A new small-sized stem salamander from the Middle Jurassic of Western Siberia, Russia.
Salamanders (Caudata) are one of the three modern groups of amphibians known from the Middle Jurassic. The early stages of evolution of these amphibians are still poorly known, especially for stem taxa of Jurassic age. A new small-sized stem salamander, Egoria malashichevi gen. et sp. nov., from the Middle Jurassic (Bathonian) Itat Formation of the Berezovsk Quarry locality in Western Siberia, Russia, is described on the basis of isolated vertebrae, including an atlas centrum and a fragmentary trunk vertebra centrum previously referred to an undescribed salamander taxon ("Berezovsk salamander A"). The new taxon is diagnosed by the following unique combination of vertebral characters: atlantal anterior cotyles with elliptical anterior outline, located at an angle of approximately 135-137 degrees to each other; wide posterior portion of the atlantal centrum; ossified portion of the intercotylar tubercle represented by dorsal and ventral lips; absence of a deep depression on the ventral surface of the atlantal centrum; absence of pronounced ventrolateral ridges on the atlas; absence of spinal nerve foramina; presence of a pitted texture on the ventral and lateral surfaces of the centra and lateral surfaces neural arch pedicels; presence of a short atlantal neural arch with its anterior border situated behind the level of the anterior cotyles; short trunk vertebrae; and upper transverse process (= diapophysis) larger than lower transverse process (= parapophysis) on the trunk vertebrae; notochordal canal opens in the upper half of the cotyle (= the lower portion of the centrum is more massive and less compact than the upper portion). The microanatomical organization of the atlas and trunk vertebrae is characterized by the presence of inner cancellous endochondral bone. The small body size (about 180-215 mm) of Egoria malashichevi gen. et sp. nov. indicates that that not all stem salamanders were large neotenic forms (up to 550-600 mm in Urupia and Marmorerpeton) and hints at a broader ecological role for stem salamanders.


Clinical and cost-effectiveness of home-based cardiac rehabilitation compared to conventional, centre-based cardiac rehabilitation: Results of the FIT@Home study.
Aim Although cardiac rehabilitation improves physical fitness after a cardiac event, many eligible patients do not participate in cardiac rehabilitation and the beneficial effects of cardiac rehabilitation are often not maintained over time. Home-based training with telemonitoring guidance could improve participation rates and enhance long-term effectiveness. Methods and results We randomised 90 low-to-moderate cardiac risk patients entering cardiac rehabilitation to three months of either home-based training with telemonitoring guidance or centre-based training. Although training adherence was similar between groups, satisfaction was higher in the home-based group ( p = 0.02). Physical fitness improved at discharge ( p < 0.01) and at one-year follow-up ( p < 0.01) in both groups, without differences between groups (home-based p = 0.31 and centre-based p = 0.87). Physical activity levels did not change during the one-year study period (centre-based p = 0.38, home-based p = 0.80). Healthcare costs were statistically non-significantly lower in the home-based group (€437 per patient, 95% confidence interval -562 to 1436, p = 0.39). From a societal perspective, a statistically non-significant difference of €3160 per patient in favour of the home-based group was found (95% confidence interval -460 to 6780, p = 0.09) and the probability that it was more cost-effective varied between 97% and 75% (willingness-to-pay of €0 and €100,000 per quality-adjusted life-years, respectively). Conclusion We found no differences between home-based training with telemonitoring guidance and centre-based training on physical fitness, physical activity level or health-related quality of life. However, home-based training was associated with a higher patient satisfaction and appears to be more cost-effective than centre-based training. We conclude that home-based training with telemonitoring guidance can be used as an alternative to centre-based training for low-to-moderate cardiac risk patients entering cardiac rehabilitation.


[Neurocysticercosis: a clinical and pathological study of 27 necropsied cases].
Neurocysticercosis is the most frequent and widespread neuroparasitosis of the human being. The development of brain and leptomeningeal lesions, with subsequent symptoms, are mainly related with the immune status of the host, and to the number and evolutional phase of the parasites. We present the pathological findings in 27 necropsies of patients with neurocysticercosis, which accounted for 3.1% of the necropsies. 77% of the patients were male and the age ranged from 18 to 85 years. In 26% there was previous history of alcoholism. Clinicopathological study showed that 50% of the cases were classified as asymptomatic form, 11% epileptic form, 11% intraventricular form and 11% combined form. 33% of the patients presented seizures as a factor of aggravation of the clinical picture. There was a single cysticercus in 60% of the cases, the cellulosae form present in 82% and the racemous form in 7% of the cases; the remaining 11% had both forms present. In 30% of the patients the cause of death was directly related with the presence of the cysticercus in the central nervous system. Our findings confirm the high morbidity of this disease.


Patient with Disorders of Sex Development (DSD): A Case Report from a Tertiary Care Hospital in Thiruvananthapuram, India.
46 XX male syndrome, a rare case of infertility was first reported by de la Chapelle in 1964. In newborn males, the incidence rate of the syndrome varies from 1/9000 to 1/20000. Here, a case of 46 XX male syndrome is reported with clinical, biochemical and genetic changes of the patient and normal masculine features. A 29 year old male with infertility registered at the Sree Avittom Thirunal Hospital of Government Medical College, Thiruvananthapuram for fertility treatment. He was diagnosed with non obstructive azoospermia in repeated semen analysis. Chromosomal analysis on peripheral blood lymphocytes has revealed 46 XX male syndrome and the result was confirmed with Fluorescent In situ Hybridization (FISH). Real time polymerase chain reaction failed to detect genes on azoospermia factor regions, AZFa, AZFb and AZFc of Y chromosome, but detected SRY gene positivity. Masculine features of patient were normal except small sized testis, ejaculatory dysfunction and azoospermia. Appearance of the external genitalia will be generally normal in 46 XX with SRY positive males and generally difficult to identify before puberty because there will not be any significant clinical indication. The present case report demonstrates that mere physical or clinical examination may not disclose the genetic defects. Therefore, in addition to general examination, it is essential to perform genetic analysis on men with infertility.


Recent advances in single-cell engineered live biotherapeutic products research for skin repair and disease treatment.
The human microbiome has emerged as a key player in maintaining skin health, and dysbiosis has been linked to various skin disorders. Amidst growing concerns regarding the side effects of antibiotic treatments, the potential of live biotherapeutic products (LBPs) in restoring a healthy microbiome has garnered significant attention. This review aims to evaluate the current state of the art of the genetically or metabolically engineered LBPs, termed single-cell engineered LBPs (eLBPs), for skin repair and disease treatment. While some studies demonstrate promising outcomes, the translation of eLBPs into clinical applications remains a significant hurdle. Substantial concerns arise regarding the practical implementation and scalability of eLBPs, despite the evident potential they hold in targeting specific cells and delivering therapeutic agents. This review underscores the need for further research, robust clinical trials, and the exploration of current advances in eLBP-based bioengineered bacterial chassis and new outlooks to substantiate the viability and effectiveness of eLBPs as a transformative approach in skin repair and disease intervention.


Next-generation AAV vectors for clinical use: an ever-accelerating race.
During the past five decades, it has become evident that Adeno-associated virus (AAV) represents one of the most potent, most versatile, and thus most auspicious platforms available for gene delivery into cells, animals and, ultimately, humans. Particularly attractive is the ease with which the viral capsid-the major determinant of virus-host interaction including cell specificity and antibody recognition-can be modified and optimized at will. This has motivated countless researchers to develop high-throughput technologies in which genetically engineered AAV capsid libraries are subjected to a vastly hastened emulation of natural evolution, with the aim to enrich novel synthetic AAV capsids displaying superior features for clinical application. While the power and potential of these forward genetics approaches is undisputed, they are also inherently challenging as success depends on a combination of library quality, fidelity, and complexity. Here, we will describe and discuss two original, very exciting strategies that have emerged over the last three years and that promise to alleviate at least some of these concerns, namely, (i) a reverse genetics approach termed "ancestral AAV sequence reconstruction," and (ii) AAV genome barcoding as a technology that can advance both, forward and reverse genetics stratagems. Notably, despite the conceptual differences of these two technologies, they pursue the same goal which is tailored acceleration of AAV evolution and thus winning the race for the next-generation AAV vectors for clinical use.


Organic solvent-induced bipolar disorder: a case report.
Many studies have reported neurological and neuropsychiatric symptoms, including a significantly increased risk of depression and suicide, from exposure to low to moderate levels of organic solvents. However, few studies have reported a link between organic solvent exposure and bipolar disorder. The authors present a case of a 43-y-old man who developed new-onset bipolar disorder following exposure to organic solvents in a textile printing plant. The man had elevated blood levels of several common solvents. His symptoms abated following avoidance of solvent exposures at his workplace and after nutritional and sauna detoxification treatments that one of the authors formulated to clear xenobiotics. Following avoidance and detoxification, the patient's blood concentrations of organic solvents fell to undetectable levels and his manic symptoms disappeared, with no significant recurrences over the past 13 y, as evaluated by the authors and his other physicians.


Antisense oligonucleotide-mediated knockdown of Mpzl3 attenuates the negative metabolic effects of diet-induced obesity in mice.
Previously, we demonstrated that global knockout (KO) of the gene encoding myelin protein zero-like 3 (Mpzl3) results in reduced body weight and adiposity, increased energy expenditure, and reduced hepatic lipid synthesis in mice. These mice also exhibit cyclic and progressive alopecia which may contribute to the observed hypermetabolic phenotype. The goal of the current study was to determine if acute and peripherally restricted knockdown of Mpzl3 could ameliorate the negative metabolic effects of exposure to a high-fat and sucrose, energy-dense (HED) diet similar to what was observed in global Mpzl3 KO mice in the absence of a skin phenotype. Mpzl3 antisense oligonucleotide (ASO) administration dose-dependently decreased fat mass and circulating lipids in HED-fed C57BL/6N mice. These changes were accompanied by a decrease in respiratory exchange ratio, a reduction in energy expenditure and food intake, a decrease in expression of genes regulating de novo lipogenesis in white adipose tissue, and an upregulation of genes associated with steroid hormone biosynthesis in liver, thermogenesis in brown adipose tissue and fatty acid transport in skeletal muscle. These data demonstrate that resistance to the negative metabolic effects of HED is a direct effect of Mpzl3 knockdown, rather than compensatory changes that could be associated with deletion of Mpzl3 during development in global KO mice. Inhibiting MPZL3 could be a potential therapeutic approach for the treatment of obesity and associated dyslipidemia.


