Age-associated power decline from running, jumping, and throwing male masters world records.
BACKGROUND/STUDY CONTEXT: The capacity to perform everyday tasks is directly related to the muscular power the body can develop (see Appendix). The age-related loss of power is a fact, but the characterization or the rate of muscle power loss remains an open issue. Data useful to study the decline of the skeletal muscles power are largely available from sources other than medical tests, e.g., from track and field competitions of Masters athletes. The aim of our study is to identify the age-related decline trend of the power developed by the athletes in carrying out the track and field events. Absolute male world records of 16 events were collected along with world records of male Masters categories. Performance was normalized with respect to the absolute record; the performance of various age groups is consequently represented by a number ranging from 1 (world absolute records) to 0 (null performance). The performance of a jumping event is transformed into a parameter proportional to the power developed by the athletes: the displacement of the center of gravity of the athlete. Throwing events are further normalized for the decreasing weight of the implements with the increasing age of the Masters athletes. Most track and field events show a linear decline to 70 years. The annual rate of power decline for all the events (running, throwing, and jumping), using a simplified synthesis, is 1.25% per year. The events that involve mostly upper limbs (shot put, javelin throw) show a higher rate of decline (1.4% per year) compared to those where the lower limbs are mostly involved (long jump 1.1%, track events 0.6-0.7% per year). This analysis of muscle power decline is only partially in line with the results of works based on clinical tests. A clarification of the reasons for such discrepancy may provide clinically significant information. Human power decline in Masters athletes was analyzed, adopting a coherent approach based on an extended database. Skeletal muscle power starts declining after the age of 30, with slight variations depending on the events. This conclusion is in line with only some of the previous studies. The various trend lines point to 0 at the age of 110 years, which is in line with the present human survival age. The study can be further developed with a suitable database for male and female Masters performances to facilitate longitudinal studies, which are currently lacking.


Phosphorothioate oligonucleotide quantification by μ-liquid chromatography-mass spectrometry.
Phosporothioate oligonucleotides represent an important class of therapeutic oligonucleotides, in which none-bridging oxygen atoms of the phosphate groups are replaced by sulfur. These oligonucleotides are designed to treat disease by modulating gene expression of an affected individual. As the development and application of these therapeutical oligonucleotides require analytical support, the development, validation, and application of an assay for the quantitative analysis of a phosporothioate oligonucleotide in rat plasma is described. The method employs ion-pair reversed-phase chromatography on a monolithic capillary column with acetonitrile gradients in cyclohexyldimethylammonium acetate for separation and high-resolution tandem mass spectrometry for detection of nucleic acids. Chromatographic parameters (i.e. column temperature, mobile phase composition) as well as mass spectrometric parameters (i.e. spray voltage, gas flow, and capillary position, scan mode) have been optimized for sensitive oligonucleotide quantification. Furthermore, a solid-phase extraction method was developed which enabled processing of 10 μl of plasma. The five-point calibration curve showed linearity over the range of concentrations from 100 to 1,000 nM of the oligonucleotide. The limit of detection was 50 nM. The intra- and inter-day precision and accuracies were always better than 10.2 %. Using this assay, we performed a pharmacokinetic study of the phosporothioate oligonucleotide in rat treated with a single intravenous dose of 0.39 μmol/kg. The assay sensitivity was sufficient to study the early phase elimination of the oligonucleotide. Small amounts of the oligonucleotide were detectable up to 3 h after dosing.


Cerebral lactate correlates with early onset pneumonia after aneurysmal SAH.
Pneumonia is a significant medical complication following aneurysmal subarachnoid hemorrhage (aSAH). The aSAH may initiate immune interactions leading to depressed immunofunction, followed by an increased risk of infection. It remains unclear as to whether there is a possible association between cerebral metabolism and infections. Clinical and microdialysis data from aSAH patients prospectively included in the CoOperative Study on Brain Injury Depolarisations protocol Berlin were analyzed. Levels of glucose, lactate, pyruvate, and glutamate were measured hourly using microdialysis in the cerebral extracellular fluid. The occurrence of pneumonia (defined by positive microbiological cultures) and delayed ischemic neurological deficits (DIND) was documented prospectively. Eighteen aSAH patients (52.7 ± 10.7 years), classified according to the World Federation of Neurological Surgeons in low (I-III, n = 9) and high (IV-V, n = 9) grades, were studied. Eight patients (45%) experienced DIND, 10 patients (56%) pneumonia (mean onset day 2.6). Lactate was elevated at day 3 in infected patients (n = 9, median = 6.82 mmol/L) vs. patient without infections (n = 6, median = 2.90 mmol/L, p = 0.036). The optimum cut-off point to predict pneumonia at day 3 was 3.57 mmol/L with a sensitivity of 0.77, and a specificity of 0.66 (area under curve was 0.833 with p = 0.034). Lactate at day 7 was higher in DIND patients compared to no-DIND-patients (p = 0.016). Early elevated lactate correlated with occurrence of bacterial pneumonia, while late elevations with DIND after aSAH. Future investigations may elucidate the relationship between cerebral lactate and markers of immunocompetence and more detailed to identify patients with higher susceptibility for infections.


Increased prevalence of ventricular fibrillation in patients with type 2 diabetes mellitus.
Diabetes mellitus (DM) is an independent risk for cardiovascular disease. Furthermore, patients with DM have increased risk for ventricular arrhythmia that is thought to be secondary to coronary artery disease (CAD) or congestive heart failure (CHF). We hypothesized that DM may cause ventricular arrhythmias independent of CAD or CHF. Using a large database, we evaluated the occurrence of ventricular fibrillation in patients with DM adjusting for CAD and CHF. We used patient treatment files (PTF), documents of inpatients' admissions containing discharge diagnoses (ICD-9 codes) from all Veterans Health Administration Hospitals. The patients were stratified in two groups: ICD-9 code for DM (293 124) and a control group with ICD-code for hypertension (HTN) but no DM (552 623). ICD-9 codes for ventricular fibrillation were used for this study. We performed uni- and multivariant analysis adjusting for comorbid conditions. Ventricular fibrillation was present in 563 (0.2%) vs 781 (0.1%) in the control group. Using multivariate analysis, DM remained independently associated with ventricular fibrillation (odds ratio: 1.7; confidence interval: 1.5-1.9; P < 0.000). Patients with DM have significantly higher prevalence of ventricular fibrillation independent of CAD or CHF, which in part may explain the higher risk of sudden death in patients with DM.


Continuous investigation of the nasal cycle over 48 hours.
Previous results on the nasal cycle refer to measurements over up to 24h. The long-term rhinoflowmetry (LRFM) allows continuous observations over a longer period. The aim of the study was to observe the nasal cycle for the first time over 48h under everyday conditions. The LRFM was continuously applied to 30 rhinologically healthy subjects (20 female, 10 male) over 48h. The different types of nasal cycle were classified as follows: "classic", "in concert", "one-sided", "no-cycle" and "mixed". The focus of this study was on the results over the entire 48 hours. The comparison of the two consecutive days was also made. A nasal cycle could be detected in 100% of the subjects over 48h. With 97%, the mixed type most commonly occurred as a combination of classical and in concert components. In all subjects, classical cycle components could be detected at least once. The no-cycle type was not observed. In the awake state, the mixed type dominated (80%), as a combination of classical and in concert parts. In the sleep state, the classical type was the most common type (97%). The average phase duration was 206 ± 83 minutes. In the very first continuous 48-hour study on the nasal cycle, 100% of the subjects presented a nasal cycle. The LRFM method is the only one that offers the possibility to perform continuous measurements over a longer period during daily routine. The results of previous single-stage examination methods should thus be questioned.


Increased Speed Elicited More Automatized but Less Predictable Control in Cyclical Arm and Leg Movements.
The present study explores variations in the degree of automaticity and predictability of cyclical arm and leg movements. Twenty healthy adults were asked to walk on a treadmill at a lower-than-preferred speed, their preferred speed, and at a higher-than-preferred speed. In a separate, repetitive punching task, the three walking frequencies were used to cue the target pace of the cyclical arm movements. Movements of the arms, legs, and trunk were digitized with inertial sensors. Whereas absolute slope values (|β|) of the linear fit to the power spectrum of the digitized movements (p < .001, η2 = .676) were systematically smaller in treadmill walking than in repetitive punching, sample entropy measures (p < .001, η2 = .570) were larger reflecting the former task being more automated but also less predictable than the latter task. In both tasks, increased speeds enhanced automatized control (p < .001, η2 = .475) but reduced movement predictability (p = .008, η2 = .225). The latter findings are potentially relevant when evaluating effects of task demand changes in clinical contexts.


Characterising conditions that favour potentiation of noise induced hearing loss by chemical asphyxiants.
Hearing loss is the most common occupational disease in the United States with noise serving as the presumed causative agent in most instances; noise is identified as a prominent factor in approximately 10 million individuals in the United States with hearing impairments. Despite the characterisation of noise exposures that yield temporary and permanent threshold shifts and partial elucidation of mechanisms that are responsible for noise-induced hearing loss (NIHL), there remain significant knowledge gaps concerning factors causing NIHL. One such knowledge gap concerns potentiation of NIHL by simultaneous exposure to chemical agents. We have pursued investigation of the exposure conditions that facilitate the potentiation of NIHL by carbon monoxide. The selection of these specific agents is predicated upon the ubiquitous nature of exposure to chemical asphyxiants and a preliminary understanding of the mechanisms by which chemical asphyxiants disrupt hearing. Our data indicate that the potentiation of NIHL by carbon monoxide increases as a function of carbon monoxide concentration at levels of 500 ppm and above, but that the extent of potentiation shows a non-linear relationship to total noise energy with the greatest potentiation shown at moderate noise exposures that produce limited permanent threshold shifts. Further, the potentiation of NIHL by carbon monoxide appears to saturate as noise severity is increased such that at the most severe conditions used, the effects of carbon monoxide on NIHL are obscured totally by the noise effect. Finally, the data presented demonstrate that carbon monoxide is able to impair the recovery of NIHL that normally occurs when periods of silence are interspersed within noise exposure.


