Fed levels of amino acids are required for the somatotropin-induced increase in muscle protein synthesis.
Chronic somatotropin (pST) treatment in pigs increases muscle protein synthesis and circulating insulin, a known promoter of protein synthesis. Previously, we showed that the pST-mediated rise in insulin could not account for the pST-induced increase in muscle protein synthesis when amino acids were maintained at fasting levels. This study aimed to determine whether the pST-induced increase in insulin promotes skeletal muscle protein synthesis when amino acids are provided at fed levels and whether the response is associated with enhanced translation initiation factor activation. Growing pigs were treated with pST (0 or 180 microg x kg(-1) x day(-1)) for 7 days, and then pancreatic-glucose-amino acid clamps were performed. Amino acids were raised to fed levels in the presence of either fasted or fed insulin concentrations; glucose was maintained at fasting throughout. Muscle protein synthesis was increased by pST treatment and by amino acids (with or without insulin) (P<0.001). In pST-treated pigs, fed, but not fasting, amino acid concentrations further increased muscle protein synthesis rates irrespective of insulin level (P<0.02). Fed amino acids, with or without raised insulin concentrations, increased the phosphorylation of S6 kinase (S6K1) and eukaryotic initiation factor (eIF) 4E-binding protein 1 (4EBP1), decreased inactive 4EBP1.eIF4E complex association, and increased active eIF4E.eIF4G complex formation (P<0.02). pST treatment did not alter translation initiation factor activation. We conclude that the pST-induced stimulation of muscle protein synthesis requires fed amino acid levels, but not fed insulin levels. However, under the current conditions, the response to amino acids is not mediated by the activation of translation initiation factors that regulate mRNA binding to the ribosomal complex.


Venous or arterial samples for activated clotting time measurements: a systematic review.
The systematic review aims to investigate the effect of sampling source on activated clotting time (ACT) measurement within cardiovascular surgery and cardiac catheterisation. It also examines the evidence surrounding novel clot assessment techniques and associated sampling variation. A comprehensive electronic search was conducted using PubMed, MEDLINE, Scopus, Cochrane database, and Google Scholar until 20th June 2020. All studies reporting sampling source variability of ACT in cardiac surgery, vascular surgery and cardiac catheterisation were included. Fourteen studies were included in the systematic review. Inconsistent reports of variability were seen in cardiac surgery and cardiac catheterisation. There were no studies directly examining ACT variability in vascular surgery. Novel clot assessment techniques have been validated in cardiac surgery, but measurements vary depending on sampling source. Sampling source should be kept consistent to facilitate effective haemostatic strategies. More research is needed regarding variability in vascular surgery and novel clot assessment techniques.


A Decade of Lessons Learned from Integration Strategies in the Netherlands.
In the Netherlands multiple single, cross sector and cross governance level policy reforms were introduced to improve health and social care and decrease fragmentation. In addition to legislative and funding measures, the governmental strategy was to set up long-lasting improvement programs and supported by applied research. Five national improvement programs on chronic disease management, maternity care, youth care, care for older people and dementia care were analysed. The Laws of integration of Leutz were used as an analytical framework. The programs demonstrated a mixture of employing policy, quality and financial measures to stimulate coherence and integration. The Laws that Leutz formulated are to a large extent applicable in the Dutch context. However, the characteristics of the system of governance being corporatist in its structure and its culture imply that it is hard to distinguish single actors being in the lead. Integration is a more complex process and requires more dynamics, than the law 'keep it simple, stupid' suggests. In the Dutch context integration implies a permanent pursuit of aligning mechanisms for integration. Sustainable integration requires long-standing efforts of all relevant stakeholders and cannot be achieved quickly. It may take a decade of consistently applying a mix of policy instruments.


Natural history of hepatitis B virus infection: pediatric perspective.
Hepatitis B virus (HBV) infection is an important disease globally. Chronic HBV infection may result in serious complications. Its transmission may be either perinatal or horizontal. Perinatal transmission is particularly important after the implementation of a universal vaccination program. Through either route, chronic carrier status is usually established in early childhood. The course of the disease course is determined by the host-virus interaction. The host's immune system initially tolerates the virus, and then gradually attempts to clear it. The virus, on the other hand, tries to avoid host immune system attack by a strategy involving targeted epitope mutations. By generating mutants, the virus can survive attacks from the host's immune system, enabling the infection to persist. Different individuals have different responses to HBV infection; genetic polymorphisms in cytokines, hormones, and other immune modulators may affect the final outcome of chronic HBV infection. Due to the implementation of a universal infant HBV vaccination program, HBV infection is now under control. Unfortunately, there still are some cases of vaccination failure. Very high maternal viremia, in utero infection, or escape mutants are possible reasons for vaccination failure. Immunocompromised hosts also risk vaccination failure. Blood or organ donors with occult HBV infection are possible sources for immunocompromised hosts. These victims of vaccination failure may exhibit a different disease course due to chronic HBV infection from those who acquired the infection before the universal vaccination era. The achievement of our ultimate goal of HBV elimination depends on a globally effective universal vaccination program, as well as the application of some novel successful medications to control those who are already infected.


Hypoxia-induced sympathetic inhibition of the fetal plasma insulin response to hyperglycemia.
Large-for-delivery date babies, considered characteristic of diabetic pregnancy, are believed to result from fetal hyperinsulinemia. Paradoxically, infant birth weights tend to be low-for-delivery date in mothers with more severe diabetes. We tested the hypothesis that hypoxemia in such fetuses leads to sympathoadrenal stimulation and inhibition of insulin secretion; and, thus, produces a net reduction in the growth-promoting effects. Fetal sheep were prepared with chronic peripheral and adrenal cannulas. Fetal blood gases, lactate, norepinephrine, and epinephrine secretion rates; and plasma norepinephrine, glucose, and immunoreactive insulin concentrations were determined at 30-min intervals during a 2-h baseline period and a 4-h period of hyperglycemia divided into 2-h segments of hypoxemia (with and without alpha-blockade) and hyperoxia. Hypoxemia-hyperoxia sequences were varied randomly. Well-oxygenated fetuses responded to a threefold increase in glucose with a sixfold increase in plasma immunoreactive insulin. With hypoxemia, norepinephrine and epinephrine secretion were elevated and the insulin response was blocked. With hypoxemia and phentolamine blockade, the insulin response was enhanced with a 10-fold increase above baseline. In severe maternal diabetes with vascular disease or with poor control and very high glucose levels, the fetus is likely to be relatively hypoxemic. Our experiments suggest that in this situation, the fetal insulin response to hyperglycemia will be attenuated; this effect is mediated, at least partly, through sympathoadrenal stimulation.


[Sonographic findings in complications of cystic echinococcosis].
Apart from the difficult differential diagnosis of hydatid liver disease, diagnostic problems may increase in chronic disease because of complications. Compression or infiltration of bile ducts is the most common complication occurring in 16%. Other complications are infiltration of adjacent organs and structures, for instance the right kidney and the diaphragm, or the (often iatrogenic) rupture of hydatid cysts with intraperitoneal spread. Preoperative sonographic diagnosis is important in influencing the surgical procedure.


The occurrence of epilepsy and febrile seizures in Virginian and Norwegian twins.
Twin studies provide an efficient method for examining the importance of genetic and environmental factors in the etiology of disorders such as epilepsy. Population-based twin registries are especially valuable for studies of this type since effects of reporting and self-selection biases on the resulting data are minimized. Among 14,352 twin pairs contained in the Virginia and Norwegian twin panels for whom questionnaire information was available, there was a history of epilepsy in one or both members of 286 pairs; febrile seizures were reported in 257 pairs. Analyses of questionnaire data revealed no significant differences in concordance rates between Virginian and Norwegian twins for either epilepsy or febrile seizures. Probandwise concordance rates for epilepsy were 0.19 in monozygotic twins and 0.07 in dizygotic twins. Analogous rates for febrile seizures were 0.33 (monozygotic) and 0.11 (dizygotic). These results provide further evidence that genetic factors do have a role in the expression of epilepsy and febrile seizures.


Stabilization of Octastatin, a somatostatin analogue. Preparation of freeze-dried products for parenteral injection.
Octastatin (RC-160, vapreotide INN) is a somatostatin analogue being developed for use in oncological, enterologic and neuroendocrine applications. The pharmaceutical form is a freeze-dried preparation for parenteral injection use. Three dosage forms containing 0.5, 1.5 and 15 mg of vapreotide base have been investigated. Various freeze-drying conditions, stabilizing agents, membranes for sterile filtration and heating procedures have been examined. The formulation with glutamic acid-sodium glutamate buffer as a stabilizing agent, the type of membrane for filtration and the freeze-drying procedure have been found appropriate for subsequent industrial production. No evident degradation was observed either after manufacturing, or after a three-week accelerated stability study at 50 degrees C and 70% relative humidity.


The photoelectron x-ray microscope, a possible tool for analytical soft x-ray microscopy.
In the soft x-ray region, different techniques have been recently developed which can give images of biological objects at an intermediate resolution between optical and electron microscopes. At these wavelengths, very little sample preparation is required because the image contrast is directly dependent upon the chemical composition of the sample itself and on the x-ray wavelength. X-ray microscopy can be extended to absorption microanalysis with a similar resolution, provided that the basic microscope can work through a large range of wavelengths. The photoelectron x-ray microscope that we are developing at LURE satisfies this condition. Its principle is to make a contact x-ray image of the object on a plane photocathode and then, to magnify the secondary electron image, into which it is converted, by means of an emission electron microscope. In the present state of the art, the expectable detection limit, for element maps of 0.1 micron resolution, would be near 1% in concentration.