[A motivational approach of cognitive efficiency in nursing home residents].
Despite a widespread concern with self-determined motivation (behavior is engaged in "out of pleasure" or "out of choice and valued as being important") and psychological adjustment in later life (well-being, satisfaction in life, meaning of life, or self-esteem), very little is known about the existence and nature of the links between self-determined motivation and cognitive efficiency. The aim of the present study was to investigate theses links in nursing home residents in the framework of the Self-determination theory (SDT) (Deci & Ryan, 2002), in which motivational profile of a person is determined by the combination of different kinds of motivation. We hypothesized that self-determined motivation would lead to higher cognitive efficiency. Participants. 39 (32 women and 7 men) elderly nursing home residents (m= 83.6 ± 9.3 year old) without any neurological or psychiatric disorders (DSM IV) or depression or anxiety (Hamilton depression rating scales) were included in the study. Methods. Cognitive efficiency was evaluated by two brief neuropsychological tests, the Mini mental state examination (MMSE) and the Frontal assessment battery (FAB). The motivational profile was assessed by the Elderly motivation scale (Vallerand & 0'Connor, 1991) which includes four subscales assessing self- and non-self determined motivation to engage oneself in different domains of daily life activity. Results. The neuropsychological scores were positively and significantly correlated to self-determined extrinsic motivation (behavior is engaged in "out of choice" and valued as being important), and the global self-determination index (self-determined motivational profile) was the best predictor of the cognitive efficiency. Conclusion. The results support the SDT interest for a qualitative assessment of the motivation of the elderly people and suggest that a motivational approach of cognitive efficiency could help to interpret cognitive performances exhibited during neuropsychological assessment.


Factors affecting unmet need for family planning in southern nations, nationalities and peoples region, ethiopia.
High fertility and low contraceptive prevalence characterize Southern Nations, Nationalities and Peoples Region. In such populations, unmet needs for contraception have a tendency to be high, mainly due to the effect of socio-economic and demographic variables. However, there has not been any study examining the relationship between these variables and unmet need in the region. This study, therefore, identifies the key socio- demographic determinants of unmet need for family planning in the region. The study used data from the 2000 and 2005 Ethiopian Demographic and Health Surveys. A total of 2,133 currently married women age 15-49 from the 2000 survey and 1,988 from the 2005 survey were included in the study. Unmet need for spacing, unmet need for limiting and total unmet need were used as dependent variables. Socio- demographic variables (respondent's age, age at marriage, number of living children, sex composition of living children, child mortality experience, place of residence, respondent's and partner's education, religion and work status) were treated as explanatory variables and their relative importance was examined on each of the dependent variables using multinomial and binary logistic regression models. Unmet need for contraception increased from 35.1% in 2000 to 37.4% in 2005. Unmet need for spacing remained constant at about 25%, while unmet need for limiting increased by 20% between 2000 and 2005. Age, age at marriage, number of living children, place of residence, respondent's education, knowledge of family planning, respondent's work status, being visited by a family planning worker and survey year emerged as significant factors affecting unmet need. On the other hand, number of living children, education, age and age at marriage were the only explanatory variables affecting unmet need for limiting. Number of living children, place of residence, age and age at marriage were also identified as factors affecting total unmet need for contraception. unmet need for spacing is more prevalent than unmet need for limiting. Women with unmet need for both spacing and limiting are more likely to be living in rural areas, have lower level of education, lower level of knowledge about family planning methods, have no work other than household chores, and have never been visited by a family planning worker. In order to address unmet need for family planning in the region, policy should set mechanisms to enforce the law on minimum age for marriage, improve child survival and increase educational access to females. In addition, the policy should promote awareness creation about family planning in rural areas.


A support to biological validation of oxygenation parameters.
Blood gas analyzers are able to provide information on a wide range of oxygenation parameters. Some of these data are complex. Their biological significance or clinical consistency are not always well known. This article aims to define these parameters, their reference values according to the type of sample; and to outline the possible errors during their interpretation. Thus, these reliable results can be integrated into the diagnostic procedure. We will see that the information provided by physicians plays an important role in their interpretation (temperature, patient ventilation condition, type of sample…). Knowing the physiological significance of complex data such as the oxygen alveolar-arterial gradient, or the estimated fraction of shunt, as well as the factors influencing them, allows us to improve their biological validation as accurately as possible. Finally, we will summarize the major oxygenation disorders and their impact on the results of blood gas analysis.


[Selective fasicular neurotomy for spastic equinovarus foot deformity in cerebral palsy children].
Spasticity is usually treated by rehabilitation, orthosis, chemical denervations, orthopaedic surgery and neurosurgery. Selective fascicular neurotomy is a neurosurgical procedure consisting in partial section of selected motor nerves innervating spastic muscles. Neurotomy is indicated in cases of localised disabling spasticity without musculotendinous shortening, resistant to chemical denervation and for which a motor nerve block with anaesthetic has given a good functional result. Neurotomy includes division of the afferent Ia and Ib fibers, unable to recover, leading to permanent disappearance of the spasticity. Neurotomy also includes section of the motor efferent fibers with transient paresis as a result. In adults, neurotomy provides functional improvement in 81 to 97% of cases. In case of posterior tibial neurotomy, improved walking stability and a decrease in foot equinus and knee recurvatum is observed. In children, the risk of deformity recurrence seems higher because of motor axonal reinnervation: indications must therefore be carefully considered and rehabilitation provided after surgery.


Phosphorus, but not calcium, affects manganese absorption and turnover in chicks.
Two balance studies with growing chicks were conducted to evaluate the effects of excess Ca or excess P on endogenous fecal Mn excretion and true Mn absorption. An isotope-dilution technique was used to estimate endogenous manganese in excreta. Supplements were added to a corn-soybean diet containing 1% Ca, 0.7% P (0.5% available P) and 37 mg Mn/kg. In Experiment 1, supplemental Ca levels of 0, 0.5 and 1.0% from feedgrade limestone were compared. True absorption of Mn was not affected by Ca level (P greater than 0.10) and averaged 2.8% for birds fed the Mn-unsupplemented diet. In Experiment 2, a 2 x 3 factorial arrangement of treatments included: 100 and 1000 mg/kg supplemental Mn (from MnSO4.H2O) and 0, 0.4 and 0.8% added P supplied by dicalcium phosphate. Excess P significantly decreased true absorption of Mn (P less than 0.01). In birds fed 100 mg/kg supplemental Mn, absorption of Mn decreased 22% as excess P increased from 0 to 0.8%, whereas in birds fed 1000 mg/kg supplemental Mn, Mn absorption decreased 59% as a result of 0.8% P supplementation. These results confirm that the antagonism of Mn by inorganic P is due to reduced gut absorption of Mn.


Characterizing learning deficits and hippocampal neuron loss following transient global cerebral ischemia in rats.
The 2-vessel-occlusion + hypotension (2VO + H) model of transient global cerebral ischemia results in neurodegeneration within the CA1 field of the hippocampus, but previous research has failed to demonstrate robust or reliable learning/memory deficits in rats subjected to this treatment. In the present study, sensitive behavioral protocols were developed in an effort to characterize the cognitive impairments following 2VO + H more precisely. Adult rats were exposed to 10 min of bilateral carotid occlusion with simultaneous hypotension. Following recovery, 2VO + H and control rats were subjected to a series of behavioral tests (locomotor activity, sensorimotor battery, water maze [cued, place, learning set], object recognition, and radial arm maze) over an extended recovery period followed by an assessment of neuronal loss in the dorsal hippocampus. The 2VO + H treatment was associated with long-lasting spatial learning deficits in the absence of other behavioral impairments and with neurodegeneration in dorsal hippocampal CA1. Water maze protocols that placed higher memory demands upon the rats (relatively "hard" vs. "easy") were more sensitive for detecting ischemia-induced deficits. We have shown that the use of appropriate behavioral tests (e.g., a relatively difficult place learning task) allowed for the observation of robust spatial learning deficits in a model previously shown to induce relatively subtle behavioral effects. Thus, the 2VO + H model induces both hippocampal neuronal loss and long-term learning deficits in rats, providing a potentially useful model for evaluating therapeutic efficacy.


Formant centralization ratio: a proposal for a new acoustic measure of dysarthric speech.
The vowel space area (VSA) has been used as an acoustic metric of dysarthric speech, but with varying degrees of success. In this study, the authors aimed to test an alternative metric to the VSA-the formant centralization ratio (FCR), which is hypothesized to more effectively differentiate dysarthric from healthy speech and register treatment effects. Speech recordings of 38 individuals with idiopathic Parkinson's disease and dysarthria (19 of whom received 1 month of intensive speech therapy [Lee Silverman Voice Treatment; LSVT LOUD]) and 14 healthy control participants were acoustically analyzed. Vowels were extracted from short phrases. The same vowel-formant elements were used to construct the FCR, expressed as (F2u + F2a + F1i + F1u) / (F2i + F1a), the VSA, expressed as ABS([F1i x (F2a - F2u) + F1a x (F2u - F2i) + F1u x (F2i - F2a)] / 2), a logarithmically scaled version of the VSA (LnVSA), and the F2i /F2u ratio. Unlike the VSA and the LnVSA, the FCR and F2i/F2u ratio robustly differentiated dysarthric from healthy speech and were not gender sensitive. All metrics effectively registered treatment effects and were strongly correlated with each other. Albeit preliminary, the present findings indicate that the FCR is a sensitive, valid, and reliable acoustic metric for distinguishing dysarthric from unimpaired speech and for monitoring treatment effects, probably because of reduced sensitivity to interspeaker variability and enhanced sensitivity to vowel centralization.