Primary aldosteronism presenting as embolic myocardial infarction.
Primary aldosteronism is now recognized as the most common cause of secondary hypertension. Increasing evidence has demonstrated increased cardiovascular events in primary aldosteronism patients. Heart failure and atrial fibrillation are the most common cardiovascular complications occurring in these patients, and a few cases of coronary artery disease have been reported. Herein, we report a rare case of primary aldosteronism in a patient who presented with myocardial infarction associated with coronary embolism. A 52-year-old woman was admitted to our hospital because of chest pain. ST-segment elevation was observed on an electrocardiogram. Although no significant stenosis was observed, embolization of the far distal left anterior descending artery was noticed on angiography. Blood test results revealed hypokalemia and increased aldosterone-renin ratio. Abdominal computed tomography revealed an adenoma in the left adrenal gland. After adrenalectomy, the serum potassium level normalized, and blood pressure was well controlled. Primary aldosteronism must be considered in patients who have had various cardiovascular diseases, including embolisms and situations in which the discrimination of secondary hypertension is necessary.


The role of reactive oxygen species in mitochondrial permeability transition.
We have provided evidence that mitochondrial membrane permeability transition induced by inorganic phosphate, uncouplers or prooxidants such as t-butyl hydroperoxide and diamide is caused by a Ca(2+)-stimulated production of reactive oxygen species (ROS) by the respiratory chain, at the level of the coenzyme Q. The ROS attack to membrane protein thiols produces cross-linkage reactions, that may open membrane pores upon Ca2+ binding. Studies with submitochondrial particles have demonstrated that the binding of Ca2+ to these particles (possibly to cardiolipin) induces lipid lateral phase separation detected by electron paramagnetic resonance experiments exploying stearic acids spin labels. This condition leads to a disorganization of respiratory chain components, favoring ROS production and consequent protein and lipid oxidation.


[The set-up of an in vitro model for stable knockdown of MyD88 by lentivirus-based RNAi in IEC-6 cell line and the study on its early apoptosis].
Intestinal inflammatory disease is a kind of non-specific disease with morbidity increasing yearly. It has been proved that the Toll like receptor 4 (TLR4) signaling pathways are closely related to intestinal inflammatory diseases. Myeloid differentiation protein 88 (Myd88) is a critical adaptor protein of TLR4 signaling and critical for the study of intestinal inflammatory disease, but stable Myd88 knockdown in vitro models of cell line are still very few. In the present study, an HIV-1-based lentivirus three-plamid packaging system was used for the construction of a lentivirual vector mediating RNA interference (RNAi) against Myd88 in intestinal fossae epithelial cell line-6 (IEC-6). Real-time PCR and Western blot were used to detect Myd88 expression. Annexin V staining and flowcytometry (FLM) were applied to detect and evaluate the early apoptosis. The results showed that lentiviral vectors containing the shRNA expression cassette specifically targeting Myd88 were constructed and efficiently stably knocked down Myd88 expression in IEC-6 cell line. Early apoptosis was significantly decreased after Myd88 knockdown. This study successfully constructed a lentivirus-based RNAi for Myd88 and detailed the key technique combined with characteristics of the early apoptosis after the Myd88 knockdown, provided a novel, stable and repeatable in vitro model for the pathogenesis, targeting therapeutic study for the intestinal inflammatory diseases.


Symptomatic myocarditis in Kawasaki disease.
Kawasaki disease (KD) is an acute febrile illness of infants and young children that is characterized by a medium vessel vasculitis, most commonly involving the coronary arteries. Though subclinical myocarditis is rather common in KD, symptomatic congestive heart failure is extremely uncommon. The authors report a 9-y-old boy who developed heart failure (ejection fraction 28%) in the acute phase of KD. He was initially treated with intravenous immunoglobulin (2 g/kg) without much clinical improvement. He was then given 5 daily pulses of intravenous methylprednisolone followed by tapering doses of oral prednisolone. The child showed prompt clinical recovery and remains well on follow-up. The present case serves to highlight the fact that methylprednisolone can be considered upfront as rescue therapy in children with KD who have symptomatic congestive cardiac failure during the acute stage of the disease.


Exogenous brassinolide treatment regulates phenolic accumulation in mung bean sprouts through the modulation of sugar and energy metabolism.
The effects of exogenous brassinolide (BR) treatment (3.0 μmol L-1 ) on phenolic biosynthesis in mung bean sprouts were investigated. This investigation included the analysis of sugar content, substrates within the phenylpropane pathway, energy substances, enzymatic activity within the phenylpropane pathway, sugar metabolism and energy metabolism. Results showed that BR treatment significantly increased the levels of total phenolics, p-hydroxybenzoic acid, p-coumaric acid, gallic acid, fumalic acid and caffeic acid. This enhancement was accomplished through the elevation of l-phenylalanine levels and the activation of enzymes associated with the phenylpropane pathway in mung bean sprouts, including phenylalanine ammonia-lyase, cinnamate 4-hydroxylase and 4-coumarate CoA ligase. Furthermore, BR treatment induced alterations in sugar metabolism in mung bean sprouts as evidenced by the increased levels of glucose, fructose, sucrose and phosphoenolpyruvate. Moreover, increased activity was observed for enzymes linked to sucrose metabolism and glycolysis in the BR-treated group. Concurrently, BR treatment bolstered the levels of adenosine triphosphate and energy charge in mung bean sprouts, which was attributed to the activation of H+ -adenosine triphosphatase, Ca2+ -adenosine triphosphatase and succinic dehydrogenase. These results suggest that BR treatment can accelerate the accumulation of phenolic compounds in mung bean sprouts. This effect is achieved not only through the activation of the phenylpropane pathway, but also through the modulation of sugar and energy metabolism. The modulation provides ample energy and a substrate for the biosynthesis of phenolics. © 2023 Society of Chemical Industry.


Investigation of the Longevity of the Endoscopic Midface Lift.
To our knowledge, until now, the efficacy and durability of the transtemporal endoscopic preperiosteal midface lift has not been reported in the literature. To determine the efficacy and longevity of the endoscopic preperiosteal midface lift using objective measurements and validated aesthetic scales. This retrospective review included patients 18 years or older who were treated for aging midface by endoscopic midface lift by the senior author (A.E.W.) between June 2000 and August 2016. Patients were categorized based on length of follow-up into 3 groups: (1) short-term (1-3 years), (2) intermediate-term (3-5 years), and (3) long-term (>5 years). Endoscopic preperiosteal midface lift. (1) Objective measurements of midfacial height (the width of the interzygomatic distance of the midface to the medial canthus [WIZDOM-MC]), (2) validated regional aesthetic scales, and (3) global aesthetic scoring systems measured preoperatively, 3 to 6 months postoperatively, and at the most recent follow-up visit. Adult patients 18 years or older (median [range] age, 59 [31-79] years) who were treated for aging midface by undergoing an endoscopic midface lift were included in this study. The medical records of 143 patients were reviewed (135 women and 8 men). The endoscopic midface lift resulted in objective improvement in midfacial height. The median WIZDOM-MC decreased by 3.4 mm after the endoscopic midface lift (interquartile range [IQR], 2.3-4.4 mm; P < .001), thus shortening the elongated lower eyelid. At 5 to 15 years after surgery, there was a sustained decrease in median WIZDOM-MC of 2.1 mm (IQR, 0.8-3.1 mm; P < .001). Improvement in the infraorbital hollow was also sustained in patients at more than 5 years' follow-up (IQR, 0-1.0; P < .001). Improvements in upper cheek fullness and lower cheek fullness were maintained at 3 to 5 years and tended to be at baseline at more than 5 years. Global aesthetic improvement scores remained significantly improved at 5 to 15 years' follow-up. There is a significant, objective improvement in midfacial height after the endoscopic midface lift that persists for up to 15 years. Validated midfacial scales and global aesthetic scoring systems demonstrate sustained improvement in midface appearance over time. Surgery that minimally disrupts the zygomatic and orbicularis retaining ligaments can provide long-lasting aesthetic improvements. 4.


Cerebral venous sinus thrombosis and posterior reversible encephalopathy syndrome in a preeclamptic woman.
Cerebral venous sinus thrombosis (CVST) and posterior reversible encephalopathy syndrome (PRES) are two rare diseases which may present with similar symptoms and signs. We report a case with coexisting PRES and CVST in a preeclamptic woman. A 24-year-old woman, G2 P1, at 33 wk and 5 d of pregnancy presented with headache. Her blood pressure was 180/120 mmHg and urinary test revealed +3proteinuria. Cesarean section was performed with indications of severe preeclampsia, intrauterine growth retardation and fetal distress. Cranial MR venography of the patient revealed thrombiin superior sagittal sinus, confluenssinuum, right transverse and right sigmoid sinus and diffusion MRI showed increased signal intensity (vasogenicoedema) in cortical and subcortical areas of parietooccipital and posterior frontal lobes.The patient was treated with magnesium sulfate and heparin successfully. After treatment period, control cranial MRI and diffusion MRI were normal. Thrombi within the sinuses were totally regressed. Albeit rare, these two diseases should be kept in mind especially in preeclamptic/eclamptic patients that present with neurological symptom and/or sign.


Coma from long-term overingestion of isoniazid.
Overingestion of isoniazid can cause confusion, slurred speech, seizures, coma, and death. Most cases of a central nervous system toxic reaction due to isoniazid use result from sudden intentional or accidental overdose. We describe a patient taking 1200 mg of isoniazid daily for 6 weeks who presented to the hospital with confusion and lethargy that progressed to coma. Within 30 minutes of receiving 1 g of intravenous pyridoxine hydrochloride, the patient was fully alert and lucid. The diagnosis of a toxic reaction to isoniazid was delayed by the possibility of concurrent active neurosyphilis and the failure to initially consider isoniazid poisoning in a patient without a history of sudden isoniazid overdose.


Effects of Cynodon dactylon on Stress-Induced Infertility in Male Rats.
Cynodon dactylon (Family: Poaceae) is known to be a tackler in Indian mythology and is offered to Lord Ganesha. It is found everywhere, even on waste land, road side, dry places, and spreads vigorously on cultivated ground. This study was carried out with an objective to test if the constituents of this plant are useful in coping stress-induced sexual In this study, we considered immobilization stress to induce male infertility and the effect of C. dactylon in restoration of the dysfunction was evaluated by considering sexual behavioral observations, sexual performance, fructose content of the seminal vesicles, epididymal sperm concentration and histopathological examinations as parameters. Treatment of rats under stress with methanolic extract of C. dactylon has shown a promising effect in overcoming stress-induced sexual dysfunction, sexual performance, fructose content, sperm concentration and its effect on accessory sexual organs and body weight. We conclude that active constituents of C. dactylon present in methanolic extract have a potent aphrodisiac and male fertility activity.


