[Leiomyosarcoma of the prostate. Report of a case].
Sarcomas of the prostate are rare tumors and are predominantly rhabdomyosarcoma in children and leiomyosarcoma in the young adult (less than 50 years). We report on a rare case of prostate sarcoma in a 49-year-old patient whose presenting features were those of rapidly evolving prostatism and dyschezia (rectal constipation). The diagnosis was established histopathologically by cytology and biopsy. Despite the initial chemotherapeutic treatment, the course of the disease was fulminant and the patient died from multiple lymphatic metastases. We discuss its embryonal origin, clinical features, differential diagnosis and underscore the need for sequential combined treatment with chemotherapy, surgery and post-operative radiotherapy.


Substitutions of glutamate 110 and 111 in the middle helix 4 of human apolipoprotein A-I (apoA-I) by alanine affect the structure and in vitro functions of apoA-I and induce severe hypertriglyceridemia in apoA-I-deficient mice.
Hypertriglyceridemia is a common pathological condition in humans of mostly unknown etiology. Here we report induction of dyslipidemia characterized by severe hypertriglyceridemia as a result of point mutations in human apolipoprotein A-I (apoA-I). Adenovirus-mediated gene transfer in apoA-I-deficient (apoA-I(-)(/)(-)) mice showed that mice expressing an apoA-I[E110A/E111A] mutant had comparable hepatic mRNA levels with WT controls but greatly increased plasma triglyceride and elevated plasma cholesterol levels. In addition, they had decreased apoE and apoCII levels and increased apoB48 levels in very low-density lipoprotein (VLDL)/intermediate-density lipoprotein (IDL). Fast protein liquid chromatography (FPLC) analysis of plasma showed that most of cholesterol and approximately 15% of the mutant apoA-I were distributed in the VLDL and IDL regions and all the triglycerides in the VLDL region. Hypertriglyceridemia was corrected by coinfection of mice with recombinant adenoviruses expressing the mutant apoA-I and human lipoprotein lipase. Physicochemical studies indicated that the apoA-I mutation decreased the alpha-helical content, the stability, and the unfolding cooperativity of both lipid-free and lipid-bound apoA-I. In vitro functional analyses showed that reconstituted HDL (rHDL) particles containing the mutant apoA-I had 53% of scavenger receptor class B type I (SR-BI)-mediated cholesterol efflux capacity and 37% capacity to activate lecithin:cholesterol acyltransferase (LCAT) as compared to the WT control. The mutant lipid-free apoA-I had normal capacity to promote ATP-binding cassette transporter A1 (ABCA1)-dependent cholesterol efflux. The findings indicate that subtle structural alterations in apoA-I may alter the stability and functions of apoA-I and high-density lipoprotein (HDL) and may cause hypertriglyceridemia.


Physician-pharmacist collaborative care model for buprenorphine-maintained opioid-dependent patients.
To develop a physician-pharmacist collaborative practice for opioid-dependent patients designed to increase access to treatment, optimize patient care, reduce cost, minimize physician burden, and prevent diversion. Suburban health department. Physician-pharmacist buprenorphine/naloxone maintenance practice. Traditionally, health department buprenorphine/naloxone patients have been referred to community physicians at considerable cost with varying outcomes. In this pilot project, patients were managed using a drug therapy management model. Intake assessments and follow-up appointments were conducted by the pharmacist. The pharmacist debriefed with the physician and documented each interaction, allowing for efficient assessment completion. The physician appended notes, when applicable, and cosigned each patient's record. The pharmacist prevented diversion by gathering data from outside providers, pharmacies, and laboratories. This health department program improved care by producing structure and expanding treatment options. A total of 12 patients completed full intakes with 135 follow-up appointments equating to an estimated savings of $22,000. The program demonstrated a 91% attendance rate, 100% 6-month retention rate, and 73% 12-month retention rate. Overall, 127 (98%) urine toxicology screens were positive for buprenorphine and 114 (88%) were positive for buprenorphine and negative for opioids. Physician and pharmacist collaboration optimized care of buprenorphine-maintained patients. Data from this pilot were used to develop a permanent physician-pharmacist program and to obtain approval for the first state-approved opioid use disorder drug therapy management protocol.


Mutation-order divergence by sexual selection: diversification of sexual signals in similar environments as a first step in speciation.
The origin of species remains a central question, and recent research focuses on the role of ecological differences in promoting speciation. Ecological differences create opportunities for divergent selection (i.e. 'ecological' speciation), a Darwinian hypothesis that hardly requires justification. In contrast, 'mutation-order' speciation proposes that, instead of adapting to different environments, populations find different ways to adapt to similar environments, implying that speciation does not require ecological differences. This distinction is critical as it provides an alternative hypothesis to the prevailing view that ecological differences drive speciation. Speciation by sexual selection lies at the centre of debates about the importance of ecological differences in promoting speciation; here, we present verbal and mathematical models of mutation-order divergence by sexual selection. We develop three general cases and provide a two-locus population genetic model for each. Results indicate that alternative secondary sexual traits can fix in populations that initially experience similar natural and sexual selection and that divergent traits and preferences can remain stable in the face of low gene flow. This stable divergence can facilitate subsequent divergence that completes or reinforces speciation. We argue that a mutation-order process could explain widespread diversity in secondary sexual traits among closely related, allopatric species.


[Rethoracotomies and repeat operations on the lungs].
The article generalizes materials of 148 rethoracotomies. Main complications are described. Grounds are given for the use of perfusion through the xenospleen at the early postoperative period in order to liquidate the coagulated haemothorax mainly after pulmonectomy. An original method of determination of the coefficient of relative viscosity of the exudate on the absorbing base is described. The method allows the objective control of infectivity of the pleural exudate to be performed. The clinical use of different methods of detoxication in the preoperative period is substantiated: UVI of blood, hemocarbosorption and xenohemosorption, which allowed to reduce lethality after rethoracotomies and reoperations on the lungs.


Similar local neuronal dynamics may lead to different collective behavior.
This report is concerned with the relevance of the microscopic rules that implement individual neuronal activation, in determining the collective dynamics, under variations of the network topology. To fix ideas we study the dynamics of two cellular automaton models, commonly used, rather in-distinctively, as the building blocks of large-scale neuronal networks. One model, due to Greenberg and Hastings (GH), can be described by evolution equations mimicking an integrate-and-fire process, while the other model, due to Kinouchi and Copelli (KC), represents an abstract branching process, where a single active neuron activates a given number of postsynaptic neurons according to a prescribed "activity" branching ratio. Despite the apparent similarity between the local neuronal dynamics of the two models, it is shown that they exhibit very different collective dynamics as a function of the network topology. The GH model shows qualitatively different dynamical regimes as the network topology is varied, including transients to a ground (inactive) state, continuous and discontinuous dynamical phase transitions. In contrast, the KC model only exhibits a continuous phase transition, independently of the network topology. These results highlight the importance of paying attention to the microscopic rules chosen to model the interneuronal interactions in large-scale numerical simulations, in particular when the network topology is far from a mean-field description. One such case is the extensive work being done in the context of the Human Connectome, where a wide variety of types of models are being used to understand the brain collective dynamics.


CKAP2 Promotes Ovarian Cancer Proliferation and Tumorigenesis Through the FAK-ERK Pathway.
Upregulation of cytoskeleton-associated protein 2 (CKAP2) has been observed in ovarian cancer. This study aimed to determine the effects of overexpression of CKAP2 on cell proliferation and tumorigenesis and to explore the potential signal pathway in the oncogenic process. Expression of CKAP2 in tissue of ovarian cancer patients was detected. Human cancer cell line SKOV3 was overexpressed with CKAP2 and measured for cell growth and mobility. Moreover, CKAP2 effect was estimated using mouse tumor xenografts. mRNA expression levels of related genes were assessed. Expression levels of CKAP2 and p-ERK2 in SKOV3 cells were detected before and after treatment of focal adhesion kinase (FAK) inhibitor. mRNA and protein levels of CKAP2 were significantly elevated in human ovarian tumor tissues. Overexpression of CKAP2 in SKOV3 cells promoted cell proliferation and migration. Implantation of overexpressed SKOV3 cells showed significant tumorigenesis ability. mRNA expression levels of proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), and SNAI1 were elevated in overexpressed SKOV3 cells. Cells with CKAP2 overexpression also had significantly increased p-ERK2 level. Moreover, FAK inhibitor treatment significantly decreased CKAP2 expression levels as well as the phosphorylation level of ERK2 in SKOV3 cells. This study suggests that overexpression of CKAP2 enhanced proliferation and mobility of carcinoma cells through the FAK-ERK2 signaling pathway.


PMD monitoring in traffic-carrying optical systems and its statistical analysis.
Differential group delay (DGD) experienced by the optical signal in in-service terrestrial optical fiber systems has been monitored for the first time without the requirement of looping-back, in which the live traffic carried in the fiber was used as the probing signal. The relationship between the measured DGD using this technique and the actual fiber PMD parameter is formulated and verified by field experiments.


mRNA expressions of peroxisome proliferator-activated receptor gamma coactivator 1α, tumor necrosis factor-α, and interleukin-6 in paraspinal muscles of patients with lumbar kyphosis: a preliminary study.
Kyphosis is a spine deformity that can lead to falls and reduced quality of life. Peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) regulates mitochondrial biogenesis and is important for proper functioning of skeletal muscle, including the paraspinal muscles, which support and allow movement of the spine. The role of PGC-1α in paraspinal muscles in lumbar kyphosis has not been examined. We also examined the expressions of the proinflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6. We obtained paraspinal muscle specimens from 12 patients who underwent posterior lumbar surgery. RNA was isolated from these samples, and quantitative PCR was performed to compare the expression levels of PGC-1α, TNF-α, and IL-6 mRNA between patients with decreased lumbar lordosis (LL) and normal LL patients. TNF-α and IL-6 mRNA expressions in paraspinal muscles were significantly higher in the decreased LL group than in the normal LL group (P=0.048 for both). PGC-1α mRNA expression was slightly increased in the decreased LL group, but the difference was not significant. Age was significantly positively correlated with PGC-1α mRNA expression (P=0.010). PGC-1α mRNA expression was significantly positively correlated with TNF-α mRNA expression (P=0.022). LL was significantly negatively correlated with PGC-1α, TNF-α, and IL-6 mRNA expressions (P=0.015, 0.036, and 0.010, respectively). TNF-α and IL-6 mRNA expressions in paraspinal muscles were significantly higher in the decreased LL group than in the normal LL group. LL was significantly negatively correlated with PGC-1α, TNF-α, and IL-6 mRNA expressions. PGC-1α mRNA expression levels in paraspinal muscles may be affected by lumbar kyphosis.