Involvement of RFC3 in tamoxifen resistance in ER-positive breast cancer through the cell cycle.
Since the establishment of the molecular subtyping system, ER positive breast cancer was considered to be the most prevalent type of breast cancer, and endocrine therapy was a very important solution. However, numerous studies have shown that the cell cycle plays a key role in the progression and metastasis of breast cancer. The present study showed that RFC3 was involved in the cell cycle through DNA replication. Furthermore, RFC3 expression was significantly higher in breast cancer-resistant cells than in parental cells, which correlated with the cell cycle. We confirmed these results by established drug-resistant cell lines for breast cancer, raw letter analysis and immunohistochemical analysis of primary and recurrent tissues from three ER+ breast cancers. In addition, analysis of the results through an online database revealed that RFC3 expression was significantly associated with poor prognosis in ER+ breast cancer. We also demonstrated that in ER positive breast cancer-resistant cells, knockdown of RFC3 blocked the S-phase of cells and significantly attenuated cell proliferation, migration and invasion. Furthermore, RFC3 overexpression in ER positive breast cancer cells enhanced cell proliferation, migration and invasion. Taking all these findings into account, we could conclude that RFC3 was involved in endocrine resistance in breast cancer through the cell cycle. Thus, RFC3 may be a target to address endocrine therapy resistance in ER positive breast cancer and may be an independent prognostic factor in ER positive breast cancer.


Tandem Substitutions in Somatic Hypermutation.
Upon antigen recognition, activation-induced cytosine deaminase initiates affinity maturation of the B-cell receptor by somatic hypermutation (SHM) through error-prone DNA repair pathways. SHM typically creates single nucleotide substitutions, but tandem substitutions may also occur. We investigated incidence and sequence context of tandem substitutions by massive parallel sequencing of V(D)J repertoires in healthy human donors. Mutation patterns were congruent with SHM-derived single nucleotide mutations, delineating initiation of the tandem substitution by AID. Tandem substitutions comprised 5,7% of AID-induced mutations. The majority of tandem substitutions represents single nucleotide juxtalocations of directly adjacent sequences. These observations were confirmed in an independent cohort of healthy donors. We propose a model where tandem substitutions are predominantly generated by translesion synthesis across an apyramidinic site that is typically created by UNG. During replication, apyrimidinic sites transiently adapt an extruded configuration, causing skipping of the extruded base. Consequent strand decontraction leads to the juxtalocation, after which exonucleases repair the apyramidinic site and any directly adjacent mismatched base pairs. The mismatch repair pathway appears to account for the remainder of tandem substitutions. Tandem substitutions may enhance affinity maturation and expedite the adaptive immune response by overcoming amino acid codon degeneracies or mutating two adjacent amino acid residues simultaneously.


Ligand induced conformational changes of the human serotonin transporter revealed by molecular dynamics simulations.
The competitive inhibitor cocaine and the non-competitive inhibitor ibogaine induce different conformational states of the human serotonin transporter. It has been shown from accessibility experiments that cocaine mainly induces an outward-facing conformation, while the non-competitive inhibitor ibogaine, and its active metabolite noribogaine, have been proposed to induce an inward-facing conformation of the human serotonin transporter similar to what has been observed for the endogenous substrate, serotonin. The ligand induced conformational changes within the human serotonin transporter caused by these three different types of ligands, substrate, non-competitive and competitive inhibitors, are studied from multiple atomistic molecular dynamics simulations initiated from a homology model of the human serotonin transporter. The results reveal that diverse conformations of the human serotonin transporter are captured from the molecular dynamics simulations depending on the type of the ligand bound. The inward-facing conformation of the human serotonin transporter is reached with noribogaine bound, and this state resembles a previously identified inward-facing conformation of the human serotonin transporter obtained from molecular dynamics simulation with bound substrate, but also a recently published inward-facing conformation of a bacterial homolog, the leucine transporter from Aquifex Aoelicus. The differences observed in ligand induced behavior are found to originate from different interaction patterns between the ligands and the protein. Such atomic-level understanding of how an inhibitor can dictate the conformational response of a transporter by ligand binding may be of great importance for future drug design.


Incubation of double labelled coproporphyrinogen with chicken red cell haemolysates, chemical and TLC fractionation of extracts.
Further evidence is presented for the enzymic conversion of protoporphyrinogen to protoporphyrin by observing the loss of 3H counts by 3H and 14C labelled coproporphyrinogen when incubated in chicken red cell haemolysates. Use was made of chemical and TLC fractionation of porphyrin extracts after incubation and a loss of half the 3H was again found. Evidence is presented for the role of harderoporphyrinogen as a natural intermediate in this conversion. The relevance of the findings in the porphyrias, and in particular variegate porphyria, is discussed. It is suggested that the enzymic process involved in the conversion of protoporphyrinogen to protoporphyrin may be deficient in variegate porphyria.


Pseudomonas putida KT2440 response to nickel or cobalt induced stress by quantitative proteomics.
Nickel and cobalt are obligate nutrients for the gammaproteobacteria but when present at high concentrations they display toxic effects. These two metals are present in the environment, their origin being either from natural sources or from industrial use. In this study, the effect of inhibitory concentrations of Ni or Co was assessed on the soil bacterium Pseudomonas putida KT2440 using a proteomic approach. The identification of more than 400 spots resulted in the quantification of 160 proteins that underwent significant variations in cells exposed to Co and Ni. This analysis allowed us to depict the cellular response of P. putida cells toward metallic stress. More precisely, the parallel comparison of the two proteomes showed distinct responses of P. putida to Ni or Co toxicity. The most striking effect of Co was revealed by the accumulation of several proteins involved in the defense against oxidative damage, which include proteins involved in the detoxification of the reactive oxygen species, superoxides and peroxides. The up-regulation of the genes encoding these enzymes was confirmed using qRT-PCR. Interestingly, in the Ni-treated samples, sodB, encoding superoxide dismutase, was up-regulated, indicating the apparition of superoxide radicals due to the presence of Ni. However, the most striking effect of Ni was the accumulation of several proteins involved in the synthesis of amino acids. The measurement of the amount of amino acids in Ni-treated cells revealed a strong accumulation of glutamate.


Assessment of a karate performer's position estimation system without any markers.
Karate has become more popular, and researches have been conducted on training methods and motion analysis related to karate. The AR system for karate is an effective system for training and for the audience to understand the performance. To develop the AR system, it is necessary to acquire the movement of the performer. The purpose of the research is to assess a motion capture system to estimate a karate performer's full-body position and posture from HoloLens 2, without wearing any attachments. We used ThreeDPoseUnityBarracuda to estimate the position and posture of the performer's joints. In the experiment, the estimated joint's positions were compared with actual positions using the inertial three-dimensional motion capture. As results, although the error increased when the performer's movement was large, the median error between the estimated and actual positions was a maximum of 0.24 m at the x-coordinate of the right hand, and high accuracy was obtained when the performer's movement was small.


Amyloid neuropathies.
Peripheral neuropathy is a common complication of many of the systemic amyloidoses. Although the cause of neuropathy is not entirely clear, it is likely related to amyloid deposition within the nerve. This may lead to focal, multifocal, or diffuse neuropathies involving sensory, motor and/or autonomic fibers. The presenting symptoms depend on the distribution of nerves affected. One of the most common phenotypes is sensorimotor polyneuropathy, which is characterized by symptoms of neuropathic pain, numbness, and in advanced cases weakness. Symptoms begin in the feet and ultimately progress to the proximal legs and hands. The most common focal neuropathy is a median neuropathy at the wrist, clinically known as carpal tunnel syndrome. Carpal tunnel symptoms may include pain and sensory disturbances in the lateral palm and fingers; hand weakness may ensue if the focal neuropathy is severe. Autonomic neuropathy may affect a variety of organ systems such as the cardiovascular, gastrointestinal, and genitourinary systems. Symptoms may be non-specific making the diagnosis of autonomic neuropathy more difficult to identify. However, it is important to recognize and distinguish autonomic neuropathy from diseases of the end-organs themselves. This article reviews the inherited and acquired amyloidoses that affect the peripheral nervous system including familial amyloid polyneuropathy, and primary, secondary and senile amyloidosis. We emphasize the clinical presentation of the neurologic aspects of these diseases, physical examination findings, appropriate diagnostic evaluation, treatment and prognosis.


Spinal and cortical inhibition in Huntington's chorea.
In this article we studied spinal and cortical inhibitory mechanisms in patients with Huntington's disease. To evaluate spinal cord inhibitory circuitries, we assessed reciprocal inhibition between antagonist forearm muscles and the recovery cycle of the H reflex in the flexor carpi radialis. Patients showed a significant decrease in the presynaptic phase of reciprocal inhibition reaching a minimum at the conditioning-test interval of 20 msec and an abnormal facilitation of the test H reflex at the conditioning test interval of 40 to 60 msec. Throughout its time course (10-200 msec), the H reflex recovery cycle showed a more prominent facilitation in patients than in control subjects. To assess whether the observed pathophysiological abnormalities might have arisen from an abnormal motor cortical excitability, we examined the recovery cycle of the motor potentials evoked by paired transcranial magnetic stimuli. We found that the inhibitory mechanisms controlling motor cortical excitability were normal. An interpretation of the spinal cord abnormalities is that the intrinsically normal but deafferentated motor cortex in Huntington's disease partly loses its inhibitory control, thus disinhibiting spinal cord circuitry. Our findings from paired transcranial magnetic stimulation suggest that cortical motor areas are not hyperexcitable in Huntington's disease. Hence, the postulated thalamocortical overactivity in experimental models of Huntington's disease needs to be reappraised.


[Analysis of communication between blind people and Nursing students].
Analysis of how three duos of sighted Nursing students and blind people perceived communication in free recorded interaction. It was based on Discourse Analysis with an analytic tool constituted by an interview after the communication moment and by concepts characteristic of the reference framework. The analysis process revealed discourse formations about communication, visual impairment and social inclusion. The communication moment was assessed positively, constructing paraphrases in their discourse. Recording is a factor of emotional change at the start of the interaction for the Nursing students and blind people alike. It provoked meaning in the discourse of two blind persons and one student through founding silence. A discussion is started about the theme and about the incorporation of new technologies for Nursing research.


Sensitization to individual allergens and bronchial responsiveness in the ECRHS. European Community Respiratory Health Survey.
Little is known about the relation of bronchial responsiveness (BHR) to sensitization to individual allergens, or its variation between countries. Data were obtained for BHR, specific immunoglobulin E and confounding variables from 11,215 subjects, aged 20-44 yrs at the start of the European Community Respiratory Health Survey, in 34 centres in 15 countries. The relation of BHR to sensitization to cat, house dust mite, timothy grass and Cladosporium was estimated by means of multiple regression for each centre, and combined across centres by random effects meta-analysis, controlling for baseline lung function, height, sex, season of testing, age, smoking and age/sex and age/smoking interactions. BHR was greater, on average, in those sensitized to cat (p=0.023), house dust mite (p<0.001) and timothy grass (p=0.018), but not to Cladosporium (p=0.60), and increased with degree of sensitization (p<0.001). All relations showed heterogeneity between centres, although to a lesser extent in the relation to sensitization to house dust mite. More variation in bronchial responsiveness was explained by sensitization and degree of sensitization to the individual allergens than by atopy defined as any positive test in each centre, but the relative importance of each allergen varied. The use of atopy as a single variable in relation to bronchial hyperresponsiveness may be misleading.


