[A case of solitary pulmonary nodule caused by Mycobacterium avium].
A 56-year-old male without respiratory symptoms, past history nor familial history, was admitted to our hospital because of pulmonary solitary nodule on the chest radiograph. Computed tomograph showed a smooth surface nodule in the left lower lobe (segment 8). Bronchofiberscopy could not give any specific histological findings nor bacteriological findings, therefore the patient underwent partial pulmonary resection by videoassisted thoracoscopic surgery. Pathology of the resected specimen revealed epithelioid cell granuloma with giant cells but not any acid-fast bacilli. He was treated with rifampicin and isoniazid for "tuberculoma". After three weeks, thirty colonies grew on an Ogawa's egg medium, which were identified as Mycobacterium avium by PCR. There are few reports about the solitary pulmonary nodule due to M. avium-intracellurale complex infection, however, it is supposed that there are many "tuberculoma's" without bacteriological differentiation between tuberculosis and nontuberculous mycobacterial infection. It is difficult to diagnose a solitary pulmonary nodule caused by nontuberculous mycobacterial infection with bronchofiberscopy, and the location of the lesion is usually subpleural, therefore it is thought that videoassisted thoracoscopic surgery is valied for the diagnosis of solitary pulmonary nodule due to nontuberculous mycobacterium.


The TCR-delta repertoire in human intestine undergoes characteristic changes during fetal to adult development.
The TCR-delta repertoire in adult human intestine is oligoclonal and unique in each individual. In the present study, changes in the junctional regions of TCR-delta transcripts in human intestine that occur during development from fetal to adult life were used to characterize fundamental changes in the TCR-delta repertoire in the human intestinal tract during ontogeny. At mid-gestation, the fetal repertoire was polyclonal, but limited, in its junctional diversity by the relative lack of N region nucleotide additions and by the frequent formation of coding region joins at regions of short sequence homology. In addition, identical TCRDV2 transcripts that resemble canonical TCR-delta sequences in mice were present in the intestine of different fetuses. In the early period after birth, the intestinal TCR-delta repertoire was polyclonal, and more diverse than the fetal repertoire, with junctional regions that contained extensive N nucleotide additions and frequently were as complex as those of adults. The intestinal TCR-delta repertoire showed increasing restriction with age and, by 14 to 17 yr, the repertoire was oligoclonal and resembled the repertoire of individuals in the sixth to seventh decade. Moreover, the adult TCR-delta repertoire was almost identical at multiple sites throughout the intestine, suggesting a model in which gammadelta T cell clones, selected by ligands in the intestinal tract, undergo expansion and recirculation before lodging throughout the small intestine or colon.


Renal fibrosis: insight from proteomics in animal models and human disease.
Chronic kidney disease (CKD) is the end-point of a number of renal and systemic diseases. The high incidence and financial burden of CKD makes it imperative to diagnose CKD at early stages when therapeutic interventions are far more effective. A key component of CKD is the development of renal fibrosis. Renal fibrosis is a complex process, associated with many cell types and pathways, resulting in structural and functional alterations. Identification of specific biomarkers of renal fibrosis may thus not only help us to understand the pathophysiological mechanisms involved in this process, but also improve diagnosis in the clinic. In this review, the existing literature on proteomic approaches to study renal fibrosis is presented and evaluated. The importance of using animal models along with patient material is discussed and future directions, considered key to this field, are proposed.


Effective use of fluorides in the People's Republic of China--a model for WHO Mega Country initiatives.
Poor dental health has been reported in the Chinese National Surveys of Oral Health. With the changing lifestyle and growing consumption of sugars, the incidence of dental caries may well continue to rise, compounded by limited access to professional care. The increasing oral disease burden could become a major public health problem in China, leading to considerable personal and health service costs. There is a desperate need for systematic implementation of preventive programmes. Currently, China is strengthening the prevention of chronic diseases, which provides an excellent opportunity to integrate oral disease prevention into the overall non-communicable disease (NCD) prevention programmes. In order to address this growing public health problem, the World Health Organization (WHO) Global Oral Health Programme advocates the effective use of fluoride as an essential approach to prevent dental caries in the 21st century--part of the WHO Global Oral Health Strategy. Population-wide automatic fluoridation measures are considered the most effective, complemented by appropriate use of toothpastes containing fluoride. There are wide variations of fluoride levels in drinking water in China and, in many areas, the levels of fluoride in drinking water are lower than the recommended levels. The use of toothpaste containing fluoride is still too low in some areas and decreases with age. Those who live in rural areas have limited access to affordable toothpastes containing fluoride. In March 2006, as part of the WHO Mega Country Health Promotion Network initiatives, the WHO Global Oral Health Programme organised a three-day symposium in Beijing, People's Republic of China. The aim of the symposium was to bring together international experience and Chinese expertise to facilitate policy development for effective use of fluoride in China, highlighting the benefits of, and barriers to, the implementation of different fluoridation programmes at the strategic levels as well as for operational planning. This article reports the proceedings of the meeting. In summary, China is a Mega country with much diversity and disparity. The situation in China is unique with endemic fluorosis due to other non-water sources of fluoride in some areas and a considerable dental caries burden in others. It is important to regulate the appropriate exposure to fluoride to obtain the benefits and avoid adverse effects of fluorides, controlling enamel fluorosis without jeopardising the prevention of dental caries. Various complementary fluoridation programmes can be considered for different population groups with varying needs, strategies that bring about additive effects. A multi-tier policy making approach at national, regional and provincial levels can be employed, based on sound evidence. The roles of WHO, Ministry of Health and the National Committee for Oral Health (NCOH) were emphasised. Lessons learned from the Chinese experience will prove invaluable to other countries with similar socio demographic characteristics that are in the same process of developing and implementing fluoridation policies and programmes.


The implications of acute rejection for allograft survival in contemporary U.S. kidney transplantation.
We examined the frequency and clinical impact of acute rejection (AR) in contemporary U.S. kidney transplantation. Data for Medicare-insured kidney transplant recipients in 2000 to 2007 (n=48,179) were drawn from the United States Renal Data System. AR events were ascertained from Organ Procurement and Transplantation Network reports. AR was subclassified as antibody (Ab)-treated AR or other management (non-Ab-treated AR). Associations of AR with subsequent all-cause graft loss were estimated with time-varying Cox regression. Covariates included recipient, donor, and transplant factors in the United Network for Organ Sharing Kidney Allocation Review Committee survival model. The frequencies of non-Ab-treated AR per 100 graft-years at risk among standard criteria donor recipients over the first 6, 12, 24, and 36 months after transplantation were 9.93, 8.43, 5.71, and 4.70, respectively. Non-Ab-treated AR was consistently more than twice as common as Ab-treated AR by risk period and donor type. Development of Ab-treated AR predicted a greater risk of graft loss than non-Ab-treated AR. The relative risk for graft loss from Ab-treated AR continuously increased with later timing of AR after transplantation, whereas risk associated with non-Ab-treated AR peaked for events reported in months 13 to 24 after kidney transplantation. Regardless of the diagnosis time, the relative risk of graft loss was higher in the first 89 days after a given AR report compared with 90 days and beyond. AR events recognized later after transplantation have more serious graft loss implications, especially within the first 89 days after AR reporting. This observation may reflect reduced intensity of monitoring, delays in diagnosis, or clinicopathologic features of late AR.


