence of vanadate resulted in a slower ATP recovery, while intracellular pH and PCr recovery was not affected. These results indicate that vanadate alters glucose utilization and (Na+, K+)-ATPase activity and thereby influences the response of the myocardium to an ischemic insult.


Pulmonary Fibrosis Secondary to FOLFOX Chemotherapy: A Case Report.
A 54-year-old female presented with a 2-week history of increasing shortness of breath and fever. She had a history of a poorly differentiated sigmoid adenocarcinoma for which she underwent an anterior resection 6 months prior to admission, followed by 12 cycles of adjuvant FOLFOX chemotherapy. The patient was treated for a severe community-acquired pneumonia; however, she remained hypoxic. A chest CT revealed extensive right-sided fibrotic changes, tractional dilatation of the airways and ground glass density, which had developed since a staging CT scan performed 2 months previously. Although her symptoms improved with steroid therapy, repeat imaging revealed that right hydropneumothorax had developed, and this required the insertion of a chest drain. Following its successful removal, the patient continues to improve clinically and radiographically. The rapid onset and nature of these changes is consistent with a drug-induced fibrotic lung disease secondary to FOLFOX chemotherapy. The phenomenon is underreported and yet, it is relatively common: it occurs in approximately 10% of patients who are treated with antineoplastic agents, although information specifically relating to FOLFOX-induced pulmonary toxicity is limited. It is associated with significant morbidity and mortality, but is often hard to differentiate from other lung conditions, making the diagnosis a challenge. Pulmonary toxicity is an important complication associated with antineoplastic agents. It should be considered in any patient on a chemotherapeutic regimen who presents with dyspnoea and hypoxia in order to try to reduce the associated morbidity and mortality.


Purification of a soluble isoform of guanylyl cyclase-activating-factor synthase.
The soluble form of guanylyl cyclase-activating-factor (GAF) synthase from rat cerebellum was purified to homogeneity by sequential affinity chromatographic steps on adenosine 2',5'-bisphosphate (2',5'-ADP)-Sepharose and calmodulin-agarose. Enzyme activity during purification was bioassayed by the L-arginine-, NADPH-, and Ca2+/calmodulin-dependent formation of a plasma membrane-permeable nitric oxide-like factor that stimulated soluble guanylyl cyclase in RFL-6 cells. With calmodulin and NADPH as cofactors, purified soluble GAF synthase induced an increase of 1.05 mumol of cGMP per 10(6) RFL-6 cells per 3 min per mg of protein. The coproduct of this signal-transduction pathway appeared to be L-citrulline. GAF synthase catalyzed the conversion of 107 nmol of L-arginine into L-citrulline per min per mg of protein. Based on these assays, this represents a purification of GAF synthase of approximately 10,076- and 8925-fold with recoveries of 16% and 19%, respectively. Rechromatography of the purified enzyme on Mono P (isoelectric point = 6.1 +/- 0.3), Mono Q, and Superose 12 or 6 resulted in no further purification or increase in specific activity. A Stokes radius of 7.9 +/- 0.3 nm and a sedimentation coefficient s20,w of 7.8 +/- 0.2 S were used to calculate a molecular mass of about 279 +/- 25 kDa for the native enzyme. SDS/PAGE revealed a single protein band with a molecular mass of about 155 +/- 3 kDa. These data suggest that soluble GAF synthase purified from rat cerebellum is a homodimer of 155-kDa subunits and that enzyme activity is dependent upon the presence of calmodulin.


The Role of Sleeve Gastrectomy on Preventing Type 2 Diabetes Mellitus.
To investigate the effect of bariatric surgery on HbA1c and serum cortisol levels in morbidly obese patients without type 2 diabetes mellitus. Twenty-nine patients who underwent sleeve gastrectomy and whose body mass index was> 40 were included in the present study. Patients' files were reviewed retrospectively. Those with diabetes mellitus and those with age <18 were excluded from the study. Pre-operative and 1-year post operative data were documented. The obtained data were analysed by SPSS statistical program. The mean age of the patients was 27.4 ± 8.4. 5 of the patients were male, and 24 were female. The mean body mass index of the patients was 44 ± 2.3. 1 patient [3.4%] had hypertension. Four patients [13.7%] had gastroesophageal reflux disease. The number of smokers was 7 [24.1%], and the number of alcohol users was 3 [10.3%]. There was a statistically significant decrease in HbA1c, body mass index values after operation [p value <0.01], but cortisol was not different [p value = 0.72]. In this present study we found that bariatric surgery caused a significant decrease in HbA1c levels in non-diabetic patients, suggesting that bariatric surgery may prevent Type 2 Diabetes Mellitus in obese patients.


The Most Demanding Scenarios of Play in Basketball Competition From Elite Under-18 Teams.
The main purpose of this study was to describe the most demanding scenarios of match play in basketball through a number of physical demand measures (high-intensity accelerations and decelerations, relative distance covered, and relative distance covered in established speed zones) for four different rolling average time epochs (30, 60, 180, and 300 s) during an official international tournament. A secondary purpose was to identify whether there were significant differences in physical demand measures among playing positions (centers, guards, and forwards) and levels (two best classified teams in the tournament and remaining teams), match scoring (winning, losing, and drawing), and playing periods (match quarter) at the moment of the most demanding scenarios. Data were collected from 94 male under 18 (U18) elite basketball players (age: 17.4 ± 0.7 years; stature: 199.0 ± 11.9 cm; body mass: 87.1 ± 13.1 kg) competing in a Euroleague Basketball Tournament. Measures were compared via a Bayesian inference analysis. The results revealed the presence of position-related differences [Bayesian factor (BF) > 10 (at least strong evidence) and standardized effect size (δ) > 0.6 (at least moderate)] so that centers covered a lower relative distance at speed zone 1 and had lower high-intensity accelerations and decelerations than guards. However, the Bayesian analysis did not demonstrate the existence of significant differences in any physical demand measure in relation to the playing level, match scoring, and playing periods at the moment of the most demanding scenarios. Therefore, this study provides coaches and strength and conditioning specialists with a most demanding scenario reference on physical demands that can be used as an upper limit threshold in the training and rehabilitation monitoring processes.


Vitamin Fortification of Fluid Milk.
Vitamin concentrates with vitamins A and D are used for fortification of fluid milk. Although many of the degradation components of vitamins A and D have an important role in flavor/fragrance applications, they may also be source(s) of off-flavor(s) in vitamin fortified milk due to their heat, oxygen, and the light sensitivity. It is very important for the dairy industry to understand how vitamin concentrates can impact flavor and flavor stability of fluid milk. Currently, little research on vitamin degradation products can be found with respect to flavor contributions. In this review, the history, regulations, processing, and storage stability of vitamins in fluid milk are addressed along with some hypotheses for the role of vitamin A and D fortification on flavor and stability of fluid milk.


External fixation via the anterior inferior iliac spine for proximal femoral fractures in young patients.
Acute treatment of young patients with proximal femoral fracture (PFF) remains a challenge for trauma surgeons due to major fracture displacement and heavy pain in clinical practice. Traditional methods have a variety of intrinsic defaults and cannot successfully manage the requirements of young patients. Benefiting from our anatomic research, we explored a new method of external fixation for this specific trauma and evaluated its feasibility and clinical outcomes. Twenty-three young multiple-trauma patients with PFF were included in this study. Surgical treatment was applied using an external fixator via the anterior inferior iliac spine (AIIS). Electronic patient records, surgical characteristics, clinical outcomes, and complications were reviewed for each patient. The mean surgical time was 30.3 ± 7.3 min. The mean blood loss was 25.3 ± 10.8 mL. No iatrogenic nerve palsy, pin tract infection, failure of external fixation, or bedsores were observed. The postoperative visual analog scale score was significantly lower than the preoperative score (P < 0.01). The mean fracture reduction rate of the femur was 58.1 ± 17.0%, and the mean degree of reduction was 13.5 ± 6.9°. The mean external fixation time was 7.6 ± 4.0 days and intramedullary nailing was performed. The mean hospital, follow-up, and healing times were 28.7 ± 8.7 days, 23.5 ± 7.9 months, and 22.8 ± 5.7 weeks, respectively. The Harris Hip Score indicated excellent or good results in 20 patients. Collectively, the results of this study revealed that external fixation via the AIIS is a safe, rapid, and effective method for acute treatment of PFF in young patients.


Glomerulopathies with Fibrillary Deposits.
The glomerulopathies associated with the deposition of extracellular fibrils in the glomeruli are subdivided into Congo red positive (amyloidosis) and Congo red negative (non-amyloidotic glomerulopathies) based on Congo red staining. The non-amyloidotic glomerulopathies are divided into immunoglobulin-derived and non-immunoglobulin-derived glomerulopathies. The immunoglobulin-derived glomerulopathies: fibrillary glomerulopathy (FGn) and immunotactoid glomerulopathy (ITG) are rare glomerulopathies. The diagnosis of fibrillary-immunotactoid glomerulopathy depends on electron microscopy, which shows the presence of microfibrils in the glomeruli. The microfibrils in FGn are randomly arranged with diameters less than 30 nm. The microfibrils in ITG are larger than 30 nm with a visible lumen (microtubules), focally arranged in parallel bundles. Patients with fibrillary-immunotactoid glomerulopathy present with proteinuria (usually in the nephrotic range), microscopic hematuria, arterial hypertension, and chronic kidney disease that progresses to kidney failure over months to years. Currently, there are no guidelines for the treatment of fibrillary-immunotactoid glomerulopathy, although immunotactoid glomerulopathy could be associated with underlying hematologic disorders with the need for clone-directed therapy.