Spike firing in the lateral cerebellar cortex correlated with movement and motor parameters irrespective of the effector limb.
Neuronal signals in the lateral aspect of the macaque cerebellar cortex were studied during a visually guided reaching task. During the performance of this task, the firing rate of most neurons was significantly modulated when reaching with either the ipsilateral or the contralateral arm. In some of these reach-modulated cells, we found that spike firing was correlated with the direction and speed of the reach. These correlations with motor parameters were present during reaching with either the ipsilateral or the contralateral arm. Based on these observations we suggest that spike firing in the lateral cerebellum was correlated with movement and motor parameters irrespective of the effector limb.


Regulation of locomotion and motoneuron trajectory selection and targeting by the Drosophila homolog of Olig family transcription factors.
During the development of locomotion circuits it is essential that motoneurons with distinct subtype identities select the correct trajectories and target muscles. In vertebrates, the generation of motoneurons and myelinating glia depends on Olig2, one of the five Olig family bHLH transcription factors. We investigated the so far unknown function of the single Drosophila homolog Oli. Combining behavioral and genetic approaches, we demonstrate that oli is not required for gliogenesis, but plays pivotal roles in regulating larval and adult locomotion, and axon pathfinding and targeting of embryonic motoneurons. In the embryonic nervous system, Oli is primarily expressed in postmitotic progeny, and in particular, in distinct ventral motoneuron subtypes. oli mediates axonal trajectory selection of these motoneurons within the ventral nerve cord and targeting to specific muscles. Genetic interaction assays suggest that oli acts as part of a conserved transcription factor ensemble including Lim3, Islet and Hb9. Moreover, oli is expressed in postembryonic leg-innervating motoneuron lineages and required in glutamatergic neurons for walking. Finally, over-expression of vertebrate Olig2 partially rescues the walking defects of oli-deficient flies. Thus, our findings reveal a remarkably conserved role of Drosophila Oli and vertebrate family members in regulating motoneuron development, while the steps that require their function differ in detail.


Ultraprecise Antigen 10-in-1 Pool Testing by Multiantibodies Transistor Assay.
Effective screening of infectious diseases requires a fast, cheap, and population-scale testing. Antigen pool testing can increase the test rate and shorten the screening time, thus being a valuable approach for epidemic prevention and control. However, the overall percent agreement (OPA) with polymerase chain reaction (PCR) is one-half to three-quarters, hampering it from being a comprehensive method, especially pool testing, beyond the gold-standard PCR. Here, a multiantibodies transistor assay is developed for sensitive and highly precise antigen pool testing. The multiantibodies capture SARS-CoV-2 spike S1 proteins with different configurations, resulting in an antigen-binding affinity down to 0.34 fM. The limit of detection reaches 3.5 × 10-17 g mL-1SARS-CoV-2 spike S1 protein in artificial saliva, 4-5 orders of magnitude lower than existing transistor sensors. The testing of 60 nasopharyngeal swabs exhibits ∼100% OPA with PCR within an average diagnoses time of 38.9 s. Owing to its highly precise feature, a portable integrated platform is fabricated, which achieves 10-in-1 pooled screening for high testing throughput. This work solves the long-standing problem of antigen pool testing, enabling it to be a valuable tool in precise diagnoses and population-wide screening of COVID-19 or other epidemics in the future.


A novel model for neuroendocrine toxicology: neurobehavioral effects of BPA exposure in a prosocial species, the prairie vole (Microtus ochrogaster).
Impacts on brain and behavior have been reported in laboratory rodents after developmental exposure to bisphenol A (BPA), raising concerns about possible human effects. Epidemiological data suggest links between prenatal BPA exposure and altered affective behaviors in children, but potential mechanisms are unclear. Disruption of mesolimbic oxytocin (OT)/vasopressin (AVP) pathways have been proposed, but supporting evidence is minimal. To address these data gaps, we employed a novel animal model for neuroendocrine toxicology: the prairie vole (Microtus ochrogaster), which are more prosocial than lab rats or mice. Male and female prairie vole pups were orally exposed to 5-μg/kg body weight (bw)/d, 50-μg/kg bw/d, or 50-mg/kg bw/d BPA or vehicle over postnatal days 8-14. Subjects were tested as juveniles in open field and novel social tests and for partner preference as adults. Brains were then collected and assessed for immunoreactive (ir) tyrosine hydroxylase (TH) (a dopamine marker) neurons in the principal bed nucleus of the stria terminalis (pBNST) and TH-ir, OT-ir, and AVP-ir neurons in the paraventricular nucleus of the hypothalamus (PVN). Female open field activity indicated hyperactivity at the lowest dose and anxiety at the highest dose. Effects on social interactions were also observed, and partner preference formation was mildly inhibited at all dose levels. BPA masculinized principal bed nucleus of the stria terminalis TH-ir neuron numbers in females. Additionally, 50-mg/kg bw BPA-exposed females had more AVP-ir neurons in the anterior PVN and fewer OT-ir neurons in the posterior PVN. At the 2 lowest doses, BPA eliminated sex differences in PVN TH-ir neuron numbers and reversed this sex difference at the highest dose. Minimal behavioral effects were observed in BPA-exposed males. These data support the hypothesis that BPA alters affective behaviors, potentially via disruption of OT/AVP pathways.


Ultrastructure of Na,K-transport vesicles reconstituted with purified renal Na,K-ATPase.
To study the size and structure of the Na,K-pump molecule, the ultrastructure of phospholipid vesicles was examined after incorporation of purified Na,K-ATPase which catalyzes active coupled transport of Na+ and K+ in a ratio close to 3Na/2K. The vesicles were analyzed by thin sectioning and freeze-fracture electron microscopy after reconstitution with different ratios of Na,K-ATPase protein to lipid, and the ultrastructural observations were correlated to the cation transport capacity. The purified Na,K-ATPase reconstituted with phospholipids to form a very uniform population of vesicles. Thin sections of preparations fixed with glutaraldehyde and osmium tetroxide showed vesicles limited by a single membrane which in samples stained with tannic acid appeared triple-layered with a thickness of 70 A. Also, freeze-fracture electron microscopy demonstrated uniform vesicles with diameters in the range of 700-1,100 A and an average value close to 900 A. The vesicle diameter was independent of the amount of protein used for reconstitution. Intramembrane particles appeared only in the vesicle membrane after introduction of Na,K-ATPase and the frequency of intramembrane particles was proportional to the amount of Na,K-ATPase protein used in the reconstitution. The particles were evenly distributed on the inner and the outer leaflet of the vesicle membrane. The diameter of the particles was 90 A and similar to our previous values for the diameter of intramembrane particles in the purified Na,K-ATPase. The capacity for active cation transport in the reconstituted vesicles was proportional to the frequency of intramembrane particles over a range of 0.2-16 particles per vesicle. The data therefore show that active coupled Na,K transport can be carried out by units of Na,K-ATPase which appear as single intramembrane particles with diameters close fo 90 A in the freeze-fracture micrographs.


[Amplitude and time characteristics of latent auditory evoked potentials in occupational hearing disorders with and without the recruitment phenomenon].
Cortical evoked potentials (CEP) of workers exposed to industrial noise were recorded by an Amplaid MK-6 unit (Italy). They suffered from neurosensory hypoacusis with or without the recruitment phenomenon. The results were compared with those derived from patients with neurosensory hypoacusis of vascular origin, aggravated by the recruitment phenomenon, and in the cortical structures of the hearing organ in the case of neurosensory hypoacusis of both vascular and noise origin. Increase of the N2 with observations made on normal controls who were not exposed to industrial noise. CEP were found to give reliable information about changes peak latency may be used for differential diagnosis of neurosensory hypoacusis of vascular or noise origin. Decrease of the P2--N2 amplitude in response to 1 kHz stimulation may also help discriminate neurosensory hypoacusis of vascular or noise origin.


Genome-Scale Metabolic Network Reconstruction and In Silico Analysis of Hexanoic acid Producing Megasphaera elsdenii.
Hexanoic acid and its derivatives have been recently recognized as value-added materials and can be synthesized by several microbes. Of them, Megasphaera elsdenii has been considered as an interesting hexanoic acid producer because of its capability to utilize a variety of carbons sources. However, the cellular metabolism and physiology of M. elsdenii still remain uncharacterized. Therefore, in order to better understand hexanoic acid synthetic metabolism in M. elsdenii, we newly reconstructed its genome-scale metabolic model, iME375, which accounts for 375 genes, 521 reactions, and 443 metabolites. A constraint-based analysis was then employed to evaluate cell growth under various conditions. Subsequently, a flux ratio analysis was conducted to understand the mechanism of bifurcated hexanoic acid synthetic pathways, including the typical fatty acid synthetic pathway via acetyl-CoA and the TCA cycle in a counterclockwise direction through succinate. The resultant metabolic states showed that the highest hexanoic acid production could be achieved when the balanced fractional contribution via acetyl-CoA and succinate in reductive TCA cycle was formed in various cell growth rates. The highest hexanoic acid production was maintained in the most perturbed flux ratio, as phosphoenolpyruvate carboxykinase (pck) enables the bifurcated pathway to form consistent fluxes. Finally, organic acid consuming simulations suggested that succinate can increase both biomass formation and hexanoic acid production.