Prostaglandin E2 potentiates mesenchymal stem cell-induced IL-10+IFN-γ+CD4+ regulatory T cells to control transplant arteriosclerosis.
Mesenchymal stem cells (MSCs) are known for their immunomodulatory functions. We previously demonstrated that bone marrow-derived MSCs effectively control transplant arteriosclerosis (TA) by enhancing IL-10(+) and IFN-γ(+) cells. The objective of this study is to elucidate the mechanism by which MSCs induce IL-10(+)IFN-γ(+)CD4(+) regulatory T type 1 (T(R)1)-like cells. In an MLR system using porcine PBMCs, MSC-induced IL-10(+)IFN-γ(+)CD4(+) cells, which confer resistance to allogeneic proliferation in an IL-10-dependent manner, resemble T(R)1-like cells. Both cyclooxygenase-derived PGE(2) and IDO help to induce T(R)1-like cells by MSCs. MSCs constitutively secrete PGE(2), which is augmented in allogeneic reactions. However, T(R)1-like cells were deficient in PGE(2) and 4-fold less potent than were MSCs in suppressing MLR. PGE(2) mimetic supplements can enhance the immunosuppressive potency of T(R)1-like cells. In a porcine model of allogeneic femoral arterial transplantation, MSC-induced T(R)1-like cells combined with PGE(2), but not either alone, significantly reduced TA at the end of 6 wk (percentage of luminal area stenosis: T(R)1-like cells + PGE(2): 11 ± 10%; PGE(2) alone: 93 ± 8.7%; T(R)1-like cells alone: 88 ± 2.4% versus untreated 94 ± 0.9%, p < 0.001). These findings indicate that PGE(2) helps MSC-induced IL-10(+)IFN-γ(+)CD4(+) T(R)1-like cells inhibit TA. PGE(2) combined with MSC-induced T(R)1-like cells represents a new approach for achieving immune tolerance.


Immunization against parasitic diseases of fish.
Parasitologists have not, in the past, exploited the immune system to protect fish against parasitic diseases. In the past few years, however, there has been an increased interest in adopting this strategy, and we have made steady and promising progress against a few parasites which are of economic importance. Amyloodinium ocellatum is an ectoparasitic dinoflagellate on brackish and marine fishes, which may also cause problems to aquarium fishes. Antiserum from fish inoculated intraperitoneally (i.p.) with living dinospores of the parasite immobilizes and agglutinates living dinospores; it also reduces parasite infectivity in cell culture. Cryptobia salmositica is a pathogenic haemoflagellate of salmonids on the Pacific coast of North America, causing mortality in semi-natural and intensive salmon culture facilities. A live attenuated vaccine inoculated i.p. protects susceptible juvenile and adult fish for at least 24 months. The protection involves production of complement fixing antibodies, phagocytosis, and antibody-dependent and antibody-independent T-cell cytotoxicity. A monoclonal antibody against a surface membrane glycoprotein (199-200 kDa is therapeutic in that it significantly reduces parasitaemias when inoculated into fish with acute disease. Ichthyophthirius multifiliis is an ectoparasitic ciliate of freshwater fishes with world wide distribution, usually causing disease when fish are stressed and/or when environmental conditions are favourable for parasite multiplication. Live theronts injected into the body cavity protect fish, and monoclonal antibodies with immobilizing activity upon parasites have been developed. There is some evidence of passive transfer of protective immunity from immune to naive fish, and to eggs. Diplostomum spathaceum is an intestinal parasite of gulls; the metacercaria stage of the parasite encyst and causes disease and mortality in numerous species of freshwater fish in Europe and in North America. Fish injected i.p. with sonicated/killed cercariae or metacercariae have fewer metacercariae in the eyes and survives longer. Lepeophtheirus salmonis and Caligus elongatus are parasitic copepods (sea lice), and they are important parasites of Atlantic salmon in cage cultures. A vaccine against fish lice is plausible, and the efficacy of about 20 candidate antigens in protecting fish is being tested.


Properties of non-NMDA excitatory amino acid-activated channels in isolated retinal horizontal cells.
The excitatory amino acid glutamate is believed to be the neurotransmitter used by some photoreceptors in the teleost retina. Past studies have shown that exogenous glutamate, and its analogs, are capable of affecting second-order retinal neurons in a manner consistent with the action of a photoreceptor transmitter. In an effort to characterize the properties of retinal glutamate channels on second-order neurons, non-NMDA excitatory amino acid-activated channels were studied in single horizontal cells isolated from the retina of the white bass. Using patch-clamp techniques single glutamate, kainate, and quisqualate channels were recorded. Two categories of channels were observed. The first was labeled slow-channels. Single-channel conductances and open times for this channel showed a range of values, but the average for channels activated by glutamate was 12 pS and 5.6 msec; quisqualate, 8.5 pS and 8.8 msec; and kainate, 8.5 pS and 4.5 msec. Openings of slow-channels elicited by the agonists tended to occur in bursts with a mean burst length of 38 msec. The bursts were punctuated by numerous, brief closings. The second channel category was termed fast channels. The agents glutamate, quisqualate, and kainate all activated channels in this category with open times of 1-2 msec and 2 prominent conductances in the range of about 10 and 20-30 pS. Activity of the fast channels tended to be noisy and no bursting behavior was observed.


Differential responses of antioxidative enzymes and lipid peroxidation to salt stress in salt-tolerant Plantago maritima and salt-sensitive Plantago media.
The changes in plant growth, relative water content (RWC), stomatal conductance, lipid peroxidation and antioxidant system in relation to the tolerance to salt stress were investigated in salt-tolerant Plantago maritima and salt-sensitive Plantago media. The 60 days old P. maritima and P. media seedlings were subjected to 0, 100 and 200 mM NaCl for 7 days. Reduction in shoot length was higher in P. media than in P. maritima after exposure to 200 mM NaCl, but 100 mM NaCl treatment did not show any effect on shoot length of P. maritima. Shoot dry weight decreased in P. media and did not change in P. maritima. Two hundred millimolar NaCl treatment had no effect on leaf RWC in P. maritima, but it was reduced in P. media. Salt stress caused reduction in stomatal conductance being more pronounced in P. media than in P. maritima. Activities of superoxide dismutase (SOD; EC 184.108.40.206), catalase (CAT; EC 188.8.131.52), glutathione reductase (GR; EC 22.214.171.124) decreased in P. media with increasing salinity. Ascorbate peroxidase (APX; EC 188.8.131.52) activity in leaves of P. media was increased and showed no change under 100 and 200 mM NaCl, respectively. However, activities of CAT, APX and GR increased under 200 mM NaCl while their activities did not change under 100 mM NaCl in P. maritima. SOD activity in leaves of P. maritima increased with increasing salinity. Concomitant with this, four SOD activity bands were identified in leaves of P. maritima, two bands only were observed in P. media. Peroxidase (POX; EC 220.127.116.11) activity increased under both salt concentrations in P. maritima, but only under 200 mM NaCl in P. media. Confirming this, five POX activity bands were identified in leaves of P. maritima, but only two bands were determined in P. media. Malondialdehyde levels in the leaves increased under salt stress in P. media but showed no change and decreased in P. maritima at 100 and 200 mM NaCl, respectively. These results suggest that the salt-tolerant P. maritima showed a better protection mechanism against oxidative damage caused by salt stress by its higher induced activities of antioxidant enzymes than the salt-sensitive P. media.