Morin Hydrate Inhibits TREM-1/TLR4-Mediated Inflammatory Response in Macrophages and Protects Against Carbon Tetrachloride-Induced Acute Liver Injury in Mice.
This study aims to investigate the protective effects of morin hydrate (MH) against acute liver injury induced by carbon tetrachloride (CCl4) in mice and to elucidate the possible molecular mechanism of action. Mice were pretreated with MH (50 mg/kg body weight) or vehicle by oral gavage once daily for 5 days, followed by intraperitoneal injection of a single dose of CCl4 (1 ml/kg in olive oil). Mice were sacrificed 24 h later; the blood and liver samples were harvested for analysis. We also used the model of lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages in vitro and examined the effects of MH and its mechanism of action on the inflammatory response. Our results revealed that MH remarkably attenuated liver histopathological alterations, serum transaminases, hepatocytes death, and inflammatory response induced by CCl4. Importantly, MH reduced expression of the triggering receptor expressed on myeloid cells-1 (TREM-1) and toll-like receptor 4 (TLR4) both in vivo and in vitro experiments. This inhibitory effect MH on expression of the TREM-1 and TLR4 in cell culture was further heightened after TREM-1 knockdown with small interfering RNA (siRNA). Moreover, MH dramatically suppressed the inhibitor of kappa B α (IκBα) degradation and subsequent nuclear factor-kappa B (NF-κB) p65 translocation into the nucleus and NF-κB-mediated cytokines, such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and IL-6. Additionally, MH also ameliorated CCl4-induced oxidative stress by enhancing the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression in the injured livers. Taken together, MH has hepatoprotective activity, and this effect may be elicited by attenuating macrophage-mediated inflammatory responses via inhibition TREM-1/TLR4/NF-κB signaling and by regulating hepatic oxidative stress via enhancement Nrf2/HO-1 antioxidant pathway.


Physical activity, but not body mass index, predicts less disability before and after stroke.
To determine whether physical activity and body mass index (BMI) predict instrumental or basic activities of daily living (I/ADL) trajectories before or after stroke compared to individuals who remained stroke-free. Using a prospective cohort, the Health and Retirement Study, we followed adults without a history of stroke in 1998 (n = 18,117) for up to 14 years. We estimated linear regression models of I/ADL trajectories comparing individuals who remained stroke-free throughout follow-up (n = 16,264), those who survived stroke (n = 1,374), and those who died after stroke and before the next interview wave (n = 479). We evaluated whether I/ADL trajectories differed by physical activity or BMI at baseline (before stroke), adjusting for demographic and socioeconomic covariates. Compared to those who were physically active, stroke survivors who were physically inactive at baseline had a lower probability of independence in ADLs and IADLs 3 years after stroke (risk difference = -0.18 and -0.16 for ADLs and IADLs, respectively). However, a similar difference in the probability of independence was also present 3 years before stroke, and we observed no evidence that physical activity slowed the rate of decline in independence before or after stroke. Unlike the results for physical activity, we did not observe a consistent pattern for the probability of independence in ADLs or IADLs comparing obese stroke survivors to normal-weight or to overweight stroke survivors 3 years before stroke or 3 years after stroke. Physical inactivity predicts a higher risk of being dependent both before and after stroke.


Precise sequential DNA ligation on a solid substrate: solid-based rapid sequential ligation of multiple DNA molecules.
Ligation, the joining of DNA fragments, is a fundamental procedure in molecular cloning and is indispensable to the production of genetically modified organisms that can be used for basic research, the applied biosciences, or both. Given that many genes cooperate in various pathways, incorporating multiple gene cassettes in tandem in a transgenic DNA construct for the purpose of genetic modification is often necessary when generating organisms that produce multiple foreign gene products. Here, we describe a novel method, designated PRESSO (precise sequential DNA ligation on a solid substrate), for the tandem ligation of multiple DNA fragments. We amplified donor DNA fragments with non-palindromic ends, and ligated the fragment to acceptor DNA fragments on solid beads. After the final donor DNA fragments, which included vector sequences, were joined to the construct that contained the array of fragments, the ligation product (the construct) was thereby released from the beads via digestion with a rare-cut meganuclease; the freed linear construct was circularized via an intra-molecular ligation. PRESSO allowed us to rapidly and efficiently join multiple genes in an optimized order and orientation. This method can overcome many technical challenges in functional genomics during the post-sequencing generation.


Explorable three-dimensional digital model of the female pelvis, pelvic contents, and perineum for anatomical education.
The anatomy of the pelvis is complex, multilayered, and its three-dimensional organization is conceptually difficult for students to grasp. The aim of this project was to create an explorable and projectable stereoscopic, three-dimensional (3D) model of the female pelvis and pelvic contents for anatomical education. The model was created using cryosection images obtained from the Visible Human Project, in conjunction with a general-purpose three-dimensional segmentation and surface-rendering program. Anatomical areas of interest were identified and labeled on consecutive images. Each 2D slice was reassembled, forming a three-dimensional model. The model includes the pelvic girdle, organs of the pelvic cavity, surrounding musculature, the perineum, neurovascular structures, and the peritoneum. Each structure can be controlled separately (e.g. added, subtracted, made transparent) to reveal organization and/or relationships between structures. The model can be manipulated and/or projected stereoscopically to visualize structures and relationships from different angles with excellent spatial perception. Because of its ease of use and versatility, we expect this model may provide a powerful teaching tool for learning in the classroom or in the laboratory.


Some effect of subinbilitory concentrations of penicillin on the structure and division of staphylococci.
A strain of Staphylococcus aureus was planted on filter membranes placed on Trypticase soy agar (BBL). After incubation, the membranes with growing staphylococci were transferred to Trypticase soy agar containing a subinhibitory concentration of penicillin (one-third minimal inhibitory concentration) and again incubated. The membranes were then returned to drug-free agar and incubated once more. Counts of the colony-forming units and electron microscopy were carried out at several time intervals. When grown on agar containing penicillin, the staphylococci formed what appeared to be abnormally large cells with multiple and unusually thick septa. Examination of a number of sections showed that these large cells were in reality clusters of staphylococci that had divided but failed to separate. When these large cells were subsequently grown on drug-free agar, smaller cells and normal staphylococci emerged. Subinhibitory concentrations of penicillin do not kill staphylococci; they seem to inhibit lysis of cross walls, preventing the separation of otherwise divided cells.


Genetic variation analysis of the Bali street dog using microsatellites.
Approximately 800,000 primarily feral dogs live on the small island of Bali. To analyze the genetic diversity in this population, forty samples were collected at random from dogs in the Denpasar, Bali region and tested using 31 polymorphic microsatellites. Australian dingoes and 28 American Kennel Club breeds were compared to the Bali Street Dog (BSD) for allelic diversity, heterozygosities, F-statistics, GST estimates, Nei's DA distance and phylogenetic relationships. The BSD proved to be the most heterogeneous, exhibiting 239 of the 366 total alleles observed across all groups and breeds and had an observed heterozygosity of 0.692. Thirteen private alleles were observed in the BSD with an additional three alleles observed only in the BSD and the Australian dingo. The BSD was related most closely to the Chow Chow with a FST of 0.088 and also with high bootstrap support to the Australian dingo and Akita in the phylogenetic analysis. This preliminary study into the diversity and relationship of the BSD to other domestic and feral dog populations shows the BSD to be highly heterogeneous and related to populations of East Asian origin. These results indicate that a viable and diverse population of dogs existed on the island of Bali prior to its geographic isolation approximately 12,000 years ago and has been little influenced by domesticated European dogs since that time.


Sex differences in post-coital behaviors in long- and short-term mating: an evolutionary perspective.
Few empirical studies have been devoted to exploring behaviors occurring immediately following sexual intercourse. Therefore, this study conducts an exploratory investigation of various post-coital behaviors that the authors propose may reflect the divergent adaptive reproductive strategies of each sex as understood from an evolutionary perspective. An online questionnaire was administered to 170 individuals examining sex differences in post-coital compared to pre-coital activities related to pair-bonding with long-term mates, as well as a variety of common post-coital activities comparing short- and long-term mating contexts. It was found that females were more likely than males to initiate and place greater importance on several behaviors related to intimacy and bonding following sex with long-term partners. Males were more likely to initiate kissing before sex, and females after sex. Intimate talk and kissing were rated by both sexes as more important before intercourse with a long-term partner, whereas cuddling and professing one's love was rated more important after sex. In a second set of more specific post-coital behaviors, females were more likely to engage in post-coital behaviors related to bonding with both short- and long-term partners, whereas males were more likely to engage in ones that were extrinsically rewarding or increased the likelihood of further coital acts.


The accessory middle cerebral artery: anatomic report.
An accessory middle cerebral artery (MCA) usually originates between the A1 and proximal A2 segment of the anterior cerebral artery, reaches the sylvian fissure, and supplies the territory of the MCA. This anomaly has been associated with cerebral aneurysms and Moyamoya disease. We report an accessory MCA arising from the A2 segment. A cadaveric head, fixed in formalin solution and injected with red and blue silicone on its vascular tree to trace intracranial and extracranial vessels, was dissected. An accessory MCA was found arising from the A2 segment of the anterior cerebral artery and feeding the basal and inferior surface of the inferior frontal gyrus. In our specimen, the vessel was associated with intracranial aneurysms at other locations. Although anomalies of the MCA are rare, neurosurgeons must be familiar with such anatomic variations. An accessory MCA can be associated with Moyamoya disease and aneurysms at its junction with the anterior cerebral artery. Patients with this anomaly may, therefore, have an increased risk for developing aneurysms and other neurovascular complications. By obstructing the surgical view, an accessory MCA may increase the difficulty of exposing lesions in the vicinity of the optic chiasm.