Delta Subunit-Containing Gamma-Aminobutyric Acid A Receptor Disinhibits Lateral Amygdala and Facilitates Fear Expression in Mice.
Maintaining gamma-aminobutyric acidergic (GABAergic) inhibition in the amygdala within a physiological range is critical for the appropriate expression of emotions such as fear and anxiety. The synaptic GABA type A receptor (GABAAR) is generally known to mediate the primary component of amygdala inhibition and prevent inappropriate expression of fear. However, little is known about the contribution of the extrasynaptic GABAAR to amygdala inhibition and fear. By using mice expressing green fluorescent protein in interneurons (INs) and lacking the δ subunit-containing GABAAR (GABAA(δ)R), which is exclusively situated in the extrasynaptic membrane, we systematically investigated the role of GABAA(δ)R in regulating inhibition in the lateral amygdala (LA) and fear learning using the combined approaches of immunohistochemistry, electrophysiology, and behavior. In sharp contrast to the established role of synaptic GABAAR in mediating LA inhibition, we found that either pharmacological or physiological recruitment of GABAA(δ)R resulted in the weakening of GABAergic transmission onto projection neurons in LA while leaving the glutamatergic transmission unaltered, suggesting disinhibition by GABAA(δ)R. The disinhibition arose from IN-specific expression of GABAA(δ)R with its activation decreasing the input resistance of local INs and suppressing their activation. Genetic deletion of GABAA(δ)R attenuated its role in suppressing LA INs and disinhibiting LA. Importantly, the GABAA(δ)R facilitated long-term potentiation in sensory afferents to LA and permitted the expression of learned fear. Our findings suggest that GABAA(δ)R serves as a brake rather than a mediator of GABAergic inhibition in LA. The disinhibition by GABAA(δ)R may help to prevent excessive suppression of amygdala activity and thus ensure the expression of emotion.


Propriospinal bypass of the serotonergic system that can facilitate stepping.
The neurotransmitter systems mediating spinal locomotion in response to epidural spinal cord stimulation (ES) have not been identified. Here, we examine the role of the serotonergic system in regulating locomotor behavior of decerebrated cats during ES at L4-L5. ES elicited coordinated, weight-bearing, hindlimb stepping with plantar foot placement on a moving treadmill belt. Ketanserin [a 5-hydroxytryptamine (serotonin) (5-HT)(2/7) receptor antagonist] depressed this locomotor activity: only weak rhythmic movements without plantar foot placement and depressed EMG activity were observed. Cyproheptadine, a nonselective 5-HT blocker, prevented facilitation of stepping by epidural stimulation. These data demonstrate an important role of the serotonergic system in facilitating locomotion in the presence of epidural stimulation. In the presence of ketanserin, passive movements of one forelimb in a step-like manner immediately induced stepping of both hindlimbs with EMG patterns similar to those observed with ES without ketanserin. Thus, a non-5-HT-dependent spinal circuitry projecting from the cervical to the lumbar region of the spinal cord can facilitate stepping. The specific neurotransmitters responsible for this forelimb-facilitated stepping of the hindlimbs are unknown. These data suggest that a 5-HT(2/7) receptor-dependent pathway that processes hindlimb locomotor-like proprioception to facilitate hindlimb stepping can be complemented with proprioceptive afferents from the forelimbs via a non-5-HT(2/7) receptor neurotransmitter system. Thus, different neurotransmitter receptor systems can be used to mediate the same type of sensory event, i.e., locomotor-like proprioception to facilitate the same motor task, i.e., hindlimb stepping.


Chromatographic Data Segmentation Method: A Hybrid Analytical Approach for the Investigation of Antiviral Substances in Medicinal Plant Extracts.
The methodology described in this article will significantly reduce the time required for understanding the relations between chromatographic data and bioactivity assays. The methodology is a hybrid of hypothesis-based and data-driven scientific approaches. In this work, a novel chromatographic data segmentation method is proposed, which demonstrates the capability of finding what volatile substances are responsible for antiviral and cytotoxic effects in the medicinal plant extracts. Up until now, the full potential of the separation methods has not been exploited in the life sciences. This was due to the lack of data ordering methods capable of adequately preparing the chromatographic information. Furthermore, the data analysis methods suffer from multidimensionality, requiring a large number of investigated data points. A new method is described for processing any chromatographic information into a vector. The obtained vectors of highly complex and different origin samples can be compared mathematically. The proposed method, efficient with relatively small sized data sets, does not suffer from multidimensionality. In this novel analytical approach, the samples did not need fractionation and purification, which is typically used in hypothesis-based scientific research. All investigations were performed using crude extracts possessing hundreds of phyto-substances. The antiviral properties of medicinal plant extracts were investigated using gas chromatography-mass spectrometry, antiviral tests, and proposed data analysis methods. The findings suggested that (i) β- cis-caryophyllene, linalool, and eucalyptol possess antiviral activity, while (ii) thujones do not, and (iii) α-thujone, β-thujone, cis- p-menthan-3-one, and estragole show cytotoxic effects.


[Resection and reconstruction of the chest wall for primary or metastatic tumours].
The aim of the study was to assess mortality and the complication rate after the extensive resection of chest wall tumour and subsequent soft tissue reconstruction. We wanted to evaluate the justification for major surgery in the group of patients with primary or secondary tumours, including those with an advanced stage of disease. A total of 35 patients after major chest wall resection within an eight-year period (2000-2008) were analysed retrospectively. A major resection was defined as resection of 75 cm2 or more of full thickness of the chest wall. There were 19 cases of primary malignant tumour of the chest wall, 10 cases of secondary tumour, and 6 cases of benign or semi-malignant lesions. The chest was stabilised with the help of either polypropylene or a double layer mesh of polyester covered with polyurethane. For soft tissue reconstruction, a musculocutaneous flap was used in 18 cases. The number of resected ribs ranged from two to seven. The vertebral body was partially resected in four cases, and total sternectomy was performed in two cases. This surgery was carried out with potentially curative intent in 30 (85.7%) and with palliative intent in five patients (14.3%). No post-operative mortality occurred. The complication rate was 17.1 %. The one-year survival rate was 88.6 %. There were seven long-term survivors at 5 or more years after resection of the chest wall for soft tissue sarcoma. Local recurrence occurred in six patients (17.1%). Neither the type of prosthesis nor the type of surgical procedure influenced the complication rate. Chest wall resection is an established surgical procedure in the treatment of primary chest wall tumours and, occasionally, solitary metastatic disease. The groups of patients reported in the literature have been heterogeneous and usually small, and thus an estimation of the true risk of the major procedure is difficult. Three studies involving large patient groups published in the last 11 years have shown morbidity in 24.4%, 33.2% and 46.0% of patients and mortality in 7.0%, 3.8% and 4.1% of patients, respectively. The results in our group of unselected patients are comparable with these studies; however, we did not perform extensive procedures like pneumonectomy and chest wall resection, or extended fore quarter amputation. CONCLUSIONS Complete resection of the chest wall is feasible even in advanced tumours without significant peri-operative morbidity and mortality. Major chest wall resection as a palliative procedure remains selective for motivated patients in a good physical condition but with low quality of life caused by a chest wall tumour.


Claudin-8 modulates paracellular permeability to acidic and basic ions in MDCK II cells.
Renal net acid excretion requires tubular reabsorption of filtered bicarbonate, followed by secretion of protons and ammonium in the collecting duct, generating steep transtubular gradients for these ions. To prevent passive backleak of these ions, the tight junctions in the collecting duct must be highly impermeable to these ions. We previously generated a Madin-Darby canine kidney (MDCK II) cell line with inducible expression of claudin-8, a tight junction protein expressed in the collecting duct. In these cells, claudin-8 was shown to function as a paracellular barrier to alkali metal and divalent cations. We have now used this model to test the hypothesis that claudin-8 also functions as a paracellular barrier to acidic or basic ions involved in renal acid excretion. We developed a series of precise and unbiased methods, based on a combination of diffusion potential, short-circuit current, and pH stat measurements, to estimate paracellular permeability to protons, ammonium and bicarbonate in MDCK II cells. We found that under control conditions (i.e. in the absence of claudin-8), these cells are highly permeable to the acidic and basic ions tested. Interestingly, proton permeation exhibited an unusually low activation energy similar to that in bulk solution. This suggests that paracellular proton transfer may occur by a Grotthuss mechanism, implying that the paracellular pores are sufficiently wide to accommodate water molecules in a freely mobile state. Induction of claudin-8 expression reduces permeability not only to protons, but also to ammonium and bicarbonate. We conclude that claudin-8 probably functions to limit the passive leak of these three ions via paracellular routes, thereby playing a permissive role in urinary net acid excretion.


In vitro effects of pomegranate juice and pomegranate polyphenols on foodborne viral surrogates.
Pomegranate juice (PJ) has gained popularity because of its associated antioxidant, antimicrobial, anticancer, and anti-inflammatory properties. However, its effects against epidemiologically significant foodborne viruses have not been investigated. In the absence of culturable human noroviruses, feline calicivirus (FCV-F9), murine norovirus (MNV-1), and MS2 (ssRNA) bacteriophage were used as foodborne viral surrogates. The aim of this research was to study the effects of PJ and pomegranate polyphenols (PP) on foodborne viral infectivity. Viruses at high (∼ 7 log(10) PFU/mL) or low (∼ 5 log(10) PFU/mL) titers were mixed with equal volumes of PJ, 8, 16, and 32 mg/mL of PP, or water (control) and incubated for 1 h at room temperature. Viral infectivity after treatments was evaluated using standardized plaque assays. PJ decreased the titer of FCV-F9, MNV-1, and MS2 by 2.56, 1.32, and 0.32 log(10) PFU/mL, respectively, for low titers and 1.20, 0.06, and 0.63 log(10) PFU/mL, respectively, for high titers. Interestingly, FCV-F9 was undetectable after exposure to the three tested PP solutions using both low and high titers. MNV-1 at low initial titers was reduced by 1.30, 2.11, and 3.61 log(10) PFU/mL and at high initial titers by 1.56, 1.48, and 1.54 log(10) PFU/mL with 4, 8, and 16 mg/mL of PP treatment, respectively. MS2 at low initial titers was reduced by 0.41, 0.45, and 0.93 log(10) PFU/mL and at high initial titers by 0.32, 0.41, and 0.72 log(10) PFU/mL after 4, 8, and 16 mg/mL of PP treatment, respectively. PJ and PP resulted in titer reductions of foodborne virus surrogates after 1 h exposure, showing promise for use in hurdle technologies and/or for therapeutic or preventive use. To suggest the use of PJ and PP as natural remedies for foodborne viral illness prevention, their mechanism of action against viral infectivity needs to be further investigated.