[The relationship between medicine and medical suppliers].
In the last decades, many voices from academic medicine are questioning the relationship between the pharmaceutical industry or other medical suppliers and physicians. Conflict of interest has thus become a major issue of concern in medicine and is becoming increasingly important for medical journals and clinical work. Conflicts of interest may emerge in the daily practice of medicine, in medical and pharmacological research, in the process of publication of medical journals and in the dissemination of public and private medical information, such as conferences, lectures, books, pamphlets, monographs, etc. The credibility of physicians has been hampered in recent years by the proliferating connections between them and medical suppliers. The public seems to be increasingly skeptical of clinical medicine, since corporate actions placing profit over public health are usual. Research centers and projects as well as medical journals are considered an extension of the marketing arm of pharmaceutical companies. This undermines the credibility of medical practice, research work and pharmaceutical information, submitted to journals and later included in meta-analysis, influencing therapeutic guidelines. In the meantime, while disclosure has become standard practice in North America, it is not widely used in Latin-America and Europe. If independent researchers are financed by agencies not related to the industry, the problems caused by the increasing financial ties between the pharmaceutical industry and researchers could be overcome, avoiding conflicts of interest. Better disclosure policies and financial tie regulations are also urgently needed.


Novel algorithm for automated genotyping of microsatellites.
Microsatellites or short tandem repeats (STRs) are abundant in the human genome with easily assayed polymorphisms, providing powerful genetic tools for mapping both Mendelian and complex traits. Microsatellite genotyping requires detection of the products of polymerase chain reaction (PCR) amplification by electrophoresis, and analysis of the peak data for discrimination of the true allele. A high-throughput genotyping approach requires computer-based automation at both the detection and analysis phases. In order to achieve this, complicated peak patterns from individual alleles must be interpreted in order to assign alleles. Previous methods consider limited types of noise peaks and cannot provide enough accuracy. By pattern recognition of various types of noise peaks, such as stutter peaks and additional peaks, we have achieved an overall average accuracy of 94% for allele calling in our actual data. Our algorithm is crucial for a high-throughput genotyping system for microsatellite markers by reducing manual editing and human errors.


Oxidation of p-dimethylaminomethylbenzylamine by pig kidney diamine oxidase. A new method for spectrophotometric assay.
1. The oxidation of some para-substituted benzylamines by diamine oxidase produces the corresponding aldehydes. This was studied to develop a spectrophotometric method for following the enzyme reaction, as the aldehydes produced absorb strongly at 250nm where the substrates are almost optically transparent. 2. p-Dimethylaminomethylbenzylamine was the most useful substrate and full details of its preparation are given. The synthesis of its related oxidation product, p-dimethylaminomethylbenzaldehyde, is also described. 3. The effects of variations in pH, ionic strength, temperature and oxygenation on the reaction are described and the usefulness of the method is illustrated by several applications and assessed by comparison with the standard spectrophotometric assay.


The current referral patterns for temporomandibular joint disorders (TMD) in Greater Manchester.
Temporomandibular joint disorders (TMD) affect up to 50% of the population. Chronic TMD may have a significant impact on patients' quality of life and is associated with a significant cost burden to health services. The aim of this study was to investigate the incidence of TMD in Greater Manchester and to determine the most appropriate setting for its management. Data were retrospectively collected on the demographics, symptoms and management provided to patients referred for TMD. There were 789 referrals analysed; 616 to a Tertiary Centre and 173 to a District General Hospital (DGH). The most common reason for referral was pain (82%), followed by limitation in opening (55%) and clicks or sounds (44%). 27% of referrals were managed with a splint and 12% were provided with advice or a patient information leaflet prior to referral. The effect of chronic pain on patients' quality of life and the cost burden of its management compels us to review current practices in referral and management of TMD. Barriers to provision of treatment in primary care may include a lack of training, remuneration or confidence. These may be overcome with the development of self-care plans for patients and a care pathway for practitioners. Based on existing evidence, timely and conservative management of TMD should be encouraged in primary care, enabling better outcomes to be achieved for patients and the maintenance of the experience and skill level of specialist services in secondary care.


Synthesis and assembly of immunoglobulins by malignant human plasmacytes. I. Myelomas producing gamma-chains and light chains.
Three basic patterns of gamma-globulin synthesis are described in malignant human plasmacytes: extreme unbalanced synthesis where only L chains are synthesized; unbalanced synthesis in which intact gammaG globulin and an excess of free L chains are synthesized and secreted; and balanced synthesis where H and L chains appear to be synthesized in equimolar amounts. Studies of the cellular products appear to reflect the biosynthetic processes of the cells in a more reliable fashion than does analysis of serum or urinary proteins. The absence of Bence Jones proteins from the urine does not necessarily indicate that free L chains are not being synthesized and secreted at the cellular level. Similarly, the completed globulin molecule secreted by malignant plasma cells may not be demonstrable by examination of serum. Patterns of globulin synthesis in human myelomatous tissues vary as do patterns of globulin synthesis in mouse plasmacytomas. Pulse-chase studies of the cells from one patient showed that a gammaG myeloma protein was assembled via an HL (half molecule) intermediate.


Sarafotoxin, a novel vasoconstrictor peptide: phosphoinositide hydrolysis in rat heart and brain.
Sarafotoxins, a group of 21-residue cardiotoxic peptides from snake venom that induce coronary vasoconstriction, show high-affinity binding to rat atrial and brain membranes and activate the hydrolysis of phosphoinositides. Neither their binding nor their activity is affected by blockers or activators of known receptors and ion channels, suggesting that sarafotoxins act either directly on the phosphoinositide phosphodiesterase system or on a novel receptor. Their amino acid sequence shows a high degree of homology with that of endothelin, a recently described 21-residue vasoconstrictor peptide found in porcine aortic endothelium. This is remarkable, since endothelin is a natural compound of the mammalian vascular system while sarafotoxins are highly toxic components of snake venom.


