Intraoperative wake-up test in neonatal neurosurgery.
Intraoperative wake-up test (WPT) still remains the gold standard to monitor anterior spinal cord function during spinal surgery. However, the test requires patient cooperation and hence difficult to perform in very young children or mentally challenged. In this report, we describe a WPT in a newborn during surgical repair of a large myelomeningocele. We relied on mivacurium for intubation and the relaxant effect was allowed to wear-off to permit the use of intraoperative nerve stimulator. We used desflurane and propofol infusion for rapid titration of the anesthetic depth and BIS monitor to 'gauge' the 'wakefulness' of the child during the WPT. We employed lidocaine infusion to improve tolerance to the tracheal tube and to bestow beneficial effect on intracranial pressure during surgery and the WPT. The results of the WPT were judged to be satisfactory after confirming flexion and extension of the lower extremities at the hip and knee level, correlating it with the BIS values, and comparing it with the preoperative status. Frequently associated prematurity, higher possibility of remaining intubated in the immediate postoperative period and any new onset neurologic deficit not becoming apparent until after extubation makes intraoperative neuromonitoring relevant in this age group. Our methodology of management has permitted us to perform a delicate test safely and will allow us to repeat the WPT if needed during neonatal neurosurgery.


Real-time correlation of crystallization and segmental order in conjugated polymers.
Modulating the segmental order in the morphology of conjugated polymers is widely recognized as a crucial factor for achieving optimal electronic properties and mechanical deformability. However, it is worth noting that the segmental order is typically associated with the crystallization process, which can result in rigid and brittle long-range ordered crystalline domains. To precisely control the morphology, a comprehensive understanding of how highly anisotropic conjugated polymers form segmentally ordered structures with ongoing crystallization is essential, yet currently elusive. To fill this knowledge gap, we developed a novel approach with a combination of stage-type fast scanning calorimetry and micro-Raman spectroscopy to capture the series of specimens with a continuum in the polymer percent crystallinity and detect the segmental order in real-time. Through the investigation of conjugated polymers with different backbones and side-chain structures, we observed a generally existing phenomenon that the degree of segmental order saturates before the maximum crystallinity is achieved. This disparity allows the conjugated polymers to achieve good charge carrier mobility while retaining good segmental dynamic mobility through the tailored treatment. Moreover, the crystallization temperature to obtain optimal segmental order can be predicted based on Tg and Tm of conjugated polymers. This in-depth characterization study provides fundamental insights into the evolution of segmental order during crystallization, which can aid in designing and controlling the optoelectronic and mechanical properties of conjugated polymers.


Surgical and nonsurgical treatment of cubital tunnel syndrome in pediatric and adolescent patients.
Few studies have investigated the presence or treatment of cubital tunnel syndrome in pediatric or adolescent patients. We conducted this retrospective investigation to quantify success rates of nonsurgical care and to assess patient outcomes after surgical intervention. We identified 39 extremities treated for cubital tunnel syndrome between 2000 and 2009 at one institution. We documented patient demographic data, precipitating events, symptomatology, physical examination findings, and treatment for all patients. We assessed patient-rated outcomes with validated measures including the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire and the visual analog scale (VAS). Subjective complaints at the time of presentation included 16 extremities with ulnar nerve instability at the elbow, 21 extremities with pain at the elbow, and 15 extremities with numbness and tingling in the ring and small fingers. Physical examination revealed 33 extremities with a positive Tinel sign and 20 extremities with a positive elbow flexion-compression test. In the nonsurgical group (9), pretreatment DASH scores averaged 32 and posttreatment DASH scores averaged 11. Pretreatment recall VAS pain scores had a median of 7, and were similar to posttreatment scores, which had a median of 3. In the surgical group (30), DASH scores averaged 46 before surgery and improved to 7 at final follow-up. The VAS pain scores improved from a median of 8 before surgery to 2 after surgery. A total of 30 patients (from both groups) were treated with a trial of nonsurgical care without symptom resolution. Cubital tunnel syndrome in pediatric or adolescent patients is rare. It can be treated successfully with surgical intervention. Although nonsurgical treatment is unlikely to relieve symptoms in this patient population, a trial of nighttime splinting, activity modification, and anti-inflammatory medications remains appropriate for most patients. Surgical intervention is effective for symptom relief if nonsurgical care fails. Therapeutic III.


[Therapeutic tactics in placenta praevia].
Ultrasonic screening of pregnant females revealed 299 cases with placental presentation and the patterns of placenta migrations were established and studied. The area of placental presentation in various periods of pregnancy was estimated, anamnestic risk factors for abnormal progression of the pregnancy were identified, three patterns of placental migration were distinguished: rapid, moderate and slow. A model of placental migration was developed and the pregnancy management was pathogenetically substantiated and defined.


A novel point mutation (Pro84-->Ser) of the low density lipoprotein receptor gene in a family with moderate hypercholesterolemia.
To obtain insight into the possibility that genetic variation of the structure of the low density lipoprotein (LDL) receptor protein could result in subtle changes of serum cholesterol levels, we used single-strand conformation polymorphism (SSCP) to screen all 18 exons of the LDL receptor gene in a panel of subjects with moderate hypercholesterolemia. One novel mutation, replacing C to T at nucleotide 313 and predicted to cause a substitution of serine for proline at codon 84, was identified in a single proband. A convenient PCR assay based on the use of primer-introduced restriction fragment length polymorphism was set up for the detection of this mutation. However, the pathophysiologic significance of the Pro84-->Ser replacement remains to be clarified, as serum LDL cholesterol levels were not significantly higher in mutation carriers vs. non-carriers in the affected family, and no other proband was identified, on screening of DNA samples from 350 Finns. The Pro84-->Ser mutation represents the second single-amino acid change of the LDL receptor protein so far reported which is not associated with the clinical phenotype of familial hypercholesterolemia.


Non-Communicable Disease Mortality and Risk Factors in Formal and Informal Neighborhoods, Ouagadougou, Burkina Faso: Evidence from a Health and Demographic Surveillance System.
The expected growth in NCDs in cities is one of the most important health challenges of the coming decades in Sub-Saharan countries. This paper aims to fill the gap in our understanding of socio-economic differentials in NCD mortality and risk in low and middle income neighborhoods in urban Africa. We use data collected in the Ouagadougou Health and Demographic Surveillance System. 409 deaths were recorded between 2009-2011 among 20,836 individuals aged 35 years and older; verbal autopsies and the InterVA program were used to determine the probable cause of death. A random survey asked in 2011 1,039 adults aged 35 and over about tobacco use, heavy alcohol consumption, lack of physical activity and measured their weight, height, and blood pressure. These data reveal a high level of premature mortality due to NCDs in all neighborhoods: NCD mortality increases substantially by age 50. NCD mortality is greater in formal neighborhoods, while adult communicable disease mortality remains high, especially in informal neighborhoods. There is a high prevalence of risk factors for NCDs in the studied neighborhoods, with over one-fourth of the adults being overweight and over one-fourth having hypertension. Better-off residents are more prone to physical inactivity and excessive weight, while vulnerable populations such as widows/divorced individuals and migrants suffer more from higher blood pressure. Females have a significantly lower risk of being smokers or heavy drinkers, while they are more likely to be physically inactive or overweight, especially when married. Muslim individuals are less likely to be smokers or heavy drinkers, but have a higher blood pressure. Everything else being constant, individuals living in formal neighborhoods are more often overweight. The data presented make clear the pressing need to develop effective programs to reduce NCD risk across all types of neighborhoods in African cities, and suggest several entry points for community-based prevention programs.


Glucocorticoid feedback uncovers retrograde opioid signaling at hypothalamic synapses.
Stressful experience initiates a neuroendocrine response culminating in the release of glucocorticoid hormones into the blood. Glucocorticoids feed back to the brain, causing adaptations that prevent excessive hormone responses to subsequent challenges. How these changes occur remains unknown. We found that glucocorticoid receptor activation in rodent hypothalamic neuroendocrine neurons following in vivo stress is a metaplastic signal that allows GABA synapses to undergo activity-dependent long-term depression (LTDGABA). LTDGABA was unmasked through glucocorticoid receptor-dependent inhibition of Regulator of G protein Signaling 4 (RGS4), which amplified signaling through postsynaptic metabotropic glutamate receptors. This drove somatodendritic opioid release, resulting in a persistent retrograde suppression of synaptic transmission through presynaptic μ receptors. Together, our data provide new evidence for retrograde opioid signaling at synapses in neuroendocrine circuits and represent a potential mechanism underlying glucocorticoid contributions to stress adaptation.


Learning disabilities and vision problems: are they related?
Vision problems can interfere with the process of learning. However, vision problems are not the cause of learning disabilities. If a child or adolescent is diagnosed as having a learning disability, refraction and eye muscle function must be assessed. If no disorders are found or, if found and corrected, the treatment of choice for the learning disability is special education.


Phosphite utilization by the marine picocyanobacterium Prochlorococcus MIT9301.
Primary productivity in the ocean's oligotrophic regions is often limited by phosphorus (P) availability. In low phosphate environments, the prevalence of many genes involved in P acquisition is elevated, suggesting that the ability to effectively access diverse P sources is advantageous for organisms inhabiting these regions. Prochlorococcus, the numerically dominant primary producer in the oligotrophic ocean, encodes high-affinity P transporters, P regulatory proteins and enzymes for organic phosphate utilization, but its ability to use reduced P compounds has not been previously demonstrated. Because Prochlorococcus strain MIT9301 encodes genes similar to phnY and phnZ, which constitute a novel marine bacterial 2-aminoethylphosphonate (2-AEPn) utilization pathway, it has been suggested that this organism might use 2-AEPn as an alternative P source. We show here that although MIT9301 was unable to use 2-AEPn as a sole P source under standard culture conditions, it was able to use phosphite. Phosphite utilization by MIT9301 appears to be mediated by an NAD-dependent phosphite dehydrogenase encoded by ptxD. We show that phosphite utilization genes are present in diverse marine microbes and that their abundance is higher in low-P waters. These results strongly suggest that phosphite represents a previously unrecognized component of the marine P cycle.