Determinants of physician acceptance of assignment: an examination of Medicare beneficiary characteristics.
This study examines the degree to which patient characteristics predict physicians' ad hoc decisions regarding acceptance of Medicare assignment. The study is based on a random sample of Medicare Part B enrollees living independently in the Salem, Oregon metropolitan area. Beneficiary characteristics and beneficiary reports of physician behavior are obtained from an hour long face-to-face survey. The findings show that patient characteristics are significant predictors of physician behavior. Those respondents with poor health, no supplementary coverage to Medicare Part B, and who are more sensitive to the cost of health care are significantly more likely to report that their physician accepts assignment than are respondents without these characteristics. Policy and research implications are discussed.


Regional location of alpha 1-antichymotrypsin and alpha 1-antitrypsin genes on human chromosome 14.
The human protease inhibitor genes alpha 1 antitrypsin (alpha 1-PI) and alpha 1-antichymotrypsin (alpha 1-ACT) are acute-phase proteins which are induced in response to inflammation. These inhibitors function to limit the activity of serine proteases in vivo. alpha 1-PI acts as an inhibitor of neutrophil elastase to protect the elastin fibers of the lung. Genetic deficiencies of alpha 1-PI result in development of chronic pulmonary emphysema. The physiologic role of alpha 1-ACT has not been clearly defined, but it also appears to function in the maintenance of protease-protease inhibitor equilibrium in the lung. Nucleic acid and protein sequence homologies detected between alpha 1-PI and alpha 1-ACT suggested an evolutionary relationship. Gene mapping experiments were performed to determine if these protease inhibitor genes reside at the same chromosomal locus in man. In situ hybridization data demonstrate that both alpha 1-PI and alpha 1-ACT map to the same region, q31-q32.3, on chromosome 14.


Vasospasm after aneurysmal subarachnoid hemorrhage: recent advances in endovascular management.
In a rapidly advancing specialty, it is essential to review the recent studies of alternative new treatments and present their efficacy, safety and outcome. We discuss the recent advances in the endovascular treatment of cerebral vasospasm following aneurysmal subarachnoid hemorrhage in the past few years with special focus on the literature regarding this subject in the last 18-24 months. The recent findings are as follows: effect of papaverine on brain oxygen; recent evaluation concerning nimodipine use; combined intraarterial and intravenous use of milrinone; illustration of the numerous recent studies on nicardipine; the safety and efficacy of high-dose intraarterial verapamil; outcome and adverse effects of intraarterial fasudil; transluminal balloon angioplasty; and recent evaluation of its efficacy and evaluation of its prophylactic use. Endovascular treatment, including intraarterial vasodilators and transluminal balloon angioplasty, has a very important place in the management of symptomatic vasospasm related to aneurysmal subarachnoid hemorrhage. The efficacy of intraarterial vasodilators has been proven. Numerous studies and analysis of different treatments of cerebrovascular vasospasm took place in the past period. This allowed more understanding and evaluation of their outcome, safety and efficacy helping physicians to choose better treatments to adopt. It emphasizes also the aspects that need more study and research.


Effects of combinations of cytokines on murine antigen-specific B lymphocytes.
Cytokines are among the most important mediators in the immune response. They act on B lymphocytes at various stages along the activation pathway. To study the effects of combinations of cytokines, we have used an antigen-specific single B cell-cloning system devised in this laboratory. We report here that IL-1 can enhance the proliferative response and IgM secretion by B cells induced by IL-6. The results of a similar study demonstrated that IL-1 can also enhance the effects of IL-5 on B cell proliferation and IgM secretion in an additive manner. Kinetic analyses showed that IL-1 had to be present from the beginning of the culture for an optimum cooperative effect, whereas the addition of IL-6 could be delayed up to 2 days without a significant reduction of the response. In contrast, IL-5 had to be added together with IL-1 at the onset of culture to promote an optimum response. The responses elicited by IL-1 plus IL-6, IL-1 plus IL-5, and IL-4 plus IL-5 were almost identical. The addition of further cytokines to these cultures gave no enhancement above the effects observed with the two-cytokine combinations.


Biomechanics, energetics and coordination during extreme swimming intensity: effect of performance level.
The present study aimed to examine how high- and low-speed swimmers organise biomechanical, energetic and coordinative factors throughout extreme intensity swim. Sixteen swimmers (eight high- and eight low-speed) performed, in free condition, 100-m front crawl at maximal intensity and 25, 50 and 75-m bouts (at same pace as the previous 100-m), and 100-m maximal front crawl on the measuring active drag system (MAD-system). A 3D dual-media optoelectronic system was used to assess speed, stroke frequency, stroke length, propelling efficiency and index of coordination (IdC), with power assessed by MAD-system and energy cost by quantifying oxygen consumption plus blood lactate. Both groups presented a similar profile in speed, power output, stroke frequency, stroke length, propelling efficiency and energy cost along the effort, while a distinct coordination profile was observed (F(3, 42) = 3.59, P = 0.04). Speed, power, stroke frequency and propelling efficiency (not significant, only a tendency) were higher in high-speed swimmers, while stroke length and energy cost were similar between groups. Performing at extreme intensity led better level swimmers to achieve superior speed due to higher power and propelling efficiency, with consequent ability to swim at higher stroke frequencies. This imposes specific constraints, resulting in a distinct IdC magnitude and profile between groups.


Multiresolution statistical analysis of high-resolution digital mammograms.
A multiresolution statistical method for identifying clinically normal tissue in digitized mammograms is used to construct an algorithm for separating normal regions from potentially abnormal regions; that is, small regions that may contain isolated calcifications. This is the initial phase of the development of a general method for the automatic recognition of normal mammograms. The first step is to decompose the image with a wavelet expansion that yields a sum of independent images, each containing different levels of image detail. When calcifications are present, there is strong empirical evidence that only some of the image components are necessary for the purpose of detecting a deviation from normal. The underlying statistic for each of the selected expansion components can be modeled with a simple parametric probability distribution function. This function serves as an instrument for the development of a statistical test that allows for the recognition of normal tissue regions. The distribution function depends on only one parameter, and this parameter itself has an underlying statistical distribution. The values of this parameter define a summary statistic that can be used to set detection error rates. Once the summary statistic is determined, spatial filters that are matched to resolution are applied independently to each selected expansion image. Regions of the image that correlate with the normal statistical model are discarded and regions in disagreement (suspicious areas) are flagged. These results are combined to produce a detection output image consisting only of suspicious areas. This type of detection output is amenable to further processing that may ultimately lead to a fully automated algorithm for the identification of normal mammograms.


Supercritical Carbon Dioxide (scCO2) Extraction of Phenolic Compounds from Lavender (Lavandula angustifolia) Flowers: A Box-Behnken Experimental Optimization.
Due to their numerous health benefits associated with various diseases and anti-oxidation properties, the phenolic compounds collectively referred to as phytochemicals have attracted a lot of interest, however, a single extraction method for polyphenols has not been developed yet. Supercritical fluid extraction, a green extraction method, provides the final product without organic solvent residues. In this work the extraction of lavender was performed using supercritical carbon dioxide. A statistical experimental design based on the Box-Behnken (B-B) method was planned, and the extraction yields and total phenolic contents were measured for three different variables: pressure, temperature and extraction time. The ranges were 200-300 bar, 40-60 °C and 15-45 min. The extracts yields from scCO2 extraction were in the range of 4.3-9.2 wt.%. The highest yield (9.2 wt.%) was achieved at a temperature of 60 °C under the pressure of 250 bar after 45 min. It also corresponded to the highest total phenolic content (10.17 mg GAE/g extract). Based on the study, the statistically generated optimal extraction conditions to obtain the highest total phenolic compounds concentration from flowers of Lavandula angustifolia were a temperature of 54.5 °C, pressure of 297.9 bar, and the time of 45 min. Based on the scavenging activity percentage (AA%) of scCO2 extracts, it is concluded that the increase of extraction pressure had a positive influence on the increase of AA% values.


Isolation of mesophyll protoplasts from mature leaves of soybeans.
A procedure based on a combined cellulase-Pectolyase Y-23 enzyme digestion and metrizamide-sorbitol gradient purification protocol was developed for isolating mesophyll protoplasts from mature leaves of soybean (Glycine max L. Merr.). Based on chlorophyll content, this procedure results in a 10 to 15% protoplast yield from fully expanded mature leaves and a 20 to 30% yield from young (expanding) leaves within 3 hours. Isolated protoplasts displayed high rates of HCO(3) (-)-dependent photosynthesis; greater than 75 micromoles O(2) evolved per milligram chlorophyll per hour at 25 degrees C. This photosynthetic rate is comparable to that of mesophyll cells isolated mechanically from the same leaves.


The role of the speech-language pathologist in the schools for the treatment of voice disorders: working within the framework of the individuals with disabilities education improvement act.
The role of the speech-language pathologist (SLP) has developed considerably over the past 20 years given the medical and technological advances in life-sustaining procedures. Children born with congenital, surgical, or "medically fragile" conditions become mainstreamed into regular school-based settings, thus extending the traditional role of the treating SLP and multidisciplinary team. Understanding the impact of associated voice disorders on educational performance requires dissemination of additional and important information, as eligibility decisions for students in school-based settings must be made within the framework of the federal legislation and regulations governing the provision of services for students with disabilities. This article discusses how to identify children with voice disorders under the Individuals with Disabilities Education Improvement Act (IDEA), the role of the SLP in various triaging scenarios, and how models of voice therapy can be integrated in a school-based setting.


Preliminary study of jointed snaffle vs. crossunder bitless bridles: quantified comparison of behaviour in four horses.
The study tested the null hypothesis that if a horse is ridden in a snaffle bridle and then a crossunder bitless bridle, there will be no change in its behaviour. It was predicted that there would be change and that behaviour would improve when bitless. Four horses, none of which had ever been ridden in a crossunder bitless bridle, were ridden through two 4 min, exercise tests, first bitted then bitless. An independent judge marked the 27 phases of each test on a 10 point scale and comments and scores were recorded on a video soundtrack. The results refuted the null hypothesis and upheld the predictions. Mean score, when bitted, was 37%; and through the first 4 min of being bitless, 64%. A binomial probability distribution suggested that the results were significantly different from random effects. All 4 horses accepted the crossunder bitless bridle without hesitation. Further studies are warranted and it is hoped that others will build on this new field of investigation. The authors are of the opinion that the bit can be a welfare and safety problem for both horse and horseman. Equestrian organisations that currently mandate use of the bit for competitions are urged to review their rules.