The Influence of Maturity Status on Dynamic Balance Following 6 Weeks of Eccentric Hamstring Training in Youth Male Handball Players.
Information about when to apply an appropriate eccentric hamstring strength training stimulus during long-term athlete development is essential for effective programming and improving balance performance. This study examined the effects of six-week eccentric hamstring training on dynamic balance performance in youth handball players of different maturity statuses (pre- or post-peak height velocity (PHV)). A randomized controlled design with 45 young male handball players (14.6 ± 0.3 years) from a local national handball club were randomly allocated to a 6 week, twice weekly eccentric hamstring training in two experimental groups: a pre-PHV (maturation offset: −2.13 ± 0.63, n = 10) and post-PHV (maturation offset: 0.79 ± 0.34, n = 12) group and two control groups: maturation offset: −2.09 ± 0.61, n = 10 and maturation offset: 0.55 ± 0.67, n = 13. Dynamic balance performance was evaluated by using the composite score during the lower quarter Y-balance test from pre- and post-intervention. A significant effect on balance scores was found from pre to post (F = 11.4; p = 0.002; η2p = 0.22), intervention (F = 5.4; p = 0.025; η2p = 0.12), and maturation (F = 369; p < 0.001; η2p = 0.9), but no significant interaction effects were found (F ≥ 3.3; p ≥ 0.077; η2p ≤ 0.07). Post hoc analysis revealed that the post-PHV group had a higher score than the pre-PHV group. Furthermore, that dynamic balance increased in the post-PHV group after intervention much more in the control post-PHV group. It was concluded that somatic maturation influences dynamic balance performance and that eccentric hamstring training results in greater improvement in balance performance in young male handball players for the post-pubertal group.


Electric Properties of Adsorbed Polystyrenesulfonate.
Counterion polarization of sodium and magnesium polystyrenesulfonate (NaPSS and MgPSS), adsorbed in an excess onto ellipsoidal beta-ferric hydrous oxide particles (beta-FeOOH), is studied in both the absence and the presence of added simple electrolytes, NaCl and MgCl(2). The amplitude of the low-frequency (10(2)-10(4) Hz) and the high-frequency (10(4)-10(6) Hz) electro-optical effects of NaPSS is found to decrease with increasing NaCl concentration, while the critical frequency of relaxation of both effects remains unchanged. Addition of MgCl(2) to the suspension containing MgPSS also reduces the amplitude of the low-frequency electro-optical effect, but the amplitude of the high-frequency effect increases. The increased number of mobile (not bound) divalent ions, which produce larger charge fluctuation, could explain the high-frequency effect increase in the presence of a small excess of MgCl(2). Substitution of Na(+) counterions of PSS by Mg(2+) is found to increase the critical frequency of relaxation and to reduce the amplitude of the low-frequency effect, probably due to the strong repulsion between bound divalent counterions. The polyion length remains nearly unchanged during this substitution, as evidenced by the constant relaxation time of the polyelectrolyte-coated particles. The increase of counterion valence is not found to affect the amplitude of the high-frequency electro-optical effect in the absence of added salt. Copyright 1999 Academic Press.


Temperature Decline in Embryological Culture Dishes outside Incubator.
In embryological culture dishes, there is a temperature decline when they are removed outside incubators. This study aimed at investigating the effects of this temperature decline within a certain time frame, the type of culture dish with or without the use of laminar air flow and whether it is possible to achieve a sufficient thermal control with the use of a heating stage. In this experimental study, the temperatures of four different types of polystyrene dishes [50 mm intracytoplasmic sperm injection (ICSI), 35 mm, 60 mm, 90 mm], filled with culture medium and oil were recorded for a period of 10 minutes outside the incubator. Temperature was measured with an infrared thermographic camera. The reference temperature was 37°C. Four parameters were analyzed: the type of dishes, air flow, a heating stage at 37°C and 38.5°C. There was a time-dependant significant temperature decline outside the incubator in all types of dishes and under all experimental conditions. Under air flow temperature decline increased compared to the no air flow condition. The use of a heating stage at either 37°C or 38.5°C slightly improved the situation in most cases. After three minutes out of the incubator without a heating stage and air flow, the temperature was <34°C; with air flow and without a heating stage the temperature was <33°C. When a heating stage was used, the temperature was <36°C, except when using ICSI dishes. When ICSI dishes were on a heating stage they maintained a temperature close to 37°C with or without air flow. In all experimental conditions the highest decline was recorded with the 90 mm dishes. Time is crucial for managing the temperature decline in culture dishes when out of the incubator. Under air laminar flow, the heat loss is greater, when with a heating stage at 37°C or better at 38.5°C this loss decreases but still exists. ICSI flat bottom dishes give the best results when heated stages are used. Flat bottom dishes maintain the temperature rather efficiently. Based on our findings, the use of flat bottom dishes should become a universal practice in in vitro fertilization (IVF).


Surgical Treatment of Fibroosseous Lesion in Young Patient with Reduced Mouth Opening.
Fibrous dysplasia is a benign fibroosseous disorder that can affect the maxillary bones, causing aesthetic deformity and functional impairment. This article reports the case of a 13-year-old male patient at the time of diagnosis. The patient showed increased facial volume with relevant asymmetry, having reported the onset of the condition 12 months before. Upon examination, the patient presented an 8-mm mouth opening and an acute inflammatory process associated with tooth 37 pericoronal hood. Upon imaging exam, exuberant bone growth in the left mandibular ramus area of ground glass aspect was observed. After incisional biopsy, fibrous dysplasia was diagnosed and sequentially treated with osteoplasty and coronoid process removal. The patient evolved to a 43-mm mouth opening and favorable aesthetics without recurrence in a 3-year follow-up period. In this case, coronoidectomy and bone plasty proved to be effective, returning aesthetics and function. The patient is supposed to be followed up in the long term.


[Proteoglycans of animal tissue and their effect on DNA synthesis].
A procedure for isolation of proteoglycans (PG) from rat liver and lung has been developed. The effect of PG on DNA and RNA synthesis in fragments of mouse embryo tissue was investigated. PG were shown to inhibit DNA synthesis. This effect was tissue-specific but species-nonspecific. Under the same conditions various glycosaminoglycans (chondroitin sulfates and heparin) had no effect on DNA synthesis. No effect of PG on RNA synthesis was observed. Possible mechanisms of PG effect are discussed.


Potential of medicinal plants as antimicrobial and antioxidant agents in food industry: a hypothesis.
Many food preservation strategies can be used for the control of microbial spoilage and oxidation; however, these quality problems are not yet controlled adequately. Although synthetic antimicrobial and antioxidant agents are approved in many countries, the use of natural safe and effective preservatives is a demand of food consumers and producers. This paper proposes medicinal plants, traditionally used to treat health disorders and prevent diseases, as a source of bioactive compounds having food additive properties. Medicinal plants are rich in terpenes and phenolic compounds that present antimicrobial and antioxidant properties; in addition, the literature revealed that these bioactive compounds extracted from other plants have been effective in food systems. In this context, the present hypothesis paper states that bioactive molecules extracted from medicinal plants can be used as antimicrobial and antioxidant additives in the food industry.


Oligosaccharides from milk.
Feeding infants breast milk of healthy mothers is associated with a lower incidence of infectious and allergic diseases. Although this effect is of multifactorial origin, it is widely accepted that the entire intestinal flora of breast-fed infants provides antiinfective properties and is an important stimulating factor for the postnatal development of the immune system. The effect of human milk on the postnatal development of the intestinal flora cannot be attributed to a single ingredient. It is generally accepted, however, that human milk oligosaccharides play a key role in this matter. Apart from their prebiotic effects, there is also evidence that human milk oligosaccharides act as receptor analogs to inhibit the adhesion of pathogens on the epithelial surface and interact directly with immune cells. Because of their complexity, oligosaccharides with structures identical to human milk oligosaccharides are not yet available as dietary ingredients. In the current search for alternatives, non-milk-derived oligosaccharides have gained much attention. As 1 example, a mixture of neutral galacto-oligosaccharides and long chain fructo-oligosaccharides have been identified as effective prebiotic ingredients during infancy. Furthermore, another class of oligosaccharides with a potential physiological benefit could be those found in animal milks. Most of the oligosaccharides detected in domestic animal milks have some structural features in common with human milk oligosaccharides. One important fact is the occurrence of sialic acids such as N-acetylneuraminic acids. However, total amounts and individual structures are still different from those in human milk oligosaccharides. Although these structural similarities between animal milk and human milk oligosaccharides are promising, further studies are needed to prove the equivalence of their function.


Evaluating performance of reconstruction algorithms for 3-D [15O] water PET using subtraction analysis.
Positron emission tomography (PET) [15O] activation studies have benefited significantly from three-dimensional (3-D) data acquisition. However, they have been slow to take advantage of new 3-D reconstruction techniques. Compared with the widely used 3-D reprojection reconstruction (3DRP), the advantage of signal and noise for iterative algorithms has been outweighed by concern about long and complicated reconstruction procedures and inconsistent performance. Most pseudo-3-D algorithms, such as rebinning methods, aim at increasing the speed of reconstruction but lack further resolution improvement or noise control. Although many evaluations have been conducted through simulations and phantom experiments, the spatially varying nature of signal and noise and the complexity of biological effects have complicated the interpretation of real data based on simulation or phantom results. We have taken a different approach and used the analysis of real data directly as a measure with which to compare three reconstruction algorithms: 3DRP, iterative filtered backprojection with median root prior (IFBP-MRP), and Fourier rebinning followed by two-dimensional (2-D) filtered backprojection (FORE-FBP) for [15O] PET. Two subjects, each with 32 scans acquired in four sessions during a finger opposition motor task, are analyzed using subtraction. A fixed volume-of-interest (VOI) measurement in regions related to the task demonstrates that at high resolution, IFBP-MRP has the best signal-to-noise performance followed by 3DRP and FORE-FBP; however, this advantage gradually diminishes as the resolution decreases. For a voxel measurement derived from the image of each reconstruction, all three algorithms are capable of detecting highly activated regions. Although there are some differences in the size, shape, and center location of the activated foci, our preliminary results suggest that IFBP-MRP does offer enhanced signal with some noise control compared with 3DRP for the analysis of high-resolution images. If images are to be analyzed at an intermediate to lower resolution, FORE-FBP provides a significant reduction of reconstruction time compared with 3DRP.