Effects of hypoxia on function and morphology of in vitro frog gastric mucosa.
The effects of gaseous hypoxia and reoxygenation on oxynticopeptic (OPC) and surface mucous cells (SMC) were examined in in vitro bullfrog gastric fundic mucosae mounted in Ussing chambers. Forskolin-stimulated H+ secretion, transmucosal potential difference (PD), and electrical resistance (R) were monitored in tissues incubated in HCO3(-)-free or HCO3(-)-containing buffer. At serosal pH (pHs) 7.2, 1 h of hypoxia with 100% N2 resulted in a decrease in PD, increase in R, and complete inhibition of H+ secretion. After 30 min of hypoxia, the morphology of OPC changed from the secretory to the nonsecretory state without recognizable cytopathology. Destructive changes in OPC increased progressively at pHs 7.2 as the hypoxic period was prolonged from 4 to 24 h. After 4 h of reoxygenation following 12-24 h of hypoxia, OPC remained necrotic and H+ secretion showed no recovery, whereas in some areas where SMC were exfoliated adjacent SMC showed epithelial restitution. The recovery of H+ secretion and PD during 2 h of reoxygenation after 4 h of hypoxia at pHs 6.0 and 6.8 was less than that at 7.2 and 8.0 and was greater in the presence of serosal HCO3- than its absence at pHs 7.2. These results suggest that, in in vitro frog gastric mucosa, 1) OPC are more vulnerable to hypoxia than SMC, 2) basolateral acidosis exaggerates hypoxic injury of OPC, and 3) serosal HCO3- protects OPC from hypoxic injury.


The distribution of vasoactive intestinal polypeptide-like, substance P-like and bombesin-like immunoreactivity in the digestive system of the sheep.
Peptides which are possibly related to the non-cholinergic, non-adrenergic division of the autonomic nervous system have been identified by immunofluorescence in the digestive system of mature sheep. Vasoactive intestinal polypeptide-, substance P-, and bombesin-like immunoreactivity were localized in neural elements throughout the ovine gastrointestinal tract (g.i.t.). Vasoactive intestinal polypeptide-like immunoreactivity (VIP-l.i.) was demonstrable in the submaxillary, parotid and the sublingual salivary glands close to small blood vessels and the acini. VIP-l.i. was also demonstrable in the upper oesophagus in connective tissue near small blood vessels. In the forestomachs, abomasum, and small and large intestines reactive fibres were present in the mucosa, submucosa, smooth muscle layers and the plexuses. The plexuses also contained reactive nerve cell bodies. VIP-reactive fibres were found in the pancreas, the gall bladder and the common bile and pancreatic duct but were not found in the intestinal mesentery, portal vein, and liver tissue. Substance P-like immunoreactivity (SP-l.i.) was demonstrable in nerve fibres in all the layers of the g.i.t. and in nerve cell bodies in the gut plexuses. The pancreas and the gall bladder also contained a few scattered fibres. Additionally, SP-l.i. was present in open-type endocrine cells throughout the mucosa of the small and large intestines but no SP-l.i. was found in the salivary glands or the oesophagus. Bombesin-like immunoreactivity (B-l.i.) was associated with nerve fibres and was demonstrable in the mucosa and myenteric plexuses throughout the g.i.t. B-l.i. in the smooth muscle appeared to be restricted to nerve fibres in the forestomachs, the abomasum, and the upper small intestine. No B-l.i. was found in the salivary glands, oesophagus, liver tissue, pancreas, gall bladder or intestinal mesentery.


Spotlight on the academic multidisciplinary team: proposals from the 3rd NIHR Newcastle BRC Academic Geriatric Medicine Workshop.
High-quality care for older people is best delivered by multidisciplinary teams involving a range of professions. Similarly, if research evidence is to effectively inform practice, it needs to be designed and executed by teams that are both multidisciplinary and multiprofessional. Here, we summarise the discussions from a 1-day workshop convened by the National Institute for Health and Care Research (NIHR) Newcastle Biomedical Research Centre in Spring 2021, which focussed on multidisciplinary academic teams. Barriers to success include small numbers of clinical academic researchers across all professions focussing on older people, and lack of career pathways, role models and support for non-medical clinical researchers. The workshop identified strengths in the tradition of multidisciplinary working in the care of older people, research questions that lend themselves naturally to multidisciplinary working, increasing interest from funders in multidisciplinary research, and untapped opportunities for greater commercial engagement. Initiatives to improve engagement of students and trainees, mentorship, career pathways, networking across research centres and possibly developing a national School of Older People's Care Research are all ways that we can ensure the growth of multidisciplinary research to best serve older people's health and social care in the future.


[Conscience, principled refusal and ethics of refusal to provide treatment to a patient's request].
There are situations in which refusal to provide treatment according to a patient's request may be justified by ethical rules and principles of medical ethics. This article explores such situations, analyzing the various factors which a physician may consider when refusal to provide treatment is at stake. The article focuses on three major states of affairs under which the question of whether a physician has liberty to refuse to treat may occur: refusals deriving from conflicts between the physician's personal values and ones reflected in the proposed treatment; refusals stemming from general considerations to be classified as policy reasons; and refusals following a clinical assessment as to the proposed treatment, expected chances of recovery and expected benefit to the patient. The ethical analysis of the article leads to the conclusion that a physician may (although he/she does not have a right to) refuse to provide medical treatment following a patient's request when the physician's refusal originates in conscientious resistance. However, the physician may not refuse to treat when refusal is based on policy considerations or concerns third parties not immediately involved in the physician-patient relationship. In addition, a physician may refuse to provide treatment following a medical assessment when and if the proposed treatment is not urgently required, if the provision of treatment may create risks to the patient's health, if its conferral may inflict pain or suffering exceeding its expected benefits to the patient, or the proposed treatment is futile and its chances to combat the disease are significantly minimal.


Access to Firearms among Orange County Youth: A School-Based Study.
School-associated firearm violence among children and adolescents is a national public concern. The objective of this study was to determine the accessibility of firearms, methods of firearm access and firearm safety knowledge among middle and high school students in Orange County, California. After permission from school officials and parents was obtained, a 24-question survey was distributed to 176 students in grades 6 through 12 at four schools in Orange County. Data was collected over a 12-month period beginning in February 2003. Data analysis was presented in proportions. In addition, cross tabulations were performed to determine which factors were associated with access to guns, having fired a gun, and firearm possession at school. The mean age of participants was 16.1 years. Seventy-seven (45%) were male, 121 (69%) Hispanic, and 171 (94%) were of middle income. Four participants (2.3%) admitted to gang involvement, 47 (26.7%) had fired a gun. Those more likely to have fired a gun appeared to be non-Hispanic males (p= 0.001). Seventy-five (43%) reported access to a gun. Older students and those in grades 9 to 12 were more likely to have access to a gun (p= 0.01), which they stated could be obtained from their homes, friends or relatives (4.5% to 22%). No students admitted to bringing a gun to school. Two (1.1%) students stated that they had thought of using a gun at school. One hundred one students (62%) were taught firearm safety by their parent(s). Almost half of the students in this study acknowledged that they could gain access to a gun and two students had thought about using a gun at school. Firearm education, safety and counseling are of paramount importance to ensure safety among school youths.


[Acute chest pain and normal high-sensitivity cardiac troponin levels; is this the end of the story?]
In patients presenting with acute chest pain, acute myocardial infarction should first be ruled out as a cause as these patients will often need coronary revascularisation. In the remaining patients, those with normal high-sensitivity cardiac troponin levels should undergo additional cardiac investigations to discriminate patients with an episode of unstable angina pectoris from those who have a non-cardiac cause of the chest pain. In the large majority (86%), the medical history does not raise suspicion of angina pectoris and an exercise test will show normal results; in these patients, further cardiac imaging does not seem to be indicated. In conclusion, less cardiac imaging and more non-cardiac investigations are required in patients with acute chest pain and normal high-sensitivity cardiac troponin levels.


Prevalence, neurobiology, and treatments for apathy in prodromal dementia.
Apathy, characterized by diminished motivation, is a highly prevalent neuropsychiatric symptom in dementia. However, there is a substantial knowledge gap with regard to prevalence rates, neurobiological underpinnings, and effective treatments for apathy in pre-dementia states, including mild cognitive impairment (MCI) and mild behavioral impairment (MBI). We conducted a comprehensive literature search using MEDLINE, Embase, and PsycINFO databases to identify available research on apathy in prodromal dementia. Apathy has consistently been detected in individuals with MCI with varying prevalence rates, and only recently has literature discussed the prevalence of apathy in MBI. Few pharmacological treatments have been utilized for apathy, with galantamine and risperidone showing mild reductions in apathetic behaviors. Non-pharmacological interventions in prodromal dementia are beginning to be explored and show promise, but few studies have replicated those results. More comprehensive guidelines for diagnosing apathy and further research investigating neurobiological mechanisms of apathy in MCI and MBI are required in order to effectively treat apathetic patients in prodromal dementia.


Computational prediction of structure-activity relationships for the binding of aminocyclitols to β-glucocerebrosidase.
Glucocerebrosidase (GCase, acid β-Glucosidase) hydrolyzes the sphingolipid glucosylceramide into glucose and ceramide. Mutations in this enzyme lead to a lipid metabolism disorder known as Gaucher disease. The design of competitive inhibitors of GCase is a promising field of research for the design of pharmacological chaperones as new therapeutic agents. Using a series of recently reported molecules with experimental binding affinities for GCase in the nanomolar to micromolar range, we here report an extensive theoretical analysis of their binding mode. On the basis of molecular docking, molecular dynamics, and binding free energy calculations using the linear interaction energy method (LIE), we provide details on the molecular interactions supporting ligand binding in the different families of compounds. The applicability of other computational approaches, such as the COMBINE methodology, is also investigated. The results show the robustness of the standard parametrization of the LIE method, which reproduces the experimental affinities with a mean unsigned error of 0.7 kcal/mol. Several structure-activity relationships are established using the computational models here provided, including the identification of hot spot residues in the binding site. The models derived are envisaged as important tools in ligand-design programs for GCase inhibitors.