Stereotactic core needle biopsy of nonpalpable breast lesions: initial experience with a promising technique.
To evaluate the correlation between the pathological findings of stereotactic core needle biopsy (SCNB) and the prebiopsy mammographic findings, as well as the pathological findings of lesions that were subsequently removed by surgical excision. A retrospective review of 97 consecutive patients who underwent 100 SCNBs of suspicious nonpalpable mammographic lesions. The criterion standard is surgical excisional biopsy with needle localization. Mammographic findings were graded according to the American College of Radiology Breast Imaging Reporting and Data System. The pathological findings of SCNB were categorized into 4 groups: benign and specific, benign and nonspecific, premalignant, and malignant. Surgical excision of the lesion was performed if the pathological finding on SCNB was nonconcordant with the prebiopsy mammogram and when premalignant or malignant lesions were found. The pathological findings of lesions that were subsequently removed by surgical excision were compared with those of SCNB. Community-based private multispecialty ambulatory practice. A population-based sample composed of 97 patients who had grade III, IV, or V lesions on routine screening mammograms. Stereotactic core needle biopsy of nonpalpable mammographic lesions. Percentage of patients whose SCNB results were concordant with the mammographic findings and the pathological findings on subsequent surgical excision. Concordance between SCNB and mammography occurred in 97% of biopsy specimens. Concordance between the pathological findings of SCNB and those of surgically excised lesions occurred in 92.5% of biopsy specimens. We had 1 false-negative result. We had no false-positive diagnosis of cancer with SCNB. On the basis of accumulating literature and our own initial experience, SCNB is a promising, safe, and cost-effective procedure.


Photophysics and Nonlinear Absorption of Gold(I) and Platinum(II) Donor-Acceptor-Donor Chromophores.
A series of Au(I) and Pt(II) acetylide complexes of a π-conjugated donor-acceptor-donor (D-A-D) chromophore were studied to develop quantitative structure-property relationships for their photophysical and nonlinear optical properties. The D-A-D chromophore consists of a "TBT" unit, where T = 3-hexyl-2,5-thienylene and BTD = 2,1,3-benzothiadiazole, capped with ethynylene groups. The D-A-D chromophore is functionalized with Au(I)PR3 (R = -Me and -Ph) and trans-Pt(II)(PR3)2-CCPh (R = -Me and -Bu) "auxochromes". All of the metal complexes were characterized by ground-state absorption, photoluminescence, nanosecond transient absorption, and two-photon absorption (2PA) spectroscopy. The experiments provided quantitative values of the photophysical parameters, including rates for radiative decay and intersystem crossing (ISC), triplet yields, and two-photon absorption cross sections. Pronounced solvatochromism in the fluorescence spectra suggests an enhanced dipole moment in the excited state of the complexes compared to the unmetalated TBT chromophore. The gold complexes feature larger fluorescence quantum yields and longer emission lifetimes compared to platinum. The Pt(II) complexes exhibit enhanced triplet-triplet absorption, reduced triplet-state lifetimes, and larger singlet oxygen quantum yields, consistent with more efficient ISC compared to the Au(I) complexes. When excited by 100 fs pulses, all of the D-A-D chromophores exhibit moderate two-photon absorption in the near-infrared between 700 and 900 nm. The 2PA cross section for the Au(I) complexes is almost the same as the unmetalated D-A-D chromophore (∼100 GM). The Pt(II) complexes exhibit significantly enhanced 2PA compared to the other chromophores, reaching 1000 GM at 750 nm. Taken together, the results indicate that the Pt(II) center is considerably more effective in inducing singlet-triplet ISC and in enhancing the 2PA cross section. This result reveals the greater promise for Pt(II) acetylides in chromophores for temporal and frequency agile nonlinear absorption.


Revision of the Absolute Configurations of Chelocardin and Amidochelocardin.
Even with the aid of the available methods, the configurational assignment of natural products can be a challenging task that is prone to errors, and it sometimes needs to be corrected after total synthesis or single-crystal X-ray diffraction (XRD) analysis. Herein, the absolute configuration of amidochelocardin is revised using a combination of XRD, NMR spectroscopy, experimental ECD spectra, and time-dependent density-functional theory (TDDFT)-ECD calculations. As amidochelocardin was obtained via biosynthetic engineering of chelocardin, we propose the same absolute configuration for chelocardin based on the similar biosynthetic origins of the two compounds and result of TDDFT-ECD calculations. The evaluation of spectral data of two closely related analogues, 6-desmethyl-chelocardin and its semisynthetic derivative 1, also supports this conclusion.


Four-part displaced proximal humeral fractures: treatment with hemiarthroplasty.
Between 1996 and 2000 a total of 25 hemiarthroplasties of the shoulder in just as many patients were carried out. A total of 15 were followed-up (minimum 1 year, maximum 5 years, mean 2.5 years; mean age 75.5 years). The Constant score showed a mean of 73.26 points (with a maximum score of 90 and a minimum of 40). One patient obtained a reduced Constant score (40 points) because of severe lesions of the rotator cuff and continuous pain, even during the night. Patients reported that they were satisfied in 75% of cases. We believe that the integrity of the cuff is an essential condition for final success, alongside important indications such as type of fracture, bone quality, age and motivations of the patient, with respect for rules governing method of implantation and protocols for rehabilitation used.


The Sonogel-Carbon electrode as a sol-gel graphite-based electrode.
In this work, a novel sol-gel-based procedure to obtain solid carbon composite electrodes is proposed. The procedure is based on the use of sonocatalysis to apply high-energy ultrasound directly to the precursors; this way, ultrasonic cavitation is achieved so that hydrolysis with acidic water is promoted in the absence of any additional solvent and the time needed to get a unique phase is reduced drastically. The mix of sonogel with spectroscopic grade graphite leads to a new type of sol-gel electrode: the Sonogel-Carbon electrode. The amount of water, necessary for hydrolysis to occur, has been studied, as well as the sol pH value and the electrochemical behavior of the Sonogel-Carbon electrode in Britton-Robinson buffer. Mechanical renewal of the electrodes surfaces and background signal stability for at least 42 days have been also tested. We have carried out some tests to check the ability of the synthesized material to give electrochemical response when redox species are present in the background electrolyte. Mechanical and electrochemical studies indicate that the Sonogel-Carbon electrode shows good properties for use as an electrochemical sensor.


Ethnography: research method or philosophy?
From pioneering beginnings at the Chicago School of Sociology in the 20s and 30s, ethnography (as described in other articles in this issue) has developed into an important methodology that is widely used by social scientists ( 1 ). It was from the 30s a split began to appear between ethnography as practised by social scientists, and ethnographic methods used by anthropologists. Anthropology continued to study the culture of races, while social scientists used the same methods to look at culture on a social level. Sociologists realised that the methodology of ethnography was just as appropriate to the description of everyday Western cultures as it was to that of more distant cultures.


Urinary incontinence in women: Direct costs of routine care.
The purpose of this study was to estimate the direct costs of routine care for urinary incontinence (UI) in community-dwelling, racially diverse women. In the Reproductive Risks for Incontinence Study at Kaiser population-based study, 528 women with UI weekly or more quantified resources that were used for UI. Routine care costs were calculated with the use of national resource costs ($2005). Potential predictors of these outcomes were examined by multivariable linear regression. Mean age was 55 +/- 9 (SD) years. Among women with weekly UI, 69% reported incontinence-related costs. Median weekly cost was $1.83 (25%-75% interquartile range [IQR], $0.50, $5.23), increasing from $0.93 (IQR, $0, $3) for moderate to $7.82 (IQR, $5, $37) for very severe incontinence. Costs that increased with incontinence severity (P < .001) and body mass index (P < .001) were 2.2-fold higher for African American versus white women (P < .0001) and 42% higher for women with mixed versus stress incontinence (P < .05). Women pay a mean of >$250 per year out-of-pocket for UI routine care. Effective incontinence treatment may decrease costs.


Tunable Multicolor Lanthanide Supramolecular Assemblies with White Light Emission Confined by Cucurbituril[7].
Macrocyclic confinement-induced supramolecular luminescence materials have important application value in the fields of bio-sensing, cell imaging, and information anti-counterfeiting. Herein, a tunable multicolor lanthanide supramolecular assembly with white light emission is reported, which is constructed by co-assembly of cucurbit[7]uril (CB[7]) encapsulating naphthylimidazolium dicarboxylic acid (G1 )/Ln (Eu3+ /Tb3+ ) complex and carbon quantum dots (CD). Benefiting from the macrocyclic confinement effect of CB[7], the supramolecular assembly not only extends the fluorescence intensity of the lanthanide complex G1 /Tb3+ by 36 times, but also increases the quantum yield by 28 times and the fluorescence lifetime by 12 times. Furthermore, the CB[7]/G1 /Ln assembly can further co-assemble with CD and diarylethene derivatives (DAE) to realize the intelligently-regulated full-color spectrum including white light, which results from the competitive encapsulation of adamantylamine and CB[7], the change of pH, and photochromic DAE. The multi-level logic gate based on lanthanide supramolecular assembly is successfully applied in anti-counterfeiting system and information storage, providing an effective method for the research of new luminescent intelligent materials.


[Relation between dopamine and serotonin motor effects on isolated rat duodenum. Possible participation of an excitatory dopaminergic receptor].
The experimental facts presented here allow us to establish a relationship between DA motor effects on isolated rat duodenum, studied in a previous work, (excito-motor between 10(-9) M and 10(-5) M and inhibitor beyond 10(-5) M) and the functional aptitude of this duodenum to answer to 5-HT : 5-HT excito-motor effects are amplified by DA at concentrations less than or equal to 2.6 X 10(-6) M and on the contrary antagonized by DA at concentrations above 5 X 10(-6) M. On the other hand, DA excito-motor effects do not appear on 5-HT-desensitized duodenums. The study of 5-HT dose-response curves in the presence of different concentrations of DA suggests that the amplification of serotonergic effects observed with small DA concentrations can be possibly related to the additional effects of 5-HT on its own receptors and of DA on another receptor. The receptor involved in DA excito-motor action seems to be closely related to the 5-HT receptor since its effects are blocked by the same molecules (methylsergide, cyproheptadine) and since DA excito-motor action is no more evident on 5-HT-desensitized duodenums, but several arguments support the specificity of this receptor for DA (though it is not blocked by haloperidol). Some of its effects are in line with those of DA receptors made conspicuous in other territories and not blocked by haloperidol : central and human colon receptors. On the contrary, DA used at high concentrations (greater than or equal to 5 X 10(-6) M) seems to be able to occupy serotonergic sites, preventing 5-HT access to its receptors until its concentration is high enough to displace DA. From a functional point of view, this antagonistic effect of DA at high concentrations against 5-HT excito-motor effects could facilitate alpha- and beta-mediated inhibitory effects.