Covid-19 and the role of smoking: the protocol of the multicentric prospective study COSMO-IT (COvid19 and SMOking in ITaly).
The emergency caused by Covid-19 pandemic raised interest in studying lifestyles and comorbidities as important determinants of poor Covid-19 prognosis. Data on tobacco smoking, alcohol consumption and obesity are still limited, while no data are available on the role of e-cigarettes and heated tobacco products (HTP). To clarify the role of tobacco smoking and other lifestyle habits on COVID-19 severity and progression, we designed a longitudinal observational study titled COvid19 and SMOking in ITaly (COSMO-IT). About 30 Italian hospitals in North, Centre and South of Italy joined the study. Its main aims are: 1) to quantify the role of tobacco smoking and smoking cessation on the severity and progression of COVID-19 in hospitalized patients; 2) to compare smoking prevalence and severity of the disease in relation to smoking in hospitalized COVID-19 patients versus patients treated at home; 3) to quantify the association between other lifestyle factors, such as e-cigarette and HTP use, alcohol and obesity and the risk of unfavourable COVID-19 outcomes. Socio-demographic, lifestyle and medical history information will be gathered for around 3000 hospitalized and 700-1000 home-isolated, laboratory-confirmed, COVID-19 patients. Given the current absence of a vaccine against SARS-COV-2 and the lack of a specific treatment for -COVID-19, prevention strategies are of extreme importance. This project, designed to highly contribute to the international scientific debate on the role of avoidable lifestyle habits on COVID-19 severity, will provide valuable epidemiological data in order to support important recommendations to prevent COVID-19 incidence, progression and mortality.


Ophiobolin A, a sesterterpenoid fungal phytotoxin, displays higher in vitro growth-inhibitory effects in mammalian than in plant cells and displays in vivo antitumor activity.
Ophiobolin A, a sesterterpenoid produced by plant pathogenic fungi, was purified from the culture extract of Drechslera gigantea and tested for its growth-inhibitory activity in both plant and mammalian cells. Ophiobolin A induced cell death in Nicotiana tabacum L. cv. Bright Yellow 2 (TBY-2) cells at concentrations ≥10 µM, with the TBY-2 cells showing typical features of apoptosis-like cell death. At a concentration of 5 µM, ophiobolin A did not affect plant cell viability but prevented cell proliferation. When tested on eight cancer cell lines, concentrations <1 µM of ophiobolin A inhibited growth by 50% after 3 days of culture irrespective of their multidrug resistance (MDR) phenotypes and their resistance levels to pro-apoptotic stimuli. It is, thus, unlikely that ophiobolin A exerts these in vitro growth-inhibitory effects in cancer cells by activating pro-apoptotic processes. Highly proliferative human keratinocytes appeared more sensitive to the growth-inhibitory effects of ophiobolin A than slowly proliferating ones. Ophiobolin A also displayed significant antitumor activity at the level of mouse survival when assayed at 10 mg/kg in the B16F10 mouse melanoma model with lung pseudometastases. Ophiobolin A could, thus, represent a novel scaffold to combat cancer types that display various levels of resistance to pro-apoptotic stimuli and/or various MDR phenotypes.


Treatment Outcomes and Risk Factors for In-Hospital Mortality in Patients with Acute Aortic Occlusion.
The aims of the present study are to determine the outcomes after acute aortic occlusion (AAO) and analyze the risk factors for in-hospital mortality. We retrospectively analyzed 24 patients who were diagnosed with AAO from 2002 to 2017 in our registered data. Demographic and radiologic characteristics of AAOs were retrospectively collected. Perioperative treatment outcomes including in-hospital mortality were also assessed and the risk factors of in-hospital mortality were analyzed. The median symptom duration was 21 hours. Five patients had complete paraplegia and 10 patients (41.7%) were initially evaluated for central nervous system disorders instead of acute arterial occlusion. The etiology was determined to be aortoiliac thrombosis in 17 patients (70.8%) and embolic occlusion in 7. Surgical revascularization was performed in 23 patients, and one patient did not receive any treatment. The overall in-hospital mortality was 34.8% (8/23) and 30-day mortality was 26.1%. In the univariate analysis, age (P=0.040), preoperative renal insufficiency (serum creatinine over 1.5 mg/dL at the time of presentation) (P=0.008), postoperative acute kidney injury (need for dialysis or an increase in serum creatinine of >50.0% within 48 hours) (P=0.006), combined external iliac artery occlusion (P=0.019) and combined bilateral internal iliac artery occlusion (P=0.039) were associated with in-hospital mortality. A substantial number of AAO patients were initially evaluated for a central nervous system lesion, which led to a delay in diagnosis. Thus, vascular examinations should always be performed in every patient presenting with lower limb neurologic deficits. Age, perioperative renal function, and combined iliac artery occlusion were associated with the prognosis of AAOs.


Median nerve stimulation induces analgesia via orexin-initiated endocannabinoid disinhibition in the periaqueductal gray.
Adequate pain management remains an unmet medical need. We previously revealed an opioid-independent analgesic mechanism mediated by orexin 1 receptor (OX1R)-initiated 2-arachidonoylglycerol (2-AG) signaling in the ventrolateral periaqueductal gray (vlPAG). Here, we found that low-frequency median nerve stimulation (MNS) through acupuncture needles at the PC6 (Neiguan) acupoint (MNS-PC6) induced an antinociceptive effect that engaged this mechanism. In mice, MNS-PC6 reduced acute thermal nociceptive responses and neuropathy-induced mechanical allodynia, increased the number of c-Fos-immunoreactive hypothalamic orexin neurons, and led to higher orexin A and lower GABA levels in the vlPAG. Such responses were not seen in mice with PC6 needle insertion only or electrical stimulation of the lateral deltoid, a nonmedian nerve-innervated location. Directly stimulating the surgically exposed median nerve also increased vlPAG orexin A levels. MNS-PC6-induced antinociception (MNS-PC6-IA) was prevented by proximal block of the median nerve with lidocaine as well as by systemic or intravlPAG injection of an antagonist of OX1Rs or cannabinoid 1 receptors (CB1Rs) but not by opioid receptor antagonists. Systemic blockade of OX1Rs or CB1Rs also restored vlPAG GABA levels after MNS-PC6. A cannabinoid (2-AG)-dependent mechanism was also implicated by the observations that MNS-PC6-IA was prevented by intravlPAG inhibition of 2-AG synthesis and was attenuated in Cnr1-/- mice. These findings suggest that PC6-targeting low-frequency MNS activates hypothalamic orexin neurons, releasing orexins to induce analgesia through a CB1R-dependent cascade mediated by OX1R-initiated 2-AG retrograde disinhibition in the vlPAG. The opioid-independent characteristic of MNS-PC6-induced analgesia may provide a strategy for pain management in opioid-tolerant patients.


Electrochemical synthesis, X-ray single crystal, IR spectroscopic, and quantum chemical investigation of molybdenum and tungsten hexamethoxides.
The anodic oxidation of molybdenum metal in MeOH at both low anodic and cathodic current density (0.025 A/cm2) and electrolyte temperatures kept below 20 degrees C provides an efficient approach to Mo(OMe)6 (I). W(OMe)6 (II) can be obtained from the electrolytes, prepared via anodic dissolution of tungsten, by fractional crystallization. The symmetrically independent units in the structures of I and II, being isomorphous, follow the C1 (slightly distorted D2d) symmetry. Theoretical calculations performed for a free molecule of I indicate that this low symmetry may be the result of the packing of the molecules in the crystal structure and also an inherent property imposed by the bonding in this compound. Crystal data for I: Mo(OMe)6 at 22 degrees C, a = 7.0976(13), b = 6.6103(12), and c = 12.286(2) A, beta = 90.068(3) degrees, V = 576.41(18) A3, monoclinic P2/n, Z = 2. Crystal data for II: W(OMe)6 at 22 degrees C, a = 7.1164(19), b = 6.6414(18), and c = 12.304(3) A, beta = 90.047(5) degrees, V = 581.5(3) A3, monoclinic P2/n, Z = 2.


TSH enhancement of FT4 to FT3 conversion is age dependent.
We previously reported increasing free T3 (FT3) to free T4 (FT4) ratios as thyroid-stimulating hormone (TSH) increases within the normal range in children. It is not known if this phenomenon is age-related among humans, as previously reported in rats. This study examines the relationships between TSH and FT3/FT4 ratios in different ages. Retrospective examination of thyroid tests from patients without thyroid disease from community clinics. Free T3, free T4, and TSH levels from 527 564 sera collected from patients aged 1 year or greater were studied. Exclusion criteria were the following: missing data, TSH greater than 7.5mIU/L, and medications that may interfere with thyroid hormone activity. A total of 27 940 samples remaining after exclusion were stratified by age. Samples with available anthropometric data were additionally stratified for body mass index (BMI). Correlations of TSH to FT4, FT3, and FT3/FT4 ratios by age group were examined. Up to age 40, for each increasing TSH quartile, FT3 and the FT3/FT4 ratio increased and FT4 decreased significantly (for both FT3, FT4 and FT3/FT4 ratio, P<0.05 for every TSH quartile when compared with the 1st quartile, except FT3 in the 30-40 age group). In older age groups, increasing TSH was not associated with increased FT3/FT4 ratio. As TSH levels increase, FT3/FT4 ratios increase until age 40, but this differential increase does not occur in older age groups. This may reflect a decrease in thyroxine (T4) to triiodothyronine (T3) conversion with age, which may be part of the aging process.


Insertion reactions of GaCp*, InCp* and In[C(SiMe3)3] into the Ru-Cl bonds of [(p-cymene)RuIICl2]2 and [Cp*RuIICl]4.
The first carbonyl free ruthenium/low valent Group 13 organyl complexes are presented, obtained by insertion of ER (ER = GaCp*, InCp*, In[C(SiMe(3))(3)]) into the Ru-Cl bonds of [(p-cymene)RuCl2]2, [Cp*RuCl]4 and [Cp*RuCl2]2. The compound [(p-cymene)RuCl2]2 reacts with GaCp*, giving a variety of isolated products depending on the reaction conditions. The Ru-Ru dimers [{(p-cymene)Ru}2(GaCp*)4(mu3-Cl)2] and the intermediate [{(p-cymene)Ru}2(mu-Cl)2] were isolated, as well as monomeric complexes [(p-cymene)Ru(GaCp*)3Cl2], [(p-cymene)Ru(GaCp*)2GaCl3] and [(p-cymene)Ru(GaCp*)2Cl2(DMSO)]. The reaction of [Cp*RuCl]4 with ER gives "piano-stool" complexes of the type [Cp*Ru(ER)3Cl](ER = InCp*, In[C(SiMe3)3], GaCp*. The chloride ligand in complex can be removed by NaBPh4, yielding [Cp*Ru(GaCp*)3]+[BPh4]-. The reaction of [Cp*RuCl2]2 with GaCp* however, does not lead to an insertion product, but to the ionic Ru(II) complex [Cp*Ru(GaCp*)3]+[Cp*GaCl3]-. The ER ligands in complexes 3, 5, 6, 7 and 8 are equivalent on the NMR timescale in solution due to a chloride exchange between the three Group 13 atoms even at low temperatures. The solid state structures, however, exhibit a different structural pattern. The chloride ligands exhibit two coordination modes: either terminal or bridging. The new compounds are fully characterized including single crystal X-ray diffraction. These results point out the different reactivities of the two precursors and the nature of the neutral p-cymene and the anionic Cp* ligand when bonding to a Ru(II) centre.