A Qualitative Exploration of Adult Baby/Diaper Lover Behavior From an Online Community Sample.
This study examined qualitative data on 1,795 male, 139 female, and 78 transgender members of the adult baby/diaper lover (ABDL) online community. Using grounded theory, the analyses examined a description of ABDL practices, explored evidence of subgroups within the ABDL community, and examined the degree to which ABDL behavior involves sexual motivations. Overall, the data suggest there is a fair amount of diversity within the ABDL community. Most participants enjoy wearing diapers or engaging in age regression (as babies or children), and the importance of incontinence may vary. ABDL practices can reflect bondage play for some individuals and a way to cope with medical problems for others. Overall, there is modest evidence of more than two ABDL subgroups. Although a large number of individuals do not see their ABDL practices as sexual in nature, there is a clear contingent that describes sexual motivations. For some, sex during ABDL activity violates conceptions of baby play. Nonsexual motivations include a desire to relax or be carefree as well as a desire to be nurtured. Some diaper lovers and adult babies have the same goals but achieve them in different ways. ABDL practices may be as diverse as seemingly typical sexual behaviors.


Genome complexity and organization in the red imported fire ant Solenopsis invicta Buren.
The red imported fire ant Solenopsis invicta is the most destructive invading arthropod in the southern United States, yet little is known about its genome complexity and organization. Here we report the size, organization and GC content of S. invicta genome. DNA reassociation kinetics using S1 nuclease assay and a modified second-order kinetics model indicated that the S. invicta genome is approximately 0.62 picograms or 5.91 x 10(8) base pairs, composed of 36% unique, 41% moderately repetitive and 23% highly repetitive/foldback sequences. Comparison of the reassociation kinetics of short and long DNA fragments revealed that the sequence arrangement follows a pattern of short period interspersion, as in most organisms with relatively large genomes. Melting-temperature analysis showed that the GC content of the fire ant genomic DNA is 34.8%, similar to that of most eukaryotic organisms. The results reveal that the fire ant genome is much larger and more complex than those of a number of hymenopteran insects studied to date. Our study provides a foundation for further analysis and genetic manipulation of the S. invicta genome.


Glucose and the risk of hypertension in first-degree relatives of patients with type 2 diabetes.
To test the hypothesis that plasma glucose (PG) levels is associated with the incidence of hypertension (HT) in nondiabetic and non-hypertensive first-degree relatives (FDR) of people with type 2 diabetes (T2D). A total of 1089 FDR without diabetes and/or HT of consecutive patients with T2D 30-70 years old were examined and followed for a mean (s.d.) of 6.9 (1.7) years for HT incidence. At baseline and through follow-up, participants underwent a standard 75 gm 2-h oral glucose tolerance test. HT was defined according to the criteria of the Seventh Report of Joint National Committee. We used Cox proportional hazard models to estimate hazard ratio for incident HT and plotted a receiver operating characteristic curve to assess discrimination. The PG levels at baseline were associated with incidence of HT, independently of age, gender, obesity and high cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, education and systolic blood pressure. Those with impaired glucose tolerance were 54% (hazard ratio 1.54; 95% confidence interval (CI) 1.33, 1.77) more likely to develop HT than those with normal glucose tolerance. Those with impaired fasting glucose were also 23% (hazard ratio 1.23; 95% CI 1.01, 1.50) more likely to develop HT. High PG levels were consistently associated with incident HT.


[Patient's reaction to surgical trauma in surgical treatment of duodenal ulcer].
Evaluation of metabolism and state of central hemodynamics in 134 patients with duodenal ulcer before the operation and at the early postoperative period was carried out. It was established that pronouncement of postaggressive response of an organism to trauma in surgical treatment of a duodenal ulcer didn't depend on a type of the operation due to use of the modern methods of anesthesia. Therefore, moderate pronouncement of such a response after the organ-preserving operations can't be a criterium for the wide use of surgical treatment of an uncomplicated duodenal ulcer.


Ultrasound-assisted catheter directed thrombolysis for pulmonary embolus during extracorporeal membrane oxygenation.
Acute pulmonary embolism (PE) is the third most common cause of cardiovascular death. For patients who are hemodynamically unstable, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support has been shown to provide hemodynamic stability, and allow time for definitive treatment and recovery. Ultrasound-assisted catheter directed thrombolysis (USAT) has the potential to be a safe adjunct and expedite right ventricular (RV) recovery for patients requiring VA-ECMO for PE. A review of all VA-ECMO patients from January 2017 to September 2019 was performed. A total of 49 of these patients were cannulated due to a PE. USAT therapy was used as an adjunct in 6 (12%) of these patients. These 6 patients were given standardized USAT therapy with EKOs catheters at 1 mg/h of tissue plasminogen activator with an unfractionated heparin infusion for additional systemic anticoagulation. Outcomes, including in-hospital death, 90-day survival, RV recovery, and complications, were examined in the cohort of patients that received USAT as an adjunct to ECMO. Median age was 54 years old. Five of the six patients presented with a massive PE and had a PE severity score of Class V. One patient presented with a submassive PE with a Bova score of 2, but was cannulated to VA-ECMO in the setting of worsening RV function. All patients demonstrated recovery of RV function, were free from in-hospital death, and were alive at 90-day follow-up. Ekosonic endovascular system therapy may be a safe and feasible adjunct for patients on VA-ECMO for PE, and allow for survival with RV recovery with minimal complications.


The future of the clinical nurse specialist in the USA.
In light of the climate of healthcare reform, the future of the traditional clinical nurse specialist is tenuous while that of the nurse practitioner is bright. The merger of these two traditional roles into a unified advanced practice nurse (APN) role is critical now for the profession of nursing, for patients and for the entire healthcare arena. The following describes how the APN will be a leader in providing health care both in the USA and internationally and a primary mover toward WHO's goal of "health for all".


Altered peroxisome-proliferator activated receptors expression in human endometrial cancer.
Peroxisome proliferator-activated receptors (PPARs) belong to a family of nuclear hormone receptors acting as transcriptional factors, recently involved also in carcinogenesis. Present study was undertaken to evaluate the presence and subcellular localization of different PPAR isoforms (α, β, γ) in healthy endometrial tissue (n = 10) and endometrial carcinoma (FIGO I, endometrioides type, G1, n = 35). We sought to analyze PPARs mRNA content as well as protein immunohistochemical expression that was further quantified by Western Blot technique. For both PPARα and PPARβ, protein expression was significantly higher in endometrial cancers compared to normal endometrial mucosa. In opposite, PPARγ protein expression was lower in endometrial cancer cells. In each case, immunohistochemical reaction was confined to the perinuclear and/or nuclear region. At the transcriptional level, the content of mRNA of all PPAR subunits did not follow the protein pattern of changes. These results provide evidence for altered PPAR's protein expression and disregulation of posttranslational processes in endometrial cancers.


Corneal thickness as a risk factor for visual field loss in patients with preperimetric glaucomatous optic neuropathy.
To determine whether central corneal thickness (CCT) is a risk factor for visual field loss development among patients diagnosed with preperimetric glaucomatous optic neuropathy (GON). Observational cohort study. The study included 98 eyes of 98 patients with GON, with a mean follow-up time of 4.3 +/- 2.7 years. Diagnosis of GON was based on masked assessment of optic disk stereophotographs. All patients had normal standard automated perimetry visual fields at baseline. Criteria for visual field abnormality were derived from a prior study. Several clinical factors (CCT, intraocular pressure, vertical cup-to-disk ratio, refraction, age, gender, family history of glaucoma, high blood pressure, cardiovascular disease, and migraine) were investigated to ascertain whether there is an association with development of repeatable visual field loss. Cox proportional hazards models were used to obtain hazard ratios (HR) and identify factors that predicted which individuals developed glaucomatous visual field loss during the follow-up period. Thirty-four patients (35%) developed repeatable visual field abnormality during follow-up. In multivariate analysis, risk factors that predicted the development of visual field loss were a thinner CCT (adjusted HR = 1.62/40 microm thinner; P =.023; 95% confidence interval [CI]: 1.07-2.45), higher baseline intraocular pressure (adjusted HR = 1.07/mm Hg; P =.022; 95% CI: 1.01-1.14), and larger baseline vertical cup-to-disk ratio (adjusted HR = 1.63/0.1 larger; P =.009; 95% CI: 1.13-2.35). The mean +/- standard deviation CCT of GON patients who developed visual field loss was 543 +/- 36 microm compared with 565 +/- 35 microm of those who did not develop visual field abnormalities (P =.005, Student t test). Central corneal thickness is a risk factor for development of visual field loss among patients diagnosed with preperimetric GON. It is important to consider CCT when establishing target intraocular pressure of patients with GON.


Chromate reduction by immobilized palladized sulfate-reducing bacteria.
Resting cells of Desulfovibrio vulgaris NCIMB 8303 and Desulfovibrio desulfuricans NCIMB 8307 were used for the hydrogenase-mediated reduction of Pd(II) to Pd(0). The resulting hybrid palladium bionanocatalyst (Bio-Pd(0)) was used in the reduction of Cr(VI) to the less environmentally problematic Cr(III) species. The reduction of Cr(VI) by free and agar-immobilized Bio-Pd(0) was evaluated. Investigations using catalyst suspensions showed that Cr(VI) reduction was similar ( approximately 170 nmol Cr(VI)/h/mg Bio-Pd(0)) when Bio-Pd(0) was produced using D. vulgaris or D. desulfuricans. Continuous-flow studies using D. vulgaris Bio-Pd(0) with agar as the immobilization matrix investigated the effect of Bio-Pd(0) loading, inlet Cr(VI) concentration, and flow rate on the efficiency of Cr(VI) reduction. Reduction of Cr(VI) was highest at a D. vulgaris Bio-Pd(0) loading of 7.5 mg Bio-Pd(0)/mL agar (3:1 dry cell wt: Pd(0)), an input [Cr(VI)] of 100 microM, and a flow rate of 1.75 mL/h (approx. 3.5 column volumes/h). A mathematical interpretation predicted the activity of the immobilized Bio-Pd(0) for a given set of conditions within 5% of the value found by experiment. Considering the system as an 'artificial enzyme' analog and application of applied enzyme kinetics gave an apparent K(m) value (K(m app)) of 430 microM Cr(VI) and a determined value of flow-through reactor activity which differed by 11% from that predicted mathematically.