Hypertension and sensorimotor peripheral neuropathy in type 2 diabetes.
The mechanisms responsible for the onset of sensorimotor peripheral diabetic neuropathy (SMPN) remain largely unknown. To address this issue, we studied the relationship between traditional cardiovascular risk factors, parameters of metabolic control, and the presence of SMPN in patients with type 2 diabetes of relatively short duration. Blood pressure, glycated hemoglobin, lipid profile, and the presence of micro- and macrovascular complications were assessed and monitored in 31 consecutive ambulatory patients with type 2 diabetes (age 60.7 +/- 7.5 years, mean +/- SD) within 10 years of diagnosis (mean diabetes duration 6.0 +/- 2.3 years). Clinical and neurophysiological features of SMPN were present in 10 patients (SMPN+, 32%). There were no significant differences in age, gender distribution, diabetes duration, body mass index, metabolic control, and serum cholesterol between SMPN- and SMPN+ patients. However, the prevalence of hypertension (i.e. blood pressure >/=140/90 mm Hg) was higher in SMPN+ patients (10/10 vs. 13/21, chi(2 =) 5.13, p = 0.025). Regression analysis showed that, after correcting for age, gender, duration of diabetes, glycated hemoglobin, and cholesterol, the presence of hypertension was independently associated with SMPN (R(2) = 0.17, p = 0.023). There is a strong association between hypertension and SMPN in type 2 diabetic patients with relatively short duration of disease. This relationship is independent of other risk factors.


[Embolization of cerebral arteriovenous malformations--methods and clinical results].
Interventional treatment by neuroradiological embolisation of cerebral arteriovenous angiomas has become an alternative to surgical exstirpation especially in problematic localisations and large-size malformations. Clinical results showing a marked reduction in attacks and recurrent haemorrhages, evident from a three-year report on 17 patients, confirm the value of the method even in case of only subtotal occlusion of the malformation.


Impact of animation-supported consent on complaints and serious incidents due to failure to inform.
Introduction of digital animations to explain medical procedures before consent to treatment (animation-supported consent) has been shown to improve patient-reported understanding of a procedure's benefits, risks and alternatives. We examined whether introduction of animation-supported consent is associated with a change in the incidence of complaints and serious incidents due to failure to inform. Multi-language animations explaining 10 cardiac procedures, in coronary intervention, electrophysiology and cardiac surgery, (www.explainmyprocedure.com) were introduced at a London cardiac centre from April 2019. Complaints and serious incidents due to failure to inform were identified from the hospital Datix database for the two years before introducing animation-supported consent (no animation group) and the two years afterwards (animation group), together with the total number of procedures and major complications recorded during these periods. We compared the incidence of complaints and serious incidents, expressed as a proportion of the number of major complications, recorded during each period. There were 580 complications among 21 855 procedures performed in the no animation group and 411 complications among 18 254 procedures in the animation group. There were 14 complaints or serious incidents due to failure to inform in the no animation group and 3 in the animation group; rates of 2.41% (14/580) and 0.73% (3/411), respectively (P < 0.001 for difference). In this observational comparison, introduction of animation-supported consent was associated with a 70% reduction in complaints or serious incidents due to failure to inform before consent. This has significant quality and cost implications for improving consent pathways in clinical practice.


PyLDM - An open source package for lifetime density analysis of time-resolved spectroscopic data.
Ultrafast spectroscopy offers temporal resolution for probing processes in the femto- and picosecond regimes. This has allowed for investigation of energy and charge transfer in numerous photoactive compounds and complexes. However, analysis of the resultant data can be complicated, particularly in more complex biological systems, such as photosystems. Historically, the dual approach of global analysis and target modelling has been used to elucidate kinetic descriptions of the system, and the identity of transient species respectively. With regards to the former, the technique of lifetime density analysis (LDA) offers an appealing alternative. While global analysis approximates the data to the sum of a small number of exponential decays, typically on the order of 2-4, LDA uses a semi-continuous distribution of 100 lifetimes. This allows for the elucidation of lifetime distributions, which may be expected from investigation of complex systems with many chromophores, as opposed to averages. Furthermore, the inherent assumption of linear combinations of decays in global analysis means the technique is unable to describe dynamic motion, a process which is resolvable with LDA. The technique was introduced to the field of photosynthesis over a decade ago by the Holzwarth group. The analysis has been demonstrated to be an important tool to evaluate complex dynamics such as photosynthetic energy transfer, and complements traditional global and target analysis techniques. Although theory has been well described, no open source code has so far been available to perform lifetime density analysis. Therefore, we introduce a python (2.7) based package, PyLDM, to address this need. We furthermore provide a direct comparison of the capabilities of LDA with those of the more familiar global analysis, as well as providing a number of statistical techniques for dealing with the regularization of noisy data.


Application of transmission infrared spectroscopy and partial least squares regression to predict immunoglobulin G concentration in dairy and beef cow colostrum.
The objective of this study was to explore the potential of transmission infrared (TIR) spectroscopy in combination with partial least squares regression (PLSR) for quantification of dairy and beef cow colostral immunoglobulin G (IgG) concentration and assessment of colostrum quality. A total of 430 colostrum samples were collected from dairy (n = 235) and beef (n = 195) cows and tested by a radial immunodiffusion (RID) assay and TIR spectroscopy. Colostral IgG concentrations obtained by the RID assay were linked to the preprocessed spectra and divided into combined and prediction data sets. Three PLSR calibration models were built: one for the dairy cow colostrum only, the second for beef cow colostrum only, and the third for the merged dairy and beef cow colostrum. The predictive performance of each model was evaluated separately using the independent prediction data set. The Pearson correlation coefficients between IgG concentrations as determined by the TIR-based assay and the RID assay were 0.84 for dairy cow colostrum, 0.88 for beef cow colostrum, and 0.92 for the merged set of dairy and beef cow colostrum. The average of the differences between colostral IgG concentrations obtained by the RID- and TIR-based assays were -3.5, 2.7, and 1.4 g/L for dairy, beef, and merged colostrum samples, respectively. Further, the average relative error of the colostral IgG predicted by the TIR spectroscopy from the RID assay was 5% for dairy cow, 1.2% for beef cow, and 0.8% for the merged data set. The average intra-assay CV% of the IgG concentration predicted by the TIR-based method were 3.2%, 2.5%, and 6.9% for dairy cow, beef cow, and merged data set, respectively.The utility of TIR method for assessment of colostrum quality was evaluated using the entire data set and showed that TIR spectroscopy accurately identified the quality status of 91% of dairy cow colostrum, 95% of beef cow colostrum, and 89% and 93% of the merged dairy and beef cow colostrum samples, respectively. The results showed that TIR spectroscopy demonstrates potential as a simple, rapid, and cost-efficient method for use as an estimate of IgG concentration in dairy and beef cow colostrum samples and assessment of colostrum quality. The results also showed that merging the dairy and beef cow colostrum sample data sets improved the predictive ability of the TIR spectroscopy.


Acidic residues in the lactococcal multidrug efflux pump LmrP play critical roles in transport of lipophilic cationic compounds.
The proton motive force-driven efflux pump LmrP confers multidrug resistance on Lactococcus lactis cells by extruding a wide variety of lipophilic cationic compounds from the inner leaflet of the cytoplasmic membrane to the exterior of the cell. LmrP contains one cysteine (Cys(270)), which was replaced by alanine. This cysteine-less variant was used in a cysteine scanning accessibility approach. All 19 acidic residues in LmrP were replaced one by one by cysteine and subsequently challenged with the large thiol reagent fluorescein maleimide. The labeling pattern strongly indicates that only three acidic residues (Asp(142), Glu(327), and Glu(388)) are membrane-embedded. The roles of these residues in drug recognition were evaluated based on transport experiments with two cationic substrates, ethidium and Hoechst 33342, after replacing each of these residues with cysteine, alanine, lysine, glutamate, or aspartate. The obtained results suggest that the negative charges at positions 142 and 327 are not critical for the transport function but are important for drug recognition by LmrP. Surprisingly, the residues Cys(142) and Cys(327) become accessible for fluorescein maleimide upon binding of substrates, indicating a movement of these residues from a nonpolar to a polar environment. Substrate binding apparently results in a conformational change in this region of the protein and a reorientation of a lipid-embedded, hydrophobic substrate-binding site to an aqueous substrate translocation pathway.


Patients with rib fractures: use of incentive spirometry volumes to guide care.
Rib fractures pose significant risk to trauma patients. Effective pain control and the ability to take deep breaths are crucial for optimal recovery, and these are key elements in current clinical guidelines. These guidelines use incentive spirometry volumes along with other assessment values to guide patient care. However, despite current guidelines, nurses do not routinely document inspired respiratory volumes. This article provides trauma nurses with the rationale for documenting and tracking incentive spirometry volumes to improve outcomes for patients with rib fractures. This promotes early detection of respiratory decline and early interventions to improve pain control and pulmonary function.


Influences of microparticle radius and microchannel height on SSAW-based acoustophoretic aggregation.
The use of acoustic waves for microfluidic aggregation has become widespread in chemistry, biology and medicine. Although numerous experimental and analytical studies have been undertaken to study the acoustophoretic aggregation mechanisms, few studies have been conducted to optimise the device design. This paper presents a numerical investigation of the acoustophoresis of microparticles suspended in compressible liquid. The wall of the rectangular microchannel is made of Polydimethylsiloxane (PDMS), and Standing Surface Acoustic Waves (SSAW) are introduced into the channel from the bottom wall. First, the relative amplitude of the acoustic radiation force and the viscous drag force is evaluated for particles of different radii ranging from 0.1μm to 15μm. Only when the particle size is larger than a critical value can the particles accumulate at acoustic pressure nodes (PNs). The efficiency of the particle accumulation depends on the microchannel height, so an extensive parametric study is then undertaken to identify the optimum microchannel height. The optimum height, when normalised by the acoustic wavelength, is found to be between 0.57 and 0.82. These findings provide insights into the design of acoustophoretic devices.