[Some environmental and hygienic aspects of preschool children's health in an industrial town].
The results of a medical genetic study of the spread of congenital morphogenetic types (CMGT) among 3-7-year-old children living in Magnitogorsk whose territory is highly polluted with chemical compounds are presented. In Magnitogorsk, the mean of CMGT cases per child is 2.89, which is much greater than the respective values for environmentally favorable cities and towns in Russia. The most common signs are as follows: diastema (137.79 cases per 1000 children), clinodactyly (135.98 per 1000), epicanthus (122.44 per 1000), and wide umbilical ring (110.71 per 1000).


Lymphoepithelial lesions in the salivary glands of primary Sjögren's syndrome patients: the perfect storm?
In patients with primary Sjögren's syndrome (pSS), inflamed salivary gland (SG) tissue may contain lymphoepithelial lesions (LELs). LELs are histopathological phenomena whereby B cells are present in hyperplastic ductal epithelium of the SG. Despite the potential role of LELs in pSS pathogenesis, studies on their formation, detection, and prevalence in benign lesions (not complicated with lymphoma) are scarce. Recent evidence however shows that LELs are present in approximately half of the patients with pSS, both in minor and major SGs. Migration of a small number of B cells into the epithelium appears to be a critical initial step in LEL formation. These intra-epithelial B cells are proliferative, exhibit an innate-like phenotype, and may be linked to MALT lymphoma development. Alongside intra-epithelial B cells, the hyperplastic epithelial partner in LELs also engages in the local immune reaction. Epithelial cells are a source of cytokines and chemokines, with CXCL10 in particular playing a potential role in LEL formation. Importantly, LELs also have a negative impact on the maintenance of SG homeostasis by SG progenitor cell (SGPC) populations, likely due to dysregulation of SGPC lineage commitment or induction of plasticity. In conclusion, LEL formation mirrors a perfect storm of B and epithelial cell interaction culminating in increased risk of B cell derailment and SGPC dysregulation in pSS patients. We therefore argue that attenuation of LEL formation is an important treatment goal to preserve SG function and prevent B cell derailment in pSS.


Fluctuation-driven flocking movement in three dimensions and scale-free correlation.
Recent advances in the study of flocking behavior have permitted more sophisticated analyses than previously possible. The concepts of "topological distances" and "scale-free correlations" are important developments that have contributed to this improvement. These concepts require us to reconsider the notion of a neighborhood when applied to theoretical models. Previous work has assumed that individuals interact with neighbors within a certain radius (called the "metric distance"). However, other work has shown that, assuming topological interactions, starlings interact on average with the six or seven nearest neighbors within a flock. Accounting for this observation, we previously proposed a metric-topological interaction model in two dimensions. The goal of our model was to unite these two interaction components, the metric distance and the topological distance, into one rule. In our previous study, we demonstrated that the metric-topological interaction model could explain a real bird flocking phenomenon called scale-free correlation, which was first reported by Cavagna et al. In this study, we extended our model to three dimensions while also accounting for variations in speed. This three-dimensional metric-topological interaction model displayed scale-free correlation for velocity and orientation. Finally, we introduced an additional new feature of the model, namely, that a flock can store and release its fluctuations.


Case 286: Sarcoidlike Granulomatosis and Lymphadenopathy-Thoracic Manifestations of Nivolumab Drug Toxicity.
History A 70-year-old man had a posterior left thigh lesion confirmed to be biopsy-proven melanoma. The patient underwent wide excision and sentinel node biopsy, which showed absence of residual melanoma. Two years later, the patient noticed a subcentimeter subcutaneous lump in his thigh. Repeat excisional biopsy showed involvement of the surrounding soft tissue, consistent with a satellite lesion. Follow-up combined PET/CT revealed satellite nodules around the primary lesion, enabling confirmation of subcutaneous metastatic disease. The patient was subsequently started on nivolumab, an anti-programmed cell death 1 (PD-1) immune checkpoint inhibitor that blocks PD-1 and is approved as a first-line treatment in patients with advanced metastatic melanoma. On the baseline scan prior to starting nivolumab, there were no CT findings that suggested metastatic disease, nor were there enlarged mediastinal or hilar lymph nodes. Five months after initiation of nivolumab treatment, the first follow-up chest CT scan was performed and showed new findings in the mediastinum and bilateral lungs. The patient remained asymptomatic during the treatment period. Furthermore, the subcutaneous metastatic disease remained stable during the treatment period, and no other site of metastatic disease was noted on follow-up CT scans obtained during the first 5 months of treatment. The patient had no prior history of infectious or occupational exposures. During the nivolumab treatment cycle, his pertinent laboratory values and physical examination findings were unremarkable.


Speech timing in Parkinson's and Huntington's disease.
The purpose was to determine the effects of two different basal ganglia diseases on speech planning, initiation, and production. Patients with Parkinson's Disease (PD) and Huntington's Disease (HD) were compared with normal subjects on speech timing tasks. Speech reaction time was unimpaired, while changes in duration at different speech rates were affected differently in the two patient groups. In HD, changes in the duration of syllables, of pauses between phrases, and of sentences were all reduced, while in PD only the control of sentence duration was impaired. The HD patients had reduced syllable repetition rates, but both patient groups maintained their repetition rates over 5 sec. The ratios of word to phrase time, and of phrase to sentence time, remained constant across regular and fast speaking rates and did not differ from normal in either patient group. The results suggest that PD and HD patients are not impaired in speech planning or initiation, but have poor control over the duration of speech events.


The TEAD4-YAP/TAZ protein-protein interaction: expected similarities and unexpected differences.
The Hippo pathway controls cell homeostasis, and its deregulation can lead to human diseases. In this pathway, the YAP and TAZ transcriptional cofactors play a key role in stimulating gene transcription through their interaction with the TEAD transcriptional factors. Our study of YAP and TAZ peptides in biochemical and biophysical assays shows that both proteins have essentially the same affinity for TEAD. Molecular modeling and structural biology data suggest that they also bind to the same site on TEAD. However, this apparent similarity hides differences in the ways in which the two proteins interact with TEAD. The secondary structure elements of their TEAD binding site do not contribute equally to the overall affinity, and critical interactions with TEAD are made through different residues. This convergent optimization of the YAP/TAZ TEAD binding site suggests that the similarity in the affinities of binding of YAP to TEAD and of TAZ to TEAD is important for Hippo pathway functionality.


Three generations of schizophrenia.
The author presents a case report of a three-generational family with six schizophrenic members. Two children of the index couple, age 20 and 18, have recently been diagnosed as having schizophrenia; two other children are being observed for the development of schizophrenic symptoms. The genetics of schizophrenia are discussed and issues raised about early screening in families with such a strong schizophrenic history.