A developmental timing switch promotes axon outgrowth independent of known guidance receptors.
To form functional neuronal connections, axon outgrowth and guidance must be tightly regulated across space as well as time. While a number of genes and pathways have been shown to control spatial features of axon development, very little is known about the in vivo mechanisms that direct the timing of axon initiation and elongation. The Caenorhabditis elegans hermaphrodite specific motor neurons (HSNs) extend a single axon ventrally and then anteriorly during the L4 larval stage. Here we show the lin-4 microRNA promotes HSN axon initiation after cell cycle withdrawal. Axons fail to form in lin-4 mutants, while they grow prematurely in lin-4-overexpressing animals. lin-4 is required to down-regulate two inhibitors of HSN differentiation--the transcriptional regulator LIN-14 and the "stemness" factor LIN-28--and it likely does so through a cell-autonomous mechanism. This developmental switch depends neither on the UNC-40/DCC and SAX-3/Robo receptors nor on the direction of axon growth, demonstrating that it acts independently of ventral guidance signals to control the timing of HSN axon elongation.


Trials of arsenic trioxide in multiple myeloma.
Several reports on the use of arsenic trioxide (ATO), mainly in acute promyelocytic leukemia, have led to a renewed interest in ATO in the management of malignancies, especially those of hematologic origin such as multiple myeloma (MM). MM remains an incurable disease, with median survival rates of 4-6 years. Thus, newer treatments with good safety profiles are needed to improve the quality of responses, prolong progression, and increase overall survival. The current state of the art regarding the role of ATO in the management of MM and the rationale for this consideration is reviewed. Preclinical evidence suggests that one of the mechanisms in which ATO exerts its antimyeloma effect is by immunologic mechanisms. One such mechanism appears to be achieved by a marked increase in lymphokine-activated killer (LAK)-mediated killing and up-modulation of CD38 and CD54, two molecules involved in cell-cell interactions. Two phase II trials have shown that the drug appears to be clinically effective. With the improved understanding of the interaction between the myeloma cell and its microenvironment as well as the cytokine support system, it does not appear than any particular agent will be able to control the disease permanently. In the clinical arena, the next generation of studies will be designed to combine different molecules to take advantage of non-overlapping toxicities and to compromise the extensive and redundant myeloma support system, thus controlling the disease in a chronic phase.


Thermal Stability and Fire Properties of Salen and Metallosalens as Fire Retardants in Thermoplastic Polyurethane (TPU).
This study deals with the synthesis and evaluation of salen based derivatives as fire retardants in thermoplastic polyurethane. Salens, hydroxysalens and their first row transition metal complexes (salen-M) were synthesized (Copper, Manganese, Nickel and Zinc). They were then incorporated in thermoplastic polyurethane (TPU) with a loading as low as 10:1 weight ratio. The thermal stability as well as the fire properties of the formulations were evaluated. Thermogravimetric analysis (TGA) showed that different coordination metals on the salen could induce different decomposition pathways when mixed with TPU. The Pyrolysis Combustion Flow Calorimetry (PCFC) results showed that some M-salen have the ability to significantly decrease the peak heat release rate (-61% compared to neat TPU) and total heat released (-63% compared to neat TPU) when formulated at 10:1 wt % ratio in TPU. Mass Loss Cone Calorimetry (MLC) results have shown that some additives (salen-Cu and salen-Mn) exhibit very promising performance and they are good candidates as flame-retardants for TPU.


Sternal wound infection after myocardial revascularization with internal mammary artery.
The use of the bilateral mammary artery in myocardial revascularisation in diabetic patients has been thought to increase the risk of sternal wound infection. We studied unilateral IMA grafting retrospectively in 701 consecutive patients to determine the incidence of sternal wound infection. One hundred and six patients were diabetic; 595 were non-diabetic. Both groups of patients were comparable for age, number of bypasses, and cardiopulmonary bypass time. No patient in the diabetic group developed mediastinitis; two patients of 595 in the non-diabetic group (0.3%) developed mediastinitis. Incidence of subcutaneous wound infection was slightly higher in the diabetic group than in the non-diabetic group (2% vs 0.3%) but was not statistically significant. We conclude that unilateral internal mammary artery grafting in diabetics is not associated with increased risk of sternal wound infection and should remain the conduit of choice for myocardial revascularization.


[The reasons for the ineffective treatment of patients with newly diagnosed destructive pulmonary tuberculosis].
As many as 350 patients with ineffective treatment of freshly detected destructive pulmonary tuberculosis were analyzed in retrospection. The following four groups of causes of ineffective treatment of these cases were identified: tardy detection and late start of the treatment (49.71%); features of the tuberculous process, the extent to which it has spread in particular; dangerous complications and intercurrent illnesses (66.57%); a not-rational treatment of a patient with tuberculosis (85.14%); untimely discontinuance of treatment (38.86%). In a major proportion of patients these causes tended to be combined, which fact is to be kept in mind in one's daily work for such causes to be cleared away.


Substitution with Alternative Anti-TNFα Therapy (SAVANT)-Outcomes of a Crohn's Disease Cohort Undergoing Substitution Therapy with Certolizumab.
Biological therapy targeting tumor necrosis factor-alfa has revolutionized the treatment of Crohn's disease (CD). Our study retrospectively reviewed clinical outcomes of 60 patients administratively substituted from Infliximab or Adalimumab to Certolizumab. Maintenance of disease and failure rates after substitution of anti-tumor necrosis factor-alfa agents in CD patients were monitored over 1 year, and this is the first outcomes study of patients maintained on Infliximab or Adalimumab substituted to Certolizumab. A hospital pharmacy directive required all patients on biological therapy to be administratively substituted to Certolizumab therapy. This single-center retrospective analysis initially included 68 CD patients presenting at Louisiana State University Health Sciences Center-Shreveport. Clinical, endoscopic, and serologic data were compared at baseline and at 4 intervals over 1 year. Of 60 enrolled CD patients, 45 (75%) successfully transitioned to Certolizumab and had stable disease at 1 year. Of the 15 (25%) patients who "failed" substitution at 1 year, 5 were returned to Adalimumab and 7 to Infliximab; 3 were maintained on steroids awaiting subsequent therapy. Importantly, when patients were segregated on the basis of initial disease control, it was found that 3 (12.5%) previously well-controlled patients failed therapy, whereas 12 (33.3%) who initially had active disease failed Certolizumab substitution. Our study found that 25% of CD patients substituted to Cimzia failed substitution, whereas 75% still exhibited a good clinical response with stable disease at 1 year. Our findings indicate that disease status and behavior at the time of biological substitution may predict therapeutic responsiveness.


The effects of sow parity on digestibility of proximate components and minerals during lactation as influenced by diet and microbial phytase supplementation.
Ninety-six (Finnish Landrace x Dutch Landrace) reproductive sows were used at parities 1, 3, 5, and 7 + 8 from d 107 of gestation to d 21 of lactation to investigate the effects of diet and parity on apparent total tract digestibility (ATTD). Animals were randomly assigned to one of four dietary treatments. Dietary treatments were 1) a P-deficient (1.1 g digestible P [dP]/kg) Dutch semipractical diet; 2) Diet 1 supplemented with 400 FTU Aspergillus niger phytase per kilogram of diet (1.7 g dP/kg); 3) a corn-soybean meal-based diet (1.3 g dP/kg); and 4) Diet 3 supplemented with extra monocalcium phosphate (MCP; 2.4 g dP/kg of diet). Animals were fed twice daily at 2.8 times maintenance (418 kJ ME/ BW75) from d 8 to the end of lactation. Feces and urine were collected during d 11 to 13 and d 18 to 20 of lactation. The ATTD of DM, OM, ash, CP, Ca, Mg, and total P (P < .01) were higher for the corn-soybean meal-based diets than for the Dutch semipractical diet not supplemented with phytase. Addition of MCP enhanced total P ATTD by an average of 6.7 percentage units. Addition of microbial phytase improved Ca, Mg, and total P ATTD, but the effects were dependent on the stage of lactation. Lower ATTD of OM and CP were seen for first parity animals compared with higher parity sows. The ATTD of Mg increased with increasing parity. Parity had little effect on the ATTD of minerals during lactation, and dietary effects were prominent and followed a similar trend to those seen in growing-finishing pigs.


A rapid decrease in epidermal growth factor-binding capacity accompanies the terminal differentiation of mouse myoblasts in vitro.
Specific mitogens stimulate the proliferation and repress the differentiation of mouse myoblasts (MM14). When mitogens are depleted, MM14 cells cease proliferation, commit to terminal differentiation, and become refractory to growth stimulation. The behavior of mitogen receptors during the transition from a proliferative to a permanently postmitotic state was examined using the epidermal growth factor receptor (EGFR) as a model system. Whereas proliferating myoblasts bound substantial amounts of EGF, their binding capacity declined rapidly upon exposure to low-mitogen medium. The decline became irreversible when a cell differentiated. Within 24 h, less than 5% of the original EGF binding capacity remained. Since the ability to internalize and degrade bound EGF was unaffected, the change presumably reflected a decrease in EGFR availability. Several observations indicated that loss of EGFR following mitogen removal is related to differentiation rather than the result of starvation or cell-cycle arrest. First, the decline is correlated with the absence of a single mitogen (fibroblast growth factor) and is independent of serum concentrations. Second, myoblasts that are either cycling through G1 or arrested at G0, but prevented from differentiating, all bind large amounts of EGF. These findings suggest that specific reduction in mitogen receptors could be part of a mechanism whereby terminally differentiating cells become refractory to mitogenic stimulation.