FK506 bypasses the effect of erythroferrone in cancer cachexia skeletal muscle atrophy.
Skeletal muscle atrophy is a hallmark of cachexia, a wasting condition typical of chronic pathologies, that still represents an unmet medical need. Bone morphogenetic protein (BMP)-Smad1/5/8 signaling alterations are emerging drivers of muscle catabolism, hence, characterizing these perturbations is pivotal to develop therapeutic approaches. We identified two promoters of "BMP resistance" in cancer cachexia, specifically the BMP scavenger erythroferrone (ERFE) and the intracellular inhibitor FKBP12. ERFE is upregulated in cachectic cancer patients' muscle biopsies and in murine cachexia models, where its expression is driven by STAT3. Moreover, the knock down of Erfe or Fkbp12 reduces muscle wasting in cachectic mice. To bypass the BMP resistance mediated by ERFE and release the brake on the signaling, we targeted FKBP12 with low-dose FK506. FK506 restores BMP-Smad1/5/8 signaling, rescuing myotube atrophy by inducing protein synthesis. In cachectic tumor-bearing mice, FK506 prevents muscle and body weight loss and protects from neuromuscular junction alteration, suggesting therapeutic potential for targeting the ERFE-FKBP12 axis.


Gentoo penguins (Pygoscelis papua) react to underwater sounds.
Marine mammals and diving birds face several physiological challenges under water, affecting their thermoregulation and locomotion as well as their sensory systems. Therefore, marine mammals have modified ears for improved underwater hearing. Underwater hearing in birds has been studied in a few species, but for the record-holding divers, such as penguins, there are no detailed data. We played underwater noise bursts to gentoo penguins (Pygoscelis papua) in a large tank at received sound pressure levels between 100 and 120 dB re 1 µPa RMS. The penguins showed a graded reaction to the noise bursts, ranging from no reactions at 100 dB to strong reactions in more than 60% of the playbacks at 120 dB re 1 µPa. The responses were always directed away from the sound source. The fact that penguins can detect and react to underwater stimuli may indicate that they make use of sound stimuli for orientation and prey detection during dives. Further, it suggests that penguins may be sensitive to anthropogenic noise, like many species of marine mammals.


Rational design of heme enzymes for biodegradation of pollutants toward a green future.
Environmental pollutants, such as industrial dyes and halophenols, are harmful to human health, which urgently demand degradation. Bioremediation has been shown to be a cost-effective and ecofriendly approach. As reviewed herein, significant progress has been made in the last decade for biodegradation of both industrial dyes and halophenols, by engineering of native dye-decolorizing peroxidases (DyPs) and dehaloperoxidases (DHPs), and by design of artificial heme enzymes in both native and de novo protein scaffolds. The catalytic efficiency of artificial DyPs and DHPs can be rationally designed comparable to or even beyond those of natural counterparts. The enzymes are on their way from laboratory to industry and will play more crucial roles in environmental protection toward a green future.


Kinin generation in acute pneumonia and chronic bronchitis.
Kinins are potent inflammatory mediators, liberated from kininogens by different kininogenases. The aim of this study was to investigate the kinin generation pathways in acute and chronic inflammation of the lower airways. We studied bronchoalveolar lavage fluid (BALF) of patients with acute pneumonia, patients with chronic bronchitis and healthy controls. Kinins were determined by radioimmunoassay (RIA). Plasma kallikrein (pl-Kal), alpha2-macroglobulin (alpha2-M) and toluenesulphonylarginine methyl ester (TAME) esterase activity (TAME-ea) were studied in BALF before and after gel filtration chromatography. Plasma kallikrein and alpha2-M were measured using two newly developed sandwich enzyme-linked immunosorbent assays (ELISAs). TAME-ea was measured by a radiochemical assay. After gel filtration, inhibition of TAME-ea with benzamidine, soy-bean-trypsin inhibitor (SBTI) and aprotinin was performed. Kinins and TAME-ea did not differ significantly between acute pneumonia and chronic bronchitis, whereas pl-Kal and alpha2-M values were significantly higher in acute pneumonia. Gel filtration revealed the highest TAME-ea peak in acute pneumonia corresponding with the first alpha2-M peak at approximately 800 kDa, whereas in chronic bronchitis the highest peak was found at approximately 40 kDa. The inhibition test showed that the TAME-ea peak at approximately 800 kDa was due to pl-Kal and the TAME-ea peak at approximately 40 kDa was mainly due to tissue kallikrein. High peaks of alpha2-M and pl-Kal were found in pneumonia and only small peaks were seen in chronic bronchitis. We conclude that in acute airway inflammation kinins seem to be mainly generated by plasma kallikrein whereas in chronic inflammation, kininogenases other than plasma kallikrein, such as tissue kallikrein, seem to be more important.


Expression of p16 protein and cyclin D1 in periampullary carcinomas.
The majority of the tumors in periampullary region are pancreatic and ampulla of Vater carcinomas. The aim of this study was to compare histopathological features of ampulla of Vater carcinomas with pancreatic ductal adenocarcinomas and to determine diagnostic and predictive values of p16 protein and cyclin D1 expression. Tissue samples from pancreatic ductal adenocarcinomas and ampulla of Vater carcinomas were obtained from 31 patients who underwent pancreticoduodenectomy for periampullary carcinoma. The study group was composed of 12 women and 19 men. Their median age was found to be 62.32 years (range 26-85 years). The parameters analyzed in the study included lymph node metastases, perineural invasion, differentiation, duodenal invasion, grade of intraepithelial neoplasia and p16 and cyclin D1 expression in tumoral and peritumoral pancreatic tissues. In both tumor groups, the loss of p16 protein expression was significantly correlated with perineural invasion (p = 0.0001). Perineural invasion was more frequent in the pancreatic ductal adenocarcinoma group than the ampulla of Vater carcinoma group (p = 0.01). When desmoplasia and lymphoplasmacytic stromal infiltration were examined, desmoplastic reaction was significantly higher in pancreatic ductal adenocarcinomas than ampulla of Vater carcinomas (p = 0.01). No significant difference was observed between tumor groups for Cyclin D1 (p > 0.05). The results suggest that loss of p16 protein expression may be a sign for poor prognosis in periampullary cancers that is correlated mainly with perineural invasion. Desmoplastic stromal reaction may be a distinctive feature for pancreatic ductal adenocarcinoma compared with ampulla of Vater carcinoma.


Comparative pathology in ferrets infected with H1N1 influenza A viruses isolated from different hosts.
Virus replication and pulmonary disease pathogenesis in ferrets following intranasal infection with a pandemic influenza virus strain (A/California/4/09 [CA09]), a human seasonal influenza H1N1 virus isolate (A/New Caledonia/20/99 [Ncal99]), a classical swine influenza H1N1 virus isolate (A/Swine/Iowa/15/30 [Sw30]), or an avian H1N1 virus isolate (A/Mallard/MN/A108-2355/08 [Mal08]) were compared. Nasal wash virus titers were similar for Ncal99 and Sw30, with peak virus titers of 10(5.1) 50% tissue culture infectious doses (TCID(50))/ml and 10(5.5) TCID(50)/ml occurring at day 3 postinfection (p.i.), respectively. The mean peak titer for CA09 also occurred at day 3 p.i. but was higher (10(7) TCID(50)/ml). In contrast, the peak virus titers (10(3.6) to 10(4.3) TCID(50)/ml) for Mal08 were delayed, occurring between days 5 and 7 p.i. Disease pathogenesis was characterized by microscopic lesions in the nasal turbinates and lungs of all ferrets; however, Sw30 infection was associated with severe bronchointerstitial pneumonia. The results demonstrate that although CA09 is highly transmissible in the human population and replicates well in the ferret model, it causes modest disease compared to other H1N1 viruses, particularly Sw30 infection.


Treating acute ischemic stroke.
Acute ischemic stroke (AIS) is a common disorder that has only one associated approved therapy: intravenous tissue plasminogen activator (iv t-PA). A limiting factor to the use of iv t-PA is that it must be initiated within 3 h of stroke onset. Efforts to expand the therapeutic time window are underway and include image evaluation of the ischemic penumbra to target those patients who are most appropriate for treatment. Intra-arterial t-PA is also used only in some treatment centers despite convincing proof of efficacy of this therapy. Devices to restore perfusion that have been approved in the US for recanalization exist, but these are not approved for use in stroke therapy. Many neuroprotective drugs have been evaluated as potential acute stroke therapies, but none have shown efficacy, hence the future of neuroprotection as a strategy for acute ischemic stroke therapy remains uncertain.


Off-label prescription of genetically modified organism medicines in europe: emerging conflicts of interest?
Recently, the first human medicine containing a genetically modified organism (GMO medicine) was authorized for use in the European market. Just as any medicinal product, the market authorization for a GMO medicine contains a precise description of the therapeutic use for which the medicinal product is intended. Within this use, the application of the GMO medicine is permitted, without the need for the institution to obtain a specific permit. In practice, however, medicinal products are also frequently prescribed for treatment outside the registered therapeutic use, a practice that is referred to as "off-label use." While off-label use of conventional medicines is permitted and has been very useful, the off-label use of GMO medicines is not covered in the European Union (EU) legislation or guidelines and falls under each member state's national environmental legislation. This implies that in the Netherlands and most other EU member states, an environmental permit will be required for any institution that uses the GMO medicine outside the registered application(s). In the Netherlands, this permit is identical to the permits required for the execution of clinical trials involving nonregistered GMOs. The application procedure for such permit is time-consuming. This process can therefore limit the therapeutic options for medical professionals. As a consequence, desired treatment regimens could be withheld for certain patient (groups). To make future off-label use of GMO medicines permissible in a way that is acceptable for all stakeholders, regulators should adopt a proactive attitude and formulate transparent legislative procedures for this. Only then the field can maintain the public acceptance of GMO medicines, while maintaining the freedom to operate of medical professionals.