Postinjury Exercise and Platelet-Rich Plasma Therapies Improve Skeletal Muscle Healing in Rats But Are Not Synergistic When Combined.
Skeletal muscle injuries are the most common sports-related injury and a major concern in sports medicine. The effect of platelet-rich plasma (PRP) injections on muscle healing is still poorly understood, and current data are inconclusive. To evaluate the effects of an ultrasound-guided intramuscular PRP injection, administered 24 hours after injury, and/or posttraumatic daily exercise training for 2 weeks on skeletal muscle healing in a recently established rat model of skeletal muscle injury that highly mimics the muscle trauma seen in human athletes. Controlled laboratory study. A total of 40 rats were assigned to 5 groups. Injured rats (medial gastrocnemius injury) received a single PRP injection (PRP group), daily exercise training (Exer group), or a combination of a single PRP injection and daily exercise training (PRP-Exer group). Untreated and intramuscular saline-injected animals were used as controls. Muscle force was determined 2 weeks after muscle injury, and muscles were harvested and evaluated by means of histological assessment and immunofluorescence microscopy. Both PRP (exhibiting 4.8-fold higher platelet concentration than whole blood) and exercise training improved muscle strength (maximum tetanus force, TetF) in approximately 18%, 20%, and 30% of rats in the PRP, PRP-Exer, and Exer groups, respectively. Specific markers of muscle regeneration (developmental myosin heavy chain, dMHC) and scar formation (collagen I) demonstrated the beneficial effect of the tested therapies in accelerating the muscle healing process in rats. PRP and exercise treatments stimulated the growth of newly formed regenerating muscle fibers (1.5-, 2-, and 2.5-fold increase in myofiber cross-sectional area in PRP, PRP-Exer, and Exer groups, respectively) and reduced scar formation in injured skeletal muscle (20%, 34%, and 41% of reduction in PRP, PRP-Exer, and Exer groups, respectively). Exercise-treated muscles (PRP-Exer and Exer groups) had significantly reduced percentage of dMHC-positive regenerating fibers (35% and 47% decrease in dMHC expression, respectively), indicating that exercise therapies accelerated the muscle healing process witnessed by the more rapid replacement of the embryonic-developmental myosin isoform by mature muscle myosin isoforms. Intramuscular PRP injection and, especially, treadmill exercise improve histological outcome and force recovery of the injured skeletal muscle in a rat injury model that imitates sports-related muscle injuries in athletes. However, there was not a synergistic effect when both treatments were combined, suggesting that PRP does not add any beneficial effect to exercise-based therapy in the treatment of injured skeletal muscle. This study demonstrates the efficacy of an early active rehabilitation protocol or single intramuscular PRP injection on muscle recovery. The data also reveal that the outcome of the early active rehabilitation is adversely affected by the PRP injection when the two therapies are combined, and this could explain why PRP therapies have failed in randomized clinical trials where the athletes have adhered to postinjection rehabilitation protocols based on the principle of early, active mobilization.


Primary treatment and relative survival by stage and age in vulvar squamous cell carcinoma: A population-based SweGCG study.
Vulvar cancer affects mainly elderly women and with an ageing population the incidence has increased. We explored the primary treatment patterns and relative survival of patients with vulvar squamous cell carcinoma (VSCC) by stage and age-group. A population-based nationwide study on women diagnosed with VSCC between 2012 and 2016 and registered in the Swedish Quality Registry for Gynecologic Cancer (SQRGC). Main outcome was 5-year relative survival (RS) estimated by the Pohar Perme method. The relative risk of excess mortality (EMRR) between different groups was analyzed by Poisson regression. The age-standardized relative survival (AS-RS) was estimated for the total cohort. Median follow-up time was 41 months. The study population included 657 women; 33% were ≥ 80 years old. FIGO stage I was most common (55%). Primary surgery was performed in 96% stage I, 65% stage II, 80% stage III and 28% stage IV. In women ≥80 years, exploration of the groins and chemoradiotherapy was less often performed. They also received lower mean doses of radiation than younger women. The 5-year AS-RS was 74%. 5-year RS was 84% for stage I, 60% for stage II, 54% for stage III and 35% for stage IV. The EMRR for women ≥80 years compared with women <60 years was 4.3 (p < 0.001); 4.9 (p < 0.001) for stages I-II and 3.5(p = 0.007) for stage III. In general, primary treatment of patients with vulvar squamous cell carcinoma in Sweden adhered to guidelines. Areas of improvement include treatment for stage II and for the very old.


Handwriting as an objective tool for Parkinson's disease diagnosis.
To date, clinical assessment remains the gold standard in the diagnosis of Parkinson's disease (PD). We sought to identify simple characteristics of handwriting which could accurately differentiate PD patients from healthy controls. Twenty PD patients and 20 matched controls wrote their name and copied an address on a paper affixed to a digitizer. Mean pressure and mean velocity was measured for the entire task and the spatial and temporal characteristics were measured for each stroke. Results of the MANOVAs for the temporal, spatial, and pressure measures (stroke length, width, and height; mean pressure; mean time per stroke; mean velocity), for both the name writing and address copying tasks, showed significant group effects (F(6,32) = 6.72, p < 0.001; F(6,31) = 14.77, p < 0.001, respectively). A discriminant analysis was performed for the two tasks. One discriminant function was found for the group classification of all participants (Wilks' Lambda = 0.305, p < 0.001). Based on this function, 97.5% of participants were correctly classified (100% of the controls and 95% of PD patients). A Kappa value of 0.947 (p < 0.001) was calculated, demonstrating that the group classification did not occur by chance. In this pilot study we identified two simple short and routine writing tasks which differentiate PD patients from healthy controls. These writing tasks have future potential as cost-effective, fast and reliable biomarkers for PD.


Neuron-specific methylome analysis reveals epigenetic regulation and tau-related dysfunction of BRCA1 in Alzheimer's disease.
Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by pathology of accumulated amyloid β (Aβ) and phosphorylated tau proteins in the brain. Postmortem degradation and cellular complexity within the brain have limited approaches to molecularly define the causal relationship between pathological features and neuronal dysfunction in AD. To overcome these limitations, we analyzed the neuron-specific DNA methylome of postmortem brain samples from AD patients, which allowed differentially hypomethylated region of the BRCA1 promoter to be identified. Expression of BRCA1 was significantly up-regulated in AD brains, consistent with its hypomethylation. BRCA1 protein levels were also elevated in response to DNA damage induced by Aβ. BRCA1 became mislocalized to the cytoplasm and highly insoluble in a tau-dependent manner, resulting in DNA fragmentation in both in vitro cellular and in vivo mouse models. BRCA1 dysfunction under Aβ burden is consistent with concomitant deterioration of genomic integrity and synaptic plasticity. The Brca1 promoter region of AD model mice brain was similarly hypomethylated, indicating an epigenetic mechanism underlying BRCA1 regulation in AD. Our results suggest deterioration of DNA integrity as a central contributing factor in AD pathogenesis. Moreover, these data demonstrate the technical feasibility of using neuron-specific DNA methylome analysis to facilitate discovery of etiological candidates in sporadic neurodegenerative diseases.