Molecular weight distribution effects on the structure of strongly adsorbed polymers by Monte Carlo simulation.
Monte Carlo simulations are reported to study the structure of polymers adsorbed from solution onto strongly attractive, perfectly smooth substrates. Six systems spanning a range of molecular weight distributions are investigated with a coarse-grained united atom model for freely rotating chains. By employing a global replica exchange algorithm and topology altering Monte Carlo moves, a range of monomer-surface attraction from weak (0.27kT) to strong (4kT) is simultaneously explored. Thus for the first time ever, equilibrium polymer adsorption on highly attractive surfaces is studied, with all adsorbed molecules displaying similar properties and statistics. The architecture of the adsorbed layers, including density profiles, bond orientation order parameters, radii of gyration, and distribution of the adsorbed chain fractions, is shown to be highly dependent on the polydispersity of the polymer phase. The homology of polymer chains, and the ergodicity of states explored by the molecules is in contrast to the metastable, kinetically constrained paradigm of irreversible adsorption. The structure of more monodisperse systems is qualitatively similar to experimental results and theoretical predictions, but result from very different chain conformations and statistics. The polydispersity-dependent behavior is explained in the context of the competition between polymers to make contact with the surface.


Hemolytic transfusion reactions in oncology patients: experience in a large cancer center.
At The University of Texas M.D. Anderson Hospital and Tumor Institute at Houston, the incidence of hemolytic transfusion reactions over an eight-year period (1974-1981) was analyzed. Only four hemolytic transfusion reactions were reported out of 142,957 transfusions of blood (a frequency of one reaction in 35,739.25 transfusions). This could be due to the following factors: (1) Impairment of immune status related to the malignant process or temporary immunosuppression caused by intensive chemotherapy could enable patients to tolerate incompatible transfusions. (2) The reactions are overlooked or masked by the severity of disease in cancer patients in spite of an elaborate education for nurses, residents/fellows, and staff physicians about the dangers of hemolytic reactions. The figures herein reported are lower than those reported from non-oncology hospital settings.


Fully transparent quantum dot light-emitting diode integrated with graphene anode and cathode.
A fully transparent quantum dot light-emitting diode (QD-LED) was fabricated by incorporating two types (anode and cathode) of graphene-based electrodes, which were controlled in their work functions and sheet resistances. Either gold nanoparticles or silver nanowires were inserted between layers of graphene to control the work function, whereas the sheet resistance was determined by the number of graphene layers. The inserted gold nanoparticles or silver nanowires in graphene films caused a charge transfer and changed the work function to 4.9 and 4.3 eV, respectively, from the original work function (4.5 eV) of pristine graphene. Moreover the sheet resistance values for the anode and cathode electrodes were improved from ∼63,000 to ∼110 Ω/sq and from ∼100,000 to ∼741 Ω/sq as the number of graphene layers increased from 1 to 12 and from 1 to 8, respectively. The main peak wavelength, luminance, current efficiency, and optical transmittance of the fully transparent QD-LED integrated with graphene anode and cathode were 535 nm, ∼358 cd/m2, ∼0.45 cd/A, and 70-80%, respectively. The findings of the study are expected to lay a foundation for the production of high-efficiency, fully transparent, and flexible displays using graphene-based electrodes.


Bak Foong protects dopaminergic neurons against MPTP-induced neurotoxicity by its anti-apoptotic activity.
Bak Foong pill (BFP) is a well-known traditional Chinese medicine used for treatment of various gynaecological disorders. In addition, it exerts beneficial effects on other functional systems including the central nervous system. In the present study, we have investigated the possible neuroprotective action of BFP upon the nigrostriatal dopaminergic system by examining its effect on the expression patterns of tyrosine hydroxylase (TH) and dopamine transporter (DAT) in the 1-methyl-4-phenyl-1,2,3,6-tetrahyrdropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. MPTP significantly decreased TH and DAT mRNA levels in the striatum and midbrain of both female and male C57BL/6 mice. However, with BFP pre-treatment mice showed a reduced neurotoxicity, with TH and DAT mRNA levels either not affected by MPTP or affected to a lesser extent in the midbrain and striatum when compared to vehicle treated animals. Possible anti-apoptotic activity of BFP was further studied in a dopamine-secreting neuroendocrine cell line, PC12. In this assay, MPTP elevated the expression of a pro-apoptotic gene, Bax, while this expression was reduced by BFP pre-treatment. Flow cytometry results also revealed that the effect of MPTP-induced apoptosis in PC12 cell lines was significantly reduced by BFP. The present results suggest that BFP is able to protect dopaminergic neurons from neurotoxin-induced neuronal injury with anti-apoptotic activity being one of the possible mechanisms.


Commonly used surfactant, Tween 80, improves absorption of P-glycoprotein substrate, digoxin, in rats.
Tween 80 (Polysorbate 80) is a hydrophilic nonionic surfactant commonly used as an ingredient in dosing vehicles for pre-clinical in vivo studies (e.g., pharmacokinetic studies, etc.). Tween 80 increased apical to basolateral permeability of digoxin in Caco-2 cells suggesting that Tween 80 is an in vitro inhibitor of P-gp. The overall objective of the present study was to investigate whether an inhibition of P-gp by Tween 80 can potentially influence in vivo absorption of P-gp substrates by evaluating the effect of Tween 80 on the disposition of digoxin (a model P-gp substrate with minimum metabolism) after oral administration in rats. Rats were dosed orally with digoxin (0.2 mg/kg) formulated in ethanol (40%, v/v) and saline mixture with and without Tween 80 (1 or 10%, v/v). Digoxin oral AUC increased 30 and 61% when dosed in 1% and 10% Tween 80, respectively, compared to control (P < 0.05). To further examine whether the increase in digoxin AUC after oral administration of Tween 80 is due, in part, to a systemic inhibition of digoxin excretion in addition to an inhibition of P-gp in the GI tract, a separate group of rats received digoxin intravenously (0.2 mg/kg) and Tween 80 (10% v/v) orally. No significant changes in digoxin IV AUC was noted when Tween 80 was administered orally. In conclusion, Tween 80 significantly increased digoxin AUC and Cmax after oral administration, and the increased AUC is likely to be due to an inhibition of P-gp in the gut (i.e., improved absorption). Therefore, Tween 80 is likely to improve systemic exposure of P-gp substrates after oral administration. Comparing AUC after oral administration with and without Tween 80 may be a viable strategy in evaluating whether oral absorption of P-gp substrates is potentially limited by P-gp in the gut.


Isolation of vaccinia JX594 from pustules following therapy for hepatocellular carcinoma.
JX594 is an oncolytic poxvirus derived from Wyeth strain vaccinia virus. We reported the presentation of cutaneous and mucosal pustules containing laboratory-confirmed JX594 in a patient following injection of JX594. A 36-year-old man was diagnosed hepatitis B virus-associated hepatocellular carcinoma on September 19, 2011. Despite treatment with entecavir, radiofrequency ablation and transarterial chemoembolization for recurrent local tumors, the tumors recurred in both lobes and lung metastases were detected by computed tomography on September 12, 2012. The patient was treated with JX594 (Pexa-vec®) via intravenous injection on December 19, 2012. No apparent adverse effects were observed following intravenous injection other than a single fever episode. However, pustular lesions were detected on both sides of the tongue dorsum and on the proximal interphalangeal joint of the right middle finger on December 25, 1012. Biopsy samples analyzed by PCR identified the presence of the JX-594-specific hGM-CSF transgene and the disrupted viral thymidine kinase gene. Following aspiration of the lesion a scab formed that resolved within 14 days without necessitating additional treatment. Our case completely recovered and did not develop systemic or recurrent disease, the presentation of a few pustules may not necessarily require that treatment with JX594 be interrupted for patients with advanced hepatocellular carcinoma.


[Effect of substance P on nerve fiber regeneration in tissue culture].
Explants of the ganglion trigeminale from chick embryos (PNS) and of the hippocampus from fetal rats (CNS) were cultivated in maximow chambers with growth medium or maintanance medium. Varied concentrations of substance P (SP . 3 CH3COOH . 4 H2O) were added. 1. The effect of substance P (SP) is related to concentration. In the presence of 10(-7)M SP in the growth medium and of 10(-4)M SP in the maintanance medium the cultivation of PNS cultures indicates positive results. These doses are suitable. 2. Within the first 24 hours in vitro SP stimulates the index of area in PNS cultures. The index of characterizes the relation of the outgrowth zone to the explant. In CNS cultures a significant difference of this effect was not observed. 3. The index of growth of nerve fibers may compare the test cultures with the control cultures. SP significantly increases the index of fiber growth in PNS cultures. A stimulation of CNS cultures was observed, significance was not found. 4. From the beginning of the cultivation with SP up to 48 hours in vitro the growth of nerve fibers significantly increases in the treated cultures in comparison with the control cultures. After this time the growth of nerve fibers decreased and a morphological conformity of test cultures and controls was observed. 5. The role of SP is discussed in specific activity on PNS tissue in vitro. The reactive neurons may be from the medio dorsal group of cells of the sensible ganglion.