Establishing high resolution melting analysis: method validation and evaluation for c-RET proto-oncogene mutation screening.
Reliable and effective primary screening of mutation carriers is the key condition for common diagnostic use. The objective of this study is to validate the method high resolution melting (HRM) analysis for routine primary mutation screening and accomplish its optimization, evaluation and validation. Due to their heterozygous nature, germline point mutations of c-RET proto-oncogene, associated to multiple endocrine neoplasia type 2 (MEN2), are suitable for HRM analysis. Early identification of mutation carriers has a major impact on patients' survival due to early onset of medullary thyroid carcinoma (MTC) and resistance to conventional therapy. The authors performed a series of validation assays according to International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines for validation of analytical procedures, along with appropriate design and optimization experiments. After validated evaluation of HRM, the method was utilized for primary screening of 28 pathogenic c-RET mutations distributed among nine exons of c-RET gene. Validation experiments confirm the repeatability, robustness, accuracy and reproducibility of HRM. All c-RET gene pathogenic variants were detected with no occurrence of false-positive/false-negative results. The data provide basic information about design, establishment and validation of HRM for primary screening of genetic variants in order to distinguish heterozygous point mutation carriers among the wild-type sequence carriers. HRM analysis is a powerful and reliable tool for rapid and cost-effective primary screening, e.g., of c-RET gene germline and/or sporadic mutations and can be used as a first line potential diagnostic tool.


Can 3D-printing avoid discomfort-related implant removal in midshaft clavicle fractures? A four-year follow-up.
Due to the variation in shape and curvature of the clavicle, plates often have to be adjusted during surgery to acquire a good fit. Poorly fitted plates can cause discomfort, eventually requiring implant removal. 3D-printed replicas of the fractured clavicle can assist in planning of the surgical approach, plate selection and, if necessary, adjustment of the plate prior to surgery. We hypothesized this method of preoperative preparation would reduce implant-related discomfort resulting in a reduced reoperation rate MATERIALS AND METHODS: In a prospective cohort study, perioperative plate handling and clavicle fixation were timed and follow-up data were collected from participants undergoing operative treatment for a midshaft clavicle fracture. The control group (n = 7) received conventional surgery with standard precontoured plates. For the intervention group (n = 7), 3D-printed replicas of the fractured clavicle and a mirrored version of the healthy contralateral clavicle were available prior to surgery for planning of the surgical approach, and for plate selection and contouring. Primary outcome was reoperation rate due to implant-related discomfort. Secondary outcomes were complications and time differences in the different surgical phases (reduction, fixation and overall operation time) RESULTS: More participants in the control group had the plate removed due to discomfort compared to the intervention group (5/7 vs. 0/6; P = 0.012). One participant was excluded from the intervention group due to a postoperative complication; an infection occurred at the implant site. No relevant time difference in surgical plate handling was found between both groups. Preoperative preparation using 3D-printed replicas of the clavicle fracture may reduce implant removal caused by plated-related discomfort. No relevant effect on surgery time was found. Registered with 'toetsingonline.nl', trial number NL51269.075/14, 17-02-2015.


A Novel Prototype for Safe Driving Using Embedded Smart Box System.
Every day, vehicle accidents occur and many of them might be avoided if the drivers demonstrated excellent driving without mistakes. This paper presents a novel prototype applied in a real transportation system, particularly for buses, to avoid accidents, which may involve numerous victims, and even occasionally cause death. This system consists of a wearable device and embedded system with several sensors connected via Bluetooth, similar to the Internet of Things (IoT). Wearable devices are made to monitor the driver's heart rate and alert the driver if they are in a state of sleep deprivation to prevent any potential accidents. The embedded system includes a Global Positioning System (GPS), accelerometers, and gyroscopes attached to a Smart Box mounted on the bus. The embedded system alert function will be triggered if an accident occurs and automatically sends the geolocation of the accident to the registered phone number through a message using a mobile phone. The results for all scenarios were significant when measured by an automatic accident trigger via the smart box if the value of measured values in each axis exceeded 583. In conclusion, the implementation of this innovative solution at the system-level was shown to be satisfactory in terms of the safety mechanism used by the nominated drivers.


The use of warmed water treatment to induce protective immunity against the bacterial cold-water disease pathogen Flavobacterium psychrophilum in ayu (Plecoglossus altivelis).
We investigated the induction of protective immunity against bacterial cold-water disease (BCWD) caused by Flavobacterium psychrophilum by warmed water treatment in ayu (Plecoglossus altivelis). Fish were immersed in a live bacterial suspension (10⁷ CFU mL⁻¹) for 30 min and placed in 700 L concrete tanks. The 28 °C warmed water treatment lasted 3 days and began 1, 6, and 24 h after immersion in the live bacterial suspension. A naïve control fish group was immersed in a sterilized modified Cytophaga (MCY) broth instead of the bacterial suspension. Fourteen days after the immersion, agglutination antibody titers against F. psychrophilum were measured by using micro-titer methods. Fish were then exposed to a bacterial bath to infect them with live F. psychrophilum, and cumulative mortality was monitored. Fish treated with warmed water at 1, 6, and 24 h after immersion in the live bacterial suspension had cumulative mortalities of 36%, 30%, and 18%, respectively, all of which were significantly lower than the cumulative mortality of the naïve control fish (90%). Treated fish also showed high antibody titers against F. psychrophilum in agglutination tests. These results demonstrate that warmed water treatment could not only cure BCWD but also immunize the fish against the causative agent F. psychrophilum.


A comparison of RIRD within chained and multiple schedules in the treatment of vocal stereotypy.
Slaton and Hanley (2016) compared the effects of multiple and chained schedules on stereotypy and item engagement for 2 individuals who exhibited automatically maintained motor stereotypy. Contingent access to motor stereotypy (i.e., chained schedules) was more effective than time-based access (i.e., multiple schedules) at reducing motor stereotypy, increasing item engagement, and establishing stimulus control for both participants. We systematically replicated Slaton and Hanley with 2 participants by a) targeting vocal stereotypy, b) including response interruption and redirection as a treatment component across conditions, c) conducting sessions in the natural environment with teaching assistants as change agents, and d) conducting an analysis of the effective treatment component(s). Chained schedules were more effective for 1 participant, whereas both treatments were effective for the other participant. The component analysis showed that different components were necessary for effective treatment for each participant.


Predictors of blood pressure and hypertension in Tecumseh, Michigan.
Correlates of present blood pressure status are analyzed in 576 subjects (271 males, average age 32 years) in Tecumseh, Michigan. In addition to the current values, anthropometric and blood pressure data are available when the subjects were, on average, 6.9 and 22.2 years of age. Data on 351 fathers and 368 mothers when they were, on average, 32 years old are also available. Moderate, but significant correlations were found between present and past blood pressure and between past weight or skinfold thickness and the present blood pressure. These correlations were much weaker for childhood values than for values at age 22. When multiple regression techniques were used with blood pressure values at age 22 and parental values as independent variables, 40% of the present systolic blood pressure variance could be explained. Prediction of present hypertension status (blood pressure greater than 140 and/or 90 mm Hg) was evaluated by discriminant analysis. Three variables (weight at age 22, systolic blood pressure at age 22, and father's diastolic blood pressure) entered the model and accurately predicted the present blood pressure classification in 89% of the sample. When current blood pressure status was assessed with respect to previous blood pressure classification (upper 20%), family background, and overweight, a gradient of risk for hypertension was found. On the low end of risk was high childhood pressure (risk 19.1% versus 12.1% in the overall population). The highest risk occurred for those with high pressure and overweight at 22 years who also had a family background of high blood pressure (44% versus 12.1%). The prediction of hypertension from young adulthood to the early fourth decade of life is feasible and permits delineation of populations targeted for primary prevention.


Cell Surfaces in Plant-Microorganism Interactions: II. Evidence for the Accumulation of Hydroxyproline-rich Glycoproteins in the Cell Wall of Diseased Plants as a Defense Mechanism.
Enrichment of the cell wall in hydroxyproline-rich glycoprotein is involved in the defense of muskmelon (Cucumis melo) seedlings to Colletotrichum lagenarium, the causative agent of anthracnose. The extent to which this accumulation proceeds may be experimentally modified by treating plants with ethylene or growing them in the presence of free l-trans-hydroxyproline. It appears that the increase in the wall hydroxyproline-rich glycoprotein mediated through ethylene is paralleled by an increasing resistance of the host to the pathogen. Inversely, inhibiting the synthesis of this glycoprotein in diseased plants is strictly correlated to an accelerated and more intense colonization of the host by the pathogen.In both cases, the inverse relationship between the accumulation of hydroxyproline-rich glycoproteins and the ability of the pathogen to develop in the host has been checked by the quantification, in infected tissues, of glucosamine, a characteristic component of chitin-containing fungi.