The BASHY Platform Enables the Assembly of a Fluorescent Bortezomib-GV1001 Conjugate.
In this study, we show that fluorescent boronic-acid derived salicylidenehydrazone complexes (BASHY) can function as fluorescent linkers for bioconjugates that were used to monitor the delivery of the proteasome inhibitor bortezomib (Btz) to HT-29 cancer cells. BASHY complexes were structurally optimized to improve the stability of the complex in buffered conditions (ammonium acetate, pH 7 up to t 1/2 = 40 h), photophysically characterized regarding their fluorescence properties and used in confocal microscopy colocalization studies that revealed their intracellular sequestration by lipid droplets. The accumulation in these hydrophobic organelles limited the hydrolysis of the complex and consequently the drug release, a problem that was circumvented by the conjugation of the BASHY-Btz complex with a cell-penetrating peptide GV1001-C. The conjugate exhibited an improved cytoplasmic availability as confirmed by confocal fluorescence microscopy studies and an improved potency against HT-29 cancer cells (IC50 = 100 nM) as compared to the nontargeted complex (IC50 = 450 nM).


Secondary care interface: optimising communication between teams within secondary care to improve the rehabilitation journey for older people.
Effective communication between members of the multidisciplinary team is imperative for patient safety. Within the Medicine for the Elderly wards at Royal Victoria Hospital (RVH) in Dundee, we identified an inefficient process of information-sharing between the orthopaedics outpatient department (OPD) at the main teaching hospital and our hospital's rehabilitation teams, and sought to improve this by introducing several changes to the work system. Our aim was for all patients who attended the OPD clinic to have a plan communicated to the RVH team within 24 hours.Before our intervention, clinic letters containing important instructions for ongoing rehabilitation were dictated by the OPD team, transcribed and uploaded to an electronic system before the RVH team could access them. We analysed clinic attendances over a 4-week period and found that it took 15 days on average for letters to be shared with the RVH teams. We worked with both teams to develop a clinical communication tool and new processes, aiming to expedite the sharing of key information. Patients attended the OPD with this form, the clinician completed it at the time of their appointment and the form returned with the patient to RVH on the same day.We completed multiple Plan-Do-Study-Act cycles; before our project was curtailed by the COVID-19 pandemic. During our study period, seven patients attended the OPD with a form, with all seven returning to RVH with a completed treatment plan documented by the OPD clinician. This allowed rehabilitation teams to have access to clinic instructions generated by orthopaedic surgeons almost immediately after a patient attended the clinic, essentially eliminating the delay in information-sharing.The introduction of a simple communication tool and processes to ensure reliable transfer of information can expedite information-sharing between secondary care teams and can potentially reduce delays in rehabilitation.


[Microcuff pediatric tracheal tube. A new tracheal tube with a high volume-low pressure cuff for children].
Principles and characteristics of the recently introduced Microcuff paediatric tracheal tube (Microcuff, GmbH, Weinheim, Germany) with anatomically based depth markings, cuff-free subglottic tube shaft and short high volume-low pressure cuff with ultrathin cuff membrane are presented. First available tubes (ID 4.0 mm) were evaluated regarding cuff pressures required to seal the trachea and regarding the distance from the tube tip to the carina. After obtaining approval of the local ethical committee, 20 children aged 2-4 years, receiving tracheal intubation under general anaesthesia with muscle paralysis, were included. The tubes were placed during direct laryngoscopy and the glottic depth marking placed between the vocal cords. Cuff pressure to prevent audible air leakage at standardised ventilator settings (PIP 20 cm H(2)O/PEEP 5 cm H(2)O/RR20 x min(-1)) was assessed by means of a cuff pressure manometer within 5 min after intubation. Subsequently, the distance from the tube tip to the tracheal carina was measured by means of fibre bronchoscopy. Data are presented as the median (range). Patient age was 3.0 years (2.0-3.9 years), weight 13.5 kg (9.1-19.2 kg) and body length 95 cm (79-105 cm). The lowest cuff pressure required to seal the trachea ranged from 4-14 cmH(2)O (median 10 cm H(2)O), the distance from tube tip to tracheal carina was to 2.9 cm (2.0-4.5 cm). The new Microcuff paediatric tracheal tube with ultrathin high volume-low pressure cuff required tracheal sealing pressures below tracheal wall pressures usually required with uncuffed tracheal tubes for efficient sealing and ventilation at 20 cm H(2)O peak inspiratory pressure. The distance from the tube tip to carina was in the safe range in all patients.


Reversible dissociation and unfolding of the Escherichia coli aspartate receptor cytoplasmic fragment.
The thermal denaturation of a 31-kDa soluble fragment derived from the Escherichia coli aspartate receptor cytoplasmic region (c-fragment) was found to be reversible. Denaturation monitored by differential scanning calorimetry (DSC) and circular dichroism (CD) was typically over 90% reversible in pH 7.0 buffer. The wild-type c-fragment exhibited one transition (Tm = 51 degrees C), which was taken as the main denaturation transition. c-Fragments derived from signaling mutants, shown to form oligomers by gel filtration chromatography (GFC), displayed a second low-temperature transition that correlated with the disappearance of the oligomeric form in the GFC traces over the same temperature range. The CD and DSC experiments also indicated that oligomers were more folded than monomers, observations that may provide an explanation for the structural basis of the smooth-swimming signaling state of the receptor. Octyl glucoside (OG), phospholipid (PL), and glycerol were added to characterize factors that contribute to c-fragment stability. At 10 mg/mL OG, the van't Hoff enthalpy of unfolding was reduced ca. 10-fold, although at room temperature the CD spectrum indicated little change in the secondary structure. The van't Hoff enthalpy was not affected by 35% (w/v) glycerol, but the Tm increased by ca. 18 degrees C. Cooperative transitions were detected in buffer containing OG, PL, and glycerol (10 mg/mL, 2 mg/mL, 35%, respectively). The correlation between conditions where cooperative transitions are observed, and where aspartate-modulated receptor signaling has been previously observed, provides an explanation for the inhibition of signaling in OG-containing buffers without glycerol and PL.


Specific polymorphisms in the vitamin D metabolism pathway are not associated with susceptibility to Chlamydia trachomatis infection in humans.
Chlamydia trachomatis is the most common sexually transmitted bacterium worldwide. Its often asymptomatic course of infection increases chances of transmission, and increases risk of late complications. Genetic variations in the host immune system are known to impact the course of infections. Recent studies have shown a positive impact of vitamin D on the regulation of the immune system. This study assesses the impact of eight polymorphisms in five genes [VDR (rs1544410 G > A, rs2228570 C > T), CYP27B1 (rs10877012 G > T), DHCR7 (rs7944926 G > A, rs3829251 G > A), GC (rs3755967) and CYP2R1 (rs10741657 G > A, rs2060793 G > A)] on susceptibility to Chlamydia infections in humans. These polymorphisms could influence protein expression or function, and thus influence the immune system. Samples of women visiting the STD outpatient clinic in South Limburg were genotyped using the Roche Lightcycler 480. In this study, we did not observe statistically significant differences between the genotype distributions of these polymorphisms in women with or without a Chlamydia infection. This suggests that VDR, CYP27B1, DHCR7, GC and CYP2R1 do not affect the susceptibility to Chlamydia infections. However, due to its pleiotropic nature in the immune system a role for the vitamin D pathway may not be excluded from the whole clinical course of Chlamydia infections (e.g. late complications), and further research is required.


Axons of Passage and Inputs to Superior Cervical Ganglion in Rat.
Wheat germ agglutinin-horseradish peroxidase was injected into the entire (0.8 μL) or partial (rostral or caudal, 0.1-0.3 μL) superior cervical ganglion (SCG) of the rat (male Sprague-Dawley, N = 35) to examine the distribution of neurons in the middle (MCG) and inferior (ICG) cervical ganglion that send axons bypass the SCG. Whole-mounts of the SCG, cervical sympathetic trunk (CST), MCG, ICG, and sections of the brainstem and spinal cord were prepared. With entire SCG tracer injection, neurons were labeled evenly in the MCG (left: 258, right: 121), ICG (left: 848, right: 681), and CST (up to 770). Some neurons grouped in a single bulge just rostral to the MCG, which we termed as the "premiddle cervical ganglion" (pMCG). The left pMCG (120) is larger and has more neurons than the right pMCG (82). Centrally, neurons were labeled in lamina IX of cervical segments (C1: 18%, C2: 46%, C3: 33%, C4: 3%), intermediate zone of thoracic segments (T1: 31%, T2: 35%, T3: 27%, T4: 7%), and intermediate reticular nuclei (96%) and perifacial zone (4%) of brainstem. The rostral and caudal SCG injection selectively labeled neurons mainly in brainstem, C1-C2 and in T1-T2, respectively. Before projecting to their peripheral targets, many neurons in pMCG, MCG and ICG run rostrally within the CST rather than segmentally through the closest rami, from the level of SCG or above. Neurons in pMCG and MCG may have similar or complementary function and those in brainstem may be involved in the vestibulo-autonomic interaction. Anat Rec, 301:1906-1916, 2018. © 2018 Wiley Periodicals, Inc.


Effects of previous grazing treatment and consumption of locoweed on liver mineral concentrations in beef steers.
Twelve Hereford steers (average BW = 231 kg) that had previously grazed native rangeland (Range) or irrigated winter wheat pasture (Wheat) were allowed to graze locoweed-infested rangeland from April 1 to June 9, 1994 (six steers/previous grazing treatment). Relative consumption level of locoweed and other forage classes was measured as observed bites per steer. Liver biopsy and whole blood samples were obtained from each steer before and after grazing. Liver samples were analyzed for several minerals by inductively coupled plasma-atomic emission spectroscopy, and whole blood samples were analyzed for Se. Liver concentrations of Ba (P < .001), Cd (P < .001), Ca (P < .01), Cr (P < .01), Ni (P < .001), Na (P < .01), and V (P < .001) were greater and concentrations of Mn (P < .09), P (P < .01), and K (P < .07) were less in Wheat than in Range steers. Liver concentrations of Fe, Mg, S, and Zn and whole blood Se concentrations did not differ (P > .10) between the two groups. Liver concentrations of Cr (P < .04) and Mn (P < .001) were less, and Fe concentrations were greater (P < .01), in samples taken after grazing than in samples taken before grazing of locoweed-infested range. Whole blood Se concentrations decreased (P < .01) from the beginning to the end of the grazing period, but this effect was not related (P > .15) to locoweed consumption. Changes in liver concentrations of minerals were compared relative to consumption levels of all forage classes in the locoweed-infested range. Liver concentrations of Cu decreased (r2 = .45; P < .02) as the percentage of bites consumed as locoweed increased, but concentrations after grazing locoweed-infested range were still within normal ranges. Changes in liver concentrations of other minerals were not related (P > .15) to consumption of locoweed. These data indicate that previous grazing history can have significant effects on liver mineral stores and that, under our conditions, consumption of locoweed by grazing beef steers altered liver Cu concentrations. Toxic effects of locoweed consumption would likely occur before Cu deficiency would be induced by grazing locoweed-infested range; hence, supplementation of Cu would seem unlikely to alter the course of locoweed toxicosis.