Natural selection constrains neutral diversity across a wide range of species.
The neutral theory of molecular evolution predicts that the amount of neutral polymorphisms within a species will increase proportionally with the census population size (Nc). However, this prediction has not been borne out in practice: while the range of Nc spans many orders of magnitude, levels of genetic diversity within species fall in a comparatively narrow range. Although theoretical arguments have invoked the increased efficacy of natural selection in larger populations to explain this discrepancy, few direct empirical tests of this hypothesis have been conducted. In this work, we provide a direct test of this hypothesis using population genomic data from a wide range of taxonomically diverse species. To do this, we relied on the fact that the impact of natural selection on linked neutral diversity depends on the local recombinational environment. In regions of relatively low recombination, selected variants affect more neutral sites through linkage, and the resulting correlation between recombination and polymorphism allows a quantitative assessment of the magnitude of the impact of selection on linked neutral diversity. By comparing whole genome polymorphism data and genetic maps using a coalescent modeling framework, we estimate the degree to which natural selection reduces linked neutral diversity for 40 species of obligately sexual eukaryotes. We then show that the magnitude of the impact of natural selection is positively correlated with Nc, based on body size and species range as proxies for census population size. These results demonstrate that natural selection removes more variation at linked neutral sites in species with large Nc than those with small Nc and provides direct empirical evidence that natural selection constrains levels of neutral genetic diversity across many species. This implies that natural selection may provide an explanation for this longstanding paradox of population genetics.


A devastating outbreak of malignant catarrhal fever in a bison feedlot.
In early 2003, an outbreak of malignant catarrhal fever (MCF) occurred in a bison feedlot in southern Idaho. The outbreak resulted in a 51.2% (n = 825) mortality rate among bison, which had been exposed to sheep for 19 days. Diagnosis was made by detection of ovine herpesvirus 2 (sheep-associated MCF virus) DNA in tissues or peripheral blood by polymerase chain reaction (PCR), and by histological examination of tissue lesions. Peak losses occurred between 41 and 55 days postmean exposure time (PME), and reached a maximum of 41 head per day. No known cases of MCF were observed among the 177 head of bison that arrived in the lot 3 1/2 weeks after the departure of the sheep. Of the several thousand head of beef cattle in the lot during the outbreak, only a single case of MCF was identified. This outbreak illustrates the devastating impact the MCF virus can have on bison under certain exposure conditions, the high threat posed by adolescent lambs to susceptible species, the significantly greater susceptibility of bison than beef cattle to MCF, and the lack of horizontal transmission from clinically affected bison to herdmates.


Study on the Effect of Ginsenosides Rb on Blood of Tumor Mice.
The blood of cancer patients is in a state of hypercoagulability, easily leading to thrombosis. Anemia is also a complication of tumors. Anemia and thrombosis affect the treatment of tumor patients. Ginsenosides Rb were extracted from the stems and leaves of American ginseng using water-saturated ethanol and ethyl acetate in silica gel column. Tumor mice model was established by injecting H22 hepatocellular carcinoma cells into the axilla of mice. Mice were randomly divided into 6 groups: normal control group, model control group, positive control group, low dose group (7 mg/kg), middle dose group (14 mg/kg), and high dose group (35 mg/kg). After 18 days, the blood was obtained by picking the eyeball of mice. The levels of red blood cells (RBC), hemoglobin (HGB), neutrophils/lymphocytes radio (NLR), platelets (PLT), platelet distribution width (PDW), fibrinogen (FIB), and D-Dimer (D-D) were measured and compared in each group of mice. The content of obtained ginsenosides Rb reached 90.05%. This extraction process was simple and reliable. Middle dose of ginsenosides Rb could significantly increase RBC and HGB levels (P<0.05). Moreover, ginsenosides Rb could significantly reduce NLR, PLT, PDW, FIB, and D-D (P<0.01). ginsenosides Rb could significantly improve anaemia and hypercoagulation of blood in cancer mice. Ginsenosides Rb are a potential anticoagulant and antianemia drug in treating cancer.


Growing skull fractures of childhood. Case report and review of 132 cases.
Authors report a case of growing skull fracture, unusual complication of linear skull fracture in infancy and childhood. A review of 132 cases reported in literature is done with an analysis of general characteristics of this lesion. The most common localization is parietal (50%); clinical presentation is represented by development of seizures (54 cases), focal neurological deficit (57 cases) or loss of consciousness (50 cases). In 50% of cases interval time between head injury and first symptom varies between 1 day and 1 year. After the first year of age the 34.4% of patients develop seizures and 59% present loss of consciousness. Among patients from 1 day to 6 months of age, 46% develop seizures, 38% focal neurological deficit and 21% loss of consciousness. Asymptomatic presentation is more common in fronto-parietal or fronto-parieto-occipital localizations. In parieto-occipital and occipital localization (30 cases), 13 patients (43.3%) have seizures, 36.7% a focal neurological deficit and 60% loss of consciousness. In parieto-temporal localization there is a higher probability of seizures (62.5%) and loss of consciousness (62.5%). The long-term follow-up and the functional recovery in patients which undergo surgery is linked to the clinical presentation and early diagnosis.


A Study on Social Support and Depression by Gender among Adults.
This study was to compare social support and depression by gender, to investigate related factors, and to inquire effect of social support on depression by gender. This study analyzed raw data from a project funded by Jeju Province. The data were collected through home visit interview from 750 households which were selected by using randomized cluster sampling method. CES-D and MOS SSS were used for measuring depression and social support. Data obtained from 896 adults were analyzed using t-test, chi2 test and hierarchical regression. There was no significant difference of depression prevalence, presenting 15.2% for men and 14.5% for women. The related factors were marital status, educational level, and socioeconomic status for men and only socioeconomic status for women. The result of hierarchical regression presented that social support was significant on depression, showing increase of R2 from .151 to .328 when adding social support to other variables for men, increase of R2 from .058 to .192 for women. The social support was an influential factor on depression both men and women, the development of strategies considering risk population by gender for enhancing social support to prevent and to manage depression was suggested.


Gastrointestinal myoelectric activity in conscious guinea pigs.
Myoelectric activity was recorded from the gastric antrum and small intestine of conscious, unrestrained guinea pigs using bipolar Ag-Ag chloride electrodes that had been previously implanted under pentobarbital sodium/Innovar anesthesia. In fasted guinea pigs, the migrating myoelectric complex (MMC) was recorded from the small intestine and was observed to propagate aborally at a speed that declined with distance from the pylorus (range of speeds of the front of phase 3: 17.5 cm/min in the duodenum to 4.1 cm/min in the ileum). The complex was not disrupted by feeding but occurred less frequently in the freely fed state (82-min cycle period in the fasted state versus 139 min in the fed state). The complex started in the duodenum and was accompanied by a brief (6.3 +/- 0.9 min) period of inhibition of antral myoelectric activity. Slow waves were also recorded from the gastric antrum (10.3 +/- 1.3/min) and the small intestine. The frequency of intestinal slow waves was uniform along the length of the bowel (26.2 +/- 1.3/min in the duodenum to 24.7 +/- 1.3/min in the ileum). It is concluded that the guinea pig is similar to other mammalian species, so far examined, in its pattern of gastrointestinal myoelectric activity.


Pan-Cancer Analysis of the LOX Family Reveals that LOX Affects Tumor Prognosis by Affecting Immune Infiltration.
The lysyl oxidase (LOX) gene family encodes for a group of copper-dependent enzymes that play a crucial role in the cross-linking of collagen and elastin fibers in the extracellular matrix (ECM). Dysregulation of LOX gene expression has been implicated in various pathological conditions, including cancer. Several studies have shown that the LOX gene family is involved in cancer progression and metastasis. The goal of this article is to conduct a comprehensive analysis of the LOX family's role in pan-cancer multiplexes. We utilized pan-cancer multi-omics sequencing data from TCGA to investigate the relationship between LOX family genes and tumors at four different levels: mutation, copy number variation, methylation, and gene expression. In addition, we also examined the relationship between LOX family genes and tumors at the cell line level using tumor cell line sequencing data from CCLE. Taking into account the impact of LOX family genes on lung cancer, we developed a LOX family lung cancer prognostic model to forecast the disease's prognosis. Our findings revealed that LOXL2 had the highest mutation frequency in tumors, while all four LOX family genes experienced some degree of copy number variation in diverse tumors. We observed that LOX, LOXL1 to LOXL3 were predominantly highly expressed in tumors including LUAD. The expression trends of LOX and LOXL1 to LOXL3 were consistent across tumor cell lines, but differed somewhat from LOXL4. Utilizing 25 LOX family-related genes, we constructed a LOX family prognostic model that performed well in predicting the prognosis of lung cancer. Through pan-cancer analysis, we gain further knowledge of the role of LOX family genes in different tumors, offering a novel pathway for future research into the relationship between LOX family genes and tumors.


Novel use of Cytosorb™ haemadsorption to provide biochemical control in liver impairment.
We describe the use of Cytosorb™, a synthetic extracorporeal haemoperfusion adsorption column, in the management of two patients with drug induced cholestasis and a third with alcoholic hepatitis and subsequent acute on chronic liver failure. Cytosorb was used in these patients to remove bilirubin and bile acids by supporting impaired excretory hepatic function, alleviating symptoms with the intention of serving as a bridge to endogenous recovery. The first two cases demonstrate favourable biochemical and symptomatic responses; the third case demonstrated a good biochemical response but subsequently died from the complications of multiple organ failure. These cases suggest Cytosorb™ be evaluated as an adjunct to support liver excretory functions in other arenas, such as acute liver failure or overdose. It remains unclear whether extracorporeal therapies removing liver toxins allow faster or more complete spontaneous recovery of endogenous function.


Use of fondaparinux in a pregnant woman with pulmonary embolism and heparin-induced thrombocytopenia.
A serious complication of heparin treatment, heparin-induced thrombocytopenia (HIT) is rarely observed in pregnant women. Drug therapy during pregnancy should always be chosen to minimize fetal risk. The management of HIT in pregnancy represents a medical challenge. Unlike heparins, the anticoagulants used in patients with HIT do cross the placenta, with unknown fetal effects. We present a case of a 24-year-old female presenting for care at 34 weeks of gestation with acute pulmonary embolism treated initially with unfractionated heparin (UFH) and low molecular weight heparin (LMWH), who developed HIT. She was then successfully treated with fondaparinux. To the best of our knowledge, this is one of the first case reports describing a successful use of fondaparinux in the treatment of HIT in a third-trimester pregnant woman, providing a novel approach for this subset of patients.