Synthesis of apo-13- and apo-15-lycopenoids, cleavage products of lycopene that are retinoic acid antagonists.
Consumption of the tomato carotenoid, lycopene, has been associated with favorable health benefits. Some of lycopene's biological activity may be due to metabolites resulting from cleavage of the lycopene molecule. Because of their structural similarity to the retinoic acid receptor (RAR) antagonist, β-apo-13-carotenone, the "first half" putative oxidative cleavage products of the symmetrical lycopene have been synthesized. All transformations proceed in moderate to good yield and some with high stereochemical integrity allowing ready access to these otherwise difficult to obtain terpenoids. In particular, the methods described allow ready access to the trans isomers of citral (geranial) and pseudoionone, important flavor and fragrance compounds that are not readily available isomerically pure and are building blocks for many of the longer apolycopenoids. In addition, all of the apo-11, apo-13, and apo-15 lycopenals/lycopenones/lycopenoic acids have been prepared. These compounds have been evaluated for their effect on RAR-induced genes in cultured hepatoma cells and, much like β-apo-13-carotenone, the comparable apo-13-lycopenone and the apo-15-lycopenal behave as RAR antagonists. Furthermore, molecular modeling studies demonstrate that the apo-13-lycopenone efficiently docked into the ligand binding site of RARα. Finally, isothermal titration calorimetry studies reveal that apo-13-lycopenone acts as an antagonist of RAR by inhibiting coactivator recruitment to the receptor.


[Degree of hepatitis C infection risk in the health care setting].
Hepatitis C virus is the most important aetiologic agent for non A-non B hepatitis. The study of the prevalence of hepatitis C in health care workers is of primary interest because of the possible chronic evolution and the risk of cirrhosis and liver cancer. The purpose of this study was to determine the prevalence of HCV among health care workers in 5 main hospitals and local health units in Turin and analyze the influence of occupational and non occupational risk factors. Health care personnel were administered anonymous questionnaires and testing for anti-HCV antibody was performed. Prevalence rates in 4517 health care workers was 1.97%; the prevalence was higher in elderly workers (> 45 years) than in younger ones. The risk analysis did not reveal any significant correlation between HCV seroconversion and accidental blood exposure. However, a significant correlation was found with non-occupational risk factors. Unapparent infection was an unimportant risk factor for seroconversion. Hepatitis C prevalence in the population under study was comparable to that found in the general population. These results point to the need to reconsider the assumption that there is an increase of risk of seroconversion for health-care workers, in the absence of any occupational accidental exposure to hepatitis C virus.


Current trends in blood conservation in total knee arthroplasty.
There is a lack of consensus with regard to ways to minimize blood transfusions after total knee arthroplasty. We surveyed 434 members of the American Association of Hip and Knee Surgeons, each of whom averaged 18 years in practice and performed an average of between 100 and 150 knee replacements a year, about their preferences and practices regarding blood conservation during total knee arthroplasty. Of those surveyed, only 24% reported that there was a blood conservation program in place at their institutions. Fifty-nine percent of those surveyed routinely asked their patients to donate blood before unilateral and bilateral knee replacements. The amount of blood collected averaged 1.32 units (range, 1-4 units) and 2.04 units (range, 1-4 units) before unilateral and bilateral knee arthroplasty, respectively. Nearly half (47.5%) reported they rarely ever prescribed epoetin alfa because of a combination of cost, time, and labor issues. Furthermore, the majority (84%) has not had any experience with the use of antifibrinolytics. Overall, the mean transfusion rate after unilateral knee replacement was estimated to be less than 5% (range, 0%-20%) whereas the rate after bilateral knee replacement was estimated to be between 10% and 20% (range, 5%-20%).


Determination of quinolone residues in raw cow milk. Application of polar stir-bars and ultra-high performance liquid chromatography-tandem mass spectrometry.
Seventeen quinolone antibiotics were determined in cows' milk. A method of high sensitivity, selectivity and accuracy was developed. Accuracy (trueness and precision), linearity, sensitivity, selectivity, decision limit and detection capability were established following the recommendations of the Commission Decision 2002/657/EC and the Food and Drug Administration (FDA) guideline. The use of polar stir-bar sorptive extraction (SBSE) prior to UHPLC-MS/MS analysis is proposed. The variables that affect SBSE were optimised using multivariate optimisation strategies. The ionic strength, the extraction time and the sample volume were studied. pH and stir-bar coating (polydimethylsiloxane, PDMS, and polyethyleneglycol modified silicone, PEG) were studied. PEG showed the best extraction yield at pH 6. For validation, a matrix-matched calibration and a recovery assay were carried out. Limits of quantification from 0.5 μg kg-1 for nalidixic acid, flumequine and piromidic acid, to 4.0 μg kg-1 for sarafloxacin were calculated. The precision (%, RSD) was lower than 15% for all antibiotics. Recoveries in fortified samples were between 88 and 114%.


Recent Innovations in Peptide Based Targeted Drug Delivery to Cancer Cells.
Targeted delivery of chemotherapeutics and diagnostic agents conjugated to carrier ligands has made significant progress in recent years, both in regards to the structural design of the conjugates and their biological effectiveness. The goal of targeting specific cell surface receptors through structural compatibility has encouraged the use of peptides as highly specific carriers as short peptides are usually non-antigenic, are structurally simple and synthetically diverse. Recent years have seen many developments in the field of peptide based drug conjugates (PDCs), particularly for cancer therapy, as their use aims to bypass off-target side-effects, reducing the morbidity common to conventional chemotherapy. However, no PDCs have as yet obtained regulatory approval. In this review, we describe the evolution of the peptide-based strategy for targeted delivery of chemotherapeutics and discuss recent innovations in the arena that should lead in the near future to their clinical application.


Nevoid basal cell carcinoma syndrome: a review of the literature and a report of a case.
The purpose of this paper is to report the development of multiple odontogenic keratocysts (OKCs) in a 15-year-old female with nevoid basal cell carcinoma syndrome (NBCCS) and review the literature pertinent to NBCCS. Although more than 100 abnormalities have been reported in NBCCS, the development of OKCs is one of its principle features. In view of this, the patient was subjected to further medical, dermatological and radiographic investigation. Multiple basal cell naevi and skeletal anomalies associated with NBCCS were found. Because of the autosomal dominant inheritance of this syndrome, the patient's family was then investigated. The patient's father was found to have multiple OKCs. The report highlights the need for vigilance in considering the diagnosis of NBCCS in all cases of OKCs, particularly those affecting young patients.


Responses of Active Ammonia Oxidizers and Nitrification Activity in Eutrophic Lake Sediments to Nitrogen and Temperature.
Ammonium concentrations and temperature drive the activities of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB), but their effects on these microbes in eutrophic freshwater sediments are unclear. In this study, surface sediments collected from areas of Taihu Lake (China) with different degrees of eutrophication were incubated under three levels of nitrogen input and temperature, and the autotrophic growth of ammonia oxidizers was assessed using 13C-labeled DNA-based stable-isotope probing (SIP), while communities were characterized using MiSeq sequencing and phylogenetic analysis of 16S rRNA genes. Nitrification rates in sediment microcosms were positively correlated with nitrogen inputs, but there was no marked association with temperature. Incubation of SIP microcosms indicated that AOA and AOB amoA genes were labeled by 13C at 20°C and 30°C in the slightly eutrophic sediment, and AOB amoA genes were labeled to a much greater extent than AOA amoA genes in the moderately eutrophic sediment after 56 days. Phylogenetic analysis of 13C-labeled 16S rRNA genes revealed that the active AOA were mainly affiliated with the Nitrosopumilus cluster, with the Nitrososphaera cluster dominating in the slightly eutrophic sediment at 30°C with low ammonium input (1 mM). Active AOB communities were more sensitive to nitrogen input and temperature than were AOA communities, and they were exclusively dominated by the Nitrosomonas cluster, which tended to be associated with Nitrosomonadaceae-like lineages. Nitrosomonas sp. strain Is79A3 tended to dominate the moderately eutrophic sediment at 10°C with greater ammonium input (2.86 mM). The relative abundance responses of the major active communities to nitrogen input and temperature gradients varied, indicating niche differentiation and differences in the physiological metabolism of ammonia oxidizers that are yet to be described.IMPORTANCE Both archaea and bacteria contribute to ammonia oxidation, which plays a central role in the global cycling of nitrogen and is important for reducing eutrophication in freshwater environments. The abundance and activities of ammonia-oxidizing archaea and bacteria in eutrophic limnic sediments vary with different ammonium concentrations or with seasonal shifts, and how the two factors affect nitrification activity, microbial roles, and active groups in different eutrophic sediments is unclear. The significance of our research is in identifying the archaeal and bacterial responses to anthropogenic activity and climate change, which will greatly enhance our understanding of the physiological metabolic differences of ammonia oxidizers.


All-on-4® Treatment Concept in a Severely Resorbed Jaw Using Narrow-Platform Implants: A Case Report.
Although many approaches to the restoration of edentulous maxillae and mandibles have been developed, these treatments can be costly and time-consuming, and involve extensive grafting of the edentulous ridges. The All-on-4® treatment concept has been shown to be a viable alternative, with limited grafting required, using at least four regular-platform implants to support an acrylic, screw-retained provisional prosthesis before the fabrication of a definitive prosthesis. This case presentation will discuss the use of narrow-platform (3.5-mm) implants to provide a patient with a screw-retained acrylic provisional on the day of implant placement.


Regulation of lymphocyte proliferation after influenza virus infection of human mononuclear leukocytes.
Previous studies demonstrated that in vitro infection with influenza A viruses altered several functions of human monocytes-macrophages but did not detectably alter functions of human lymphocytes. However, both types of cells were infected, as determined by production and surface expression of viral antigens. In the current studies, human mononuclear leukocytes were infected in vitro and assayed for both influenza virus-induced proliferation and mitogen (phytohemagglutinin [PHAl)-induced proliferation, as well as for ability to stimulate proliferative responses by normal autologous leukocytes. The leukocytes showed proliferation in response to the infectious virus, but concomitant depressed proliferative responses to PHA. Coculture experiments suggested suppression of PHA-induced responses by the virus-infected cells. However, upon coculture with fresh autologous leukocytes (without PHA stimulation), both virus-infected macrophages and virus-infected lymphocytes induced autologous lymphocyte proliferative responses. Altered proliferative responses to mitogen stimulation after exposure to the virus were not due to diminished interleukin-1 production or diminished expression of HLA-DR by monocytes-macrophages. The expression of influenza virus antigens and resulting induction of autologous proliferative responses, combined with depressed mitogen-induced proliferation, may be important in human antiviral defense.