Effect of low-dose dual blockade of renin-angiotensin system on urinary TGF-beta in type 2 diabetic patients with advanced kidney disease.
We evaluated the renoprotective effects of dual blockade of renin-angiotensin system (RAS) by using a low-dose combination of ACE inhibiter and angiotensin II receptor blocker in type 2 diabetic patients with advanced kidney disease. The amount of proteinuria and the urinary levels of bioassayable TGF-beta1 were used as surrogate markers of renal injury and sclerosis. We performed a prospective double-blinded randomized crossover trial consisting of three 16-week treatment periods with ramipril alone (10 mg/day), candesartan alone (16 mg/day), and ramipril (5 mg/day) plus candesartan (8 mg/day) combination therapy. Twenty-one type 2 diabetic patients with overt nephropathy with a 24 h urinary protein excretion rate (UPER) of > 1.0 g/24 h and creatinine clearance (Ccr) of 30 to 59 ml/min/1.73 m2 completed the entire study. Subjects consisted of 10 female and 11 male patients with a mean age of 49 +/- 8 years and duration of diabetes ranging from 4 to 13 years. At baseline, 24-h blood pressures (BPs) were 133 +/- 6/81 +/- 7 mmHg, Ccr 40.6 +/- 4.1 ml/min/1.73 m2, 24-h UPER 4.1 +/- 1.9 g/24 h, and urinary TGF-beta1 level 28.4 +/- 16.1 pg/mg creatinine (cr). Although there was no comparable change in BP and plasma/urinary biochemical parameters, 24-h UPER was significantly reduced by the combination therapy (2.9 +/- 1.4 g/24 h) compared with that of ramipril (3.5 +/- 1.8 g/24 h) and of candesartan (3.3 +/- 2.0 g/24 h) single therapy (P < 0.05). Urinary TGF-beta1 level was reduced in all three therapies compared with that of the control (28.4 +/- 16.1 pg/mg cr) (P < 0.05). However, the combination therapy showed the most significant change (combination 19.6 +/- 10.6 pg/mg cr; ramipril 24.7 +/- 13.3 pg/mg cr; candesartan; 23.4 +/- 11.7 pg/mg cr). No significant or irreversible adverse effect was observed in the 21 patients who completed the entire study. The dual blockade of RAS with low-dose ramipril plus candesartan was found to be safe and offered additive benefits with respect to reducing proteinuria and urinary TGF-beta1 excretion in diabetic patients with advanced kidney disease. These benefits were evident as compared with single ramipril and candesartan therapies at doses two-fold greater. Further study on the dose-titration is mandatory in terms of safety and especially for maximizing renoprotection in this patient population.


New Coronavirus Variants are Creating More Challenges to Global Healthcare System: A Brief Report on the Current Knowledge.
The coronavirus is naturally mutating over time and producing new variants. Some of them are more contagious and destructive than previous strains. Also, some variants are capable of therapeutic escaping. Earlier SARS-CoV-2 variants proved that some are supercritical, and newly mutated strains are creating new challenges to the global healthcare systems. Here we aimed to evaluate different coronavirus variants and associated challenges for healthcare systems. We searched for information online and on the PubMed, Scopus, and Embase databases. We found the wild-type virus is more sensitive for neutralization and more controllable than newer variants. The Delta and Omicron variants are more highly transmissible than Alpha, Beta, and Gamma variants. Also, few strains are resistant to neutralization. Therefore, there is a chance of reinfection among the vaccinated population. The transmissibility and resistance of the recently identified Omicron variant is still unclear. The Delta variant is the most dangerous among all variants due to its high transmissibility, disease severity, and mortality rate. For poor and developing countries, oxygen supply, medication, vaccination, and device supply are challenging during epidemic waves. Slowing down the transmission, mass vaccination, vaccine redesign, re-compiling action plans, and following safety guidelines can be effective solutions to the new challenges.


A method for analyzing backward recurrence time data on residential mobility.
Data on duration of current residence are used to estimate models of duration-dependent residential mobility rates. "We use the theory of backward recurrence times in renewal processes to infer the hazard rate of residential mobility from the density of the duration of current residence. We demonstrate that the inferences made using the asymptotic solution of the density of the backward recurrence times will be severely biased if the renewal process has not reached stability. We present an unbiased finite time solution and estimate univariate and multivariate models of residential mobility rates using 1980 U.S. census data on duration of current residence. These models include mover-stayer models represented by mixture densities. The multivariate analysis shows that the most important covariates of residential mobility are age, homeownership, race, and presence of school-aged children."


Laparoscopic pyelocaliceal diverticula ablation.
Pyelocaliceal diverticula are cystic urine collections within the renal parenchyma communicating with the collecting system. They occur in 0.2% to 0.5% of the population and often contain calculi. Flank pain is the most common complaint, and most lesions are diagnosed by intravenous urography. In the past, treatment has required open renal surgery, with potential loss of renal function, or prolonged percutaneous procedures. We propose surgical treatment of caliceal diverticula by laparoscopic unroofing and fulguration. The benefits include renal preservation as well as decreased morbidity and an earlier return to work for the patient.


Single-Cell Transcriptome Reveals the Metabolic and Clinical Features of a Highly Malignant Cell Subpopulation in Pancreatic Ductal Adenocarcinoma.
Background: Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor with a high mortality rate. PDAC exhibits significant heterogeneity as well as alterations in metabolic pathways that are associated with its malignant progression. In this study, we explored the metabolic and clinical features of a highly malignant subgroup of PDAC based on single-cell transcriptome technology. Methods: A highly malignant cell subpopulation was identified at single-cell resolution based on the expression of malignant genes. The metabolic landscape of different cell types was analyzed based on metabolic pathway gene sets. In vitro experiments to verify the biological functions of the marker genes were performed. PDAC patient subgroups with highly malignant cell subpopulations were distinguished according to five glycolytic marker genes. Five glycolytic highly malignant-related gene signatures were used to construct the glycolytic highly malignant-related genes signature (GHS) scores. Results: This study identified a highly malignant tumor cell subpopulation from the single-cell RNA sequencing (scRNA-seq) data. The analysis of the metabolic pathway revealed that highly malignant cells had an abnormally active metabolism, and enhanced glycolysis was a major metabolic feature. Five glycolytic marker genes that accounted for the highly malignant cell subpopulations were identified, namely, EN O 1, LDHA, PKM, PGK1, and PGM1. An in vitro cell experiment showed that proliferation rates of PANC-1 and CFPAC-1 cell lines decreased after knockdown of these five genes. Patients with metabolic profiles of highly malignant cell subpopulations exhibit clinical features of higher mortality, higher mutational burden, and immune deserts. The GHS score evaluated using the five marker genes was an independent prognostic factor for patients with PDAC. Conclusion: We revealed a subpopulation of highly malignant cells in PDAC with enhanced glycolysis as the main metabolic feature. We obtained five glycolytic marker gene signatures, which could be used to identify PDAC patient subgroups with highly malignant cell subpopulations, and proposed a GHS prognostic score.


COVID-19 vasculitis and novel vasculitis mimics.
COVID-19 has been occasionally linked to histologically confirmed cutaneous vasculitis and a Kawasaki-like vasculitis, with these entities generally having minimal or no lung involvement and a good prognosis. Unlike these vasculitis types, patients with severe COVID-19 pneumonia can develop cutaneous vasculitis-like lesions and systemic arterial and venous thromboemboli, including cryptogenic strokes and other vasculopathy features. Proposed underlying mechanisms for these severe manifestations have encompassed immune dysregulation, including an anti-phospholipid syndrome-like state, complement activation, viral dissemination with direct systemic endothelial infection, viral RNAaemia with immunothrombosis, clotting pathway activation mediated by hypoxaemia, and immobility. In this Viewpoint, we highlight how imaging and post-mortem findings from patients with COVID-19 indicate a novel thrombosis in the pulmonary venous territory distal to the alveolar capillary bed, a territory that normally acts as a clot filtration system, which might represent an unappreciated nidus for systemic microembolism. Additionally, we suggest that this mechanism represents a novel vasculitis mimic related to COVID-19 that might lead to cryptogenic strokes across multivessel territories, acute kidney injury with haematuria, a skin vasculitis mimic, intestinal ischaemia, and other organ ischaemic manifestations. This finding is supported by pathological reports of extensive pulmonary venular thrombosis and peripheral organ thrombosis with pauci-immune cellular infiltrates. Therefore, severe COVID-19 pneumonia with extensive pulmonary intravascular coagulopathy might help to explain the numerous systemic complications of COVID-19, in which the demonstration of direct organ infection has not adequately explained the pathology.


Psychosomatic symptoms in adolescent twins. Longitudinal twin study with special reference to psychosomatic symptoms.
In a cohort study of 234 twin pairs followed from pregnancy to 12-20 years of age the psychosomatic symptoms of adolescents were inquired from their parents. Girls had symptoms more often than boys. Intrapair concordances were high. The mothers' favorite children had psychosomatic complaints more often than the father's favorites or those who were equally close to each parent. Psychosomatic complaints were more frequent in the submissive members of twin pairs and nervous symptoms in the dominant ones.


Pediatric lupus nephritis: more options, more chances?
Lupus nephritis (LN) is more common and severe in childhood-onset systemic lupus erythematosus (SLE) than in adults. It is one of the major causes of acute kidney injury (AKI) and chronic kidney disease (CKD) in children. Steroid therapy has been used as the first-line treatment for SLE since 1970, and has improved the survival of SLE patients from ∼ 50% to >80%. Over the years many immunosuppressive drugs, including pulse methylprednisolone, oral cyclophosphamide, pulse intravenous cyclophosphamide, mycophenolate mofitil, rituximab, and tacrolimus, have been combined with prednisolone, further improving survival rates to 90%-95%. However, the effectiveness of these drugs is still uncertain, as most seem very good in the beginning, but in studies examining longer-term follow-up the remission of disease does not remain. Fatal infection is still a major complication of aggressive chemotherapy, and the potential benefits as well as adverse events from each drug need to be considered. Induction of remission is the major aim of therapy, with safe and effective maintenance therapy for long-term remission. The survival rates of many published studies vary widely because of differences in patients and treatment modalities, severity of disease, renal histopathology, racial factors, and duration of follow-up. Finding the optimal treatment for SLE and related co-morbidities is highly challenging, and will likely involve a complex combination of different drugs for different patients in the search for giving them an opportunity to be free from this debilitating disease.


Improved characterisation of among-lineage rate variation in cetacean mitogenomes using codon-partitioned relaxed clocks.
There is extensive variation in substitution rates among metazoan mitochondrial genomes, including differences among lineages and among sites. Differences in substitution rates among lineages are routinely taken into account in molecular phylogenetic and dating analyses. However, this is rarely the case for differences in the lineage-specific patterns of rate variation among sites. We analysed an alignment of 32 cetacean mitogenomes using a partitioned relaxed-clock approach, in which a separate relaxed-clock model was applied to each of the three codon positions of the protein-coding genes. By comparing Bayes factors, we found overwhelming support for this model compared with a strict-clock model and less-complex models comprising fewer relaxed clocks. Our analyses reveal the presence of substantial rate heterogeneity among cetacean lineages, and that these patterns of variation differ between codon positions. However, we find no evidence of mitochondrial rate autocorrelation throughout the cetacean phylogeny. Our study confirms the feasibility of applying a partitioned relaxed-clock model to mitogenomic data, and suggests that molecular phylogenetic and dating analyses may be improved by the application of these models.