Effects of a Personalized Smartphone App on Bowel Preparation Quality: Randomized Controlled Trial.
Adequate bowel preparation is essential for the visualization of the colonic mucosa during colonoscopy. However, the rate of inadequate bowel preparation is still high, ranging from 18% to 35%; this may lead to a higher risk of missing clinically relevant lesions, procedural difficulties, prolonged procedural time, an increased number of interval colorectal carcinomas, and additional health care costs. The aims of this study are to compare bowel preparation instructions provided via a personalized smartphone app (Prepit, Ferring B V) with regular written instructions for bowel preparation to improve bowel preparation quality and to evaluate patient satisfaction with the bowel preparation procedure. Eligible patients scheduled for an outpatient colonoscopy were randomized to a smartphone app group or a control group. Both the groups received identical face-to-face education from a research physician, including instructions about the colonoscopy procedure, diet restrictions, and laxative intake. In addition, the control group received written information, whereas the smartphone app group was instructed to use the smartphone app instead of the written information for the actual steps of the bowel preparation schedule. All patients used bisacodyl and sodium picosulfate with magnesium citrate as laxatives. The quality of bowel preparation was scored using the Boston Bowel Preparation Scale (BBPS) by blinded endoscopists. Patient satisfaction was measured using the Patient Satisfaction Questionnaire-18. A total of 87 patients were included in the smartphone app group and 86 in the control group. The mean total BBPS score was significantly higher in the smartphone app group (mean 8.3, SD 0.9) than in the control group (mean 7.9, SD 1.2; P=.03). The right colon showed a significantly higher bowel preparation score in the smartphone app group (mean 2.7, SD 0.5 vs mean 2.5, SD 0.6; P=.04). No significant differences were observed in segment scores for the mean transverse colon (mean 2.8, SD 0.4 vs mean 2.8, SD 0.4; P=.34) and left colon (mean 2.8, SD 0.4 vs mean 2.6, SD 0.5; P=.07). General patient satisfaction was high for the smartphone app group (mean 4.4, SD 0.7) but showed no significant difference when compared with the control group (mean 4.3, SD 0.8; P=.32). Our personalized smartphone app significantly improved bowel preparation quality compared with regular written instructions for bowel preparation. In particular, in the right colon, the BBPS score improved, which is of clinical relevance because the right colon is considered more difficult to clean and the polyp detection rate in the right colon improves with improvement of bowel cleansing of the right colon. No further improvement in patient satisfaction was observed compared with patients receiving regular written instructions. ClinicalTrials.gov NCT03677050; https://clinicaltrials.gov/ct2/show/NCT03677050.


A Connectionist Model for Dynamic Economic Risk Analysis of Hydrocarbons Production Systems.
This study presents a connectionist model for dynamic economic risk evaluation of reservoir production systems. The proposed dynamic economic risk modeling strategy combines evidence-based outcomes from a Bayesian network (BN) model with the dynamic risks-based results produced from an adaptive loss function model for reservoir production losses/dynamic economic risks assessments. The methodology employs a multilayer-perceptron (MLP) model, a loss function model; it integrates an early warning index system (EWIS) of oilfield block with a BN model for process modeling. The model evaluates the evidence-based economic consequences of the production losses and analyzes the statistical disparities of production predictions using an EWIS-assisted BN model and the loss function model at the same time. The proposed methodology introduces an innovative approach that effectively minimizes the potential for dynamic economic risks. The model predicts real-time daily production/dynamic economic losses. The connectionist model yields an encouraging overall predictive performance with average errors of 1.954% and 1.957% for the two case studies: cases 1 and 2, respectively. The model can determine transitional/threshold production values for adequate reservoir management toward minimal losses. The results show minimum average daily dynamic economic losses of $267,463 and $146,770 for cases 1 and 2, respectively. It is a multipurpose tool that can be recommended for the field operators in petroleum reservoir production management related decision making.


Cholinergic control of nerve growth factor in adult rats: evidence from cortical cholinergic deafferentation and chronic drug treatment.
It is well documented that nerve growth factor (NGF) plays an important role in maintaining functions of cholinergic basal forebrain neurons. In the present study, we tested the hypothesis that cholinergic activity controls NGF levels in cholinoceptive neurons of the cerebral cortex and hippocampus. To address that question, we used both cholinergic deafferentation of cerebral cortex and hippocampus by cholinergic immunolesion with 192IgG-saporin and chronic pharmacological treatment of sham-treated and immunolesioned rats with the cholinergic agonist pilocarpine and the cholinergic antagonist scopolamine. We observed an increase in NGF protein levels in the cortex and hippocampus after cholinergic immunolesions and also after muscarinic receptor blockade by chronic intracerebroventricular scopolamine infusion in sham-treated rats after 2 weeks. There was no further increase in the accumulation of NGF after scopolamine treatment of immunolesioned rats. Chronic infusion of pilocarpine had no effect on cortical and hippocampal NGF protein levels in sham-treated rats. In rats with cholinergic immunolesions, however, pilocarpine did prevent the lesion-induced accumulation of NGF. There was no effect of cholinergic lesion and drug treatment on cortical or hippocampal NGF mRNA levels, consistent with the importance of NGF retrograde transport as opposed to its de novo synthesis. This study provides strong evidence for the hypothesis that there is cholinergic control of cortical and hippocampal NGF protein but not mRNA levels in adult rats.


Characterizing cannabis use reduction and change in functioning during treatment: Initial steps on the path to new clinical endpoints.
Reduction-based cannabis use endpoints are needed to better evaluate treatments for cannabis use disorder (CUD). This exploratory, secondary analysis aimed to characterize cannabis frequency and quantity reduction patterns and corresponding changes in psychosocial functioning during treatment. We analyzed 16 weeks (4 prerandomization, 12 postrandomization) of data (n = 302) from both arms of a randomized clinical trial assessing pharmacotherapy for CUD. Cannabis consumption pattern classes were extracted with latent profile modeling using self-reported (a) past-week days used (i.e., frequency) and (b) past-week average grams used per using day (i.e., quantity). Changes in mean Marijuana Problem Scale (MPS) and Hospital Anxiety and Depression Scale (HADS) scores were examined among classes. Urine cannabinoid levels were examined in relation to self-reported consumption as a validity check. Two-, three-, four-, and five-class solutions each provided potentially useful conceptualizations of associations between frequency and quantity. Regardless of solution, reductions in MPS scores varied in magnitude across classes and closely tracked class-specific reductions in consumption (e.g., larger MPS reduction corresponded to larger frequency/quantity reductions). Changes in HADS scores were less pronounced and less consistent with consumption patterns. Urine cannabinoid levels closely matched class-specific self-reported consumption frequency. Findings illustrate that frequency and quantity can be used in tandem within mixture model frameworks to summarize heterogeneous cannabis use reduction patterns that may correspond to improved psychosocial functioning. Going forward, similar analytic strategies applied to alternative metrics of cannabis consumption may facilitate construction of useful reduction-based clinical endpoints. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Differences in liquid cloud droplet effective radius and number concentration estimates between MODIS Collections 5.1 and 6 over global oceans.
Differences in cloud droplet effective radius and cloud droplet number concentration (CDNC) estimates inferred from the Aqua MODIS Collections 5.1 and 6 cloud products (MYD06) are examined for warm clouds over global oceans for the year 2008. Individual pixel level retrievals for both collections are aggregated to 1° × 1° and compared globally and regionally for the three main spectral channel pairs used for MODIS cloud optical property retrievals. Comparisons between both collections are performed for cases in which all three effective radii retrievals are classified by the MODIS Cloud Product as valid. The contribution to the observed differences of several key MYD06 Collection 6 algorithm updates are also explored, with a focus on changes to the surface reflectance model, assumed solar irradiance, above cloud emission, cloud top pressure, and pixel registration. Global results show a neutral to positive (> 50 cm-3) change for C6-derived CDNC relative to C5.1 for the 1.6 µm and 2.1 µm channel retrievals, corresponding to a neutral to -2 µm difference in droplet effective radius. For 3.7 µm retrievals, CDNC results show a negative change in the tropics, with differences transitioning toward positive values with increasing latitude spanning -25 to +50 cm-3 related to a +2.5 to -1 µm transition in effective radius. Cloud optical thickness differences were small relative to effective radius, and found to not significantly impact CDNC estimates. Regionally, the magnitude and behavior of the annual CDNC cycle are compared for each effective radius retrieval. Results from this study indicate significant intercollection differences in aggregated values of effective radius due to changes to the pre-computed retrieval lookup tables for ocean scenes, changes to retrieved cloud top pressure, solar irradiance, or above cloud thermal emission, depending upon spectral channel. The observed differences between collections may have implications for existing MODIS derived climatologies and validation studies of effective radius and CDNC.


Adipose segmentation in small animals at 7T: a preliminary study.
Small animal MRI at 7 Tesla (T) provides a useful tool for adiposity research. For adiposity researchers, separation of fat from surrounding tissues and its subsequent quantitative or semi- quantitative analysis is a key task. This is a relatively new field and a priori it cannot be known which specific biological questions related to fat deposition will be relevant in a specific study. Thus it is impossible to predict what accuracy and what spatial resolution will be required in all cases and even difficult what accuracy and resolution will be useful in most cases. However the pragmatic time constraints and the practical resolution ranges are known for small animal imaging at 7T. Thus we have used known practical constraints to develop a method for fat volume analysis based on an optimized image acquisition and image post processing pair. We designed a fat segmentation method based on optimizing a variety of factors relevant to small animal imaging at 7T. In contrast to most previously described MRI methods based on signal intensity of T1 weighted image alone, we chose to use parametric images based on Multi-spin multi-echo (MSME) Bruker pulse sequence which has proven to be particularly robust in our laboratory over the last several years. The sequence was optimized on a T1 basis to emphasize the signal. T2 relaxation times can be calculated from the multi echo data and we have done so on a pixel by pixel basis for the initial step in the post processing methodology. The post processing consists of parallel paths. On one hand, the weighted image is precisely divided into different regions with optimized smoothing and segmentation methods; and on the other hand, a confidence image is deduced from the parametric image according to the distribution of relaxation time relationship of typical adipose. With the assistance of the confidence image, a useful software feature was implemented to which enhances the data and in the end results in a more reliable and flexible method for adipose evaluation. In this paper, we describe how we arrived at our recommended procedures and key aspects of the post-processing steps. The feasibility of the proposed method is tested on both simulated and real data in this preliminary research. A research tool was created to help researchers segment out fat even when the anatomical information is of low quality making it difficult to distinguish between fat and non-fat. In addition, tool is designed to allow the operator to make adjustments to many of the key steps for comparison purposes and to quantitatively assess the difference these changes make. Ultimately our flexible software lets the researcher define key aspects of the fat segmentation and quantification. Combining the full T2 parametric information with the optimized first echo image information, the research tool enhances the reliability of the results while providing more flexible operations than previous methods. The innovation in the method is to pair an optimized and very specific image acquisition technique to a flexible but tuned image post processing method. The separation of the fat is aided by the confidence distribution of regions produced on a scale relevant to and dictated by practical aspects of MRI at 7T.