Immunogenicity of biologics in inflammatory bowel disease.
Crohn's disease and ulcerative colitis are chronic inflammatory disorders of the gastrointestinal tract. Treatment options include biologic therapies; however, a proportion of patients lose response to biologics, partly due to the formation of anti-drug antibodies (ADAbs). Concomitant immunosuppressive agents reduce the development of ADAbs. This review article aims to assess the immunogenicity of biologic therapies and their clinical implications. A comprehensive literature search was conducted for articles published January 2009 to August 2015 reporting immunogenicity to adalimumab (ADM), certolizumab pegol (CZP), golimumab, infliximab (IFX), ustekinumab, and vedolizumab in inflammatory bowel disease (IBD). Eligible articles were reviewed and quality assessed by independent reviewers. Overall, 122 publications reporting 114 studies were assessed. ADAbs were reported for all agents, but the percentage of patients developing ADAbs was extremely variable, with the highest (65.3%) being for IFX administration to patients with IBD. ADAb presence was frequently associated with a reduction in primary efficacy and a loss of response, and, for IFX, an increase in adverse events (AEs). Lower serum levels of ADM, CZP and IFX were seen in ADAbs-positive rather than ADAbs-negative patients; pharmacokinetic data were unavailable for other therapies. Little information was available regarding the timing of ADAb development; studies reported their detection from as early as 10-14 days up to months after treatment initiation. Biologic therapies carry an intrinsic risk of immunogenicity, although reported rates of ADAbs vary considerably. The clinical implications of immunogenicity are a concern for effective treatment; further research, particularly into the more recently approved biologics, is required.


MitoMiner v3.1, an update on the mitochondrial proteomics database.
Mitochondrial proteins remain the subject of intense research interest due to their implication in an increasing number of different conditions including mitochondrial and metabolic disease, cancer, and neuromuscular degenerative and age-related disorders. However, the mitochondrial proteome has yet to be accurately and comprehensively defined, despite many studies. To support mitochondrial research, we developed MitoMiner (http://mitominer.mrc-mbu.cam.ac.uk), a freely accessible mitochondrial proteomics database. MitoMiner integrates different types of subcellular localisation evidence with protein information from public resources, and so provides a comprehensive central resource for data on mitochondrial protein localisation. Here we report important updates to the database including the addition of subcellular immunofluorescent staining results from the Human Protein Atlas, computational predictions of mitochondrial targeting sequences, and additional large-scale mass-spectrometry and GFP tagging data sets. This evidence is shared across the 12 species in MitoMiner (now including Schizosaccharomyces pombe) by homology mapping. MitoMiner provides multiple ways of querying the data including simple text searches, predefined queries and custom queries created using the interactive QueryBuilder. For remote programmatic access, API's are available for several programming languages. This combination of data and flexible querying makes MitoMiner a unique platform to investigate mitochondrial proteins, with application in mitochondrial research and prioritising candidate mitochondrial disease genes.


Lateral Costal Artery: Clinical Importance of an Accessory Thoracic Artery.
The lateral costal artery has sometimes been identified as the culprit for the "steal phenomenon" after coronary artery bypass grafting, besides being occasionally used for myocardial revascularization. Its branches make anastomoses with the internal thoracic artery through lateral intercostal arteries. We aim to report, on three cases, the clinical significance of a well-developed lateral costal artery after coronary artery bypass grafting. Two out of three patients who underwent coronary artery bypass graft surgery in our center between June 2010 and August 2017, applied to us with stable angina pectoris, while the third one was diagnosed with acute coronary syndrome after applying to the emergency department. In coronary cineangiography, in all three cases, a well-developed accessory vessel arising from the proximal 2.5 cm segment of the left internal thoracic artery coursed as far as the 6th rib was detected, and it was confirmed to be the lateral costal artery. A stable angina pectoris in two of the patients was thought to be the result of steal phenomenon caused by the well-developed lateral costal artery. In the two cases with stable angina pectoris the lateral costal artery was obliterated via coil embolization. In the other case with the proximal left anterior descending artery stenosis, before percutaneous coronary intervention, the lateral costal artery was obliterated via coil embolization and the occluded subclavian artery was stented. Routine visualization in cineangiography and satisfactory surgical exploration of the left internal thoracic artery could be very helpful to identify any possible accessory branch of the left internal thoracic artery like the lateral costal artery.


R-spondin2 Suppresses the Progression of Hepatocellular Carcinoma via MAPK Signaling Pathway.
The R-spondin family plays important roles in embryonic development, including in humans. However, information on the relationship between R-spondin2 and hepatocellular carcinoma (HCC) is lacking. This study aimed was to explore the mechanisms of R-spondin2 action in the progression of HCC. By analyzing R-spondin2 expression levels in HCC tissues by IHC and database, we identified that HCC tissues had lower expression levels of R-spondin2, correlated with a poor prognosis. We also established R-spondin2-overexpressing and knockdown cell lines and measured their viabilities and invasion abilities in vitro and their oncogenic capacity in vivo. Human mRNA microarray analysis was performed to screen for mRNAs that were differentially expressed between R-spondin2-overexpressing and control HCC cells. Microarray and Western blot analyses showed significant changes in the MAPK signaling pathway after transfection. Furthermore, in vivo experiments indicated that R-spondin2 knockdown increased the tumorigenicity of HCC cells after subcutaneous implantation in mice. Altogether, our results indicate that the R-spondin2, which might be a novel tumor suppressor gene, were responsible for inhibiting the proliferation and invasion of HCC via the MAPK signaling pathway. IMPLICATIONS: R-spondin2 gene might be a novel tumor suppressor gene providing new clues to clarify the biological behavior of HCC and thus reduce patient mortality and prolong survival.


Chemometric techniques in distribution, characterisation and source apportionment of polycyclic aromatic hydrocarbons (PAHS) in aquaculture sediments in Malaysia.
This study investigated polycyclic aromatic hydrocarbons (PAHs) pollution in surface sediments within aquaculture areas in Peninsular Malaysia using chemometric techniques, forensics and univariate methods. The samples were analysed using soxhlet extraction, silica gel column clean-up and gas chromatography mass spectrometry. The total PAH concentrations ranged from 20 to 1841 ng/g with a mean of 363 ng/g dw. The application of chemometric techniques enabled clustering and discrimination of the aquaculture sediments into four groups according to the contamination levels. A combination of chemometric and molecular indices was used to identify the sources of PAHs, which could be attributed to vehicle emissions, oil combustion and biomass combustion. Source apportionment using absolute principle component scores-multiple linear regression showed that the main sources of PAHs are vehicle emissions 54%, oil 37% and biomass combustion 9%. Land-based pollution from vehicle emissions is the predominant contributor of PAHs in the aquaculture sediments of Peninsular Malaysia.


Trastuzumab effects depend on HER2 phosphorylation in HER2-negative breast cancer cell lines.
The breast cancer (BC) biomarker HER2 (Human Epidermal Receptor 2) is overexpressed in 25% of BC. Only patients with HER2-positive tumors receive HER2-targeting therapies, like trastuzumab (Herceptin). However, some women with a HER2-negative BC could benefit from trastuzumab. This could be explained by the activation/phosphorylation of HER2 that can be recognized by trastuzumab. The aim of this study is to examine trastuzumab effects on HER2 phosphorylation at tyrosine Y877 (pHER2Y877). HER2 and pHER2Y877 status were evaluated in a cohort of BC patients representative of molecular subtypes distribution (n = 497) and in a series of BC cell lines (n = 7). Immunohistochemistry against pHER2Y877 was performed on tissue micro arrays. Cellular proliferation assays were performed on BC cell lines presenting different combinations of HER2 and pHER2Y877 status and treated with increasing doses of trastuzumab (0-150 μg/ml). The prevalence of pHER2Y877 in this cohort was 6%. Nearly 5% of patients with HER2-negative tumors (n = 406, 82%) overexpressed pHER2Y877. Among triple negative BC patients (n = 39, 8%), 7.7% expressed pHER2Y877. Trastuzumab treatment decreased cell proliferation in HER2-/pHER2Y877+ BC cell lines, to an extent comparable to what occurs in HER2+ cell lines, but did not affect HER2-/pHER2Y877- cell lines. Trastuzumab sensitivity in HER2-/pHER2Y877+ cell line is specific to HER2 tyrosine 877 phosphorylation. Hence, with further confirmation in a bigger cohort, trastuzumab treatment could be envisaged as a treatment option to women presenting with HER2-/pHER2+ tumors, representing more than 1000 BC women in Canada in 2019.


Comparison between UV index measurements performed by research-grade and consumer-products instruments.
Ultraviolet radiation (UVR) exposure, skin cancer and other related diseases are not just subjects of scientific literature. Nowadays, these themes are also discussed on television, newspapers and magazines for the general public. Consequently, the interest in prevention of sun overexposure is increasing, as the knowledge of photoprotection methods and UVR levels. The ultraviolet index (UVI) is a well-known tool recommended by the World Health Organization to avoid harmful effects of UV sunlight. UVI forecasts are provided by many national meteorological services, but local UVI measurements can provide a more realistic and appropriate evaluation of UVR levels. Indeed, as scientific instruments are very expensive and difficult to manipulate, several manufacturers and retail shops offer cheap and simple non-scientific instruments for UVI measurements, sometimes included in objects of everyday life, such as watches, outfits and hand-held instruments. In this work, we compare measurements provided by several commercial non-scientific instruments with data provided by a Bentham spectrometer, a very accurate sensor used for UV measurements. Results show that only a few of the instruments analyzed provide trustworthy UVI measurements.