Alterations at the peptidyl transferase centre of the ribosome induced by the synergistic action of the streptogramins dalfopristin and quinupristin.
The bacterial ribosome is a primary target of several classes of antibiotics. Investigation of the structure of the ribosomal subunits in complex with different antibiotics can reveal the mode of inhibition of ribosomal protein synthesis. Analysis of the interactions between antibiotics and the ribosome permits investigation of the specific effect of modifications leading to antimicrobial resistances. Streptogramins are unique among the ribosome-targeting antibiotics because they consist of two components, streptogramins A and B, which act synergistically. Each compound alone exhibits a weak bacteriostatic activity, whereas the combination can act bactericidal. The streptogramins A display a prolonged activity that even persists after removal of the drug. However, the mode of activity of the streptogramins has not yet been fully elucidated, despite a plethora of biochemical and structural data. The investigation of the crystal structure of the 50S ribosomal subunit from Deinococcus radiodurans in complex with the clinically relevant streptogramins quinupristin and dalfopristin reveals their unique inhibitory mechanism. Quinupristin, a streptogramin B compound, binds in the ribosomal exit tunnel in a similar manner and position as the macrolides, suggesting a similar inhibitory mechanism, namely blockage of the ribosomal tunnel. Dalfopristin, the corresponding streptogramin A compound, binds close to quinupristin directly within the peptidyl transferase centre affecting both A- and P-site occupation by tRNA molecules. The crystal structure indicates that the synergistic effect derives from direct interaction between both compounds and shared contacts with a single nucleotide, A2062. Upon binding of the streptogramins, the peptidyl transferase centre undergoes a significant conformational transition, which leads to a stable, non-productive orientation of the universally conserved U2585. Mutations of this rRNA base are known to yield dominant lethal phenotypes. It seems, therefore, plausible to conclude that the conformational change within the peptidyl transferase centre is mainly responsible for the bactericidal activity of the streptogramins and the post-antibiotic inhibition of protein synthesis.


Effect of vision on development of multiply handicapped children.
The effect of vision on (abnormal) development was studied in a group of 81 visually and/or hearing impaired rubella children, 18 of whom had bi-lateral cataracts operated between 2-18 months, 3 children had uni-lateral cataract, and 60 children had clear media. In this group of children the effect of visual impairment on (abnormal) behaviour is enormous. Vision has in these children a greater impact on their development than hearing impairment or prenatal variables such as low birthweight. This justifies the conclusion of cataract surgery as early as possible. After surgery the environment should be manipulated in such a way, that it becomes visually attractive for the child. This might prevent strong light-gazing and/or exhibiting the phenomenon of HBE (Hand Before the Eyes). The desire for rocking and jumping should be seen in connection with stimulus deprivation, especially social ones. It is therefore recommended that these children should be offered ample experience and interaction with the environment, such as giving the child proprioceptive stimuli, rocking him in the crib or on the lap. The interest in the world outside his own body should be encouraged by manipulating the children's special interest (such as changing the objects for light gazing). The purpose for this kind of management is to develop orientation reflex, in other words to stimulate the child to give attention to the world around him and therefore learn from it. When this sort of early stimulation is provided the child's development may be not so retarded as without appropriate intervention.


Ivermectin decreases parasite load, testosterone, and potentially antler length in a group of captive red deer males (Cervus elaphus).
Secondary sex traits (SSTs) can favour males in intra-sexual competition, allowing females to reliably assess their quality. They can also be connected to other aspects of fitness, such as resistance to parasites and pathogens, as parasites have negative effects on the development of SSTs. Antlers are one of the most recognizable examples of SSTs whose development is regulated by testosterone and reflects the actual condition of the bearer. Elevated testosterone can exaggerate the size of SSTs while impairing the function of the immune system ("The Immunocompetence Handicap Hypothesis") posing a trade-off between antler development and immune function. In this study, we experimentally manipulated the parasite load in captive red deer (Cervus elaphus) males with Ivermectin during antler development for two consecutive years. Expecting an inverse proportionality between parasite load and antler size, we hypothesized the treated deer to have larger antlers than the untreated ones. Our results showed that, following the immunocompetence handicap hypothesis, parasite load was positively associated with testosterone levels. However, the application of Ivermectin suppressed the parasite load of the treated animals but did not lead to the development of larger antlers. Instead, it significantly suppressed the concentration of testosterone in the treated animals, whilst the animals that had higher testosterone also had the highest parasite load. Our findings show that Ivermectin can potentially decrease the levels of testosterone and, consequently, antler size. These findings have important implications for the management of captive populations, especially in contexts where the development of large trophies is desired.


Evaluation of protein phosphorylation site predictors.
A series of elegant phosphorylation site prediction methods have been developed, which are playing an increasingly important role in accelerating the experimental characterization of phosphorylation sites in phosphoproteins. In this study, we selected six recently published methods (DISPHOS, NetPhosK, PPSP, KinasePhos, Scansite and PredPhospho) to evaluate their performance. First, we compiled three testing datasets containing experimentally verified phosphorylation sites for mammalian, Arabidopsis and rice proteins. Then, we present the prediction performance of the tested methods on these three independent datasets. Rather than quantitatively ranking the performance of these methods, we focused on providing an understanding of the overall performance of the predictors. Based on this evaluation, we found the following results: i) current phosphorylation site predictors are not effective for practical use and there is substantial need to improve phosphorylation site prediction; ii) current predictors perform poorly when used to predict phosphorylation sites in plant phosphoproteins, suggesting that a rice-specific predictor will be required to obtain confident computational annotation of phosphorylation sites in rice proteomics research; and iii) the tested predictors are complementary to some extent, implying that establishment of a meta-server might be a promising approach to developing an improved prediction system.


Profile of 208 patients with inborn errors of immunity at a tertiary care center in South India.
Primary immune deficiencies or inborn errors of immunity (IEI) are a heterogeneous group of disorders that predispose affected individuals to infections, allergy, autoimmunity, autoinflammation and malignancies. IEIs are increasingly being recognized in the Indian subcontinent. Two hundred and eight patients diagnosed with an IEI during February 2017 to November 2021 at a tertiary care center in South India were included in the study. The clinical features, laboratory findings including microbiologic and genetic data, and treatment and outcome details were analyzed. The diagnosis of IEI was confirmed in a total of 208 patients (198 kindreds) based on relevant immunological tests and/or genetic tests. The male-to-female ratio was 1.8:1. Of the 208 patients, 72 (34.6%) were < 1 yr, 112 (53.8%) were 1-18 years, and 24 (11.5%) were above 18 years. The most common IEI in our cohort was SCID (17.7%) followed by CGD (12.9%) and CVID (9.1%). We also had a significant proportion of patients with DOCK8 deficiency (7.2%), LAD (6.2%) and six patients (2.8%) with autoinflammatory diseases. Autoimmunity was noted in forty-six (22%) patients. Molecular testing was performed in 152 patients by exome sequencing on the NGS platform, and a genetic variant was reported in 132 cases. Twenty-nine children underwent 34 HSCT, and 135 patients remain on supportive therapy such as immunoglobulin replacement and/or antimicrobial prophylaxis. Fifty-nine (28.3%) patients died during the study period, and infections were the predominant cause of mortality. Seven families underwent prenatal testing in the subsequent pregnancy. We describe the profile of 208 patients with IEI, and to the best of our knowledge, this represents the largest data on IEI from the Indian subcontinent reported so far.


Impaired autophosphorylation of insulin receptors from abdominal skeletal muscles in nonobese subjects with NIDDM.
We studied both autophosphorylation and phosphotransferase activity of insulin receptors from abdominal skeletal muscles of nonobese subjects with non-insulin-dependent diabetes mellitus (NIDDM). Partially purified insulin receptors were labeled on their alpha-subunit with 125I-labeled insulin by chemical cross-linking and on their beta-subunit by autophosphorylation with 1000 microM ATP. Thereafter, phosphorylated insulin receptors were separated from total receptors with the anti-phosphotyrosine antibody. Thus, the percentage of phosphorylated receptors in total receptors revealed the autophosphorylation activity. Using this method, we studied the function of insulin receptors from muscle obtained by biopsy during surgery in 10 nonobese NIDDM and 8' control subjects. In diabetic subjects, insulin binding capacity from abdominal skeletal muscles was 69.4% of the control subjects. Furthermore, the percentage of phosphorylated insulin receptors stimulated by 8.3 nM insulin was significantly lower than the control subjects (mean +/- SD, 29.0 +/- 12.0 vs. 56.0 +/- 7.4%, P less than 0.01), and there was a significant inverse correlation between fasting plasma glucose levels and the percentage of phosphorylated receptors among diabetic subjects (r = 0.73, P less than 0.025). Moreover, the insulin-stimulated kinase activity toward a synthetic peptide (Glu80Tyr20) was also impaired in diabetic subjects (28.5% of control). In summary, this is the first demonstration that the autophosphorylation step of insulin receptors from abdominal skeletal muscles is impaired in nonobese NIDDM subjects.


Genetic testing of inherited arrhythmias.
Syncope and risk of sudden death due to ventricular tachyarrhythmia are the common manifestations of several inherited disorders. Abnormalities of the genetic makeup may directly affect proteins controlling cardiac excitability in a structurally normal heart. Other diseases manifest primarily with ventricular arrhythmias even though the genetic mutations cause structural abnormalities of the myocardium. This is the case of arrhythmogenic right ventricular cardiomyopathy and hypertrophic cardiomyopathy. Groundbreaking discoveries, starting from the 1990s until the beginning of the current decade, have provided fundamental knowledge on the major genes that confer an increased risk of arrhythmias and sudden death. Stems of such knowledge are the availability of genetic diagnosis, genotype-phenotype correlation, and genotype-based risk stratification schemes currently used in the clinical practice. This review provides a concise description of the known genes and key mechanisms involved in the pathogenesis of inherited arrhythmias. In addition, we outline possibilities, limitations, advantages, and potential threats of genetically screening for these genes.