Rapid evolution of virus sequences in intrinsically disordered protein regions.
Nodamura Virus (NoV) is a nodavirus originally isolated from insects that can replicate in a wide variety of hosts, including mammals. Because of their simplicity and ability to replicate in many diverse hosts, NoV, and the Nodaviridae in general, provide a unique window into the evolution of viruses and host-virus interactions. Here we show that the C-terminus of the viral polymerase exhibits extreme structural and evolutionary flexibility. Indeed, fewer than 10 positively charged residues from the 110 amino acid-long C-terminal region of protein A are required to support RNA1 replication. Strikingly, this region can be replaced by completely unrelated protein sequences, yet still produce a functional replicase. Structure predictions, as well as evolutionary and mutational analyses, indicate that the C-terminal region is structurally disordered and evolves faster than the rest of the viral proteome. Thus, the function of an intrinsically unstructured protein region can be independent of most of its primary sequence, conferring both functional robustness and sequence plasticity on the protein. Our results provide an experimental explanation for rapid evolution of unstructured regions, which enables an effective exploration of the sequence space, and likely function space, available to the virus.


Investigations into the control of litter size in swine: I. Comparative studies on in vitro development of Meishan and Yorkshire preimplantation embryos.
Three experiments were conducted to examine the in vitro development of preimplantation embryos from the prolific Chinese Meishan pig. Experiment 1 was conducted to assess whether Meishan embryos would develop in vitro and retain their viability, whereas Exp. 2 and 3 examined the developmental pattern of Meishan embryos. In all three experiments, Yorkshire embryos served as a contemporary comparison. Ovulation and embryo recovery rates were not different between Meishan and Yorkshire gilts. Meishan embryos cultured for 96 h were capable of establishing pregnancies. The number of cell nuclei present after 144 h of culture was lower (P < .01) for Meishan than for Yorkshire blastocysts. Meishan preimplantation embryos exhibited a slower (P < .02) in vitro rate of development from the four-cell to the compact morula stage than did Yorkshire embryos. Early blastocysts from Meishan gilts, although morphologically similar in size, contained fewer (P < .06) cells than did their counterpart Yorkshire embryos. These data demonstrate that Meishan embryos develop more slowly and contain fewer cells than do Yorkshire embryos. This differing developmental pattern of Meishan preimplantation embryos, if similar to that previously reported in miniature swine and mice, may relate to increased embryo survival.


Resveratrol-mediated chemoprevention of diethylnitrosamine-initiated hepatocarcinogenesis: inhibition of cell proliferation and induction of apoptosis.
Hepatocellular carcinoma (HCC) is one of the most common cancers and lethal diseases. In view of the limited treatment and a grave prognosis of liver cancer, preventive control has been emphasized. Resveratrol, a polyphenol found in grape skins, peanuts, berries and red wine, has been shown to possess potent growth inhibitory effects against various human cancer cells. Although resveratrol has been found to exhibit chemopreventive actions in experimentally induced skin, breast, colon and esophagus rodent tumors, chemopreventive potential of this dietary constituent has not been explored well against experimental liver cancer. We evaluated the inhibitory effect of resveratrol using a two-stage model of rat hepatocarcinogenesis in Sprague-Dawley rats. Initiation was performed by a single intraperitoneal injection of diethylnitrosamine (DENA, 200 mg/kg), followed by promotion with phenobarbital (0.05%) in drinking water. The rats had free access to food supplemented with resveratrol equivalent to 50, 100 or 300 mg/kg body weight/day. Resveratrol treatment was started 4 weeks prior to the initiation and continued for 20 weeks. Resveratrol dose-dependently reduced the incidence, total number and multiplicity of visible hepatocyte nodules. Mean nodular volume and nodular volume as percentage of liver volume were also inhibited upon resveratrol treatment. Histopathological examination of liver tissue confirmed the protective effect of resveratrol. Immunohistochemical detection of cell proliferation and assay of apoptosis indicated a decrease in cell proliferation and increase of apoptotic cells in the livers of resveratrol-supplemented rats. Resveratrol also induced the expression of pro-apoptotic protein Bax, reduced anti-apoptotic Bcl-2 expression, with a concurrent increase in Bax/Bcl-2 ratio with respect to DENA control. The present study provides evidence, for the first time, that resveratrol exerts a significant chemopreventive effect on DENA-initiated hepatocarcinogenesis through inhibition of cell proliferation and induction of apoptosis. Resveratrol-induced apoptogenic signal during rat liver carcinogenesis may be mediated through the downregulation of Bcl-2 and upregulation of Bax expression. Due to a favorable toxicity profile, resveratrol can potentially be developed as a chemopreventive drug against human HCC.


A self-management programme for COPD: a randomised controlled trial.
Studies of programmes of self-management support for chronic obstructive pulmonary disease (COPD) have been inconclusive. The Self-Management Programme of Activity, Coping and Education (SPACE) FOR COPD is a 6-week self-management intervention for COPD, and this study aimed to evaluate the effectiveness of this intervention in primary care. A single-blind randomised controlled trial recruited people with COPD from primary care and randomised participants to receive usual care or SPACE FOR COPD. Outcome measures were performed at baseline, 6 weeks and 6 months. The primary outcome was symptom burden, measured by the self-reported Chronic Respiratory Questionnaire (CRQ-SR) dyspnoea domain. Secondary outcomes included other domains of the CRQ-SR, shuttle walking tests, disease knowledge, anxiety, depression, self-efficacy, smoking status and healthcare utilisation. 184 people with COPD were recruited and randomised. At 6 weeks, there were significant differences between groups in CRQ-SR dyspnoea, fatigue and emotion scores, exercise performance, anxiety, and disease knowledge. At 6 months, there was no between-group difference in change in CRQ-SR dyspnoea. Exercise performance, anxiety and smoking status were significantly different between groups at 6 months, in favour of the intervention. This brief self-management intervention did not improve dyspnoea over and above usual care at 6 months; however, there were gains in anxiety, exercise performance, and disease knowledge.


Performance Evaluation of the uEXPLORER Total-Body PET/CT Scanner Based on NEMA NU 2-2018 with Additional Tests to Characterize PET Scanners with a Long Axial Field of View.
The world's first total-body PET scanner with an axial field of view (AFOV) of 194 cm is now in clinical and research use at our institution. The uEXPLORER PET/CT system is the first commercially available total-body PET scanner. Here we present a detailed physical characterization of this scanner based on National Electrical Manufacturers Association (NEMA) NU 2-2018 along with a new set of measurements devised to appropriately characterize the total-body AFOV. Methods: Sensitivity, count-rate performance, time-of-flight resolution, spatial resolution, and image quality were evaluated following the NEMA NU 2-2018 protocol. Additional measurements of sensitivity and count-rate capabilities more representative of total-body imaging were performed using extended-geometry phantoms based on the world-average human height (∼165 cm). Lastly, image quality throughout the long AFOV was assessed with the NEMA image quality (IQ) phantom imaged at 5 axial positions and over a range of expected total-body PET imaging conditions (low dose, delayed imaging, short scan duration). Results: Our performance evaluation demonstrated that the scanner provides a very high sensitivity of 174 kcps/MBq, a count-rate performance with a peak noise-equivalent count rate of approximately 2 Mcps for total-body imaging, and good spatial resolution capabilities for human imaging (≤3.0 mm in full width at half maximum near the center of the AFOV). Excellent IQ, excellent contrast recovery, and low noise properties were illustrated across the AFOV in both NEMA IQ phantom evaluations and human imaging examples. Conclusion: In addition to standard NEMA NU 2-2018 characterization, a new set of measurements based on extending NEMA NU 2-2018 phantoms and experiments was devised to characterize the physical performance of the first total-body PET system. The rationale for these extended measurements was evident from differences in sensitivity, count-rate-activity relationships, and noise-equivalent count-rate limits imposed by differences in dead time and randoms fraction between the NEMA NU 2 70-cm phantoms and the more representative total-body imaging phantoms. Overall, the uEXPLORER PET system provides ultra-high sensitivity that supports excellent spatial resolution and IQ throughout the field of view in both phantom and human imaging.


The nucleolar protein Esf2 interacts directly with the DExD/H box RNA helicase, Dbp8, to stimulate ATP hydrolysis.
While 18 putative RNA helicases are involved in ribosome biogenesis in Saccharomyces cerevisiae, their enzymatic properties have remained largely biochemically uncharacterized. To better understand their function, we examined the enzymatic properties of Dpb8, a DExD/H box protein previously shown to be required for the synthesis of the 18S rRNA. As expected for an RNA helicase, we demonstrate that recombinant Dbp8 has ATPase activity in vitro, and that this activity is dependent on an intact ATPase domain. Strikingly, we identify Esf2, a nucleolar putative RNA binding protein, as a binding partner for Dbp8, and show that it enhances Dbp8 ATPase activity by decreasing the K(M) for ATP. Thus, we have uncovered Esf2 as the first example of a protein co-factor that has a stimulatory effect on a nucleolar RNA helicase. We show that Esf2 can bind to pre-rRNAs and speculate that it may function to bring Dbp8 to the pre-rRNA, thereby both regulating its enzymatic activity and guiding Dbp8 to its site of action.