Astroglial role in the pathophysiology of status epilepticus: an overview.
Status epilepticus is a medical emergency with elevated morbidity and mortality rates, and represents a leading cause of epilepsy-related deaths. Though status epilepticus can occur at any age, it manifests more likely in children and elderly people. Despite the common prevalence of epileptic disorders, a complete explanation for the mechanisms leading to development of self-limited or long lasting seizures (as in status epilepticus) are still lacking. Apart from neurons, research evidence suggests the involvement of immune and glial cells in epileptogenesis. Among glial cells, astrocytes represent an ideal target for the study of the pathophysiology of status epilepticus, due to their key role in homeostatic balance of the central nervous system. During status epilepticus, astroglial cells are activated by the presence of cytokines, damage associated molecular patterns and reactive oxygen species. The persistent activation of astrocytes leads to a decrease in glutamate clearance with a corresponding accumulation in the synaptic extracellular space, increasing the chance of neuronal excitotoxicity. Moreover, major alterations in astrocytic gap junction coupling, inflammation and receptor expression, facilitate the generation of seizures. Astrocytes are also involved in dysregulation of inhibitory transmission in the central nervous system and directly participate in ionic homeostatic alterations during status epilepticus. In the present review, we focus on the functional and structural changes in astrocytic activity that participate in the development and maintenance of status epilepticus, with special attention on concurrent inflammatory alterations. We also include potential astrocytic treatment targets for status epilepticus.


Processing of oats and the impact of processing operations on nutrition and health benefits.
Oats are a uniquely nutritious food as they contain an excellent lipid profile and high amounts of soluble fibre. However, an oat kernel is largely non-digestible and thus must be utilised in milled form to reap its nutritional benefits. Milling is made up of numerous steps, the most important being dehulling to expose the digestible groat, heat processing to inactivate enzymes that cause rancidity, and cutting, rolling or grinding to convert the groat into a product that can be used directly in oatmeal or can be used as a food ingredient in products such as bread, ready-to-eat breakfast cereals and snack bars. Oats can also be processed into oat bran and fibre to obtain high-fibre-containing fractions that can be used in a variety of food products.


Insertion of a classical nuclear import signal into the matrix domain of the Rous sarcoma virus Gag protein interferes with virus replication.
The Rous sarcoma virus Gag protein undergoes transient nuclear trafficking during virus assembly. Nuclear import is mediated by a nuclear targeting sequence within the MA domain. To gain insight into the role of nuclear transport in replication, we investigated whether addition of a "classical " nuclear localization signal (NLS) in Gag would affect virus assembly or infectivity. A bipartite NLS derived from nucleoplasmin was inserted into a region of the MA domain of Gag that is dispensable for budding and infectivity. Gag proteins bearing the nucleoplasmin NLS insertion displayed an assembly defect. Mutant virus particles (RC.V8.NLS) were not infectious, although they were indistinguishable from wild-type virions in Gag, Gag-Pol, Env, and genomic RNA incorporation and Gag protein processing. Unexpectedly, postinfection viral DNA synthesis was also normal, as similar amounts of two-long-terminal-repeat junction molecules were detected for RC.V8.NLS and wild type, suggesting that the replication block occurred after nuclear entry of proviral DNA. Phenotypically revertant viruses arose after continued passage in culture, and sequence analysis revealed that the nucleoplasmin NLS coding sequence was deleted from the gag gene. To determine whether the nuclear targeting activity of the nucleoplasmin sequence was responsible for the infectivity defect, two critical basic amino acids in the NLS were altered. This virus (RC.V8.KR/AA) had restored infectivity, and the MA.KR/AA protein showed reduced nuclear localization, comparable to the wild-type MA protein. These data demonstrate that addition of a second NLS, which might direct MA and/or Gag into the nucleus by an alternate import pathway, is not compatible with productive virus infection.


With a little help from my friends: bystander context and children's attitude toward peer helping.
This experimental vignette study examined children's perceptions and evaluations of helping a peer, in the context of friendships and in the presence of by-standing peers. A total of 1246 children (8 to 12 years) reported their attitude toward helping when either friends of the helper, friends of the recipient of help, or no bystanders were present. In agreement with the competitive altruism model, children most strongly endorsed helping when friends of the helper were present compared to the other two situations. This indicates that children take reputation concerns into account when evaluating helping situations. However, in contrast to lower prosocial children, the evaluations of higher prosocial children were not influenced by the presence of by-standing peers. These children seemed to base their evaluation on increasing the recipient's welfare and less on reputation concerns of the helper.


Death after endoscopic prostate surgery in Australia and New Zealand: a review of clinical management issues.
Endoscopic prostate surgery is an established treatment for male lower urinary tract symptoms (LUTS) and is recognized to have low mortality rates. We aimed to describe factors that may have contributed to death following endoscopic prostate surgery using data from the Australia and New Zealand Audits of Surgical Mortality (ANZASM). All urological related deaths reported to ANZASM from January 1 2012 to December 31 2019 were reviewed. Deaths related to endoscopic prostate resection (transurethral resection of prostate - TURP, laser procedures) were included. Peer reviewers identified up to three clinical management issues (CMIs), and these were analysed. CMIs were classified in order of least to most concerning: area of consideration, area of concern and adverse events. Of 1127 total urological deaths, 77 deaths were related to endoscopic prostate surgery (7.0%). Most procedures were monopolar TURP. The mean age of patients was 80.9 years (range 57.0-96.2). Leading causes of death were cardiovascular events 23/77 (29.9%) and respiratory failure 14/77 (18.2%). Assessors identified 39 CMIs in 26/77 (33.8%) patients. Twenty-three were areas of consideration, nine were areas of concern and seven identified adverse events. The most common CMIs were regarding post-operative care (14/39) and the decision to operate (13/39). Most deaths did not elicit concerns from the ANZASM peer assessors. However, the main concerns identified were surrounding decision making and rationale for operating. This highlights the importance of clear counselling and documentation during the treatment decision process.


Hydroxylation increases the neurotoxic potential of BDE-47 to affect exocytosis and calcium homeostasis in PC12 cells.
Oxidative metabolism, resulting in the formation of hydroxylated polybrominated diphenyl ether (PBDE) metabolites, may enhance the neurotoxic potential of brominated flame retardants. Our objective was to investigate the effects of a hydroxylated metabolite of 2,2',4,4'-tetra-bromodiphenyl ether (BDE-47; 6-OH-BDE-47) on changes in the intracellular Ca2+ concentration ([Ca2+]i) and vesicular catecholamine release in PC12 cells. We measured vesicular catecholamine release and [Ca2+]i using amperometry and imaging of the fluorescent Ca2+-sensitive dye Fura-2, respectively. Acute exposure of PC12 cells to 6-OH-BDE-47 (5 microM) induced vesicular catecholamine release. Catecholamine release coincided with a transient increase in [Ca2+]i, which was observed shortly after the onset of exposure to 6-OH-BDE-47 (120 microM). An additional late increase in [Ca2+]i was often observed at > or =1 microM 6-OH-BDE-47. The initial transient increase was absent in cells exposed to the parent compound BDE-47, whereas the late increase was observed only at 20 microM. Using the mitochondrial uncoupler carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) and thapsigargin to empty intracellular Ca2+ stores, we found that the initial increase originates from emptying of the endoplasmic reticulum and consequent influx of extracellular Ca2+, whereas the late increase originates primarily from mitochondria. The hydroxylated metabolite 6-OH-BDE-47 is more potent in disturbing Ca2+ homeostasis and neurotransmitter release than the parent compound BDE-47. The present findings indicate that bioactivation by oxidative metabolism adds considerably to the neurotoxic potential of PBDEs. Additionally, based on the observed mechanism of action, a cumulative neurotoxic effect of PBDEs and ortho-substituted polychlorinated biphenyls on [Ca2+]i cannot be ruled out.


Environmental pollution and human exposure to polycyclic aromatic hydrocarbons in the east Baltic region.
Environmental contamination by polycyclic aromatic hydrocarbons (PAH) and human exposure were surveyed in the east Baltic region. Polluted and heavily industrialized areas are upper Silesia in Poland, northern Bohemia in the Czech Republic, and the northeast part of Estonia. In Estonia the pollution is in a defined geographic area, where lung cancer incidence is higher than elsewhere. In Silesia, exposure of some 5 million people appears to be elevated; DNA (deoxyribonucleic acid) adduct levels in white blood cells are increased in groups of residents with apparently only environmental exposure. By extrapolation, some 150 annual lung cancer cases could be predicted due to PAH in Silesia. Air levels of benzo[a]pyrene were increased in northern Bohemia, and domestic heating and power plants using brown coal appeared to be major contributors to particulate air pollution in winter. Further studies are needed to assess health risks of PAH exposure in central and eastern Europe.


[Arguments for offering triple test serum screening for Down's syndrome to all pregnant women].
In an advisory report to the Dutch Government, the Health Council of the Netherlands has recently recommended offering triple test serum screening for Down's syndrome to all pregnant women. According to a critical review in this journal, the Council should have proposed excluding those less than 30 years of age. However, there is no age at which a logical limit can be set. Moreover, to suggest that the negative aspects of the screening will prevail for those under a specific age, denies the women involved the right to make a judgment based on their own values and preferences. Secondly, although limited resources may be a reason for limiting access to screening, doing so would be a politico-ethical decision, which raises the issue of justice. Finally, there are reasons for thinking that a new age limit would complicate the necessary counselling as opposed to making it easier.