The effect of incremental lower lip advancement on oral pressure and EMG activity of the lower lip.
During orthodontic arch expansion, the teeth are displaced against the perioral soft tissues. This can affect the equilibrium of forces that are thought to act on teeth, with consequent implications for long-term stability. The aim of this study was to investigate the effect of incremental lower lip advancement on intraoral pressure and electromyographic (EMG) activity of the lower lip. Intraoral pressure and EMG activity was measured in 10 participants (2 males, 8 females; 22 years ± 7 months) as the lower lip was incrementally advanced using three custom-made vacuum-formed stents of differing labial thicknesses (0.5, 2.5, and 4.5 mm). A task paradigm including at rest recordings and maximal voluntary contraction was completed for each tray. Resting lip pressure generated increased as the lower lip was advanced (P < 0.001). The EMG activity of the lower lip increased significantly (P < 0.001) only once the lip was advanced from 2.5 to 4.5 mm. For the pressure recordings, the response to incremental lip advancement showed considerable individual variation. These findings suggest that the initial pressure increase on the lower incisors was mostly likely due to the inherent viscoelastic properties of the lower lip, while the pressure increase between the 2.5 and 4.5 mm advancement was due to increased muscle activity. Each individual also responded to lower lip advancement in a different yet subject-specific manner.


Relevant and redundant lung function parameters in discriminating asthma from COPD.
A relevant set of lung function parameters, derived from spirometry, flow-volume curves, diffusion capacity and bodyplethysmography, to discriminate asthma from COPD was established via logistic regression analysis. All new patients, referred to the outpatient clinic and later defined as asthma or COPD, underwent extensive lung function testing with reversibility testing. Logistic regression was used to calculate the probability to be a COPD or asthma patient. Selection of relevant parameters was done via 1] forward-, 2] backward-, 3] stepwise selection and 4] the best score method. All four methods were supplemented by bootstrapping to obtain a validated selection and estimation of the logistic regression parameters. The area under the ROC curve (mean+/-sd) for respectively the forward, backward, stepwise and best score selection method is 0.9348+/-0.0115, 0.9346+/-0.0115, 0.9348+/-0.0115 and 0.9296+/-0.0121. The TLCO, VA and the postdilator MEF50, VC and PEF were selected as the most relevant parameters in discriminating asthma from COPD: they appeared most often as relevant discriminators in 500 bootstrapped samples: TLco was present in all bootstrapped samples and VA, postdilator MEF50, VC and PEF in resp. 70.8%, 46.2%, 42.8% and 36.8%. Bodyplethysmography derived parameters turned out to be of limited value. Diffusion capacity testing and spirometry/flow-volume curve after administration of bronchodilators are the methods of choicewhen having to chose between asthma or COPD.


Adapalene gel 0.1% in the treatment of infantile acne: an open clinical study.
Infantile acne is an uncommon condition in pediatric age. We determined the efficacy and safety of adapalene gel 0.1% in the treatment of infantile acne. Twelve patients were enrolled for adapalene gel 0.1% application once daily over a 16-week treatment period. Efficacy evaluation included counting the inflammatory and noninflammatory lesions by the physician and global evaluation of the improvement. After 16 weeks all patients were followed up for a 1-year period. The time of clearance of the infantile acne lesions was 3 months in four (33%) patients and 4 months in eight (67%) patients (median 3.4 months). Adapalene gel produced reductions in noninflammatory and inflammatory lesions counts. Limited side effects were observed and none of them required stopping the therapy. No patient was left with scarring. Three patients were showed mild lesions in the 1-year follow-up period. Adapalene gel 0.1% was found to be a highly effective and safe drug in the treatment of mild-to-moderate infantile acne.


Intake of Vegetables, Fruit, and Fish is Beneficial for Age-Related Macular Degeneration.
What patients should eat to reduce their risk of age-related macular degeneration (AMD) is still unclear. We investigated the effect of a diet recommended by Health Councils on AMD. Prospective population-based cohort study. Four thousand two hundred and two participants from the Rotterdam Study ≥55 years of age who were free of AMD at baseline were included and followed up for 9.1 ± 5.8 years. Incident AMD was graded on fundus photographs. Dietary data were collected using a validated 170-item food frequency questionnaire, and food intakes were categorized into food patterns based on guidelines from Health Councils. Associations with incident AMD were analyzed using Cox proportional hazards models that were adjusted for age, sex, total energy intake, smoking, body mass index, hypertension, education, and income. Seven hundred fifty-four people developed incident AMD. Intake of the recommended amounts of vegetables (≥200 g/day), fruit (2×/day), and fish (2×/week) were 30.6%, 54.9%, and 12.5%, respectively. In particular, the intake of fish (2×/week) decreased the risk of incident AMD (hazard ratio 0.76 [95% confidence interval 0.60-0.97]). Intake of the recommended amounts of all 3 food groups was only 3.7%, but adherence to this pattern showed a further reduction of the risk of incident AMD (hazard ratio 0.58 [95% confidence interval 0.36-0.93]). Younger age, higher income, and not smoking were associated with this food pattern, but the risk-lowering effects remained significant after additional adjustment for these factors. A diet of 200 grams per day of vegetables, fruit two times per day, and fish two times per week is associated with a significantly reduced risk of AMD.


SARS-CoV-2 RNAemia with a higher nasopharyngeal viral load is strongly associated with disease severity and mortality in patients with COVID-19.
This study aimed to determine the frequency of SARS-CoV-2 RNA in serum and its association with the clinical severity of COVID-19. This retrospective cohort study performed at Toyama University Hospital included consecutive patients with confirmed COVID-19. The prevalence of SARS-CoV-2 RNAemia and the strength of its association with clinical severity variables were examined. Fifty-six patients were included in this study. RNAemia was detected in 19.6% (11/56) patients on admission, and subsequently in 1.0% (1/25), 50.0% (6/12), and 100.0% (4/4) moderate, severe, and critically ill patients, respectively. Patients with RNAemia required more frequent oxygen supplementation (90.0% vs. 13.3%), ICU admission (81.8% vs. 6.7%), and invasive mechanical ventilation (27.3% vs. 0.0%). Among patients with RNAemia, the median viral loads of nasopharyngeal (NP) swabs that were collected around the same time as the serum sample were significantly higher in critically ill (5.4 log10 copies/μl; interquartile range [IQR]: 4.2-6.3) than in moderate-severe cases (2.6 log10 copies/μl; [IQR: 1.1-4.5]; p = 0.030) and were significantly higher in nonsurvivors (6.2 log10 copies/μl [IQR: 6.0-6.5]) than in survivors (3.9 log10 copies/μl [IQR: 1.6-4.6]; p = 0.045). This study demonstrated a relatively high proportion of SARS-CoV-2 RNAemia and an association between RNAemia and clinical severity. Moreover, among the patients with RNAemia, the viral loads of NP swabs were correlated with disease severity and mortality, suggesting the potential utility of combining serum testing with NP tests as a prognostic indicator for COVID-19, with higher quality than each separate test.


Yeast-like mRNA capping apparatus in Giardia lamblia.
A scheme of eukaryotic phylogeny has been suggested based on the structure and physical linkage of the RNA triphosphatase and RNA guanylyltransferase enzymes that catalyze mRNA cap formation. Here we show that the unicellular pathogen Giardia lamblia encodes an mRNA capping apparatus consisting of separate triphosphatase and guanylyltransferase components, which we characterize biochemically. We also show that native Giardia mRNAs have blocked 5'-ends and that 7-methylguanosine caps promote translation of transfected mRNAs in Giardia in vivo. The Giardia triphosphatase belongs to the tunnel family of metal-dependent phosphohydrolases that includes the RNA triphosphatases of fungi, microsporidia, and protozoa such as Plasmodium and Trypanosoma. The tunnel enzymes adopt a unique active-site fold and are structurally and mechanistically unrelated to the cysteine-phosphatase-type RNA triphosphatases found in metazoans and plants, which comprise part of a bifunctional triphosphataseguanylyltransferase fusion protein. All available evidence now points to the separate tunnel-type triphosphatase and guanylyltransferase as the aboriginal state of the capping apparatus. We identify a putative tunnel-type triphosphatase and a separate guanylyltransferase encoded by the red alga Cyanidioschyzon merolae. These findings place fungi, protozoa, and red algae in a common lineage distinct from that of metazoa and plants.


Identification and characterization of deamidation sites in the conserved regions of human immunoglobulin gamma antibodies.
Deamidation of asparagine residues of biological pharmaceuticals is a major cause of chemical degradation if the compounds are not formulated and stored appropriately. The mechanism of this nonenzymatic chemical reaction has been studied in great detail; however, the identification of deamidation sites in a given protein remains a challenge. In this study, we identified and characterized all deamidation sites in the conserved region of a recombinant monoclonal antibody. The conserved region of this antibody is shared by all human IgGs with the exception of minor differences in the hinge region. Our high-performance liquid chromatography method could separate the succinimide, isoaspartic, and aspartic acid isoforms of peptide fragments generated using trypsin. Each of the isoforms was unambiguously identified using tandem mass spectrometry. Deamidation at the identified four sites was slow for the intact, folded antibody at accelerated degradation conditions (pH 7.5 and 37 degrees C). Deamidation was enhanced after reduction, alkylation, and tryptic digestion, indicating that the three-dimensional structure of the antibody reduced deamidation. Furthermore, after the reduction, alkylation, and tryptic digestion, only 4 of a possible 25 asparagine residues showed deamidation, demonstrating the effect of the primary amino acid sequence, especially the -1 and +1 amino acids flanking the deamidation site. For instance, the amino acid motifs SNG, ENN, LNG, and LNN were found to be more prone to deamidation, whereas the motifs GNT, TNY, YNP, WNS, SNF, CNV, SNT, WNS, FNW, HNA, FNS, SNK, GNV, HNH, SNY, LNW, SNL, NNF, DNA, GNS, and FNR showed no deamidation. Our findings should help predict deamidation sites in proteins and peptides and help develop deamidation-resistant biological therapeutics.