Vascular endothelial hyperpermeability induces the clinical symptoms of Clarkson disease (the systemic capillary leak syndrome).
The systemic capillary leak syndrome (SCLS) is a rare disorder characterized by transient episodes of hypotensive shock and anasarca thought to arise from reversible microvascular barrier dysfunction. Although the high prevalence of a monoclonal gammopathy of unknown significance in SCLS suggests a pathogenic contribution of endogenous immunoglobulins, the mechanisms of vascular hyperpermeability remain obscure. Herein, we report clinical and molecular findings on 23 patients, the largest SCLS case series to date. Application of episodic SCLS sera, but neither the purified immunoglobulin fraction nor sera obtained from patients during remission, to human microvascular endothelial cells caused vascular endothelial cadherin internalization, disruption of interendothelial junctions, actin stress fiber formation, and increased permeability in complementary functional assays without inducing endothelial apoptosis. Intravenous immunoglobulin, one promising therapy for SCLS, mitigated the permeability effects of episodic sera. Consistent with the presence of endogenous, nonimmunoglobulin, circulating permeability factor(s) constrained to SCLS episodes, we found that vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang2), were elevated in episodic SCLS sera but not in remission sera. Ab-based inhibition of Ang2 counteracted permeability induced by episodic SCLS sera. Comparable experiments with anti-VEGF Ab (bevacizumab) yielded less interpretable results, probably because of endothelial toxicity of VEGF withdrawal. Our results support a model of SCLS pathogenesis in which nonimmunoglobulin humoral factors such as VEGF and Ang2 contribute to transient endothelial contraction, suggesting a molecular mechanism for this highly lethal disorder.


The Role of miRNAs in Drosophila melanogaster Male Courtship Behavior.
Drosophila melanogaster courtship, although stereotypical, continually changes based on cues received from the courtship subject. Such adaptive responses are mediated via rapid and widespread transcriptomic reprogramming, a characteristic now widely attributed to microRNAs (miRNAs), along with other players. Here, we conducted a large-scale miRNA knockout screen to identify miRNAs that affect various parameters of male courtship behavior. Apart from identifying miRNAs that impact male-female courtship, we observed that miR-957 mutants performed significantly increased male-male courtship and "chaining" behavior, whereby groups of males court one another. We tested the effect of miR-957 reduction in specific neuronal cell clusters, identifying miR-957 activity in Doublesex (DSX)-expressing and mushroom body clusters as an important regulator of male-male courtship interactions. We further characterized the behavior of miR-957 mutants and found that these males court male subjects vigorously, but do not elicit courtship. Moreover, they fail to lower courtship efforts toward females with higher levels of antiaphrodisiac pheromones. At the level of individual pheromones, miR-957 males show a reduced inhibitory response to both 7-Tricosene (7-T) and cis-vaccenyl acetate, with the effect being more pronounced in the case of 7-T. Overall, our results indicate that a single miRNA can contribute to the regulation of complex behaviors, including detection or processing of chemicals that control important survival strategies such as chemical mate-guarding, and the maintenance of sex- and species-specific courtship barriers.


Objectively Measured Physical Activity in South African Children Attending Preschool and Grade R: Volume, Patterns, and Meeting Guidelines.
To assess physical activity (PA) and determine the proportion of preschoolers meeting PA recommendations in different income settings in South Africa. Preschoolers from urban high-income (UH), urban low-income (UL), and rural low-income (RL) settings wore an ActiGraph GT3X+ accelerometer for 7 days. PA variables of interest included volume moderate- to vigorous-intensity PA (MVPA) and total PA (light- to vigorous-intensity PA), hourly PA patterns, and percentage of children meeting guidelines (180 min/d of total PA, inclusive of 60 min/d of MVPA). Between-sex differences were assessed using t tests and Mann-Whitney U tests; between-setting differences assessed using 1-way analyses of variance and Kruskal-Wallis tests. For all children (n = 229, aged 5.17 [0.69] y), average MVPA was 124.4 (37.5) minutes per day and total PA was 457.0 (61.1) minutes per day; 96.9% of children met guidelines. Boys did significantly more MVPA than girls (136.7 [39.37] vs 111.5 [30.70] min/d, P < .001), and UH preschoolers were significantly less active than UL and RL preschoolers (UH 409.1 [48.4] vs UL 471.1 [55.6] and RL 461.6 [61.4], P < .001). In both practice and research, it is necessary to explore ways to ensure that South African preschoolers from all income settings continue to engage in and benefit from healthy volumes of PA. This is especially important as preschoolers transition to a formal school environment.


Analysis of enamel rod end patterns on tooth surface for personal identification--ameloglyphics.
Ameloglyphics is the study of enamel rod end patterns on a tooth surface. Our aim was to study the in vivo analysis of enamel rod end patterns on tooth surfaces for personal identification. In this study, the maxillary left canine and 1st premolar of 30 men and 30 women were included. The cellulose acetate peel technique was used to record enamel rod endings on tooth surfaces. Photomicrographs of the acetate peel imprint were subjected to VeriFinger Standard SDK v5.0 software for obtaining enamel rod end patterns. All 120 enamel rod end patterns were subjected to visual analysis and biometric analysis. Biometric analysis revealed that the enamel rod end pattern is unique for each tooth in an individual. It shows both intra- and interindividual variation. Enamel rod end patterns were unique between the male and female subjects. Visual analysis showed that wavy branched subpattern was the predominant subpattern observed among examined teeth. Hence, ameloglyphics is a reliable technique for personal identification.


Intermittent fasting for obesity and related disorders: unveiling myths, facts, and presumptions.
Intermittent fasting (IF) is an increasingly popular method of weight loss, as an alternative to daily caloric restriction (DCR). Several forms of IF exist, such as alternate-day fasting or time-restricted feeding regimens. Some of its proponents claim several health benefits unrelated to caloric restriction or weight loss, which rely mainly on animal models. Although several studies published in the last few years confirm that IF can be a useful and safe therapeutical option for obesity and related disorders, no superiority to conventional caloric restriction diets have emerged. There are still several questions left answered. In this Review, we discuss some of the claims, unveiling myths, facts, and presumptions about several models of IF. The focus of this article is obesity, but there is a brief discussion of the potential benefits of IF on overall human health.


Automatic misclassification rejection for LDA classifier using ROC curves.
This paper presents a technique to improve the performance of an LDA classifier by determining if the predicted classification output is a misclassification and thereby rejecting it. This is achieved by automatically computing a class specific threshold with the help of ROC curves. If the posterior probability of a prediction is below the threshold, the classification result is discarded. This method of minimizing false positives is beneficial in the control of electromyography (EMG) based upper-limb prosthetic devices. It is hypothesized that a unique EMG pattern is associated with a specific hand gesture. In reality, however, EMG signals are difficult to distinguish, particularly in the case of multiple finger motions, and hence classifiers are trained to recognize a set of individual gestures. However, it is imperative that misclassifications be avoided because they result in unwanted prosthetic arm motions which are detrimental to device controllability. This warrants the need for the proposed technique wherein a misclassified gesture prediction is rejected resulting in no motion of the prosthetic arm. The technique was tested using surface EMG data recorded from thirteen amputees performing seven hand gestures. Results show the number of misclassifications was effectively reduced, particularly in cases with low original classification accuracy.


Role of mitochondria in the regulation of ferroptosis and disease.
Ferroptosis is a distinctive form of iron-dependent cell death characterized by significant ultrastructural changes in mitochondria. Given the crucial involvement of mitochondria in various cellular processes such as reactive oxygen species production, energy metabolism, redox status, and iron metabolism, mounting evidence suggests a vital role of mitochondria in the regulation and execution of ferroptosis. Furthermore, there exists a strong correlation between ferroptosis and various diseases. In this review, we aim to summarize the mechanisms underlying the induction and defense of ferroptosis, emphasizing the influence of mitochondria on this intricate process. Additionally, we provide an overview of the role of ferroptosis in disease, particularly cancer, and elucidate the mechanisms by which drugs targeting mitochondria impact ferroptosis. By presenting a theoretical foundation and reference point, this review aims to contribute to both basic cell biology research and the investigation of clinically relevant diseases.


Test for ability of decay-accelerating factor (DAF, CD55) and CD59 to alleviate complement-mediated damage of xeno-erythrocytes.
We investigated the susceptibility to human complement (C) of xeno-erythrocytes into which phosphatidylinositol (PI)-anchored human C regulatory protein, decay-accelerating factor (DAF) or CD59 had been incorporated. Erythrocytes of sheep (Esh), swine (Esw), dog (Edg), and guinea pig (Egp), unsensitized with human natural antibody (Ab), were used as xeno-target. C-mediated lysis of erythrocytes (E) was induced in both classical and alternative pathways in parallel with the density of the sensitized Ab, except for Egp. The efficacy of DAF/CD59-mediated protection of the xeno E from human C, however, differed among these E species. In both classical and alternative pathways, Esh or Esw, which are non-activator surfaces, were protected by the incorporated DAF or CD59, DAF being more effective than CD59. On the other hand, CD59 was more effective than DAF in both pathways in protection of Egp, which is an alternative pathway activator. To elucidate this different behaviour of DAF and CD59, C3 step inhibition by the incorporated DAF or CD59 was measured. DAF was effective in the suppression of classical pathway-mediated C3 deposition in Esh, Esw and Egp, but not in Edg, while CD59 exhibited negligible effects in this regard. Next, inhibition of the lysis by CD59 was tested by haemolytic assay. CD59 did not block the C5b-8-mediated lysis in any xeno E. It also barely blocked C5b-9-mediated lysis, except in the case of Egp, in which CD59 partly blocked C9 attack. Membrane constituents on targets other than the incorporated complement inhibitors may be a crucial factor in the induction of cytolysis and, presumably, in hyperacute rejection.


Dietary strategies and food practices of pediatric patients, and their parents, living with inflammatory bowel disease: a qualitative interview study.
Purpose: A growing body of scientific evidence supports the role of food and diet in the pathogenesis and management of inflammatory bowel diseases (IBD). However, little is known about the role of food and diet from the perspectives of pediatric patients and their parents. This study aimed to explore how children and adolescents with IBD and their parents coped with the illness through food and diet in their daily lives. Methods: We conducted semi-structured interviews with 28 children and adolescents with IBD, 26 parents and one grandparent. Results: Two major themes, dietary strategies and family food practices, were identified through thematic analysis. There were three types of dietary strategies: food avoidance and moderation; following a specific diet; and healthy eating. For family food practices, two subthemes were identified: impact on grocery shopping, meal planning, and cooking; and maintaining routine and normality. Conclusions: Our findings have important implications for the clinical care of pediatric IBD. Notably, IBD not only influenced the food practices of the pediatric patients, but also their parents and other family members. Healthcare professionals should consider the family unit when giving nutritional advice or developing nutritional guidelines. Personalized nutritional counselling and ongoing nutritional assessment are also warranted.