Percutaneous transforaminal endoscopic discectomy and miniincision surgery in the treatment of lumbar intervertebral disc protrusion.
Lumbar intervertebral disc protrusion (LIDP) is a frequently occurring disease and 10-20% of patients require surgical treatment. Percutaneous transforaminal endoscopic discectomy (PTED) and mini-incision surgery are currently the most common surgeries for patients. To analyze the efficacy of PTED and mini-incision surgery in the treatment of lumbar intervertebral disc protrusion, this study selected 216 patients with LIDP who were admitted to the hospital between February 2014 and June 2015. The subjects were randomly divided into an observation group and a control group, 108 each. Patients in the observation groups were treated by PTED, while patients in the control group were treated by mini-incision surgery, and treatment efficacy of the two groups was observed. The results demonstrated that the duration of surgery and length of hospital stay of the observation group were significantly shorter than those of the control group, the intraoperative blood loss of the observation group was significantly less than that of the control group and the size of surgical incision of the observation group was much smaller than that of the control group (P less than 0.05). As to clinical efficacy, in accordance with the Japanese Orthopaedic Association (JOA) score and the Visual Analogue Scale (VAS) score, results of the observation group were superior to those of the control group at 3 months after surgery (P less than 0.05). In conclusion, treating patients with LIDP through PTED can significantly improve treatment efficacy, shorten surgical and healing time and relieve pain. This therapy is worth clinical promotion.


[Differentially expressed genes identified in the main olfactory epithelium of mice with deficiency of adenylate cyclase 3 by using suppression subtractive hybridization approach].
Adenylate cyclase 3 (AC3) is one of the major players in the olfactory signaling within the main olfactory epithelium (MOE) of mice. However, we are not ascertained whether deficiency of AC3 will lead to the differential expression of related genes in the MOE. Forward and reverse subtractive libraries were constructed by suppression subtractive hybridization (SSH) approach, with MOEs from AC3(-/-) and AC3(+/+) mice. These two libraries were primarily screened by Dot blot, differential expressed clones were sequenced and analyzed by bioinformatics, and differential expressed genes were verified by qRT-PCR. A total of 386 differentially expressed clones were picked out after Dot blot. The DNA sequences of 80 clones randomly selected were determined, and 62 clones were identified by blasting in GenBank. We found that 24 up-regulated clones were corresponded to genes of kcnk3, mapk7, megf11, and 38 down-regulated clones were corresponded to tmem88b, c-mip, skp1a, mlycd, etc. Their functions were annotated with Gene Ontology (GO) and found to be mainly focused on molecular binding, cell cycle, processes of biology and cells. Five genes (kcnk3, c-mip, mlycd, tmem88b and trappc5) were verified by qRT-PCR with individuals of AC3(+/+) and AC3(-/-) mice. The data indicate that kcnk3 gene is up-regulated significantly, increasing 1.27 folds compared to control mice, whereas c-mip, mlycd, tmem88b and trappc5 are down-regulated significantly, decreasing 20%, 7%, 32% and 29% compared to the AC3(+/+)mice. The functions of these genes are closely related with K(+) channels, cell differentiation, metabolism of fats, membrane transportation, and so on. It is tempting to speculate that these genes might work together with AC3 to orchestrate the olfactory transduction signaling in the MOE.


Genomic structure and mapping of human FADD, an intracellular mediator of lymphocyte apoptosis.
Fas-associated death domain protein (FADD)/MORT1 is a 23-kDa cytoplasmic protein containing a C-terminal death domain that interacts with the intracellular death domain of the Fas transmembrane receptor. Cross-linking of Fas mediates apoptosis in a variety of cells, primarily peripheral T lymphocytes, for which this pathway plays a major role in mature lymphocyte homeostasis. We report the characterization of the human FADD gene, which spans approximately 3.6 kb and contains two exons (286 and 341 bp) separated by a 2.0-kb intron. FADD was mapped to chromosome 11q13.3 by the independent techniques of PCR screening of somatic cell hybrid mapping panels and fluorescence in situ hybridization. In addition FADD was shown by fluorescence in situ hybridization to be amplified along with other 11q13.3 genes previously studied in the breast cancer cell line MDA-MB-134-VI, raising the possibility that overexpression of mutant FADD could contribute to poor prognosis and increased invasiveness of tumors. Its known role in apoptosis has made FADD a candidate susceptibility gene for autoimmune lymphoproliferative syndrome. Now that it has been colocalized in 11q13.3 with IDDM4, a diabetes susceptibility locus, alterations in FADD should also be considered as potential contributors to insulin-dependent familial diabetes. Elucidation of the map position and gene structure of FADD will make possible linkage and mutation analysis to study the role of this gene in human diseases.


Pathogenesis of herpes simplex virus in B cell-suppressed mice: the relative roles of cell-mediated and humoral immunity.
B cell responses of Balb/c mice were suppressed using sheep anti-mouse IgM serum. At 4 weeks, both B cell-suppressed and normal littermates were infected in the ear pinna with herpes simplex virus type 1 (HSV-1). The B cell-suppressed mice failed to produce neutralizing herpes antibodies in their sera but had a normal cell-mediated immunity (CMI) response as measured by a delayed hypersensitivity skin test. Although the infection was eliminated from the ear in both B cell-suppressed and normal mice by day 10 after infection, there was an indication that B cell-suppressed mice had a more florid primary infection of the peripheral and central nervous system and also a higher incidence of a latent infection. These results support the hypothesis that antibody is important in restricting the spread of virus to the central nervous system, whereas CMI is important in clearing the primary infection in the ear pinna.


Temporomandibular Disorders and Oral Features in Idiopathic Inflammatory Myopathies (IIMs) Patients: An Observational Study.
Aim: Inflammatory idiopathic myopathies (IIMs) are inflammatory processes affecting skeletal musculature and extramuscular organs. Temporomandibular disorders (TMD) involve jaw muscles and temporomandibular joint. The aim of this observational study was to investigate the prevalence of the main TMD symptoms and signs as well as oral implications in IIM patients. Methods: The study group included 54 patients (42 women and 12 men), 22 of whom affected by dermatomyositis (DM), 29 by polymyositis (PM) and 3 by inclusion body myositis (IBM). A group of 54 patients not affected by this disease, served as CG. Oral and TMD signs and symptoms were evaluated by means of a questionnaire and through clinical examination. Results: About oral symptoms, the study group complained more frequently dysgeusia, with loss of taste or unpleasant taste (p<0.0001) and feeling of burning mouth (9.4% versus 0 controls). Xerostomia was more prevalent in the study group respect to the CG (p<0.0001). Dysphagia was reported by 48.1% of IIM patients while was absent in CG (p<0.0001). About oral signs, cheilitis (p<0.05) and oral ulcers (p<0.05) were significantly more frequent in CG. As regard to TMD symptoms, arthralgia and tinnitus didn't showed significant differences between the two groups, while neck/shoulders and masticatory muscle pain was significantly more referred in IIM patients than in the CG (p<0.05). About TMJ signs, sounds were overlapping in the two groups: click=11.1% in both IIM patients and CG (p>0.05), crepitation in 11.1% of IIM and 9.3% of controls (p>0.05). No significant difference was detected about deflection (9.3%, p>0.05), while deviation was wider in CG (p<0.05). Active opening and lateralities showed no significant differences, while endfeel was significantly increased in IIM group for a higher presence of muscular contracture. Bruxism was present only in CG. Conclusion: The data collected from this observational study seem to support the existence of a relationship between the prevalence of TMD symptoms and signs as well as oral features in patients with myositis. A remarkable reduction of salivary flow and dysphagia were more frequent and severe in IIM patients, as well as muscle contracture and myofacial pain evoked by palpation, this result being highly significant.


Enhancing the Backbone Coplanarity of n-Type Copolymers for Higher Electron Mobility and Stability in Organic Electrochemical Transistors.
Electron-transporting (n-type) conjugated polymers have recently been applied in numerous electrochemical applications, where both ion and electron transport are required. Despite continuous efforts to improve their performance and stability, n-type conjugated polymers with mixed conduction still lag behind their hole-transporting (p-type) counterparts, limiting the functions of electrochemical devices. In this work, we investigate the effect of enhanced backbone coplanarity on the electrochemical activity and mixed ionic-electronic conduction properties of n-type polymers during operation in aqueous media. Through substitution of the widely employed electron-deficient naphthalene diimide (NDI) unit for the core-extended naphthodithiophene diimide (NDTI) units, the resulting polymer shows a more planar backbone with closer packing, leading to an increase in the electron mobility in organic electrochemical transistors (OECTs) by more than two orders of magnitude. The NDTI-based polymer shows a deep-lying lowest unoccupied molecular orbital level, enabling operation of the OECT closer to 0 V vs Ag/AgCl, where fewer parasitic reactions with molecular oxygen occur. Enhancing the backbone coplanarity also leads to a lower affinity toward water uptake during cycling, resulting in improved stability during continuous electrochemical charging and ON-OFF switching relative to the NDI derivative. Furthermore, the NDTI-based polymer also demonstrates near-perfect shelf-life stability over a month-long test, exhibiting a negligible decrease in both the maximum on-current and transconductance. Our results highlight the importance of polymer backbone design for developing stable, high-performing n-type materials with mixed ionic-electronic conduction in aqueous media.


[Assessment of fluid content of the lung by thoracic radiography. Comparison of extravascular lung water measurement and results of radiological estimation methods].
Extravascular lung water (EVLW) was determined with the thermal-dye double-indicator method (119 individual measurements) in 23 patients in an intensive-care unit, and the results were compared with estimates made from largely standardized portable chest X-ray films, using the staging method of Sibbald as well as that of Halperin. There was a significant correlation with the measured EVLW for both methods. Radiologically "normal" films corresponded to a mean EVLW value of 8.4 ml/kg body-weight. Radiologically judged adjacent stages did not in all cases compare with corresponding measured EVLW values. But when EVLW values were clearly abnormal, the X-ray films always demonstrated massive interstitial or alveolar infiltrations. Measurement of EVLW enables one accurately to judge the fluid contents of the lung and is superior to the assessment of the chest X-ray film.


Production of induced secondary metabolites by a co-culture of sponge-associated actinomycetes, Actinokineospora sp. EG49 and Nocardiopsis sp. RV163.
Two sponge-derived actinomycetes, Actinokineospora sp. EG49 and Nocardiopsis sp. RV163, were grown in co-culture and the presence of induced metabolites monitored by ¹H NMR. Ten known compounds, including angucycline, diketopiperazine and β-carboline derivatives 1-10, were isolated from the EtOAc extracts of Actinokineospora sp. EG49 and Nocardiopsis sp. RV163. Co-cultivation of Actinokineospora sp. EG49 and Nocardiopsis sp. RV163 induced the biosynthesis of three natural products that were not detected in the single culture of either microorganism, namely N-(2-hydroxyphenyl)-acetamide (11), 1,6-dihydroxyphenazine (12) and 5a,6,11a,12-tetrahydro-5a,11a-dimethyl[1,4]benzoxazino[3,2-b][1,4]benzoxazine (13a). When tested for biological activity against a range of bacteria and parasites, only the phenazine 12 was active against Bacillus sp. P25, Trypanosoma brucei and interestingly, against Actinokineospora sp. EG49. These findings highlight the co-cultivation approach as an effective strategy to access the bioactive secondary metabolites hidden in the genomes of marine actinomycetes.