[Hepatitis C immunology].
This review summarizes what is currently known about the cellular and humoral immune responses to hepatitis C virus. The results of viral protein immunogenicity studies reported so far are analyzed, and points of controversy about the immunology and immunopathology of hepatitis C are discussed. A body of evidence supports the existence in hepatitis C virus-infected subjects of strong humoral and cellular immune responses. HCV Core, NS3 and NS4 proteins are the most immunogenic antigens for B cells and HLA class II-restricted CD4+ T cells. For its part, liver-infiltrating CD8+ CTL recognize epitopes within the Core, E1, E2/NS1 and NS2 proteins in a HLA class I restricted manner. CTL responses to HCV Core, NS3, NS4 and NS5 have been detected in peripheral blood of patients chronically infected with HCV. Although these B and T cell responses may contribute to clear the virus, in most cases they are unable to resolve chronic HCV infections. No protective B or T cell epitope has been found yet. It is becoming clearer that the immune response plays a fundamental role in the pathogenesis of liver disease in hepatitis C patients.


Detection of splicing events and multiread locations from RNA-seq data based on a geometric-tail (GT) distribution of intron length.
RNA sequencing (RNA-seq) measures gene expression levels and permits splicing analysis. Many existing aligners are capable of mapping millions of sequencing reads onto a reference genome. For reads that can be mapped to multiple positions along the reference genome (multireads), these aligners may either randomly assign them to a location, or discard them altogether. Either way could bias downstream analyses. Meanwhile, challenges remain in the alignment of reads spanning across splice junctions. Existing splicing-aware aligners that rely on the read-count method in identifying junction sites are inevitably affected by sequencing depths. The distance between aligned positions of paired-end (PE) reads or two parts of a spliced read is dependent on the experiment protocol and gene structures. We here proposed a new method that employs an empirical geometric-tail (GT) distribution of intron lengths to make a rational choice in multireads selection and splice-sites detection, according to the aligned distances from PE and sliced reads. GT models that combine sequence similarity from alignment, and together with the probability of length distribution, could accurately determine the location of both multireads and spliced reads.


Bupivacaine digital blocks: how long is the pain relief and temperature elevation?
The goals of this study are threefold: (1) to determine what effect epinephrine has on the duration of bupivacaine finger block anesthesia; (2) to see whether the duration of action of bupivacaine on digital pain relief is the same duration as numbness to touch/pressure; and (3) to assess the fingertip temperature changes that result from bupivacaine digital blocks. The ring fingers of both hands of 44 volunteers were randomized to injection of bupivacaine with or without 1:200,000 epinephrine. The durations of time for digits to return to normal pain, touch, pressure sensation, and fingertip temperature were measured and recorded. There were three main findings: (1) the pain block of bupivacaine lasts only half as long (15 hours) as the return to normal sensation (30 hours); (2) the effect of adding epinephrine to bupivacaine prolongs the duration of pain relief in a finger block for only an additional 1.5 hours; (3) in addition to pain relief, bupivacaine finger blocks cause fingertip hyperemia with consistent significant fingertip temperature elevation that lasts 15 hours. The duration of bupivacaine pain relief is the clinically important factor that needs to be reported in bupivacaine trials. Patients should be informed that the return of pain will occur much sooner than the return of normal sensation. Adding epinephrine to bupivacaine does not add a clinically significant length of time to pain relief. Bupivacaine finger blocks provide prolonged hyperemia and pain block to fingertips, which may be useful in the treatment of acute frostbite. Therapeutic, I.


Efficacy of an Interdisciplinary Intensive Outpatient Program in Treating Combat-Related Traumatic Brain Injury and Psychological Health Conditions.
Background: Since 2000, over 413,000 US service members (SM) experienced at least one traumatic brain injury (TBI), and 40% of those with in-theater TBIs later screened positive for comorbid psychological health (PH) conditions, including post-traumatic stress disorder (PTSD), depression, and anxiety. Many SMs with these persistent symptoms fail to achieve a recovery that results in a desirable quality of life or return to full duty. Limited information exists though to guide treatment for SMs with a history of mild TBI (mTBI) and comorbid PH conditions. This report presents the methods and outcomes of an interdisciplinary intensive outpatient program (IOP) in the treatment of SMs with combat-related mTBI and PH comorbidities. The IOP combines conventional rehabilitation therapies and integrative medicine techniques with the goal of reducing morbidity in multiple neurological and behavioral health domains and enhancing military readiness. Methods: SMs (n = 1,456) with residual symptoms from mTBI and comorbid PH conditions were treated in a 4-week IOP at the National Intrepid Center of Excellence (NICoE) at Walter Reed National Military Medical Center (WRNMMC). The IOP uses an interdisciplinary, holistic, and patient-centric rehabilitative care model. Interdisciplinary teams provide a diagnostic workup of neurological, psychiatric, and existential injuries, and from these assessments, individualized care plans are developed. Treatment response was assessed using the Neurobehavioral Symptom Inventory (NSI), PTSD Checklist-Military Version (PCL-M), Satisfaction With Life Scale (SWLS), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Epworth Sleepiness Scale (ESS), and Headache Impact Test-6 (HIT-6) and administered at admission, discharge, and at 1, 3, and 6 months post-discharge. Findings: Following treatment in the IOP, the symptomatic patients had statistically significant and clinically meaningful improvements across all outcome measures. The largest effect size was seen with GAD-7 (r = 0.59), followed by PHQ-8 (r = 0.56), NSI (r = 0.55), PCL-M (r = 0.52), ESS (r = 0.50), SWLS (r = 0.49), and HIT-6 (r = 0.42). In cross-sectional follow ups, the significant improvements were sustained at 1, 3, and 6 months post-discharge. Interpretation: This report demonstrates that an interdisciplinary IOP achieves significant and sustainable symptom recovery in SMs with combat-related mTBI and comorbid PH conditions and supports the further study of this model of care in complex medical conditions.


High-Mobility Sm-Doped Bi2 Se3 Ferromagnetic Topological Insulators and Robust Exchange Coupling.
High-mobility (Smx Bi1-x )2 Se3 topological insulators (with x = 0.05) show a Curie temperature of about 52 K, and the carrier concentration and Fermi wave vector can be manipulated by intentional Te introduction with no significant influence on the Curie temperature. The origin of the ferromagnetism is attributed to the trivalent Sm dopant, as confirmed by X-ray magnetic circular dichroism and first-principles calculations. The carrier concentration is on the order of 10(19) cm(-3) and the mobility can reach about 7200 cm(2) V(-1) s(-1) with pronounced Shubnikov-de Haas oscillations.


The impact of implementing an educational intervention to enhance a family-oriented approach in specialised palliative home care: A quasi-experimental study.
Healthcare providers' beliefs, attitudes, experiences and knowledge, which guide the care they deliver, are the key factors influencing the quality of palliative care. Education and coaching innovation are needed to translate research outcomes and adopt evidence-based nursing care into practice. To evaluate the impact of an advanced educational and coaching programme in a family systems' nursing approach for palliative care nurses in a home-care setting. A quasi-experimental study using qualitative data from open-ended questions to augment the quantitative outcome study that included a single-group, pre- and post-test design. A total population sample of nurses was recruited from a specialised palliative home care unit at a university hospital. The study utilised two self-reported questionnaires. There was a statistically significant increase in the nurses' critical appraisal of clinical nursing practice related to family nursing after participation in the educational programme than before. No statistical difference was found in items related to nurses' experience of the interaction and reciprocity in the nurse-family relationship after participation in the programme than compared to before or in nurses' cancer-related beliefs. However, there was an overall significant positive change found in attitudes towards families in the total score of the Family Practice Scale. Nurses were also more positive about the further development of their knowledge and skills in advanced family nursing evident in the qualitative data. An advanced educational intervention programme was successful in improving the nurses' knowledge, skills, satisfaction and confidence in relation to applied family nursing approach within the context of caring for families affected by advanced/final stage cancer. However, further refinement of the implementation process is needed to enhance family care improvement and the nurses' professional development in advanced family nursing in specialised palliative care.


Ethical and social issues facing obstetricians in low-income countries.
A review of publications on ethical and social issues from low-income countries was done with the aim of highlighting the major ethical and social issues facing obstetricians in these countries. Low-income countries were identified using the World Health Organization income group classification of member nations. Obstetricians in low-income countries face a wide range of special social and ethical issues that reflect the peculiarities of their practice environment characterized by poverty, low education, deep attachment to tradition and culture, low social status of women, and high levels of physician's paternalism.


[Helicobacter pylori eradication therapy for peptic ulcer disease].
Meta-analyses showed that Helicobacter pylori eradication therapy was effective for healing and prevention of recurrence of peptic ulcers in H. pylori-positive patients and that treatment of H. pylori infection was more effective than antisecretory non-eradicating therapy (with or without long-term maintenance antisecretory therapy) in preventing recurrent bleeding from peptic ulcer. H. pylori eradication therapy is effective for prevention of development of NSAID-ulcers in NSAID-naïve patients. For prevention of recurrence of NSAID-ulcers, therapy with proton pump inhibitor is effective.


The logistic model for predicting the non-gonoactive Aedes aegypti females.
To estimate, using logistic regression, the likelihood of occurrence of a non-gonoactive Aedes aegypti female, previously fed human blood, with relation to body size and collection method. This study was conducted in Monterrey, Mexico, between 1994 and 1996. Ten samplings of 60 mosquitoes of Ae. aegypti females were carried out in three dengue endemic areas: six of biting females, two of emerging mosquitoes, and two of indoor resting females. Gravid females, as well as those with blood in the gut were removed. Mosquitoes were taken to the laboratory and engorged on human blood. After 48 hours, ovaries were dissected to register whether they were gonoactive or non-gonoactive. Wing-length in mm was an indicator for body size. The logistic regression model was used to assess the likelihood of non-gonoactivity, as a binary variable, in relation to wing-length and collection method. Of the 600 females, 164 (27%) remained non-gonoactive, with a wing-length range of 1.9-3.2 mm, almost equal to that of all females (1.8-3.3 mm). The logistic regression model showed a significant likelihood of a female remaining non-gonoactive (Y=1). The collection method did not influence the binary response, but there was an inverse relationship between non-gonoactivity and wing-length. Dengue vector populations from Monterrey, Mexico display a wide-range body size. Logistic regression was a useful tool to estimate the likelihood for an engorged female to remain non-gonoactive. The necessity for a second blood meal is present in any female, but small mosquitoes are more likely to bite again within a 2-day interval, in order to attain egg maturation. The English version of this paper is available too at: http://www.insp.mx/salud/index.html.