Degradation of organic cyanides by Pseudomonas aeruginosa.
A bacterium capable of utilizing acetonitrile (methyl cyanide) as the sole source of carbon and nitrogen was isolated from soil and identified as Pseudomonas aeruginosa. This bacterium could also utilize and oxidize numerous lower-mol-wt nitrile compounds and their corresponding amides as growth substrates. A metabolite of acetonitrile in the culture medium was determined to be ammonia. The accumulation of ammonia in the culture medium was proportional to the concentration of the substrate and the inoculum. Cell extracts of the bacterium contained activities corresponding to nitrile aminohydrolase (E C 18.104.22.168) and amidase (E C 188.8.131.52), which regulate the degradation of acetonitrile. Both enzymes were inducible and hydrolyzed a wide range of substrates, and it was determined that the specific activity of amidase was far greater than the activity of nitrile aminohydrolase.


CT radiomics facilitates more accurate diagnosis of COVID-19 pneumonia: compared with CO-RADS.
Limited data was available for rapid and accurate detection of COVID-19 using CT-based machine learning model. This study aimed to investigate the value of chest CT radiomics for diagnosing COVID-19 pneumonia compared with clinical model and COVID-19 reporting and data system (CO-RADS), and develop an open-source diagnostic tool with the constructed radiomics model. This study enrolled 115 laboratory-confirmed COVID-19 and 435 non-COVID-19 pneumonia patients (training dataset, n = 379; validation dataset, n = 131; testing dataset, n = 40). Key radiomics features extracted from chest CT images were selected to build a radiomics signature using least absolute shrinkage and selection operator (LASSO) regression. Clinical and clinico-radiomics combined models were constructed. The combined model was further validated in the viral pneumonia cohort, and compared with performance of two radiologists using CO-RADS. The diagnostic performance was assessed by receiver operating characteristics curve (ROC) analysis, calibration curve, and decision curve analysis (DCA). Eight radiomics features and 5 clinical variables were selected to construct the combined radiomics model, which outperformed the clinical model in diagnosing COVID-19 pneumonia with an area under the ROC (AUC) of 0.98 and good calibration in the validation cohort. The combined model also performed better in distinguishing COVID-19 from other viral pneumonia with an AUC of 0.93 compared with 0.75 (P = 0.03) for clinical model, and 0.69 (P = 0.008) or 0.82 (P = 0.15) for two trained radiologists using CO-RADS. The sensitivity and specificity of the combined model can be achieved to 0.85 and 0.90. The DCA confirmed the clinical utility of the combined model. An easy-to-use open-source diagnostic tool was developed using the combined model. The combined radiomics model outperformed clinical model and CO-RADS for diagnosing COVID-19 pneumonia, which can facilitate more rapid and accurate detection.


Discrete colour polymorphism in the tawny dragon lizard (Ctenophorus decresii) and differences in signal conspicuousness among morphs.
Intraspecific colour variation is common in nature and can vary from the coexistence of discrete colour variants in polymorphic species to continuous variation. Whether coloration is continuous or discrete is often ambiguous and many species exhibit a combination of the two. The nature of the variation (discrete or continuous) has implications for both the genetic basis of the colour variation and the evolutionary processes generating and maintaining it. Consequently, it is important to qualify the existence of discrete morphs, particularly in relation to the animal's visual system. In this study, we quantified male throat colour variation in Ctenophorus decresii tawny dragon lizard and tested for morphological and ecological correlates of the colour variants. We confirmed that discrete throat colour morphs can be defined based on colour and pattern analyses independent of the human visual system. We also found that the colour variants differed in their conspicuousness from the background, to the lizard's visual system, which has implications for signalling. However, the morphs did not differ in morphology or microhabitat use, which suggests that these characteristics are not involved in the evolutionary maintenance of the polymorphism.


Deficiency of TRIM32 Impairs Motor Function and Purkinje Cells in Mid-Aged Mice.
Proper functioning of the cerebellum is crucial to motor balance and coordination in adult mammals. Purkinje cells (PCs), the sole output neurons of the cerebellar cortex, play essential roles in cerebellar motor function. Tripartite motif-containing protein 32 (TRIM32) is an E3 ubiquitin ligase that is involved in balance activities of neurogenesis in the subventricular zone of the mammalian brain and in the development of many nervous system diseases, such as Alzheimer's disease, autism spectrum disorder, attention deficit hyperactivity disorder. However, the role of TRIM32 in cerebellar motor function has never been examined. In this study we found that motor balance and coordination of mid-aged TRIM32 deficient mice were poorer than those of wild-type littermates. Immunohistochemical staining was performed to assess cerebella morphology and TRIM32 expression in PCs. Golgi staining showed that the extent of dendritic arborization and dendritic spine density of PCs were decreased in the absence of TRIM32. The loss of TRIM32 was also associated with a decrease in the number of synapses between parallel fibers and PCs, and in synapses between climbing fibers and PCs. In addition, deficiency of TRIM32 decreased Type I inositol 1,4,5-trisphosphate 5-phosphatase (INPP5A) levels in cerebellum. Overall, this study is the first to elucidate a role of TRIM32 in cerebellar motor function and a possible mechanism, thereby highlighting the importance of TRIM32 in the cerebellum.


Assessing Acute Symptoms Related to Occupational Exposures Among Nail Salon Technicians.
This cross-sectional field study evaluated potential associations between acute symptoms among nail technicians and exposure of chemical hazards in New Jersey salons. In 2016, an in-person safety and health survey was conducted. Data were gathered on symptoms, demographics, work history, tobacco use, area and/or task ventilation, use of personal protective equipment, and safety training. Workplace hazards were identified by observational survey during site visit walk-throughs. Of the 68 respondents from 40 participating salons whose owners agreed to participate (35% salon-level participation), most were Asian females with a self-reported history of work-associated eye, nose, throat, and skin symptoms. Few workers used personal protective equipment. Most workers had not received training in their primary language. Nail salon workers need comprehensive chemical use training. More research is needed to determine extent of exposure.


Synthesis and anti-influenza evaluation of polyvalent sialidase inhibitors bearing 4-guanidino-Neu5Ac2en derivatives.
Polyvalent sialidase inhibitors bearing 4-guanidino-Neu5Ac2en derivatives on a poly-L-glutamine backbone are described. Aiming for a longer retention time of 4-guanidino-Neu5Ac2en (zanamivir) in bronchi and lungs, we focused on supermolecules bearing 4-guanidino-Neu5Ac2en derivatives bound at their C-7 position through noncleavable alkyl ether linkages. We first found that alkylation of the 7-hydroxyl group of sialic acid derivative 8 proceeded smoothly, and produced 7-O-alkyl-4-guanidino-Neu5Ac2en derivatives 13, which exhibited equipotent inhibitory activity against not only influenza A virus sialidase but also influenza A virus in the cell culture. Next, we synthesized poly-L-glutamine bearing 7-O-alkyl-4-guanidino-Neu5Ac2en derivatives linked by amide bonds, 26, which showed enhanced antiviral activity against influenza A virus and more potent efficacy in vivo relative to a monomeric sialidase inhibitor.


Evaluating the Representativeness of US Centricity Electronic Medical Records With Reports From the Centers for Disease Control and Prevention: Comparative Study on Office Visits and Cardiometabolic Conditions.
Electronic medical record (EMR)-based clinical and epidemiological research has dramatically increased over the last decade, although establishing the generalizability of such big databases for conducting epidemiological studies has been an ongoing challenge. To draw meaningful inferences from such studies, it is essential to fully understand the characteristics of the underlying population and potential biases in EMRs. This study aimed to assess the generalizability and representativity of the widely used US Centricity Electronic Medical Record (CEMR), a primary and ambulatory care EMR for population health research, using data from the National Ambulatory Medical Care Surveys (NAMCS) and the National Health and Nutrition Examination Surveys (NHANES). The number of office visits reported in the NAMCS, designed to meet the need for objective and reliable information about the provision and the use of ambulatory medical care services, was compared with similar data from the CEMR. The distribution of major cardiometabolic diseases in the NHANES, designed to assess the health and nutritional status of adults and children in the United States, was compared with similar data from the CEMR. Gender and ethnicity distributions were similar between the NAMCS and the CEMR. Younger patients (aged <15 years) were underrepresented in the CEMR compared with the NAMCS. The number of office visits per 100 persons per year was similar: 277.9 (95% CI 259.3-296.5) in the NAMCS and 284.6 (95% CI 284.4-284.7) in the CEMR. However, the number of visits for males was significantly higher in the CEMR (CEMR: 270.8 and NAMCS: 239.0). West and South regions were underrepresented and overrepresented, respectively, in the CEMR. The overall prevalence of diabetes along with age and gender distribution was similar in the CEMR and the NHANES: overall prevalence, 10.1% and 9.7%; male, 11.5% and 10.8%; female, 9.1% and 8.8%; age 20 to 40 years, 2.5% and 1.8%; and age 40 to 60 years, 9.4% and 11.1%, respectively. The prevalence of obesity was similar: 42.1% and 39.6%, with similar age and female distribution (41.5% and 41.1%) but different male distribution (42.7% and 37.9%). The overall prevalence of high cholesterol along with age and female distribution was similar in the CEMR and the NHANES: overall prevalence, 12.4% and 12.4%; and female, 14.8% and 13.2%, respectively. The overall prevalence of hypertension was significantly higher in the CEMR (33.5%) than in the NHANES (95% CI: 27.0%-31.0%). The distribution of major cardiometabolic diseases in the CEMR is comparable with the national survey results. The CEMR represents the general US population well in terms of office visits and major chronic conditions, whereas the potential subgroup differences in terms of age and gender distribution and prevalence may differ and, therefore, should be carefully taken care of in future studies.


Influence of Resource Availability on the Foraging Strategies of the Triangle Butterflyfish Chaetodon triangulum in the Maldives.
Obligate coral feeders such as many members of the Chaetodontidae family (also known as butterflyfish) often show strong preferences for particular coral species. This is thought to have evolved through natural selection as an energy-maximising strategy. Although some species remain as highly specialised feeders throughout their lifetime, many corallivores show a degree of dietary versatility when food abundance is limited; a strategy described by the optimal foraging theory. This study aimed to examine if, within-reef differences in the feeding regime and territory size of the Triangle Butterflyfish Chaetodon triangulum occurred, as a function of resource availability. Results showed that the dietary specialisation of C. triangulum was significant in both areas of low and high coral cover (χL22 = 2.52 x 102, P<0.001 and χL22 = 3.78 x 102, P<0.001 respectively). Resource selection functions (RSFs), calculated for the two main sites of contrasting coral assemblage, showed that in the resource-rich environments, only two Genera (Acropora and Pocillopora) were preferentially selected for, with the majority of other corals being actively 'avoided'. Conversely, in territories of lower coral coverage, C. triangulum was being less selective in its prey choice and consuming corals in a more even distribution with respect to their availability. Interestingly, coral cover appeared to show no significant effect on feeding rate, however it was a primary determinant of territory size. The findings of the study agree with the predictions of the optimal foraging theory, in that where food supply is scarce, dietary specialisation is minimised and territory size increased. This results in maximising energy intake. This study represents the first scientific evidence that C. triangulum is an obligate corallivore and, as with many other butterflyfish, is therefore dependent on healthy scleractinian corals for survival.