Developmental expression and cardiac transcriptional regulation of Myh7b, a third myosin heavy chain in the vertebrate heart.
The mammalian heart expresses two myosin heavy chain (MYH) genes (Myh6 and Myh7), which are major components of the thick filaments of the sarcomere. We have determined that a third MYH, MYH7B, is also expressed in the myocardium. Developmental analysis shows Myh7b expression in cardiac and skeletal muscle of Xenopus, chick and mouse embryos, and in smooth muscle tissues during later stages of mouse embryogenesis. Myh7b is also expressed in the adult human heart. The promoter region of the Myh7b gene shows remarkable similarity between diverse species, suggesting that transcriptional control mechanisms have been conserved. Using luciferase reporter analysis in rat cardiomyocytes, it can be shown that MEF2, GATA, and E-box regulatory elements are essential for efficient expression of the Myh7b gene. In addition two conserved elements that do not correspond to consensus binding sites for known transcription factors are also essential for full transcriptional activity of the Myh7b reporter. Finally, the Myh7b gene shows a transcriptional response similar to Myh6 in response to cardiac hypertrophy.


[The changing role of the dental hygienist].
This article describes the role of the dental hygienist in the Netherlands from the start of the training of dental hygienists in 1968. With the new Individual Health Care Professionals Bill from 1997 the dental hygienists are entitled to perform more tasks than in the past. This article describes the viewpoint of the professional dental hygienist organization on the future role of the dental hygienist. Cooperation with the other members of the dental team and free entry to the dental hygienist are considered important conditions. The creation of appropriate conditions by government and insurance companies is a matter of major concern.


Is the closest facility the one actually used? An assessment of travel time estimation based on mammography facilities.
Characterizing geographic access depends on a broad range of methods available to researchers and the healthcare context to which the method is applied. Globally, travel time is one frequently used measure of geographic access with known limitations associated with data availability. Specifically, due to lack of available utilization data, many travel time studies assume that patients use the closest facility. To examine this assumption, an example using mammography screening data, which is considered a geographically abundant health care service in the United States, is explored. This work makes an important methodological contribution to measuring access--which is a critical component of health care planning and equity almost everywhere. We analyzed one mammogram from each of 646,553 women participating in the US based Breast Cancer Surveillance Consortium for years 2005-2012. We geocoded each record to street level address data in order to calculate travel time to the closest and to the actually used mammography facility. Travel time between the closest and the actual facility used was explored by woman-level and facility characteristics. Only 35% of women in the study population used their closest facility, but nearly three-quarters of women not using their closest facility used a facility within 5 min of the closest facility. Individuals that by-passed the closest facility tended to live in an urban core, within higher income neighborhoods, or in areas where the average travel times to work was longer. Those living in small towns or isolated rural areas had longer closer and actual median drive times. Since the majority of US women accessed a facility within a few minutes of their closest facility this suggests that distance to the closest facility may serve as an adequate proxy for utilization studies of geographically abundant services like mammography in areas where the transportation networks are well established.


Differential expression of laminin A and B chains during development of embryonic mouse organs.
Laminin is a large glycoprotein of basement membranes. The best described laminin from a mouse tumor contains three polypeptide chains (A, B1 and B2), but there is recent evidence that some cell types produce laminin isoforms lacking the A chain. We have here studied the occurrence of the isoforms during mouse organogenesis. In all tissues studied, the A chain mRNA and polypeptide were more weakly expressed than those of the B chains. Laminin A chain polypeptides showed a much more restricted tissue distribution than the B chains. Laminin A chain polypeptide was mainly detected in basement membranes of epithelial cells, suggesting that this chain is important for morphogenesis of epithelial sheets. Most endothelial basement membranes and all embryonic mesenchyme matrices studied seemed to lack the A chain even though they contained B chains. Several of the cells producing laminin devoid of A chain seem to produce other polypeptides that become complexed to the B chains. With an anti-laminin antiserum, which in immunoblots reacts only with A and B polypeptide chains, additional polypeptides of 160 and 190 x 10(3) Mr were co-precipitated from all tissues studied. In developing heart, a polypeptide of 300 x 10(3) Mr was co-precipitated in addition. Our data suggest that these laminin-associated polypeptides are not formed by a differential splicing of the known A chain mRNA. Northern blotting of poly (A)+ RNA showed only 10kb A chain transcripts but no truncated forms. We conclude that several cell types in the mouse embryo produce laminin variants that lack the 400 x 10(3) Mr A chain. Since a major cell binding site of laminin contains parts of the A chain, the variants should differ in biological function from laminin containing this A chain.


Using photos of basic facial expressions as a new approach to measuring implicit attitudes.
Measuring implicit attitudes is difficult due to social desirability (SD). A new method, the Emotion Based Approach (EBA), can solve this by using emotions from a display of faces as response categories. We applied this on an EBA Spirituality tool (EBA-SPT) and an Actual Situation tool (EBA-AST). Our aim was to assess the structure, reliability and validity of the tools and to compare two EBA assessment approaches, i.e., an explicit one (only assessing final replies to items) and an implicit one (assessing also the selection process). We obtained data on a sample of Czech adults (n = 522, age 30.3±12.58; 27.0% men) via an online survey; cortisol was assessed in 46 participants. We assessed the structure and psychometric properties (internal consistency and test-retest reliability; convergent, discriminant, and criterion validity) of the EBA, and examined the differences between explicit vs. implicit EBA approaches. We found an acceptable-good internal consistency reliability of the EBA tools, acceptable discriminant validity between them and low (neutral expression) to good (joy) test-retest reliability for concrete emotions assessed by the tools. An implicit EBA approach showed stronger correlations between emotions and weaker convergent validity, but higher criterion validity, than an explicit approach and standard questionnaires. Compared to standard questionnaires, EBA is a more reliable approach for measuring attitudes, with an implicit approach that reflects the selection process yielding the best results.


Light and choroidal PO2 modulation of intraretinal oxygen levels in an avascular retina.
To determine the influence that choroidal oxygen level and outer retinal oxygen demand have on oxygen availability to the inner retina when the choroid is the only source of retinal oxygenation. This condition prevails in avascular retinas and in vascularized retinas suffering vascular occlusion. Oxygen-sensitive microelectrodes were used to measure the oxygen tension as a function of depth in the naturally avascular retina of anesthetized and mechanically ventilated guinea pigs (n = 6). Choroidal PO2 was manipulated by varying the ventilation gas mixture, and outer retinal oxygen consumption was modulated by light-dark adaptation. Individual PO2 profiles were fitted to a multilayer mathematical model of PO2 distribution, and pairs of profiles at different choroidal PO2 levels, or under light and dark conditions, were fitted to an intraretinal PO2 difference model. Both models reflect the purely choroidal supply of retinal oxygenation. An increase in choroidal PO2 produced an equivalent increase in all retinal layers. Light induced a decreased oxygen consumption in the region of the inner segments of the photoreceptors, which resulted in a significant increase in PO2 in this layer, flowing on unattenuated to all inner retinal layers. The intraretinal PO2 distribution and the light- and ventilatory-induced changes in PO2 were consistent with theoretical predictions of the mathematical models. The present experimental studies confirm that when the choroid is the only source of retinal oxygenation, the full effect of increased choroidal oxygen level or reduced uptake in the outer retina passes through to the inner retinal layers if the oxygen utilization by the inner retina remains constant.


Management of severe falciparum malaria.
Plasmodium falciparum is the most common cause of severe and life-threatening malaria. Falciparum malaria causes over one million deaths every year. In Africa, a vast majority of these deaths occur in children under five years of age. The presentation of severe malaria varies with age and geographical distribution. The mortality rate is higher in adults than in children but African children develop neuro-cognitive sequelae following severe malaria more frequently. The management of severe malaria includes prompt administration of appropriate parenteral anti-malarial agents and early recognition and treatment of the complications. In children, the complications include metabolic acidosis (often caused by hypovolaemia), hypoglycaemia, hyperlacticacidaemia, severe anaemia, seizures and raised intracranial pressure. In adults, renal failure and pulmonary oedema are more common causes of death. In contrast, concomitant bacterial infections occur more frequently in children and are associated with mortality in children. Admission to critical or intensive care units may help reduce the mortality, and the frequency and severity of sequelae related to severe malaria.


Hb Hammersmith [beta 42(CD1) Phe-->Ser]: occurrence as a de novo mutation in black monozygotic twins with multiple congenital anomalies.
To present the occurrence of Hb Hammersmith as a de novo mutation in African-American twins with multiple congenital anomalies. Standard hematologic methods were used. The presence of an unstable Hb variant was confirmed by brilliant cresyl blue staining and an isopropanol stability test. Hb Hammersmith was confirmed by the sequencing of polymerase chain reaction-amplified beta-globin gene. The presence of Hb Hammersmith was confirmed in female monozygotic twins of African-American origin with congenital Heinz body hemolytic anemia and multiple congenital anomalies. The variant occurred as a de novo mutation in the twins. This report describes the occurrence of Hb Hammersmith [B42(CD1)Phe-->Ser] in African-American twins. As with the other reported cases, both twins were female. In addition to Heinz body hemolytic anemia, a low arterial O2 saturation in the proposita was shown by pulse oximetry. Multiple congenital anomalies involving various systems were also found in both twins.


Identification of the cellular source of laminin beta2 in adult and developing vertebrate retinae.
The interphotoreceptor matrix (IPM) is a specialized extracellular matrix that surrounds the inner and outer segments of photoreceptors. This matrix contains molecules that may be important in directing photoreceptor differentiation and survival. For example, one molecule that we have previously identified as a component of the IPM, laminin beta2 (formerly known as s-laminin), is implicated in the differentiation of rod photoreceptor cells. Developmentally, laminin beta2 is present before rod birth in a position that is consistent with a role in directing rod differentiation; it is found, in both the rat and skate, in the ventricular space that ultimately becomes the IPM. In this study, we identify the source of laminin beta2 in the adult and developing retina. Both immunohistochemistry in the adult skate retina and in situ hybridizations in the adult rat retina reveal that laminin beta2 is produced by Müller cells. In addition, in the skate but not the rat retina, retinal pigment epithelial cells may be an alternative source of laminin beta2. During development, however, laminin beta2 is present before the birth of Müller glial cells; at this stage of development, laminin beta2 RNA is present within the neuroepithelial layer in a pattern that is consistent with its production by neuroepithelial cells.