APC I1307K mutations and forkhead box gene (FOXO1A): another piece of an interesting correlation.
Germline nonsense and frameshift mutations in the adenomatous polyposis coli (APC) gene are found in approximately 90% of individuals affected by familial adenomatous polyposis (FAP) and a genotype-phenotype relationship has been observed. Missense mutations have also been found in a few cases, even if their role in FAP is still unknown. An association between a missense mutation, APC I1307K, and the risk of sporadic colorectal cancer (CRC) has been reported. In order to improve the knowledge about the genetic effect of APC I1307K on the phenotype, we tried a new approach using matrix-assisted laser desorption/ionization mass spectrometry (MALDI/MS). An APC mutation (I1307K) was found in an index case of a non-Jewish woman and her son with attenuated familial adenomatous polyposis (A-FAP) and no family history of cancer. In order to evaluate whether the presence and abundance of the ionic species are related to the presence of cancer or the presence of mutation, comparative analyses of 11 healthy clean-colon subjects, 59 patients with CRC (stage II n=19, stage III n=23, stage IV n=17) without polyps, and 9 FAP patients, carriers of a nonsense mutation in the APC gene, were evaluated. Comparative analysis of serum protein profiles of the index patient and her healthy son, FAP and sporadic CRC patients, and subjects with preneoplastic lesions showed a characteristic abundance of ionic species at m/z 905, which was not present in healthy controls. Two peptides were identified from MALDI/MS/MS spectra of m/z 905 belonging to the kininogen-1 precursor and the human forkhead box protein 01A (FOXO1A). FOXO1A was present in only two subjects carrying I1307K, but not in other patients. Our findings seem to suggest a relationship between m/z 905, FOXO1A and the development and growth of colorectal cancer. FOXO1A fragment determination in serum with MALDI/MS might be a promising approach for early detection of colon carcinoma or for the development of targeted therapies.


Effectiveness of mobile technology and utilization of maternal and neonatal healthcare in low and middle-income countries (LMICs): a systematic review.
Maternal and neonatal mortality are important indicators of the development of a nation and pose a severe health concern, especially in developing and Low and Middle-Income Countries (LMICs). Healthcare providers use various mobile technologies as tools to provide antenatal, delivery, and postnatal care and thereby promote maternal and child health. We conducted a systematic review to critically assess the existing literature on the effectiveness of mobile phone technology in maternal and neonatal healthcare (MNH) utilization, especially in LMICs in Asia and Africa. A systematic search strategy was developed, and Boolean combinations of relevant keywords were utilized to search relevant literature on three electronic databases (PubMed/Medline, Scopus, and Google Scholar) from 2012 to 2022. After assessing the inclusion and exclusion criteria, 25 articles were selected for systematic review. A narrative synthesis strategy was applied to summarise the information from the included literature. This review reveals that research and evaluation studies on mobile phone or Mobile Health (mHealth) and MNH service utilization substantially varied by research designs and methodology. Most studies found that mobile phone technology is highly appreciable in improving several MNH indicators, especially in LMICs. Despite the identified benefits of mobile technology in MNH utilization, some studies also mentioned challenges related to technology use and misuse, rich-poor discrimination, and disparity in phone ownership need to be addressed. There is constantly increasing evidence of mobile counseling and the use of digital technology in the MNH care system. Public health practitioners and policymakers need to make efforts to smooth the functioning of technology-based healthcare services, considering all the issues related to the confidentiality and safety of health-related data on the Internet.


Metabolism of leukotriene C4, D4 and E4 in allergic inflammation in rats.
Using an allergic inflammation model of air pouch type in rats, levels of peptide-leukotriene (LT) C4, D4 and E4 in the pouch fluid were measured chromatographically, and peptide-LT metabolizing activities in the pouch fluid in the anaphylactic phase were examined. 10 min after injection of an antigen (azobenzene arsonate-conjugated acetyl bovine serum albumin) solution into a preformed air pouch on the back of the immunized rats, LTC4 level in the pouch fluid was the highest, followed by LTD4 and LTE4. At 30 min, the order of the level was reversed to LTE4 greater than LTD4 greater than LTC4, and total amount of peptide-LTs (LTC4 + LTD4 + LTE4) was the highest. Supernatant fraction of the pouch fluid collected 30 min after the antigenic challenge, converted [3H]LTC4 into [3H]LTD4, and [3H]LTD4 into [3H]LTE4 in time- and concentration-dependent manner. [3H]LTE4 was not metabolized under these conditions. Heat denaturation of the pouch fluid diminished the conversion of [3H]LTC4 into [3H]LTD4, and [3H]LTD4 into [3H]LTE4. In the granule fraction of purified mast cells, no metabolic activity of [3H]LTs was found. In intact mast cells as well as degranulating mast cells, a small but significant amount of [3H]LTC4 was metabolized into [3H]LTD4 and [3H]LTE4. In contrast, rat serum showed potent metabolizing activities of peptide-LTs. Since plasma exudation into the pouch is very prominent in the anaphylactic phase in this model, peptide-LT metabolizing activities in the pouch fluid are suggested to be attributable to plasma leaked into the pouch during the anaphylactic phase.


Anaerobic bacteremia: the yield of positive anaerobic blood cultures: patient characteristics and potential risk factors.
The anaerobic blood culture (AN) bottle is routinely used in Japan with little discussion as to its justification or validity. We retrospectively studied the AN bottle yield of obligate anaerobes and the characteristics of, and potential risk factors in, patients with anaerobic bacteremia during a 2-year period (1999-2000) at four university hospitals and one community hospital. Thirty-four of 18,310 aerobic and anaerobic blood culture sets from 6,215 patients taken at the university hospitals, and 35 of 2,464 samples taken from 838 patients at the community hospital, yielded obligate anaerobes. Bacteroides species and Clostridium species accounted for 60% of the isolates. Fifty-seven patients from 69 blood culture sets containing anaerobes had clinically significant anaerobic bacteremia. Among these 57 patients, 24 (49%) were oncology patients, 40 (70%) had an obvious source of anaerobic infection, 15 (26%) had recent surgery and/or were in an immunosuppressed state. We concluded that the recovery rate of obligate anaerobes isolated from AN bottles was low, and the patients with anaerobic bacteremia had limited number of underlying diseases or potential risk factors for anaerobic infections. Therefore, anaerobic blood cultures may be selectively used according to the potential risk for anaerobic infections.


Podiatric pathology of lupus erythematosus.
Lupus erythematosus is an enigmatic disease. Its podiatric manifestations are largely cutaneous, but vasculitic involvements may produce complications. The authors review much of the histopathology of lupus erythematosus that is relevant to the podiatric physician and surgeon. Awareness of the serious systemic implications of lupus erythematosus and the internal medications used in treatment is part of the physician's responsibility in understanding the whole patient.