Single-incision versus multiport video-assisted thoracoscopic surgery in the treatment of lung cancer: a systematic review and meta-analysis.
Recent studies compared single-incision thoracoscopic surgery (SITS) with more widely used conventional multiport video-assisted thoracoscopic surgery in the treatment of lung cancer. To establish the safety and feasible of SITS in the treatment of lung cancer, we conducted this systematic review and meta-analysis. Eleven studies were identified from the databases of PubMed, Cochrane Library, SpringerLink, and ScienceDirect. The randomized controlled trials (RCTs) and non-randomized studies evaluated the outcomes of SITS compared with multiport video-assisted thoracoscopic surgery in the treatment of lung cancer were included for analysis. Odds ratio (OR, used to compare dichotomous variables) and weight mean difference (WMD, used to compare continuous variables) were calculated with 95% confidence intervals (CIs) based on intention-to-treat analysis. Eleven studies including 1314 patients were included for analysis. Our analysis showed that the operative time, blood loss amount, mean duration of chest tube, lymph nodes retrieved were similar between two approaches, the SITS pulmonary resection might be associated with shorter hospital stay (p = .008) and lower complication rate (p = .009) when compared with conventional multiport video-assisted thoracoscopic surgery approaches. In selected patients SITS is safe, feasible and may be considered an alternative to multiport VATS.


From A to D: A Unique Case Report of Recovery After Longitudinal Myelitis Related to Lupus.
Longitudinal myelitis secondary to an acute flare of systemic lupus erythematosus has been reported in the literature. There have been few published cases of complete functional recovery in patients with systemic lupus erythematosus-related longitudinal myelitis (systemic lupus erythematosus-related longitudinal myelitis). Of those cases, none have described in detail the rehabilitation course of treatment. In the current case, intensive rehabilitation was coupled with aggressive pharmaceutical treatment resulting in almost full functional recovery. A 23-yr-old African American woman with a history of systemic lupus erythematosus was originally admitted as an inpatient for flank pain. Overnight, she progressed rapidly to complete flaccid paraplegia classified as T3 American Spinal Injury Association Impairment Scale A based on the International Standards for Neurological Classification of Spinal Cord Injury. Throughout the next year, she participated in acute inpatient rehabilitation, followed by outpatient rehabilitation (physical, occupational, and aquatic therapies). A year after her initial hospital admission, she progressed to full community ambulation T3 American Spinal Injury Association Impairment Scale D. This case illustrates the importance of proper medical treatment and a comprehensive rehabilitation program, which improved functional outcomes for a patient with a complete spinal cord injury due to systemic lupus erythematosus-related longitudinal myelitis.


Intra-cardiac Burkitt's lymphoma mimicking acute pulmonary embolism.
Primary cardiac lymphoma is a rare clinical entity with poor prognosis and delayed diagnosis is often due to variable and non-specific clinical presentation. The case of an elderly male is reported with multiple co-morbidities, who had undergone a spinal laminectomy two weeks prior to presentation, later presented to the emergency room (E.R.) with acute chest pain, dyspnea and hypoxemia. A diagnosis of intracardiac thrombus was made, based on the clinical picture and echocardiography findings but per-operatively, he was found to have an extensive, non-resectable cardiac tumor.


Climate structuring of Batrachochytrium dendrobatidis infection in the threatened amphibians of the northern Western Ghats, India.
Batrachochytrium dendrobatidis (Bd) is a pathogen killing amphibians worldwide. Its impact across much of Asia is poorly characterized. This study systematically surveyed amphibians for Bd across rocky plateaus in the northern section of the Western Ghats biodiversity hotspot, India, including the first surveys of the plateaus in the coastal region. These ecosystems offer an epidemiological model system since they are characterized by differing levels of connectivity, edaphic and climatic conditions, and anthropogenic stressors. One hundred and eighteen individuals of 21 species of Anura and Apoda on 13 plateaus ranging from 67 to 1179 m above sea level and 15.89 to 17.92° North latitude were sampled. Using qPCR protocols, 79% of species and 27% of individuals tested were positive for Bd. This is the first record of Bd in caecilians in India, the Critically Endangered Xanthophryne tigerina and Endangered Fejervarya cf. sahyadris. Mean site prevalence was 28.15%. Prevalence below the escarpment was 31.2% and 25.4% above. The intensity of infection (GE) showed the reverse pattern. Infection may be related to elevational temperature changes, thermal exclusion, inter-site connectivity and anthropogenic disturbance. Coastal plateaus may be thermal refuges from Bd. Infected amphibians represented a wide range of ecological traits posing interesting questions about transmission routes.


Methodology and reconstruction.
The challenges presented in treating patients with so-called borderline and narcissistic personality disorders have revived interest in the subject of reconstruction, because many analysts believe that these difficulties originate in the events of the earliest preverbal phase of development. They feel that contributions from direct observation of neonates and knowledge gained from "infant psychiatry" may enable analysts to effect reconstructions that previously appeared to be only speculative. The methodological problems in applying this approach, however, may lead to foisting upon clinical observation preconceived paradigms of pathogenesis. Reconstruction depends upon a disciplined interpretation of the dynamic record of the patient's associations, which demonstrate how the past is embedded in the present. The validity of the reconstruction depends upon the application of appropriate and disciplined psychoanalytic methodology. Reconstructions constitute a special form of interpretation and are part of the psychoanalytic process.


Original Research: Predictors of COVID-19 Vaccine Hesitancy Among Asian Indians in the United States: A Cross-Sectional Descriptive Study.
Although COVID-19 is a highly infectious disease, vaccine hesitancy remains a primary barrier to attaining full population inoculation. Numerous factors related to vaccine hesitancy have been identified. The aim of this study was to explore associations between select demographic variables and COVID-19 vaccine hesitancy among Asian Indians in the United States. The study used a cross-sectional, descriptive, correlational design. The sample consisted of 363 Asian Indians living in the United States who were 18 years of age or older and were literate in English. Vaccine hesitancy was assessed using an online survey. Both descriptive and inferential statistical analyses were conducted. Inferential tests included t tests, regression analyses, and analysis of variance (ANOVA) tests. As participant age increased, there was a statistically significant proportionate increase in the total vaccine hesitancy score (P = 0.01). There were also statistically significant differences in the vaccine hesitancy scores of participants with no more than a high school degree compared to those with associate or bachelor's degrees, although this finding was based on just six participants. Although most participants had already been vaccinated, many identified reasons for feeling some degree of vaccine hesitancy. The reasons for vaccine hesitancy vary by individual and are often complex. The results of this study will help guide public health agencies and health care personnel in developing vaccination strategies tailored to the specific requirements of Asian Indians in the United States, which could reduce vaccine hesitancy in this population.


Factors contributing to the reduced invasiveness of chlorine-injured Yersinia enterocolitica.
The invasion of epithelial cells in vitro and in vivo by chlorine-injured Yersinia enterocolitica was assessed by direct microscopic observations. These experiments showed that injury by chlorine inhibited invasiveness of virulent Y. enterocolitica. Two requirements appeared to be necessary for invasiveness: the organism must be viable and metabolically active, and the organism must have certain surface components to initiate engulfment. Inhibition of RNA synthesis by rifampin and protein synthesis by chloramphenicol, tetracycline, and spectinomycin inhibited the invasiveness but not the attachment of Y. enterocolitica to epithelial cells. Membrane preparations from untreated and antimicrobial-agent-treated Y. enterocolitica blocked the invasiveness of virulent Y. enterocolitica, whereas membranes from chlorinated cells were unable to block invasiveness. Chlorine did not change the hydrophobicity or surface charge of injured Y. enterocolitica. The results indicate that invasion was more than simple association of the bacterium with the epithelial cell and involved a specific trigger to stimulate engulfment.


Description of Leptopharynx brasiliensis nov. spec. and Leptopharynx costatus gonohymen nov. subspec. (Ciliophora, Microthoracida).
Using standard morphological methods, we describe one new Leptopharynx species and a new subspecies of L. costatus, both from soil of the neotropic region. Further, we studied two populations of L. costatus costatus. Leptopharynx brasiliensis nov. spec., which was discovered in the Mato Grosso, Brazil, is a large member (60μm) of the genus with an enormous oral basket. It differs from similar congeners in having six monokinetids in kinety 6, widely spaced kinetids in kinety 1, and an average of 294 kinetids. Leptopharynx costatus gonohymen nov. subspec., which was discovered in southern Florida, makes a small (35μm) and a large morph (55μm) both with narrow oral basket. The small morph is inseparable from the small morph of L. costatus costatus, while the large morph has right-angled adoral membranelles and widely (vs. narrowly) spaced kinetids in kinety 1. The small morphs of a Brazilian and an Austrian L. costatus match Mexican and other European populations, all having on average 181-187 kinetids. As yet, we know four morphs of L. costatus that differ by body size (small vs. large), the oral basket (narrow vs. wide), membranelle 1 (present vs. absent), and the arrangement of the membranelles (flat vs. angled).


An eye-tracking method to reveal the link between gazing patterns and pragmatic abilities in high functioning autism spectrum disorders.
The present study illustrates the potential advantages of an eye-tracking method for exploring the association between visual scanning of faces and inferences of mental states. Participants watched short videos involving social interactions and had to explain what they had seen. The number of cognition verbs (e.g., think, believe, know) in their answers were counted. Given the possible use of peripheral vision that could confound eye-tracking measures, we added a condition using a gaze-contingent viewing window: the entire visual display is blurred, expect for an area that moves with the participant's gaze. Eleven typical adults and eleven high functioning adults with Autism Spectrum Disorders (ASD) were recruited. The condition employing the viewing window yielded strong correlations between the average duration of fixations, the ratio of cognition verbs and standard measures of social disabilities.


[About interdisciplinarity: epistemiological aspects and implications for nursing].
This study is about interdisciplinarity as a phenomenon and as an emerging subject in Science, which has been divided into many knowledge and professional formation specialties or disciplines, mainly in the health and nursing areas. The approach is of a critical and philosophical nature and the main intention is to point out difficulties and problems with the aim of encouraging and further advancing the discussion. General, more current concepts are presented along with epistemological ideas subjacent to the repercussions of teamwork and transcendent to the conscience beyond the subject's philosophy. The author defends her opinion and posture towards the theme using examples from her academic practice and experience at the Federal University of Rio de Janeiro's Anna Nery School of Nursing.