Platelet Function Is Associated With Dementia Risk in the Framingham Heart Study.
Background Vascular function is compromised in Alzheimer disease (AD) years before amyloid and tau pathology are detected and a substantial body of work shows abnormal platelet activation states in patients with AD. The aim of our study was to investigate whether platelet function in middle age is independently associated with future risk of AD. Methods and Results We examined associations of baseline platelet function with incident dementia risk in the community-based FHS (Framingham Heart Study) longitudinal cohorts. The association between platelet function and risk of dementia was evaluated using the cumulative incidence function and inverse probability weighted Cox proportional cause-specific hazards regression models, with adjustment for demographic and clinical covariates. Platelet aggregation response was measured by light transmission aggregometry. The final study sample included 1847 FHS participants (average age, 53.0 years; 57.5% women). During follow-up (median, 20.5 years), we observed 154 cases of incident dementia, of which 121 were AD cases. Results from weighted models indicated that platelet aggregation response to adenosine diphosphate 1.0 µmol/L was independently and positively associated with dementia risk, and it was preceded in importance only by age and hypertension. Sensitivity analyses showed associations with the same directionality for participants defined as adenosine diphosphate hyper-responders, as well as the platelet response to 0.1 µmol/L epinephrine. Conclusions Our study shows individuals free of antiplatelet therapy with a higher platelet response are at higher risk of dementia in late life during a 20-year follow-up, reinforcing the role of platelet function in AD risk. This suggests that platelet phenotypes may be associated with the rate of dementia and potentially have prognostic value.


Maternal nicotine exposure during gestation and lactation induces cardiac remodeling in rat offspring.
The aim of this study was to evaluate the effects of maternal nicotine exposure on heart morphology and fibrosis in rat offspring. Nicotine was administered to pregnant Sprague-Dawley rats by using a subcutaneous osmotic mini-pump at a dose of 6 mg/kg/day from Gestational Days 7-21 or Gestational Day 7 to Postnatal Day 14. A control group received an equal volume of saline by the same route as nicotine. Rats born to prenatal nicotine-treated dams exhibited significantly greater cell width of cardiomyocytes, fewer cardiomyocyte nuclei number, higher β-myosin heavy chain and transforming growth factor (TGF-β1) expression, and higher collagen deposition in heart compared with rats born to normal saline-treated dams on Postnatal Days 7 and 21. Postnatal nicotine exposure further enhances these effects. We conclude that TGF-β1 may be involved in the pathogenesis of cardiac remodeling induced by maternal nicotine exposure during gestation and lactation in rat offspring.


Expression of mRNA for the LH and FSH receptors in mouse oocytes and preimplantation embryos.
The gonadotrophins LH and FSH are known to regulate gonadal growth, and differentiation, endocrine function and gametogenesis. The LH receptor is expressed in ovarian theca, granulosa and luteal cells, and in testicular Leydig cells. The FSH receptor is expressed only in ovarian granulosa cells and in testicular Sertoli cells. The expression of the FSH and LH receptors was analysed by RT-PCR to study the role of these receptors in early mouse development. After reverse transcription, strategically designed nested primers were used for amplification from cDNA. Transcripts for the receptors were present in mouse oocytes and preimplantation embryos. The presence of mRNA for FSH and LH receptors in oocytes, zygotes and preimplantation embryos indicates a potential role for the gonadotrophins in the modulation of meiotic resumption and completion of oocyte maturation, as well as a beneficial effect on early embryonic development in mice.


The crystallographic chameleon: when space groups change skin.
Volume A of International Tables for Crystallography is the reference for space-group information. However, the content is not exhaustive because for many space groups a variety of settings may be chosen but not all of them are described in detail or even fully listed. The use of alternative settings may seem an unnecessary complication when the purpose is just to describe a crystal structure; however, these are of the utmost importance for a number of tasks, such as the investigation of structure relations between polymorphs or derivative structures, the study of pseudo-symmetry and its potential consequences, and the analysis of the common substructure of twins. The aim of the article is twofold: (i) to present a guide to expressing the symmetry operations, the Hermann-Mauguin symbols and the Wyckoff positions of a space group in an alternative setting, and (ii) to point to alternative settings of space groups of possible practical applications and not listed in Volume A of International Tables for Crystallography.


Infants Learn to Follow Gaze in Stages: Evidence Confirming a Robotic Prediction.
Gaze following is an early-emerging skill in infancy argued to be fundamental to joint attention and later language development. However, how gaze following emerges is a topic of great debate. Representational theories assume that in order to follow adults' gaze, infants must have a rich sensitivity to adults' communicative intention from birth. In contrast, learning-based theories hold that infants may learn to gaze follow based on low-level social reinforcement, without the need to understand others' mental states. Nagai et al. (2006) successfully taught a robot to gaze follow through social reinforcement and found that the robot learned in stages: first in the horizontal plane, and later in the vertical plane-a prediction that does not follow from representational theories. In the current study, we tested this prediction in an eye-tracking paradigm. Six-month-olds did not follow gaze in either the horizontal or vertical plane, whereas 12-month-olds and 18-month-olds only followed gaze in the horizontal plane. These results confirm the core prediction of the robot model, suggesting that children may also learn to gaze follow through social reinforcement coupled with a structured learning environment.


Enzymatic hydrolysis of beer brewers' spent grain and the influence of pretreatments.
The enzymatic saccharification of plant material has been shown to be of interest in various fields, such as the production of fruit juices(1,2) and the utilization of biomass.(3) A combination of cellulase, pectinase, and hemicellulases is usually used because of the chemical composition of the matrix of plant cell walls.For apples, beet pulp, and potato fiber, almost a complete hydrolysis of polysaccharides is obtained by combining cellulose and pectinase. For nonparenchymatic tissue, the situation is somewhat different: pectin is a minor component and the hemicellulose content is much higher. Enzyme action is restricted by the lignin barrier and by the high crystallianity of cellulose in this material. For such materials, mechanical, thermal, or chemical pretreatments are necessary to achieve hydrolysis.(4,5)This communication describes various enzymatic treatements and chemical and physical pretreatemtn, using brewers' spent grain as substrate. Spent grain is the residue of malt and grain which remains in the mash-kettle after the liquefied and saccharified starch has been removed by filtration.


Pore-scale observation of microsphere deposition at grain-to-grain contacts over assemblage-scale porous media domains using X-ray microtomography.
The prevalence of colloid deposition at grain-to-grain contacts in two porous media (spherical glass beads and angular quartz sand, 710-850 microm) was examined using X-ray microtomography (XMT) under conditions where the colloid-grain surface interaction was solely attractive (lacking an energy barrier to deposition), and under fluid velocity conditions representative of engineered filtration systems. XMT allows pore-scale observation of colloid deposition over assemblage-scale porous media domains. Colloids visible in reconstructed images were prepared by coating gold on hollow ceramic microspheres (36 microm in size) (to render densities only slightly higher than water). A significant fraction of the deposited microspheres were deposited at grain-to-grain contacts (about 20% in glass beads, 40% in quartz sand) under the conditions examined. The deposited microsphere concentrations decreased log-linearly with increasing transport distance regardless of the environment of deposition (grain-to-grain contact versus single-contact deposition). The profile shape was, therefore, consistent with filtration theory, and the observed deposition rate coefficients were also well predicted by filtration theory. The ability of filtration theory to predict the magnitude and spatial distribution of deposition demonstrates that filtration theory captures the essential elements of deposition in the absence of an energy barrier despite a lack of accounting for grain-to-grain contacts. The observed factor of 2 greater deposition at grain-to-grain contacts in quartz sand relative to equivalently sized glass beads is consistent with greater grain-to-grain contact lengths and greater fraction of small pores in the quartz sand relative to the glass beads, as determined via a pore structure analysis algorithm (medial axis algorithm).


The role of nitric oxide in Doxorubicin-induced cardiotoxicity: experimental study.
We evaluated the myocardial damage in rats treated with doxorubicin (DOX) alone and in combination with nitric oxide synthase (NOS) inhibitors. Twenty-four male Sprague Dawley rats (12 weeks old, weighing 262±18 g) were randomly assigned into 4 groups (n=6). Group I was the control group. In Group II, rats were treated with intraperitoneal (ip) injections of 3 mg/kg DOX once a week for 5 weeks. In Group III, rats received weekly ip injections of 30 mg/kg L-NAME (nonspecific NOS inhibitor) 30 min before DOX injections for 5 weeks. In Group IV, rats received weekly ip injections of 3 mg/kg L-NIL (inducible NOS inhibitor) 30 min before DOX injections for 5 weeks. Rats were weighed 2 times a week. At the end of 6 weeks, hearts were excised and then fixed for light and electron microscopy evaluation and tissue lipid peroxidation (malondialdehyde). Blood samples were also obtained for measuring plasma lipid peroxidation. Weight loss was observed in Group II, Group III, and Group IV. Weight loss was statistically significant in the DOX group. Findings of myocardial damage were significantly higher in animals treated with DOX only than in the control group. Histopathological findings of cardiotoxicity in rats treated with DOX in combination with L-NAME and L-NIL were not significantly different compared with the control group. The level of plasma malondialdehyde in the DOX group (9.3±3.4 µmol/L) was higher than those of all other groups. Our results showed that DOX cardiotoxicity was significantly decreased when DOX was given with NO synthase inhibitors.


Lung Volume Reduction Surgery on Extracorporeal Life Support.
Lung volume reduction surgery improves exercise tolerance, lung function, and quality of life for selected patients with emphysema. Lung volume reduction surgery is well established for patients in a highly elective setting. It is, however, contraindicated in cases of acute cardiorespiratory failure. We present the case of a patient with severe emphysema who had acute respiratory failure and decompensated cor pulmonale requiring life-saving venovenoarterial extracorporeal life support after admission to the emergency unit. He underwent lung volume reduction surgery with intent to wean from extracorporeal life support. He had complete functional recovery after 4 months.