Molecular genotyping of human Ureaplasma species based on multiple-banded antigen (MBA) gene sequences.
Ureaplasma urealyticum has been divided into 14 serovars. Recently, subdivision of U. urealyticum into two species has been proposed: U. parvum (previously U. urealyticum parvo biovar), comprising four serovars (1, 3, 6, 14) and U. urealyticum (previously U. urealyticum T-960 biovar), 10 serovars (2, 4, 5, 7-13). The multiple-banded antigen (MBA) genes of these species contain both species and serovar/subtype specific sequences. Based on whole sequences of the 5'-ends of MBA genes of U. parvum serovars and partial sequences of the 5'-ends of MBA genes of U. urealyticum serovars, we previously divided each of these species into three MBA genotypes. To further elucidate the relationships between serovars, we sequenced the whole 5'-ends of MBA genes of all 10 U. urealyticum serovars and partial repetitive regions of these genes from all serovars of U. parvum and U. urealyticum. For the first time, all four serovars of U. parvum were clearly differentiated from each other. In addition, the 10 serovars of U. urealyticum were divided into five MBA genotypes, as follows: MBA genotype A comprises serovars 2, 5, 8; MBA genotype B, serovar 10 only; MBA genotype C, serovars 4, 12, 13; MBA genotype D, serovar 9 only; and MBA genotype E comprises serovars 7 and 11. There were no sequence differences between members within each MBA genotype. Further work is required to identify other genes or other regions of the MBA genes that may be used to differentiate U. urealyticum serovars within MBA genotypes A, C and E. A better understanding of the molecular basis of serotype differentiation will help to improve subtyping methods for use in studies of the pathogenesis and epidemiology of these organisms.


[Influence of erbium ion concentration on Judd-Ofelt parameters of Er3+ -doped tellurite glass].
Er3+ -doped tellurite glasses with four different concentrations were fabricated, and the oscillator strength of Er3+ in the tellurite glasses were calculated through the absorption spectra of the glasses. The Judd-Ofelt intensity parameter omega i, spontaneous transition probability A, fluorescence branching ratio beta, and radiative lifetime tau rad of Er3+ were calculated on the basis of Judd-Ofelt theory, and the effect of the erbium ion concentration on the above optical parameters was also discussed. The fluorescence spectra of Er3+: (4)I(13/2)--> (4)I(15/2) transition and the lifetime of Er3+: (4)I(13/2) level of the samples were measured. The stimulated emission cross-section of (4)I(13/2)--> (4)I(15/2) transition of the samples was finally calculated by using McCumber theory. The results show that with the increase in the Er3+ concentration, the oscillator strength and spontaneous transition probability A of Er3+ increase, while the fluorescence branching ratio beta of Er3+ shows little difference. The stimulated emission cross-section of Er3+: (4)I(13/2)--> (4)I(15/2) transition of the samples changes slightly with the increase in the Er3+ concentration. All the fluorescence effective line widths for the four different Er3+ concentration samples are nearly 50 nm.


Association between the intrinsically disordered protein PEX19 and PEX3.
In peroxisomes, peroxins (PEXs) 3 and 19 are the principal protein components of the machinery required for early peroxisomal biogenesis. For further insight into the interaction of PEX3 and PEX19, we used hydrogen exchange mass spectrometry to monitor conformational changes during complex formation between PEX3 and PEX19 in vitro. Our data showed that PEX19 remained highly flexible during interaction with PEX3. However, we could detect three changes, one each in the N-and C-terminus along with a small stretch in the middle of PEX19 (F64-L74) which became shielded from hydrogen exchange when interacting with PEX3. PEX3 became more protected from hydrogen exchange in the binding groove for PEX19 with only small changes elsewhere. Most likely the N-terminus of PEX19 initiates the binding to PEX3, and then subtle conformational changes in PEX3 affect the surface of the PEX3 molecule. PEX19 in turn, is stabilized by folding of a short helix and its C-terminal folding core permitting PEX19 to bind to PEX3 with higher affinity than just the N-terminal interaction allows. Thus within the cell, PEX3 is stabilized by PEX19 preventing PEX3 aggregation.


Prophylactic mastectomy: the Rotterdam experience.
The efficacy of prophylactic mastectomy (PM) depends on the ability to remove all breast tissue and a regular mastectomy is recommended. In our study population (n=112), 103 women (94%) have chosen for immediate breast reconstruction (IBR) with a silicone prosthesis placed in a subpectoral pocket. The median follow-up after IBR was 3.5 (range 1-7) years. These 103 patients underwent 193 PM with IBR: 90 bilateral and 13 unilateral. The median follow-up after IBR was 3.5 (range 1-7) years. In 163 IBRs (82%) no complications were observed. The most common late complication was capsular contracture, significantly more around prostheses placed in a previously irradiated area. No cases of breast cancer were found after PM at a mean follow-up of 2.9 years. After breast cancer a delayed ipsilateral PM and/or contralateral PM can be considered after a disease-free interval of 2 years, also taking into account the age of onset of the first breast cancer. The prognosis of breast cancer in BRCA2 mutation patients seems to be similar to that in sporadic cancer. The most striking result of PM is the decrease of anxiety of developing breast cancer and a negative impact on their sexual life. Therefore a time delay is necessary to allow women to fully address the issues involved in PM and IBR.


Raman spectroscopic characterization of single walled carbon nanotubes: influence of the sample aggregation state.
Raman spectroscopy has been employed in analytical sciences for purity determination of carbon nanotube samples based on the consideration of G-/D-band intensity ratios. This work demonstrates the role of aggregation in these feature bands, which, in the case of single walled carbon nanotubes (SWNTs), has proved to be crucial for G-/D-band intensity ratio measurements. We have found variation in the relative intensities of G- and D-bands across a sample of SWNTs without any other treatment, discarding the possible influence of the laser beam or sample focusing. In the case of multiwalled carbon nanotubes (MWNTs), this effect is less notorious. Thus, to achieve a good representativeness of Raman measurements, it is important to consider the sample preparation procedure in order to avoid aggregation, which has an effect over the signals, making difficult the subsequent interpretation of results.