Three-dimensional modeling of the I-TevI homing endonuclease catalytic domain, a GIY-YIG superfamily member, using NMR restraints and Monte Carlo dynamics.
Using a recent version of the SICHO algorithm for in silico protein folding, we made a blind prediction of the tertiary structure of the N-terminal, independently folded, catalytic domain (CD) of the I-TevI homing endonuclease, a representative of the GIY-YIG superfamily of homing endonucleases. The secondary structure of the I-TevI CD has been determined using NMR spectroscopy, but computational sequence analysis failed to detect any protein of known tertiary structure related to the GIY-YIG nucleases (Kowalski et al., Nucleic Acids Res., 1999, 27, 2115-2125). To provide further insight into the structure-function relationships of all GIY-YIG superfamily members, including the recently described subfamily of type II restriction enzymes (Bujnicki et al., Trends Biochem. Sci., 2000, 26, 9-11), we incorporated the experimentally determined and predicted secondary and tertiary restraints in a reduced (side chain only) protein model, which was minimized by Monte Carlo dynamics and simulated annealing. The subsequently elaborated full atomic model of the I-TevI CD allows the available experimental data to be put into a structural context and suggests that the GIY-YIG domain may dimerize in order to bring together the conserved residues of the active site.


Light microscopy and morphometry of vinblastine in vivo cytotoxicity in the different developmental stages of rat incisor ameloblast epithelium.
To see whether the in vivo cytotoxicity of the antimicrotubule agent vinblastine (VB) was related to the degree of differentiation in a normal secretory cell population VB cytotoxicity in the various developmental stages of rat incisor ameloblast was studied. Normal values for cell and nucleus volumes, secretory velocity, VB dose-response curves for cell death, and proliferative and secretory activity were estimated quantitatively using simple stereological methods, 18 and 72 hours after VB administration i.v. Dose-response plots for cell death in jejunal crypt cells and the reduction of secretory activity in acinar pancreatic cells were compared with those of proliferating and secretory ameloblasts. Video light microscopy was used on 2 microns Epon sections with controlled orientation and position, permitting calculation of values on a per-cell-basis or per 10(4) microns 2 epithelial basal area. Normal cell and nuclear mean volumes (range: min.-max. value) for late-differentiating ameloblasts were 557 microns 3 (528-601) and 127 microns 3 (122-136), and for secretory ameloblasts 866 microns 3 (830-886) and 144 microns 3 (142-146). Mean volume of enamel matrix secreted per cell was around 169 microns 3 (122-202) per 24 hrs. Number of cells in the late-differentiating zone was 970(928-1003) and in the secretory zone 828 (820-835) per 10(4) microns 2 epithelial basal area. Cell death after VB in the ameloblast stem cells and pancreatic acinar cells was negligible. 72 hrs after VB, the supply of dividing cells to the proliferation zone was at lower doses increased, while at 3 mg/kg it was reduced to 72% of the normal. All proliferating cells appeared to be killed at 2 mg/kg, together with 38% of the differentiating and 34% of the secretory ameloblasts, and at 3 mg/kg, 70% and 66% respectively of the non-dividing ameloblasts were killed. The secretory output (volume of enamel matrix) of the ameloblasts exposed in the differentiating stage and now transformed into secretory cells was 72 hrs after VB 2 mg/kg reduced to 45%, while that of the mature secretory ameloblasts was reduced to 42%. After VB 3 mg/kg, the differentiated ameloblast zone retained 21% of the normal secretory output, whereas there was no output from the mature cells. Maximal accumulation of zymogen granules in pancreatic acinar cells occurred at 1 mg/kg VB. Unlike to secretory ameloblasts, the morphology of pancreatic acinar cells was normalized at 72 hrs after VB.(ABSTRACT TRUNCATED AT 400 WORDS)


Mississippian fossils from southern appalachian metamorphic rocks and their implications for late paleozoic tectonic evolution.
Fossils of Periastron reticulatum Unger emended. Beck recovered from the Erin Slate of the Talladega slate belt of Alabama establish that these rocks have a Mississippian (Kinderhookian-Tournaisian) age. The Talladega slate belt, the southwestern extension of the western Blue Ridge belt, was interpreted to have been affected by regional dynamothermal metamorphism and coeval deformation as a result of the Acadian orogeny. This fossil find indicates that metamorphism and deformation of the Talladega belt occurred after the Early Carboniferous (Alleghanian), requiring a reevaluation of tectonic interpretations of the southernmost Appalachians.


OFFl Models: Novel Schema for Dynamical Modeling of Biological Systems.
Flow diagrams are a common tool used to help build and interpret models of dynamical systems, often in biological contexts such as consumer-resource models and similar compartmental models. Typically, their usage is intuitive and informal. Here, we present a formalized version of flow diagrams as a kind of weighted directed graph which follow a strict grammar, which translate into a system of ordinary differential equations (ODEs) by a single unambiguous rule, and which have an equivalent representation as a relational database. (We abbreviate this schema of "ODEs and formalized flow diagrams" as OFFL.) Drawing a diagram within this strict grammar encourages a mental discipline on the part of the modeler in which all dynamical processes of a system are thought of as interactions between dynamical species that draw parcels from one or more source species and deposit them into target species according to a set of transformation rules. From these rules, the net rate of change for each species can be derived. The modeling schema can therefore be understood as both an epistemic and practical heuristic for modeling, serving both as an organizational framework for the model building process and as a mechanism for deriving ODEs. All steps of the schema beyond the initial scientific (intuitive, creative) abstraction of natural observations into model variables are algorithmic and easily carried out by a computer, thus enabling the future development of a dedicated software implementation. Such tools would empower the modeler to consider significantly more complex models than practical limitations might have otherwise proscribed, since the modeling framework itself manages that complexity on the modeler's behalf. In this report, we describe the chief motivations for OFFL, carefully outline its implementation, and utilize a range of classic examples from ecology and epidemiology to showcase its features.


Intensive Blood Pressure Lowering in Patients With and Patients Without Type 2 Diabetes: A Pooled Analysis From Two Randomized Trials.
The Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD-BP) study did not find a significant beneficial effect of intensive systolic blood pressure (SBP) lowering on cardiovascular events in hypertensive patients with type 2 diabetes mellitus (T2DM), while the Systolic Blood Pressure Intervention Trial (SPRINT) did find a significant beneficial effect in patients without T2DM. The objective of this analysis was to assess the effect of both T2DM and baseline cardiovascular disease risk on the treatment effect of intensive blood pressure lowering. The individual patient data from the ACCORD-BP and SPRINT studies were pooled and follow-up durations harmonized. Both studies randomized hypertensive patients to an SBP target of <120 mmHg or a target of <140 mmHg. The composite primary end point consisted of unstable angina, myocardial infarction, acute heart failure, stroke, and cardiovascular death. The interaction between intensive blood pressure lowering and both T2DM and 10-year cardiovascular risk was assessed using Cox proportional hazards models. The cohort consisted of 14,094 patients with mean age 66 ± 8.9 years and mean baseline SBP 139.5 ± 15.6 mmHg; 33.6% had T2DM. The hazard ratio for the primary composite end point was 0.82 (95% CI 0.73-0.93), P = 0.0017. The interaction between intensive blood pressure lowering and T2DM was nonsignificant (P = 0.13). The 10-year cardiovascular risk was higher in primary prevention patients with T2DM, but risk did not interact with the treatment effect (P = 0.84). Intensive blood pressure lowering may have a similar favorable effect and appears to decrease cardiovascular events in both patients with and patients without T2DM.


Effect of hyperoxia on pulmonary SIgA and its components, IgA and SC.
Oxygen therapy (hyperoxia) is essential for the treatment of some neonatal critical care conditions. The lung is the primary target for the changes induced by hyperoxia. Secretory immunoglobulin A (SIgA), IgA and secretory component (SC) reflect the local immunity in the respiratory tract induced by hyperoxia. The enzyme-linked immunosorbent assay, immunohistochemistry staining, Western blot and Real-time PCR were used to detect the levels of cytokines, IgA and SIgA in bronchoalveolar lavage as well as IgA and SC/pIgR in pulmonary tissue. The levels of IgA and SIgA in BAL fluid were gradually increased following neonatal rat development. Compared with air-inhaling group, in the hyperoxia group IgA, SIgA and other cytokines except IL-1 in BAL fluid were significantly elevated on the 3rd, 5th and 7th days, but on the 10th day TNF-α, SIgA and IgA rapidly decreased. In the hyperoxia group, both the protein expression of SC/pIgR and the mRNA expression of SC/pIgR were remarkably increased on the 3rd, 5th and 7th days, but were significantly decreased on the 10th day, respectively. The large amount of SIgA, IgA and SC in the early period of hyperoxia might protect the lungs of the neonatal rats against acute pulmonary injury, however, in the late period of hyperoxia, the abruptly drop of SIgA and its component might lead to pulmonary immunity abnormality. In hyperoxia, the increased expression of cytokines might contribute to the expression of IgA and SC.


Methylmalonic acid concentration in serum not affected in hepatic disease.
Accumulation of methylmalonic acid may provide an early clue to deficiency of cobalamin (vitamin B12) in tissue. Metabolic abnormalities involving precursors of methylmalonic acid are frequently observed in patients with hepatic diseases. To establish whether methylmalonic acid accumulates and thereby gives false-positive test results for cobalamin deficiency, we measured the concentration of methylmalonic acid in serum of patients with various hepatic diseases. Many of the patients had increased concentrations of cobalamin in serum. In serum from 70 patients, the mean concentration of methylmalonic acid (252, SE 25 nmol/L) did not differ significantly from that found in healthy subjects (211, SE 12 nmol/L). We conclude that the assay of methylmalonic acid in serum may be useful for evaluating cobalamin status in hepatic disease with functional cobalamin deficiency despite an artificially increased normal or high concentration of cobalamin in serum.


Fertile offspring derived from mouse spermatogonial stem cells cryopreserved for more than 14 years.
Approximately 80% of childhood cancers can now be cured but a side effect of treatment results in about one-third of the surviving boys being infertile or severely subfertile when they reach reproductive age. Currently, more than 1 in 5000 men of reproductive age who are childhood cancer survivors suffer from this serious quality of life problem. It is possible to obtain a testicular biopsy before treatment to preserve the spermatogonial stem cells (SSCs) of the male by cryopreservation, but the results of long-term storage of SSCs on their subsequent functional ability to generate normal offspring has not been examined in any mammalian species. Moreover, it will be necessary to increase the number of these cryopreserved SSCs to remove any contaminating malignant cells and assure regeneration of spermatogenesis. In this report, we demonstrate that long-term cryopreservation (>14 years) of testis cells from mouse, rat, rabbit and baboon safeguards SSC viability, and that these cells can colonize the seminiferous tubules of recipient testes. Moreover, mouse and rat SSCs can be cultured and re-establish complete spermatogenesis, and fertile mouse progeny without apparent genetic or epigenetic errors were generated by the sperm produced. These findings provide a platform for fertility preservation in prepubertal boys undergoing gonadotoxic treatments.