Postnatal development of corticospinal axon terminal morphology in the cat.
The corticospinal system undergoes important postnatal development, leading to the mature topography and specificity of connections. The purpose of this study was to determine the time-course of development of corticospinal axonal branching and varicosity density within the cervical gray matter. Corticospinal neurons were labeled after small injections of the anterograde tracer biotinylated dextran amine into the primary motor cortex of cats. Tracer injection and transport times were adjusted to examine labeling at 25, 35, 55, and 75 days and in adults. We measured the numbers and lengths of nonreconstructed terminal and preterminal branches and the numbers and locations of axon varicosities. We found significant age-dependent increases in all morphologic measures. At 25 days, corticospinal axon branching was sparse, with only a few scattered varicosities. By day 35, the mean number of branches, varicosities per branch, and varicosity density increased. Several morphologic measures did not increase between day 35 and 55, but further changes occurred between 55 days and maturity. Beginning around day 55, there was extensive development of small terminal axon branches with high densities of varicosities. We also found, by using spatial point analysis, that there was an age-dependent increase in varicosity clustering. Our results show for the first time that terminal and preterminal corticospinal axon branches increase in complexity during a protracted early postnatal period. This developmental period extended beyond the early postnatal period of activity-dependent refinement of the topography of terminations. Comparison with the time-course of maturation of the cortical motor representation revealed development of substantial, albeit incomplete, branching and varicosity density of CS axons before cortical motor circuits effectively drive their spinal targets.


Contouring by electronic speckle pattern interferometry with quadruple-beam illumination.
We present a new arrangement for contouring by electronic speckle pattern interferometry with four illumination beams, thereby making it unnecessary to move anything during the.


Modulating the Global Response Regulator, LuxO of V. cholerae Quorum Sensing System Using a Pyrazine Dicarboxylic Acid Derivative (PDCApy): An Antivirulence Approach.
Vibrio cholerae is a Gram-negative pathogen which causes acute diarrhoeal disease, cholera by the expression of virulence genes through quorum sensing (QS) mechanism. The QS circuit of V. cholerae is controlled by the global quorum regulator, LuxO, which at low cell density (LCD) state produces major virulence factors such as, toxin co-regulated pilus (TCP) and cholera toxin (CT) to mediate infection. On the contrary, at the high cell density (HCD) state the virulent genes are downregulated and the vibrios are detached from the host intestinal epithelial cells, promoted by HapA protease. Hence, targeting the global regulator LuxO would be a promising approach to modulate the QS to curtail V. cholerae pathogenesis. In our earlier studies, LuxO targeted ligand, 2,3 pyrazine dicarboxylic acid (PDCA) and its derivatives having desired pharmacophore properties were chemically synthesized and were shown to have biofilm inhibition as well as synergistic activity with the conventionally used antibiotics. In the present study, the QS modulatory effect of the PDCA derivative with pyrrolidine moiety designated as PDCApy against the V. cholerae virulence gene expression was analyzed at various growth phases. The data significantly showed a several fold reduction in the expression of the genes, tcp and ct whereas the expression of hapR was upregulated at the LCD state. In addition, PDCApy reduced the adhesion and invasion of the vibrios onto the INT407 intestinal cell lines. Collectively, our data suggest that PDCApy could be a potential QS modulator (QSM) for the antivirulence therapeutic approach.


Provider Perspectives on Choosing Prolonged Exposure or Cognitive Processing Therapy for PTSD: A National Investigation of VA Residential Treatment Providers.
As part of a longitudinal mixed-methods investigation on implementation of two evidence-based psychotherapies (EBPs) for Posttraumatic Stress Disorder, 164 mental health providers from 38 Department of Veterans Affairs (VA) residential treatment programs across the U.S. were asked questions about their decision-making for using Prolonged Exposure and Cognitive Processing Therapy. Many providers viewed both EBPs as equally efficacious and encouraged veterans to decide for themselves which treatment they wished to engage in. Some providers said that it was hard to know which EBP would be the most effective for a given patient, and that occasionally they started work with a veteran thinking that a particular EBP would work and were surprised when the veteran did not receive the full potential benefit of the intervention. Other providers noted that their decision-making regarding which EBP to use depended on the type and nature of the veterans' index trauma, memory of the trauma, and traumatic stress symptoms (e.g., fear versus guilt). Additional factors that impacted the choice of EBP included whether the patient already had one of the treatments before or if a provider deemed one as more compatible with their previous training. Implications for clinical practice as well as the design and improvement of training and implementation efforts are discussed.


7-Tesla MRI Evaluation of the Knee, 25 Years after Cartilage Repair Surgery: The Influence of Intralesional Osteophytes on Biochemical Quality of Cartilage.
To evaluate the morphological and biochemical quality of cartilage transplants and surrounding articular cartilage of patients 25 years after perichondrium transplantation (PT) and autologous chondrocyte transplantation (ACT) as measured by ultra-high-field 7-Tesla (7T) magnetic resonance imaging (MRI) and to present these findings next to clinical outcome. Seven PT patients and 5 ACT patients who underwent surgery on the femoral condyle between 1986 and 1996 were included. Patient-reported outcome measures (PROMs) were assessed by the clinical questionnaires: Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC), and Visual Analogue Scale (VAS) for knee pain. The morphological (MOCART score) and biochemical quality (glycosaminoglycans [GAGs] content and collagen integrity) of cartilage transplants and surrounding articular cartilage were analyzed by 7T MRI. The results of the PT and ACT patients were compared. Finally, a detailed morphological analysis of the grafts alone was performed. No statistically significant difference was found for the PROMs and MOCART scores of PT and ACT patients. Evaluation of the graft alone showed poor repair tissue quality and high prevalence of intralesional osteophyte formation in both the PT and ACT patients. Penetration of the graft surface by the intralesional osteophyte was related to biochemically damaged opposing tibial cartilage; GAG content was significantly lower in patients with an osteophyte penetrating the graft surface. Both PT and ACT patients have a high incidence of intralesional osteophyte formation 25 years after surgery. The resulting biochemical damage to the opposing tibial cartilage might be dependent on osteophyte morphology.


[Effect of Helicobacter pylori eradication from patients with gastritis evaluated by the pathological grading and cell proliferation related factors].
We used Image Analysis Processor to clarify the relation ship between cell proliferation, apoptosis and inflammation before and after eradication in H. pylori gastritis. Fifty-two patients with H. pylori gastritis were diagnosed using the Rapid Urease Test under endoscopical and histological examination. The grading of gastritis was determined by the Updated Sydney System. While the effects of Ki-67 on epithelial cell proliferation were examined by immunohistochemistry using Image Analysis Processor, and apoptosis in epithelial cells was counted after staining by in situ TDT. H. pylori density, the number of neutrophils, mononuclear cell, and number of lymphoid follicles had significantly decreased after eradication. Ki-67 labeling index significantly decreased from 11.74 percent to 0.98 percent after eradication (p < 0.0001). The apoptotic index had also decreased after eradication, but with a lack of significant difference (p < 0.06). These data suggest that H. pylori gastritis was remarkably ameliorated by eradication, have led to being capable of improving epithelial cell damage, and activity of proliferative cells and apoptotic cells were becoming normalization.


A comparison of time-and-motion and self-reporting methods of work measurement.
To compare results obtained from a time-and-motion study with those obtained using self-reporting. Nurse executives are often required to provide additional patient care services with limited personnel resources. As a result, nurse executives must evaluate the appropriate allocation of nursing personnel resources. Work measurement may be used to evaluate personnel allocation. Multiple measurement approaches are available, but few studies have compared these methods. Eight nurses were observed by a single observer during five shifts (or approximately 40 hours per nurse). After completion of the time-and-motion study, participants were to self-report their work activities during their ensuing five shifts. Mixed-effects analysis of variance was used to determine the significance of the work measurement method on percentage of total time, number of activities, and mean time per activity by activity category. Two hundred ninety hours of time-and-motion study observations and 338 hours of self-report data were available for analysis. Comparable amounts of total time were reported within the various activity categories using time-and-motion and self-reporting methods. In terms of number of activities reported, a significantly higher number of activities were reported using time-and-motion. As a result, mean activity times were significantly longer using the self-reporting method compared with time-and-motion. Nurse executives should consider continuous self-reporting as a low-cost means of quantifying allocation of time among nursing personnel. Self-reporting, however, is not recommended for estimating the total number of activities or the mean time per activity because of perceptual differences between participants of what constitutes an activity.


Aortic diameter assessment by cardiovascular magnetic resonance: do we really need contrast enhanced images?
Cardiovascular magnetic resonance (CMR) is widely used for aortic diameter assessment but there is no consensus on the sequence or cardiac cycle phase in which the measures should be taken. The most used sequence is contrast-enhanced-magnetic-resonance-angiography (angiography), usually non-ECG-triggered. An alternative is a navigated 3D-whole-heart-steady-state-free-precession sequence which is contrast-free and breath- and ECG-gated (mostly diastolic gating), producing very sharp anatomical rendering. Nonetheless, its routine use has not yet spread. Our aim was evaluating aortic diameters by a systolic-gated 3D and put additional effort in the validation of diastolic-gated 3D as alternative to angiography. We retrospectively analysed 30 patients scheduled for routine Angiography. We measured the aorta at 9 standard positions by three different sequences (angiography, 3D-diastole and 3D-systole) and compared the diameters obtained by calculating the differences and by paired t-test analysis. Diameters by 3D-systole were larger than by 3D-diastole and angiography (P<0.01). In the ascending aorta we found the maximal differences between systole and diastole and between systole and angiography which were 1.7± SD 1.02 mm and 1.5± SD 1.07 mm respectively. There was no significant difference between diastolic and angiography measurements (mean difference 0.2± SD 0.16 mm, P not significant). Our results support the use of navigated 3D-whole-heart CMR to evaluate aortic diameters. Systolic-gated 3D produces larger diameter, especially in the ascending aorta.