[Physical manifestations of anxiety during group psychotherapy].
Anxiety is always accompanied by certain somatic sensations related to certain organs. The author, using the results obtained in the course of the median group sessions, exceptionally anxiogenic in their very nature, measures the intensity of somatizations of anxiety by means of v. Zerssen questionnaire at the beginning and at the end of the sessions. He also observes the distribution of somatizations, according to organic systems (cardiovascular, respiratory, urogenital, gastrointestinal, locomotor and sensorium). What is interesting is the distribution of significantly pronounced somatizations, which indicates that the most frequently pronounced discomforts are related to sensorium. This was to be expected in view of the fact that the population of neurotic patients was being observed while other systems are approximately equally represented. The results shown indicate that the median group situation leads to an increase of anxiety, resulting in subsequent homeostasis disruptions, and to somatizations of anxiety. In such circumstances, it is locomotion that is most inhibited by group situation itself.


A comparative evaluation of chondrocyte/scaffold constructs for cartilage tissue engineering.
This study aimed to evaluate three biodegradable scaffolds as cell carriers for in vitro cartilage regeneration using mature human chondrocyte cells. We compared cell distribution, viability and morphology and we evaluated the mechanical properties of the constructs after 2 weeks of in vitro culture. The materials used as scaffolds were fibrin glue, a collagen sponge and a polyurethane foam (DegraPol(R)). Fibrin glue was found unsuitable as a chondrocyte carrier vehicle after culture times longer than a few days, probably due to significant barriers to nutrients and oxygen diffusion, and the material weakened rapidly. The collagen-based sponge was found to be unsuitable to support chondrocyte survival in vitro, although the presence of newly synthesized collagen was observed in these constructs. The synthetic biodegradable scaffold was more adequate in supporting cell survival and mechanical properties. After 2 weeks of static culture, the storage modulus obtained by dynamic shear testing was in the order of 0.7 kPa in fibrin constructs, 3.7 kPa in collagen constructs and 105 kPa in DegraPol(R) constructs. The better mechanical stability of the synthetic foam supports further investigation in the possible use of synthetic biomaterials as biodegradable scaffolds for in vitro cartilage regeneration. (Journal of Applied Biomaterials & Biomechanics 2004; 2: 55-64).


Liquid chromatography of active principles in Sophora flavescens root.
Herbal medicines were one of the major resources for healthcare in earlier stages, and some traditional herbal medicines have been in use for more than 2000 years. Currently, they are attracting more and more attention of the modern pharmaceutical industry, as scientists has become aware that herbs have almost infinite resources for medicine development. This review provides an overview of the analytical approaches applied in the researches concentrated on various aspects of the matrine-type alkaloids in Sophora flavescens root. Emphasis will be laid on the analytical processes of high-performance liquid chromatography (HPLC), capillary electrophoresis (CE), as well as gas chromatography (GC) methods. The sample extraction, separation and detection have been summarized. In addition, the applications of chromatographic determinations are introduced for the main matrine-type alkaloids in S. flavescens root, such as matrine, sophoridine, sophocarpine, lehmannine, sophoramine, oxymartine, oxysophocarpine, cytosine and aloperine. The advantages and limitations of HPLC, CE and GC methods in the analytical applications of the alkaloids are also discussed.


Predictors of axillary lymph node involvement in women with T3 breast cancers: analysis of 1988-2003 SEER data.
We investigated characteristics associated with axillary lymph node (LN) status in patients with T3 breast cancers and hypothesized that LN status is an independent predictor of survival. Characteristics associated with axillary LN metastasis among women with T3 breast cancers were identified from the 1988-2003 Surveillance, Epidemiology, and End Results (SEER) database. The primary outcome was breast cancer-specific mortality. Cox models were used to calculate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). A total of 12,778 patients with T3 breast cancers were analyzed (8201 LN+, 3695 LN-, 882 unknown). LN+ patients were more likely to be <50 y, married, and have ER+/PR+, grade 3 invasive ductal cancers (P<0.01 for each). Most patients underwent mastectomy (87.4%). Post-mastectomy radiation was more commonly used in LN+ patients (P<0.01). LN+ patients had higher breast cancer-specific mortality (36.2% versus 16.4%, P<0.01) and were more likely to die during the follow-up period (aHR = 2.87, 95% CI: 2.62-3.15) compared with LN- patients. Analysis of the SEER database indicated that several patient and tumor characteristics predict a higher likelihood of axillary LN involvement in patients with T3 breast cancers. LN status was an independent predictor of survival in women with T3 breast cancers.


Enhanced effectiveness of tocotrienol-based nano-emulsified system for topical delivery against skin carcinomas.
The potent anti-proliferative and pro-apoptotic actions of tocotrienols (T3) against cancer, but not normal tissues, have been hampered by their limited systemic bioavailabilty. Recent expansive development of diverse nanoemulsion (NE) vehicles emphasized their vast potential to improve the effective dosing of different clinical and experimental drugs of lipophilic nature, such as T3. The emphasis of the present work is to develop a pharmaceutically scalable, low-energy nano-emulsification approach for optimized incorporation of T3-rich palm oil (Tocomin®), possessing anticancer activity as a potential cutaneous delivery platform for adjunctive therapy of skin carcinomas, either alone or in combination with other chemotherapeutic agents. Different Tocomin®-NEs, obtained with different homogenization strategies, were screened based on physicochemical uniformity (droplet size, charge and polydispersity) and subjected to stress physical stability testing, along with chemical content analysis (≥90% Tocomin® - incorporation efficiency). Adopted hybrid nano-emulsification of Tocomin®, correlated with highest preservation of DPPH-radical scavenging capacity of active T3 in prototype formulation, Tocomin®-NE, which effectively permeated diffusion cell membranes 4-folds higher than propyleneglycol (PG)-admixed Tocomin® control. Against two different cell models of human cutaneous carcinoma, Tocomin®-hybrid NE demonstrated significantly stronger cytotoxic profiles (p ≤ 0.01), visible in both concentration- and time- dependent manners, with at least 5-folds lower IC50 values, compared to those estimated for the closest Tocomin®-control. The proposed hybrid nano-emulsified formulation of Tocomin® provides simple and stable delivery platform, for effective topical application against keratinocyte tumors.


Glia-specific antigen in the intracranial tumors. Immunofluorescence study.
26 gliomas and 14 non-glial tumors were examined for the presence of nervous system specific antigen (CGSA) to assess the antigenic properties of neoplastic tissue in relation to histogenesis and degree of differentiation of tumors. Double layer immunofluorescence (IMF) technique was used for the cellular localization of the antigen. CGSA was found in the cytoplasm of normal, reactive and neoplastic neuroglial cells. Well differentiated astrocytomas showed the strongest IMF reactions and largest number of IMF-positive cells. Tumors with histological signs of anaplasia displayed foci of IMF-negative cells irregularly distributed in the sections. There were no completely negative astrocytomas owing to a marked affinity of the specific astisera to the astrocytic cell line. In the oligodendrogliomas a smaller amount of the antigen was found than in the astrocytomas. Histological evidence of malignancy in these tumors was accompanied by strikingly small number of positive cells and weaker IMF reactions as compared to the well differentiated oligodendrogliomas. Anaplastic gliomas showed only traces of CGSA and non-glial tumors were entirely negative. The results suggest a deficiency of normal antigenic material in the neoplastic glia, particularly of oligodendrogliomas and anaplastic gliomas.


Sporocadaceae, a family of coelomycetous fungi with appendage-bearing conidia.
Species of Sporocadaceae are endophytic, plant pathogenic or saprobic, and associated with a wide range of host plants. Recent molecular studies that have attempted to address familial and generic boundaries of fungi belonging to Sporocadaceae were based on a limited number of samples and DNA loci. The taxonomy of this group of fungi is therefore still not fully resolved. The aim of the present study is to provide a natural classification for the Sporocadaceae based on multi-locus phylogenetic analyses, using LSU, ITS, tef-1α, tub2 and rpb2 loci, in combination with morphological data. A total of 30 well-supported monophyletic clades in Sporocadaceae are recognised, representing 23 known and seven new genera. Typifications are proposed for the type species of five genera (Diploceras, Discosia, Monochaetia, Sporocadus and Truncatella) to stabilise the application of these names. Furthermore, Neotruncatella and Dyrithiopsis are synonymised under Hymenopleella, and the generic circumscriptions of Diploceras, Disaeta, Hymenopleella, Monochaetia, Morinia, Pseudopestalotiopsis, Sarcostroma, Seimatosporium, Synnemapestaloides and Truncatella are emended. A total of 51 new species, one nomina nova and 15 combinations are introduced.


Microneedles: A smart approach and increasing potential for transdermal drug delivery system.
The most widely used methods for transdermal administration of the drugs are hypodermic needles, topical creams, and transdermal patches. The effect of most of the therapeutic agents is limited due to the stratum corneum layer of the skin, which serves as a barrier for the molecules and thus only a few molecules are able to reach the site of action. A new form of delivery system called the microneedles helps to enhance the delivery of the drug through this route and overcoming the various problems associated with the conventional formulations. The primary principle involves disruption of the skin layer, thus creating micron size pathways that lead the drug directly to the epidermis or upper dermis region from where the drug can directly go into the systemic circulation without facing the barrier. This review describes the various potential and applications of the microneedles. The various types of microneedles can be fabricated like solid, dissolving, hydrogel, coated and hollow microneedles. Fabrication method selected depends on the type and material of the microneedle. This system has increased its application to many fields like oligonucleotide delivery, vaccine delivery, insulin delivery, and even in cosmetics. In recent years, many microneedle products are coming into the market. Although a lot of research needs to be done to overcome the various challenges before the microneedles can successfully launch into the market.