In Vivo Imaging of the Intra- and Extracellular Redox Status in Rat Stomach with Indomethacin-Induced Gastric Ulcers Using Overhauser-Enhanced Magnetic Resonance Imaging.
Repeated use of nonsteroidal anti-inflammatory drugs can induce changes in the redox status, including production of reactive oxygen species (ROS), but the specific details of these changes remain unknown. Overhauser-enhanced magnetic resonance imaging (OMRI) has been used in vivo to monitor the redox status in several diseases and map tissue oxygen concentrations. We monitored the intra- and extracellular redox status in the stomach of rats with indomethacin-induced gastric ulcers using OMRI and investigated the relationship with gastric mucosal damage. One hour after oral administration of indomethacin (30 mg/kg), OMRI measurements in the stomach were made following nitroxyl probe administration. OMRI with the membrane-permeable nitroxyl probe, 4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl (TEMPOL), demonstrated a redox change toward oxidation, which was reversed by a membrane-permeable antioxidant. Conversely, imaging with the impermeable probe, 4-trimethylammonium-2,2,6,6-tetramethyl-piperidine-1-oxyl (CAT-1), demonstrated little redox change. Redox imbalance imaging of a live rat stomach with indomethacin-induced gastric ulcers was produced by dual imaging of 15N-labeled TEMPOL and 14N-labeled CAT-1, in addition to imaging with another membrane-permeable 15N-labeled probe, 3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl (MC-PROXYL), and 14N-labeled CAT-1. Pretreatment with MC-PROXYL suppressed gastric mucosal damage, whereas pretreatment with CAT-1 did not suppress ulcer formation. OMRI combined with a dual probe is a less invasive imaging technique for evaluation of intracellular ROS production contributing to the formation of gastric ulcers in the stomach of indomethacin-treated rats, which cannot be done with other methods. This method may be a very powerful tool for characterizing the pathogenesis of various diseases and may have medical applications.


Secondary rhinoplasty in unilateral cleft nasal deformity.
Secondary rhinoplasty in the unilateral cleft nose represents one of the most difficult problems in rhinoplasty surgery. The sliding cheilorhinoplasty operation is a procedure that aids the correction of the deformed cleft nose. This technique is presented in detail, with operative examples.


Transgenerational inheritance of diet-induced genome rearrangements in Drosophila.
Ribosomal RNA gene (rDNA) copy number variation modulates heterochromatin formation and influences the expression of a large fraction of the Drosophila genome. This discovery, along with the link between rDNA, aging, and disease, high-lights the importance of understanding how natural rDNA copy number variation arises. Pursuing the relationship between rDNA expression and stability, we have discovered that increased dietary yeast concentration, emulating periods of dietary excess during life, results in somatic rDNA instability and copy number reduction. Modulation of Insulin/TOR signaling produces similar results, indicating a role for known nutrient sensing signaling pathways in this process. Furthermore, adults fed elevated dietary yeast concentrations produce offspring with fewer rDNA copies demonstrating that these effects also occur in the germline, and are transgenerationally heritable. This finding explains one source of natural rDNA copy number variation revealing a clear long-term consequence of diet.


Effect of β-casomorphin-7 on myocardial hypertrophy in hyperthyroidism-induced cardiomyopathy.
The purpose of this study was to investigate the effect of β-casomorphin-7 (β-CM-7) on myocardial hypertrophy (MH) in hyperthyroidism-induced cardiomyopathy in vivo and in vitro. Thirty C56BL/6 mice were randomly divided into three groups: control group, hyperthyroidism group, and β-CM-7 treatment group. An animal model of cardiac hypertrophy of hyperthyroid heart disease (HHD) was constructed by continuous intraperitoneal injection of 100 μg of L-thyroxine (L-Thy) for 28 days, and the serum TT3 and TT4 concentrations were measured. After that, myocardial specimens were collected to measure left and right ventricular MH index, and the myocardial cell structure was observed under hematoxylin and eosin (HE) staining. Thereafter, Masson staining was adopted to determine collagen volume fraction, and hydroxylamine method was used to measure superoxide dismutase (SOD) activity, Meanwhile, DTNB direct method was applied to measure GSH-Px activity, thio-malonylurea method was utilized to measure malondialdehyde (MDA) content, and the level of reactive oxygen species (ROS) was detected by flow cytometry. Finally, the expressions of oxidative stress (OS) and inflammation-related factors in vivo and the nuclear factor-κB (NF-κB) pathway in vitro were detected by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Compared with those in control group, TT3 and TT4 were remarkably increased, the structure of myocardial cells was disordered, the interstitial fibrosis and the ventricular MH index were significantly increased, the OS and inflammatory responses were increased, and the NF-κB pathway was activated in the Hyperthyroidism group. In the β-CM-7 group, the content of TT3 and TT4 was decreased, the myocardial cell structure was slightly disturbed, the fibrosis and the ventricular MH index were reduced, OS and inflammatory response were reduced, and the NF-κB pathway was inhibited. β-CM-7 can prevent and treat MH in mice with L-Thy-induced HHD probably through regulating the NF-κB signaling pathway.


Drug discovery for neglected diseases: molecular target-based and phenotypic approaches.
Drug discovery for neglected tropical diseases is carried out using both target-based and phenotypic approaches. In this paper, target-based approaches are discussed, with a particular focus on human African trypanosomiasis. Target-based drug discovery can be successful, but careful selection of targets is required. There are still very few fully validated drug targets in neglected diseases, and there is a high attrition rate in target-based drug discovery for these diseases. Phenotypic screening is a powerful method in both neglected and non-neglected diseases and has been very successfully used. Identification of molecular targets from phenotypic approaches can be a way to identify potential new drug targets.


Suppression of autophagy by CUB domain-containing protein 1 signaling is essential for anchorage-independent survival of lung cancer cells.
CUB (C1r/C1s, urchin embryonic growth factor, BMP1) domain-containing protein 1 (CDCP1) has been implicated in promoting metastasis of cancer cells through several mechanisms, including the inhibition of anoikis, which is cell death triggered by the loss of extracellular matrix interactions. However, the mechanism inhibiting cell death regulated by CDCP1 remains elusive. Inhibition of CDCP1 expression using small interfering RNA (siRNA) induced the cell death of suspended cancer cells without cleaving caspase-3, a marker of apoptosis; cell death was not inhibited by a general caspase inhibitor, suggesting that the loss of CDCP1 induces caspase-independent cell death. In contrast, knockdown of CDCP1 as well as protein kinase Cδ (PKCδ), a downstream effector of CDCP1, in a suspension culture of lung cancer cells resulted in marked induction of membranous microtubule-associated protein 1 light chain 3 (LC3)-II protein, a hallmark of autophagy, and caused the formation of an autophagosome structure visualized using green fluorescent protein-tagged LC3-II. Expression and phosphorylation of exogenous CDCP1 by Fyn kinase reduced the formation of autophagosomes and inhibited phosphorylation of CDCP1 by PP2, a Src kinase inhibitor or inhibited PKCδ by rottlerin, stimulating autophagosome formation. Moreover, death of suspended lung cancer cells induced by CDCP1 siRNA or by PKCδ siRNA was reduced by the autophagy inhibitor 3-methyladenine. These results indicate that CDCP1-PKCδ signaling plays a critical role in inhibiting autophagy, which is responsible for anoikis resistance of lung cancer cells.


Biochemical correlates of short-term sensitization in Aplysia: temporal analysis of adenylate cyclase stimulation in a perfused-membrane preparation.
During short-term sensitization, a simple form of nonassociative learning in Aplysia, the presentation of a single brief noxious stimulus results in enhancement of the defensive withdrawal reflex lasting minutes to tens of minutes. This behavioral plasticity involves presynaptic facilitation of synaptic transmission from the mechanosensory neurons that mediate the reflex to their central target cells. This facilitation is due to cAMP-dependent protein phosphorylation. To determine whether the time course of presynaptic facilitation might be due to a persistent increase in activity of adenylate cyclase (EC 188.8.131.52) itself, persistence of the transmitter, or yet other processes, we developed a perfused-membrane method to analyze the time course of activation of adenylate cyclase by transient stimuli. After stimulation by a pulse of stimulatory transmitter, activation of adenylate cyclase decayed within 60 sec. This finding indicates that the enzyme does not remain persistently active in the absence of transmitter and suggests that short-term retention is likely to be due to other mechanisms. Possible additional mechanisms include continued activation of the cyclase by transmitter, cellular factors extrinsic to the cyclase that prolong the time course of its activation, and persistence of processes downstream from the cyclase.


Metabolic profiling reveals distinct variations linked to nicotine consumption in humans--first results from the KORA study.
Exposure to nicotine during smoking causes a multitude of metabolic changes that are poorly understood. We quantified and analyzed 198 metabolites in 283 serum samples from the human cohort KORA (Cooperative Health Research in the Region of Augsburg). Multivariate analysis of metabolic profiles revealed that the group of smokers could be clearly differentiated from the groups of former smokers and non-smokers. Moreover, 23 lipid metabolites were identified as nicotine-dependent biomarkers. The levels of these biomarkers are all up-regulated in smokers compared to those in former and non-smokers, except for three acyl-alkyl-phosphatidylcholines (e.g. plasmalogens). Consistently significant results were further found for the ratios of plasmalogens to diacyl-phosphatidylcolines, which are reduced in smokers and regulated by the enzyme alkylglycerone phosphate synthase (alkyl-DHAP) in both ether lipid and glycerophospholipid pathways. Notably, our metabolite profiles are consistent with the strong down-regulation of the gene for alkyl-DHAP (AGPS) in smokers that has been found in a study analyzing gene expression in human lung tissues. Our data suggest that smoking is associated with plasmalogen-deficiency disorders, caused by reduced or lack of activity of the peroxisomal enzyme alkyl-DHAP. Our findings provide new insight into the pathophysiology of smoking addiction. Activation of the enzyme alkyl-DHAP by small molecules may provide novel routes for therapy.