A systematic review and meta-analysis of Penner serotype prevalence of Campylobacter jejuni in low- and middle-income countries.
While Campylobacter jejuni is a leading foodborne bacterial pathogen worldwide, it poses a particular risk to susceptible populations in low- and middle-income countries (LMICs). A capsule-conjugate vaccine approach has been proposed as a potential solution, but little information exists on circulating C. jejuni capsule types in LMICs. The capsule is the major serodeterminant of the Penner typing scheme, which is based on serum recognition of Campylobacter heat-stable antigens. We conducted a systematic review and meta-analysis to estimate the distribution of Penner serotypes associated with C. jejuni enteritis in LMICs. Vaccine coverage assessments for hypothetical regional and global C. jejuni vaccines were also estimated. A systematic review of the literature published from 1980 to 2019 was performed using PubMed, Scopus, and Web of Science databases. Articles were assessed for eligibility and data were abstracted. Pooled C. jejuni serotype prevalence in LMICs was estimated by region and globally using random-effects models. A total of 36 studies were included, capturing 4,434 isolates from LMICs. Fifteen serotypes were present in a sufficient number of studies to be included in analyses. Among these, HS4c was the most common serotype globally (12.6%), though leading capsule types varied among regions. HS2, HS3c, HS4c, HS5/31, HS8/17, and HS10 were all among the 10 most common region-specific serotypes. The results of this review suggest that an octavalent vaccine could provide up to 66.9% coverage of typable strains worldwide, and 56.8-69.0% regionally. This review also highlights the paucity of available data on capsules in LMICs; more testing is needed to inform vaccine development efforts.


Neuronal inclusions of α-synuclein contribute to the pathogenesis of Krabbe disease.
Demyelination is a major contributor to the general decay of neural functions in children with Krabbe disease. However, recent reports have indicated a significant involvement of neurons and axons in the neuropathology of the disease. In this study, we have investigated the nature of cellular inclusions in the Krabbe brain. Brain samples from the twitcher mouse model for Krabbe disease and from patients affected with the infantile and late-onset forms of the disease were examined for the presence of neuronal inclusions. Our experiments demonstrated the presence of cytoplasmic aggregates of thioflavin-S-reactive material in both human and murine mutant brains. Most of these inclusions were associated with neurons. A few inclusions were detected to be associated with microglia and none were associated with astrocytes or oligodendrocytes. Thioflavin-S-reactive inclusions increased in abundance, paralleling the development of neurological symptoms, and distributed throughout the twitcher brain in areas of major involvement in cognition and motor functions. Electron microscopy confirmed the presence of aggregates of stereotypic β-sheet folded proteinaceous material. Immunochemical analyses identified the presence of aggregated forms of α-synuclein and ubiquitin, proteins involved in the formation of Lewy bodies in Parkinson's disease and other neurodegenerative conditions. In vitro assays demonstrated that psychosine, the neurotoxic sphingolipid accumulated in Krabbe disease, accelerated the fibrillization of α-synuclein. This study demonstrates the occurrence of neuronal deposits of fibrillized proteins including α-synuclein, identifying Krabbe disease as a new α-synucleinopathy.


Adaptation paths to novel motor tasks are shaped by prior structure learning.
After extensive practice with motor tasks sharing structural similarities (e.g., different dancing movements, or different sword techniques), new tasks of the same type can be learned faster. According to the recent "structure learning" hypothesis (Braun et al., 2009a), such rapid generalization of related motor skills relies on learning the dynamic and kinematic relationships shared by this set of skills. As a consequence, motor adaptation becomes constrained, effectively leading to a dimensionality reduction of the learning problem; at the same time, adaptation to tasks lying outside the structure becomes biased toward the structure. We tested these predictions by investigating how previously learned structures influence subsequent motor adaptation. Human subjects were making reaching movements in 3D virtual reality, experiencing perturbations either in the vertical or in the horizontal plane. Perturbations were either visuomotor rotations of varying angle or velocity-dependent forces of varying strength. We found that, after extensive training with both kinematic or dynamic perturbations, adaptation to unpracticed, diagonal, perturbations happened along the previously learned structure (vertical or horizontal), and resulting adaptation trajectories were curved. This effect is robust, can be observed on the single-subject level, and occurs during adaptation both within and across trials. Additionally, we demonstrate that structure learning changes involuntary visuomotor reflexes and therefore is not exclusively a high-level cognitive phenomenon.


Highly sensitive and wide-range nanoplasmonic detection of fibrinogen using erythrocyte membrane-blanketed nanoparticles.
Fibrinogen, which is a glycoprotein that circulates in the blood, plays various important biological roles, e.g., in blood coagulation, fibroblast proliferation, angiogenesis, and wound healing. Abnormal levels of fibrinogen in plasma have been identified as a key biomarker of a variety of disorders from cardiovascular diseases to hemophilia. Therefore, the development of a quantitative assay for fibrinogen in the blood has emerged as an important issue for the prevention and diagnosis of these diseases. Meanwhile, it is well known that erythrocytes can selectively capture fibrinogen because of the fibrinogen receptor expressed on their plasma membrane. Inspired by these biological interactions, herein, we devised an erythrocyte membrane (EM)-blanketed biosensor based on localized surface plasmon resonance (LSPR) for highly sensitive detection of fibrinogen. By placing the EM onto a nanoparticle-on-substrate, we enhanced the LSPR signal, achieving highly sensitive and selective detection of fibrinogen. We demonstrated that fibrinogen detection is possible over a wide concentration range, 0.001-5.000 mg/mL, which can cover normal and pathological blood fibrinogen levels. In addition, it was verified that the biosensor selectively detects fibrinogen in comparison with other human-blood-plasma components. The nanoplasmonic sensor blanketed with the EM opens up new opportunities for the development of a robust fibrinogen-sensing technology.


Isolation of bone marrow stromal cell-derived smooth muscle cells by a human SM22alpha promoter: in vitro differentiation of putative smooth muscle progenitor cells of bone marrow.
Bone marrow stromal cells (BMSCs) have many characteristics of mesenchymal stem cells that can differentiate into smooth muscle cells (SMCs). However, there have been few studies closely following the cell development of smooth muscle lineage among BMSCs. To investigate the possible existence of a cell population committed to the SMC lineage among bone marrow adhesion cells, we tried to detect and follow the in vitro differentiation of such a cell type by using a promoter-sorting method with a human SM22alpha promoter (-480 bp)/green fluorescent protein (GFP) construct. The construct was transfected to adhesion cells that appeared 5 days after the seeding of mononuclear cells from bone marrow. GFP was first detectable 5 days after the transfection in a cell population [Ad(G) cells], which expressed PDGF-beta but neither mature (calponin) nor immature (SMemb) SMC-specific proteins at that time. However, the cells were eventually grown into individual clones that expressed SMC-specific proteins (alpha-smooth muscle actin, calponin, and SM-1), suggesting that Ad(G) cells have partly at least progenitor properties. Because early studies have reported that PDGF-beta signaling plays pivotal roles in the differentiation of mesenchymal smooth muscle progenitor cells, Ad(G) cells might be putative mesenchymal smooth muscle progenitors expressing PDGF-beta. We demonstrated the presence of a cell population fated to become SMCs and followed their differentiation into SMCs among BMSCs.


Sensory supplementation through tongue electrotactile stimulation to preserve head stabilization in space in the absence of vision.
To investigate the effectiveness of a head position-based, tongue-placed biofeedback system in providing sensory supplementation to preserve head stability in space in the absence of visual information. Nine healthy young men with normal vision and no history of previous motor problems, neck injury, vertigo, neurologic disease, or vestibular impairment voluntarily participated in the experiment. They were asked to stand, their feet placed in a semitandem position, as immobile as possible in two conditions of No Vision and Vision and two conditions of No Biofeedback and Biofeedback. In the Biofeedback condition, subjects executed the postural task using a biofeedback system whose principle consisted of supplying them with additional information about their head orientation/motion with respect to gravitational vertical through electrotactile stimulation of the tongue. A system for the analysis of movement was used to record the head displacements. Without the provision of the biofeedback (No Biofeedback condition), the No Vision condition yielded increased head displacements along the mediolateral axis compared with the Vision condition. Conversely, when biofeedback was available (Biofeedback condition), no significant difference between the No Vision and Vision conditions was observed. These results suggest that healthy young subjects were able to efficiently use head position-based, tongue-placed biofeedback to suppress the head instability induced by the suppression of vision. Hence the present findings demonstrate the effectiveness of a head position-based, tongue-placed biofeedback in providing sensory supplementation to preserve head stability in space in conditions of absent visual information.


Notch3 signaling in vascular smooth muscle cells induces c-FLIP expression via ERK/MAPK activation. Resistance to Fas ligand-induced apoptosis.
Mutations in the Notch3 receptor result in the cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephelopathy (CADASIL) syndrome, a heritable arteriopathy predisposing to early onset stroke. Based upon clinical evidence that CADASIL arteriopathy results in degeneration and loss of vascular smooth muscle cells (VSMC) from the arterial wall, we postulated that Notch3 signaling is a critical determinant of VSMC survival. We initially established that both transient and constitutive Notch3 signaling promoted VSMC survival in response to the proapoptotic Fas ligand (FasL). Resistance to FasL-induced apoptosis was associated with the induction of c-FLIP, a primary inhibitor of the FasL signaling pathway. We determined that Notch3's regulation of c-FLIP was independent of the activity of the classical DNA-binding protein, RBP-Jk, but dependent upon cross-talk activation of the ERK/MAPK pathway. We extended our observations to the in vivo context by determining a coordinate regulation of Notch3 and c-FLIP within the arterial wall in response to injury. Furthermore, we defined that expression levels of Notch3 and c-FLIP are coordinately up-regulated within the neointima of remodeled arteries. Taken together, these findings provide initial evidence that Notch3 signaling may be a critical determinant of VSMC survival and vascular structure by modulating the expression of downstream mediators of apoptosis via signaling cross-talk with the ERK/MAPK pathway.


[A case of chronic Budd-Chiari syndrome].
The Budd-Chiari syndrome is a rare disease associated with occlusion of the hepatic vein by a tumor or a thrombus. It develops due to progressive narrowing or occlusion of the hepatic veins and may occasionally proceed through the chronic disease within months, rarely years as individual recurrences, with pains, enlarged liver, and mild jaundice. These patients generally have partial hepatic vein occlusion. The paper describes a long (more than 20 years) course of the Budd-Chiari syndrome in which only a special angiographic study could verify the presumptive diagnosis and reveal the cause of evolving liver cirrhosis.