Reaction Dynamics Following Ionization of Ammonia Dimer Adsorbed on Ice Surface.
The ice surface provides an effective two-dimensional reaction field in interstellar space. However, how the ice surface affects the reaction mechanism is still unknown. In the present study, the reaction of an ammonia dimer cation adsorbed both on water ice and cluster surface was theoretically investigated using direct ab initio molecular dynamics (AIMD) combined with our own n-layered integrated molecular orbital and molecular mechanics (ONIOM) method, and the results were compared with reactions in the gas phase and on water clusters. A rapid proton transfer (PT) from NH3(+) to NH3 takes place after the ionization and the formation of intermediate complex NH2(NH4(+)) is found. The reaction rate of PT was significantly affected by the media connecting to the ammonia dimer. The time of PT was calculated to be 50 fs (in the gas phase), 38 fs (on ice), and 28-33 fs (on water clusters). The dissociation of NH2(NH4(+)) occurred on an ice surface. The reason behind the reaction acceleration on an ice surface is discussed.


Effect of oxidation on the activity of angiotensin converting enzyme in the rat kidney, heart and brain.
The activities of angiotensin converting enzyme (ACE) in crude extracts of renal cortex, heart and brain of the rat were increased when the oxidizing agent diamide was added to the extracts and then the activity determined. By pretreatment of the extracts with 10 mM diamide, the activities of ACE in the extracts of heart, brain and renal cortex were about 500, 290 and 240% of the control value, determined without the diamide-pretreatment, respectively. In the lung and aorta, increments in the activity after oxidation were less than 20% of the control. No such increase was observed in the plasma. Similar results were obtained when the extracts were exposed to O2. The activity was also increased by oxidation with diamide and O2, when an extract of the human renal cortex was used. Thus, the activity of ACE in the kidney, heart and brain can be increased by oxidation.


Deciphering the Potential of Rhizobium pusense MB-17a, a Plant Growth-Promoting Root Endophyte, and Functional Annotation of the Genes Involved in the Metabolic Pathway.
Plant growth-promoting rhizobacteria (PGPR) are root endophytic bacteria used for growth promotion, and they have broader applications in enhancing specific crop yield as a whole. In the present study, we have explored the potential of Rhizobium pusense MB-17a as an endophytic bacterium isolated from the roots of the mung bean (Vigna radiata) plant. Furthermore, this bacterium was sequenced and assembled to reveal its genomic potential associated with plant growth-promoting traits. Interestingly, the root endophyte R. pusense MB-17a showed all essential PGPR traits which were determined by biochemical and PGPR tests. It was noted that this root endophytic bacterium significantly produced siderophores, indole acetic acid (IAA), ammonia, and ACC deaminase and efficiently solubilized phosphate. The maximum IAA and ammonia produced were observed to be 110.5 and 81 μg/ml, respectively. Moreover, the PGPR potential of this endophytic bacterium was also confirmed by a pot experiment for mung bean (V. radiata), whose results show a substantial increase in the plant's fresh weight by 76.1% and dry weight by 76.5% on the 60th day after inoculation of R. pusense MB-17a. Also, there is a significant enhancement in the nodule number by 66.1% and nodule fresh weight by 162% at 45th day after inoculation with 100% field capacity after the inoculation of R. pusense MB-17a. Besides this, the functional genomic annotation of R. pusense MB-17a determined the presence of different proteins and transporters that are responsible for its stress tolerance and its plant growth-promoting properties. It was concluded that the unique presence of genes like rpoH, otsAB, and clpB enhances the symbiosis process during adverse conditions in this endophyte. Through Rapid Annotation using Subsystem Technology (RAST) analysis, the key genes involved in the production of siderophores, volatile compounds, indoles, nitrogenases, and amino acids were also predicted. In conclusion, the strain described in this study gives a novel idea of using such type of endophytes for improving plant growth-promoting traits under different stress conditions for sustainable agriculture.


Characterization of a collagenolytic enzyme released from wounded planarians Dugesia japonica.
Planarians (Dugesia japonica) were cultured on gels of type I bovine collagen under various conditions that damaged the worms to test the possibility that the animals secrete a collagenolytic enzyme when they are wounded. The planarians were shown to release a potent collagenolytic enzyme around their body when the animals received damage-inducing treatments such as heating at 37 degrees C, freezing and thawing, and amputation. This release of the enzyme did not require the synthesis of RNA or protein. Isolated planarian cells did not release the enzyme even when cultured at 37 degrees C. The collagenolytic activity was found in the supernatants, but not in the insoluble fraction prepared from disintegrated tissues of the wounded animals. These results indicated that the enzyme was stored extracellularly in the normal planarian body. Partial purification of the enzyme and the action spectra of various protease inhibitors on the enzyme showed that the enzyme was a neutral type I collagen-degrading 40 kDa metalloproteinase. We named this enzyme the planarian collagenase.


Direct embryotoxicity of chromium (III) exposure during preimplantation development.
Chromium in its trivalent form (chromium (III)) is an essential component of a balanced diet, and its deficiency disturbs glucose and lipid metabolism in humans and animals. The prevailing view is that chromium (III) is notably less toxic than chromium (VI), which is genotoxic and carcinogenic. Thus, the biotransformation of environmental chromium (VI) to chromium (III) is a promising and environmentally friendly detoxification method. However, increasing evidence suggests that chromium (III) induces considerable cytotoxicity. However, the toxicity of chromium (III) to early embryos remains largely unknown. In the present study, we used in vitro fertilization (IVF) to produce mouse embryos and identified the direct embryotoxicity of chromium (III). On exposure to high concentrations of CrCl3, blastocyst formation almost completely failed and a large proportion of embryos were arrested at the 2- to 4-cell stage. At low concentrations of CrCl3, IVF embryos showed a significant decrease in blastocyst formation, reduced total cell numbers, aberrant lineage differentiation, increased oxidative stress, and apoptosis. We also found that chromium (III) exposure during the preimplantation stage, even at low concentrations, led to impaired post-implantation development. Thus, our study substantiates the direct embryotoxicity of chromium (III) during preimplantation development and prolonged impairment of development potential. The results further highlight the potential adverse effects of chromium (III) on public reproductive health with respect to increased environmental enrichment of and dietary supplementation with chromium (III) complexes.


Got curiosity?
The newest scientific models of decision-making suggest that the way we actually decide to do something is different from the story we put on it later. Organizations think that way, too. The real process of decision-making is hidden. Management is complex--and a key tool is curiosity. A critical question would be: "What experience are we creating?" When you get curious, separate what you notice from the story you tell yourself about it--even if the story is true. Look for the meaningful experience: your own, your employees', your customers', your physicians'. The essential act of management is to notice, to not look away.


Cytokines in Schizophrenia: Hope or Hype?
Although there is a cumulative evidence for the inflammation pathophysiology in schizophrenia, it has not been conclusively proven yet. One reason for this is the lack of studies that have controlled for major confounding factors such as obesity, smoking, antipsychotic use, and stress. The studies in which the major confounding factors were controlled were done in subjects in acute relapse and in treatment-resistant schizophrenia. To date, no studies have been done in stable outpatients with schizophrenia controlling for major confounding factors. Data on cerebrospinal fluid cytokines in large sample independent of confounding factors are also lacking. The efficacy signal from anti-inflammatory medications in schizophrenia has been modest. In this study, the inconsistent and nonvalidated cytokine findings independent of the confounding factors are discussed.


[The feed value in growing pigs of a new cultivar of field beans (Vicia faba L.) supplemented with DL-methionine or DL-methionine-hydroxyanalog].
A basal control mixture of barley, soy bean meal and soy bean oil was replaced by 25% of the new field bean-cultivar 'Divine' and the resulting two mixtures were supplemented with minerals, trace elements, vitamins and amino acids according to the ideal protein concept. The control diet was adjusted with DL-methionine (DL-Met), the field bean mixture either with DL-Met or DL-methionine-hydroxyanalogue (DL-MHA) assuming biological equivalence on a molar basis for both supplements. The three experimental diets were fed to growing pigs (35-40 kg bwt.). Spontaneous urine samples were analysed separately for determining parameters that characterize the acid-base status of the pigs. There were no significant differences between experimental groups in nutrient digestibilities. The level of bacterially fermentable substances was increased in the diets containing field beans. The field beans contained 14 mg ME/kg DM. There were no significant (p < 0,05) differences in N- and mineral-retentions (Ca, P, Na, K) between the treatments. The stronger alkalinity found in urine after feeding the field bean mixtures resulted from a higher electrolyte balance of the diet.


The severity of iron chlorosis in sensitive plants is related to soil phosphorus levels.
Iron (Fe) deficiency chlorosis, a major nutritional problem in plants growing on calcareous soils, is related to the content and reactivity of soil iron oxides and carbonates. The effects of other soil components, however, need elucidation. In this paper we tested the hypothesis that application of high doses of phosphorus (P) to the soil can aggravate Fe chlorosis. Lupin and sorghum were grown on 24 calcareous soils. Leaf chlorophyll concentration (LCC) in lupin decreased with increasing available P/available Fe ratio in the native soil but LCC in sorghum was unaffected by that ratio. Application of P to the soil resulted in significant reduction of LCC and dry weight in lupin. In sorghum, LCC and dry weight were positively affected by P fertilisation for soils poor in available P whereas the opposite effect was generally observed for the P-rich soils. In another experiment where olive plants were pot-grown on two soils during the 2009–2011 period, P fertilisation affected LCC negatively only in 2009 and 2011 and in the soil that was poorer in iron oxides. Application of fertiliser P to Fe chlorosis-inducing soils is likely to aggravate this deficiency. However, this effect depends on the plant and the Fe and P statuses of the soil.