Genetic differentiation and phylogeography of Mediterranean-North Eastern Atlantic blue shark (Prionace glauca, L. 1758) using mitochondrial DNA: panmixia or complex stock structure?
The blue shark (Prionace glauca, Linnaeus 1758) is one of the most abundant epipelagic shark inhabiting all the oceans except the poles, including the Mediterranean Sea, but its genetic structure has not been confirmed at basin and interoceanic distances. Past tagging programs in the Atlantic Ocean failed to find evidence of migration of blue sharks between the Mediterranean and the adjacent Atlantic, despite the extreme vagility of the species. Although the high rate of by-catch in the Mediterranean basin, to date no genetic study on Mediterranean blue shark was carried out, which constitutes a significant knowledge gap, considering that this population is classified as "Critically Endangered", unlike its open-ocean counterpart. Blue shark phylogeography and demography in the Mediterranean Sea and North-Eastern Atlantic Ocean were inferred using two mitochondrial genes (Cytb and control region) amplified from 207 and 170 individuals respectively, collected from six localities across the Mediterranean and two from the North-Eastern Atlantic. Although no obvious pattern of geographical differentiation was apparent from the haplotype network, Φst analyses indicated significant genetic structure among four geographical groups. Demographic analyses suggest that these populations have experienced a constant population expansion in the last 0.4-0.1 million of years. The weak, but significant, differences in Mediterranean and adjacent North-eastern Atlantic blue sharks revealed a complex phylogeographic structure, which appears to reject the assumption of panmixia across the study area, but also supports a certain degree of population connectivity across the Strait of Gibraltar, despite the lack of evidence of migratory movements observed by tagging data. Analyses of spatial genetic structure in relation to sex-ratio and size could indicate some level of sex/stage biased migratory behaviour.


Distribution and spatial trends of PCBs in commercial scallops from Galician littoral (NW, Spain). Possible influence of biometric parameters.
Levels and profiles of 10 individual congeners of polychlorinated biphenyls (PCBs) were studied in 3 species of commercial scallops (Pecten maximus, Chlamys varia, and Chlamys opercularis) from several Rías in Galician littoral (NW, Spain). ΣPCBs levels ranged from 2.21 to 41.0 ng/g wet weight for P. maximus, from 13.9 to 24.9 ng/g wet weight for C. varia, and from 1.58 to 24.3 ng/g wet weight for C. opercularis. The possible influence between biometric parameters (lipid content, condition index, and shell size) and PCBs levels were studied using statistical analysis (ANOVA). No relationship between biometric parameters could be established in the studied samples. Multivariate analysis showed there were differences in bioaccumulation of some PCBs congeners. Principal component analysis classifies clearly the 3 studied Rías (Ría de Ferrol, Ría de Arousa, and Ría de Vigo) taking into account PCBs levels found in the shellfish. We investigated levels and profiles of 10 congeners of PCBs in 3 commercial scallop species from the Galician littoral zone. The influence of 3 biometric parameters on polychlorinated biphenyls (PCBs) levels was also studied in order to assess results from the monitoring programs of production areas. According to PCBs levels, geographical differences were observed in commercial scallops from the 3 studied estuarine bays (Ría de Ferrol, Ría de Arousa, and Ría de Vigo).


Influence of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on mitochondrial respiration in rat liver during ischemia.
Effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, pravastatin and simvastatin, on mitochondrial respiration in ischemic rat liver were examined. Either vehicle, pravastatin (2 or 4 mg/kg per day), or simvastatin (1 or 2 mg/kg per day) was orally administered for 3 weeks. Liver ischemia was induced by cessation of the systemic circulation for 60 min. Liver mitochondria were isolated and the respiration was determined by polarography using glutamate and succinate as substrates. In the vehicle-treated group, ischemia drcreased ZO3, respiratory control index (RCI: QO3/QO4), and ADP/O ratio. Pretreatments with pravastatin and simvastatin enhanced the decreases in QO3 measured with either glutamate or succinate, and in ADP/O ratio measured with succinate. Because of decreasing QO4, HMG-CoA reductase inhibitors did not modify the changes in RCI due to ischemia. There were no significant differences in respiratory indices between pravastatin- and simvastatin-treated groups. In conclusion, HMG-CoA reductase inhibitors may enhance respiratory impairment of liver mitochondria under pathophysiological conditions, such as ischemia.


Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance.
Many different definitions for multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant (PDR) bacteria are being used in the medical literature to characterize the different patterns of resistance found in healthcare-associated, antimicrobial-resistant bacteria. A group of international experts came together through a joint initiative by the European Centre for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC), to create a standardized international terminology with which to describe acquired resistance profiles in Staphylococcus aureus, Enterococcus spp., Enterobacteriaceae (other than Salmonella and Shigella), Pseudomonas aeruginosa and Acinetobacter spp., all bacteria often responsible for healthcare-associated infections and prone to multidrug resistance. Epidemiologically significant antimicrobial categories were constructed for each bacterium. Lists of antimicrobial categories proposed for antimicrobial susceptibility testing were created using documents and breakpoints from the Clinical Laboratory Standards Institute (CLSI), the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the United States Food and Drug Administration (FDA). MDR was defined as acquired non-susceptibility to at least one agent in three or more antimicrobial categories, XDR was defined as non-susceptibility to at least one agent in all but two or fewer antimicrobial categories (i.e. bacterial isolates remain susceptible to only one or two categories) and PDR was defined as non-susceptibility to all agents in all antimicrobial categories. To ensure correct application of these definitions, bacterial isolates should be tested against all or nearly all of the antimicrobial agents within the antimicrobial categories and selective reporting and suppression of results should be avoided.


Teaching-learning partnership between nurses and long-term patients undergoing peritoneal dialysis: A qualitative study.
People with end-stage kidney disease (ESKD) receiving peritoneal dialysis (PD) have been found to alter their adherence to the renal therapeutic regimen following their initial teaching by PD nurses. Since alterations of adherence have been associated with poor health outcomes, this study focuses on persons receiving PD who rely on support and re-education from their nurses. To explore the teaching-learning partnership between people receiving PD and PD nurses, and to compare and contrast shared perspectives. The study consisted of individual semi-structured interviews of four people receiving PD and three PD nurses, using qualitative content analysis. Four shared themes and nine sub-themes emerged: "motivation" was characterised by perceptions of "staying healthy to avoid peritonitis pain and to qualify for a transplant". One sub-theme emerged exclusively in the interviewed people receiving PD: "motivation" to initiate PD through "finding meaning in life and situation". The theme "acceptance" was comprised "of diagnosis and choosing to initiate PD" and the "modification and integration into daily life". The presence of "support" arose from "personal support from family and friends", "professional care and understanding of the individual" and "professional customised and re-iterative education". The evolving "partnership" was comprised of "exposure", "personal rapport", and the "necessity of working together" in order to maintain positive health outcomes. The partnership between the PD nurse and people receiving PD for ESKD is crucial for successful health outcomes. Each partnership is unique and evolves over time. A successful partnership requires nurses to modify the educational content and teaching style to best meet the needs of people receiving PD and, most importantly, allow them to feel cared for and supported.


Electrocardiographic findings and incident coronary heart disease among participants in the Atherosclerosis Risk in Communities (ARIC) study.
The associations of many electrocardiographic (ECG) abnormalities at rest with incident coronary heart disease (CHD) are not completely established, and whether individual ECG abnormalities convey similar risk across gender and race is uncertain. We studied the independent association of several ECG findings with incident CHD, testing for effect modification by gender and race, in a large, population-based, prospective cohort study. Findings from the baseline 12-lead electrocardiograms in 1987 to 1989 were classified according to the Minnesota Code in 12,987 black and white men and women, aged 45 to 64 years, who were initially free of CHD and the use of specific cardiac medications. The incidence of CHD was ascertained through 2000. After adjustment for multiple cardiovascular risk factors, the ECG findings that had the highest hazard rate ratios (HRRs) for incident CHD, when considered singly, were left ventricular hypertrophy with ST-T strain pattern in white men (HRR 6.50) and in black women (HRR 2.31) and, in the whole cohort, major (HRR 2.27) and minor (HRR 2.47) ST depression and major T-wave abnormalities (HRR 2.12). Statistically significant associations were also found in the whole cohort for minor Q waves and left ventricular hypertrophy by the Cornell definition, but not for a prolonged QTc interval, major ventricular conduction defects, or ST elevation. In conclusion, several 12-lead ECG findings were independently associated with incident CHD in middle-aged adults. With only a few exceptions, the associations were similar for blacks and whites.


Peripartum maternal cardiomyopathy with idiopathic cardiomyopathy in the offspring. A case report.
Peripartum cardiomyopathy is an enigmatic disorder. A patient who developed it after delivery had a twin pregnancy complicated by demise of one fetus, preterm labor and subsequent preterm delivery of the viable twin, who died at 48 hours of life. The second twin had autopsy evidence of idiopathic cardiomyopathy, as did a prior child, who had died at 2 years of age. This report is the first on a woman with peripartum cardiomyopathy associated with idiopathic cardiomyopathy in her live-born infant. Our findings, in conjunction with those noted in a review of the literature, suggest that there is a subset of peripartum cardiomyopathy that may be mediated on a genetic or immunologic basis.


Threat of resource loss: The role of self-regulation in adaptive task performance.
Changes at work are often accompanied with the threat of, or actual, resource loss. Through an experiment, we investigated the detrimental effect of the threat of resource loss on adaptive task performance. Self-regulation (i.e., task focus and emotion control) was hypothesized to buffer the negative relationship between the threat of resource loss and adaptive task performance. Adaptation was conceptualized as relearning after a change in task execution rules. Threat of resource loss was manipulated for 100 participants undertaking an air traffic control task. Using discontinuous growth curve modeling, 2 kinds of adaptation--transition adaptation and reacquisition adaptation--were differentiated. The results showed that individuals who experienced the threat of resource loss had a stronger drop in performance (less transition adaptation) and a subsequent slower recovery (less reacquisition adaptation) compared with the control group who experienced no threat. Emotion control (but not task focus) moderated the relationship between the threat of resource loss and transition adaptation. In this respect, individuals who felt threatened but regulated their emotions performed better immediately after the task change (but not later on) compared with those individuals who felt threatened and did not regulate their emotions as well. However, later on, relearning (reacquisition adaptation) under the threat of resource loss was facilitated when individuals concentrated on the task at hand.


Unilateral atlantal lateral mass hypertrophy. Report of four cases.
The authors report the cases of four patients in whom they diagnosed an extremely rare and hitherto unreported clinical condition-unilateral hypertrophy of the C-1 lateral mass causing symptomatic cord compression. All patients presented with long-standing torticollis and progressive myelopathy. Three patients underwent posterior decompressive surgery and one underwent resection of the part of the lateral mass invading into the spinal canal and subsequent atlantoaxial plate and screw fixation. Clinical improvement of varying degrees occurred in all cases following surgery. The clinical recovery, however, was most remarkable in the patient who underwent resection of the bone portion indenting the cord. The follow-up periods ranged from 2 to 14 years. The remarkable similarity in the presenting clinical and radiological/neuroimaging features in all four patients suggests that unilateral hypertrophy of the lateral mass of atlas may be a defined clinical entity. The treatment strategy needs to be evaluated; however, resection of the compression-causing portion of the hypertrophic bone appears to be the best treatment option.