Bone marrow versus peripheral blood as a graft source for haploidentical donor transplantation in adults using post-transplant cyclophosphamide-A systematic review and meta-analysis.
Peripheral-blood (PB) and bone marrow (BM) are both widely used in hematopoietic stem cell transplantation (HSCT). However, it is unclear whether PB or BM produces a more satisfactory outcome in haploidentical HSCT, particularly for patients using post-transplant cyclophosphamide (PTCy), which is the standard therapy. However, to date, no meta-analysis focusing on this issue has been published. We systematically searched PubMed, MEDLINE, Web of Science, the Cochrane Library and the ClinicalTrials.gov website for studies regarding the use of BM or PB in haploidentical HSCT for hematological malignancies in adults using PTCy. Data were analyzed using Open Meta-Analyst statistical software. Fourteen studies were extracted including four comparative retrospective reports and ten single-arm reports, with a total of 1759 patients received PTCy haploidentical HSCT (462 patients received PBSCT, 1297 patients received BMT). The pooled outcomes of comparative retrospective studies showed significantly higher incidence of grade III-IV acute graft-versus-host disease (GVHD) (OR = 1.741, 95%CI 1.032-2.938), incidence of grade IIIV acute GVHD (OR = 1.778, 95%CI 1.314, 2.406) and engraftment rate (OR = 1.843, 95%CI 1.066-3.185) in the PB group. No significant differences were found on the incidence of relapse, 2-year overall survival (OS) and disease-free survival (DFS), acute IIIV GVHD and chronic GVHD between PBSCT or BMT. The efficacy of PB is not inferior to BM for patients undergoing PTCy haploidentical HSCT with regard to primary outcomes, including OS, DFS, NRM and relapse. However, with regards to convenience and pain relief, PB graft is suitable for haploidentical HSCT, but with a higher risk of acute GVHD.


Finite element analysis for comparison of spinous process osteotomies technique with conventional laminectomy as lumbar decompression procedure.
The purpose of this study was to evaluate and compare the biomechanical behavior of the lumbar spine after posterior decompression with the spinous process osteotomy (SPiO) technique or the conventional laminectomy (CL) technique using a finite element (FE) model. Three validated lumbar FE models (L2-5) which represented intact spine and two decompression models using SPiO and CL techniques at the L3-4 segment were developed. In each model, the ranges of motion, the maximal von Mises stress of the annulus fibrosus, and the intradiscal pressures at the index segment (L3-4) and adjacent segments (L2-3 and L4-5) under 7.5 Nm moments were analyzed. Facet contact forces were also compared among three models under the extension and torsion moments. Compared to the intact model, the CL and SPiO models had increased range of motion and annulus stress at both the index segment (L3-4) and the adjacent segments under flexion and torsion. However, the SPiO model demonstrated a reduced range of motion and annulus stress than the CL model. Both CL and SPiO models had an increase of facet contact force at the L3-4 segment under the torsion moment compared to that of the intact model. Under the extension moment, however, three models demonstrated a similar facet contact force even at the L3-4 model. Both decompression methods lead to postoperative segmental instability compared to the intact model. However, SPiO technique leads to better segmental stability compared to the CL technique.


A bichaperone (Hsp70-Hsp78) system restores mitochondrial DNA synthesis following thermal inactivation of Mip1p polymerase.
Mitochondrial DNA synthesis is a thermosensitive process in the yeast Saccharomyces cerevisiae. We found that restoration of mtDNA synthesis following heat treatment of cells is dependent on reactivation of the mtDNA polymerase Mip1p through the action of a mitochondrial bichaperone system consisting of the Hsp70 system and the Hsp78 oligomeric protein. mtDNA synthesis was inefficiently restored after heat shock in yeast lacking either functional component of the bichaperone system. Furthermore, the activity of purified Mip1p was also thermosensitive; however, the purified components of the mitochondrial bichaperone system (Ssc1p, Mdj1p, Mge1p, and Hsp78p) were able to protect its activity under moderate heat shock conditions as well as to reactivate thermally inactivated Mip1p. Interestingly, the reactivation of endogenous Mip1p contributed more significantly to the restoration of mtDNA synthesis than did import of newly synthesized Mip1p from the cytosol. These observations suggest an important link between function of mitochondrial chaperones and the propagation of mitochondrial genomes under ever-changing environmental conditions.


Linearly-implicit schemes for collisions in musical acoustics based on energy quadratisation.
Collision modelling represents an active field of research in musical acoustics. Common examples of collisions include the hammer-string interaction in the piano, the interaction of strings with fretboards and fingers, the membrane-wire interaction in the snare drum, reed-beating effects in wind instruments, and others. At the modelling level, many current approaches make use of conservative potentials in the form of power-laws, and discretisations proposed for such models rely in all cases on iterative root-finding routines. Here, a method based on energy quadratisation of the nonlinear collision potential is proposed. It is shown that there exists a suitable discretisation of such a model that may be resolved in a single iteration, while guaranteeing stability via energy conservation. Applications to the case of lumped as well as fully distributed systems will be given, using both finite-difference and modal methods.


Glia promote local synaptogenesis through UNC-6 (netrin) signaling in C. elegans.
Neural circuits are assembled through the coordinated innervation of pre- and postsynaptic partners. We show that connectivity between two interneurons, AIY and RIA, in Caenorhabditis elegans is orchestrated by a pair of glial cells that express UNC-6 (netrin). In the postsynaptic neuron RIA, the netrin receptor UNC-40 (DCC, deleted in colorectal cancer) plays a conventional guidance role, directing outgrowth of the RIA process ventrally toward the glia. In the presynaptic neuron AIY, UNC-40 (DCC) plays an unexpected and previously uncharacterized role: It cell-autonomously promotes assembly of presynaptic terminals in the immediate vicinity of the glial cell endfeet. These results indicate that netrin can be used both for guidance and local synaptogenesis and suggest that glial cells can function as guideposts during the assembly of neural circuits in vivo.


Proton ATPases in bacteria: comparison to Escherichia coli F1F0 as the prototype.
The F1F0 ATP synthase complex of Escherichia coli functions reversibly in coupling proton translocation to ATP synthesis or hydrolysis. The structural organization and subunit composition corresponds to that seen in many other bacteria, i.e. a membrane extrinsic F1 sector with five subunits in an alpha 3 beta 3 gamma delta epsilon stoichiometry, and a membrane-traversing F0 sector with three subunits in an a1b2c12 stoichiometry. The structure of much of the F1 sector is known from a X-ray diffraction model. During function, The gamma subunit is known to rotate within a hexameric ring of alternating alpha and beta subunits to promote sequential substrate binding and product release from catalytic sites on the three beta subunits. Proton transport through F0 must be coupled to this rotation. Subunit c folds in the membrane as a hairpin to two alpha helices to generate the proton-binding site in F0. Its structure was determined by NMR, and the structure of the c oligomer was deduced by cross-linking experiments and molecular mechanics calculations. The implications of the oligomeric structure of subunit c will be considered and related to the H+/ATP pumping ratio, P/O ratios and the cation-binding site in other types of F0. The possible limits of the structure in changing the ion-binding specificity, stoichiometry and routes of proton entrance/exit to the binding site will be considered.


Sequence and characterization of shuttle vectors for molecular cloning in Porphyromonas, Bacteroides and related bacteria.
There is a lack of shuttle vectors to be needed for investigations into the genetics of Porphyromonas gingivalis and related species. To better understand the prevalence of candidates for such tools, we have examined multiple strains of black-pigmented anaerobes (clinical and laboratory isolates) for plasmids. As no plasmids were found in P. gingivalis strains, we have used the pYH420 plasmid, derived from P. asaccharolytica, as backbone to construct a shuttle vector in combination with pUC19 from Escherichia coli. Nucleotide sequence determination of the pYH420 plasmid revealed that it contained a gene with similarity to rep from plasmid pTS1 (isolated from Treponema denticola) as well as a homolog of mobA, a member of a gene family found on mobilizable genetic elements found in the genus Bacteroides. We constructed the pG106 and pG108 shuttle vectors using parts of the pUC19 and pYH420 vectors. This resulted in a vector with a multiple cloning site (MCS) in the lacZ gene enabling us to perform blue-white colony selection. The pG106 and pG108 shuttle vectors are electro-transformable into E. coli, P. gingivalis and B. thetaiotaomicron, where they are stable. We demonstrated that these vectors were suitable in these species for applications of molecular cloning including complementation and gene expression studies. Using the pG108 vector, we complement the hcpR mutant strain of P. gingivalis and rescued its NO2- -sensitive phenotype. We also performed a gene expression study using the P-glow BS2 fluorescent reporter gene and the ahpC promoter in B. thetaiotaomicron.


Multifactorial analysis of risk factors for reduced bone mineral density among postmenopausal women.
The study aimed to determine the risk factors for reduced bone mineral density (BMD) among postmenopausal women. Two hundred and fifty-three postmenopausal women were included to the study. The study group consisted of 85 women with osteoporosis (mean age: 59.9 years) and 168 with osteopenia (mean age: 57.8 years). Patients were assigned to groups according to their BMD measured in the lumbar spine, hip and femoral neck by dual X-ray absorptiometry. Bone formation was assessed by measuring serum osteocalcin and bone resorption by measuring serum C-terminal type I α-collagen chain telopeptide. Multiple regression analysis for lumbar spine showed association of age (p = 0.001), parental history of fracture (p = 0.05), use of hormone replacement therapy (p = 0.034), bisphosphonates therapy (p < 0.001), calcium and vitamin D supplements therapy (p = 0.001), oestradiol level (p = 0.007) and body mass index (p < 0.001). Multiple regression analysis for femoral neck and hip total showed association of age (p = 0.001), parental history of fracture (p = 0.049), use of bisphosphonates (p < 0.03)) use of calcium and vitamin D supplements (p = 0.039), oestradiol level (p = 0.047). All the variables together explain 40.4% of variance in BMD for the lumbar spine and 25.6% of variance in BMD for femoral neck and hip total. The present study demonstrated correlations between the variables and BMD, which are known and widely described in the literature. Osteoporosis and osteopenia in Polish subjects appear to be associated with several known risk factors that are well described in the literature.