Impaired functions of macrophage from cystic fibrosis patients: CD11b, TLR-5 decrease and sCD14, inflammatory cytokines increase.
Early in life, cystic fibrosis (CF) patients are infected with microorganisms. The role of macrophages has largely been underestimated in literature, whereas the focus being mostly on neutrophils and epithelial cells. Macrophages may however play a significant role in the initiating stages of this disease, via an inability to act as a suppressor cell. Yet macrophage dysfunction may be the first step in cascade of events leading to chronic inflammation/infection in CF. Moreover, reports have suggested that CFTR contribute to altered inflammatory response in CF by modification of normal macrophage functions. In order to highlight possible intrinsic macrophage defects due to impaired CFTR, we have studied inflammatory cytokines secretions, recognition of pathogens and phagocytosis in peripheral blood monocyte-derived macrophages from stable adult CF patients and healthy subjects (non-CF). In CF macrophage supernatants, concentrations of sCD14, IL-1β, IL-6, TNF-α and IL-10 were strongly raised. Furthermore expression of CD11b and TLR-5 were sorely decreased on CF macrophages. Beside, no difference was observed for mCD14, CD16, CD64, TLR-4 and TLR1/TLR-2 expressions. Moreover, a strong inhibition of phagocytosis was observed for CF macrophages. Elsewhere CFTR inhibition in non-CF macrophages also led to alterations of phagocytosis function as well as CD11b expression. Altogether, these findings demonstrate excessive inflammation in CF macrophages, characterized by overproduction of sCD14 and inflammatory cytokines, with decreased expression of CD11b and TLR-5, and impaired phagocytosis. This leads to altered clearance of pathogens and non-resolution of infection by CF macrophages, thereby inducing an exaggerated pro-inflammatory response.


Analysis of bacterial community structure in sulfurous-oil-containing soils and detection of species carrying dibenzothiophene desulfurization (dsz) genes.
The selective effects of sulfur-containing hydrocarbons, with respect to changes in bacterial community structure and selection of desulfurizing organisms and genes, were studied in soil. Samples taken from a polluted field soil (A) along a concentration gradient of sulfurous oil and from soil microcosms treated with dibenzothiophene (DBT)-containing petroleum (FSL soil) were analyzed. Analyses included plate counts of total bacteria and of DBT utilizers, molecular community profiling via soil DNA-based PCR-denaturing gradient gel electrophoresis (PCR-DGGE), and detection of genes that encode enzymes involved in the desulfurization of hydrocarbons, i.e., dszA, dszB, and dszC. Data obtained from the A soil showed no discriminating effects of oil levels on the culturable bacterial numbers on either medium used. Generally, counts of DBT degraders were 10- to 100-fold lower than the total culturable counts. However, PCR-DGGE showed that the numbers of bands detected in the molecular community profiles decreased with increasing oil content of the soil. Analysis of the sequences of three prominent bands of the profiles generated with the highly polluted soil samples suggested that the underlying organisms were related to Actinomyces sp., Arthrobacter sp., and a bacterium of uncertain affiliation. dszA, dszB, and dszC genes were present in all A soil samples, whereas a range of unpolluted soils gave negative results in this analysis. Results from the study of FSL soil revealed minor effects of the petroleum-DBT treatment on culturable bacterial numbers and clear effects on the DBT-utilizing communities. The molecular community profiles were largely stable over time in the untreated soil, whereas they showed a progressive change over time following treatment with DBT-containing petroleum. Direct PCR assessment revealed the presence of dszB-related signals in the untreated FSL soil and the apparent selection of dszA- and dszC-related sequences by the petroleum-DBT treatment. PCR-DGGE applied to sequential enrichment cultures in DBT-containing sulfur-free basal salts medium prepared from the A and treated FSL soils revealed the selection of up to 10 distinct bands. Sequencing a subset of these bands provided evidence for the presence of organisms related to Pseudomonas putida, a Pseudomonas sp., Stenotrophomonas maltophilia, and Rhodococcus erythropolis. Several of 52 colonies obtained from the A and FSL soils on agar plates with DBT as the sole sulfur source produced bands that matched the migration of bands selected in the enrichment cultures. Evidence for the presence of dszB in 12 strains was obtained, whereas dszA and dszC genes were found in only 7 and 6 strains, respectively. Most of the strains carrying dszA or dszC were classified as R. erythropolis related, and all revealed the capacity to desulfurize DBT. A comparison of 37 dszA sequences, obtained via PCR from the A and FSL soils, from enrichments of these soils, and from isolates, revealed the great similarity of all sequences to the canonical (R. erythropolis strain IGTS8) dszA sequence and a large degree of internal conservation. The 37 sequences recovered were grouped in three clusters. One group, consisting of 30 sequences, was minimally 98% related to the IGTS8 sequence, a second group of 2 sequences was slightly different, and a third group of 5 sequences was 95% similar. The first two groups contained sequences obtained from both soil types and enrichment cultures (including isolates), but the last consisted of sequences obtained directly from the polluted A soil.


Early, but not late, treatment with human umbilical cord blood-derived mesenchymal stem cells attenuates cisplatin nephrotoxicity through immunomodulation.
Preemptive treatment with mesenchymal stem cells (MSCs) can attenuate cisplatin-induced acute kidney injury (AKI). However, it is uncertain whether MSC treatment after the development of renal dysfunction prevents AKI progression or if MSC immunomodulatory properties contribute to MSC therapy. In this study, human umbilical cord blood (hUCB)-derived MSCs were used to compare the effects and mechanisms of early and late MSC therapy in a murine model. After cisplatin injection into C57BL/6 mice, hUCB-MSCs were administered on day 1 (early treatment) or day 3 (late treatment). With early treatment, cisplatin nephrotoxicity was attenuated as evidenced by decreased blood urea nitrogen (BUN) and reduced apoptosis and tubular injury scores on day 3 Early treatment resulted in downregulation of intrarenal monocyte chemotactic protein-1 and IL-6 expression and upregulation of IL-10 and VEGF expression. Flow cytometric analysis showed similar populations of infiltrated immune cells in both groups; however, regulatory T-cell (Treg) infiltration was 2.5-fold higher in the early treatment group. The role of Tregs was confirmed by the blunted effect of early treatment on renal injury after Treg depletion. In contrast, late treatment (at a time when BUN levels were 2-fold higher than baseline levels) showed no renoprotective effects on day 6 Neither the populations of intrarenal infiltrating immune cells (including Tregs) nor cytokine expression levels were affected by late treatment. Our results suggest that early MSC treatment attenuates renal injury by Treg induction and immunomodulation, whereas a late treatment (i.e., after the development of renal dysfunction) does not prevent AKI progression or alter the intrarenal inflammatory micromilieu.


Bone marrow cell composition and morphology in healthy juvenile female New Zealand White rabbits (Oryctolagus cuniculus).
OBJECTIVE To provide contemporary preliminary guidelines for the morphological evaluation of bone marrow in conjunction with CBC results for healthy juvenile (3- to 6-month-old) female New Zealand White rabbits (Oryctolagus cuniculus). ANIMALS 22 female New Zealand White rabbits. PROCEDURES Each rabbit was sedated, and a blood sample (3 mL) was collected from an ear artery for a CBC, after which the rabbit was euthanized. Within 5 minutes after euthanasia, bone marrow samples were obtained from the femur for cytologic and histologic evaluation. Bone marrow specimens for cytologic evaluation were stained with modified Wright stain, and those for histologic evaluation were stained with either H&E or Prussian blue stain. RESULTS The CBC results were within published reference ranges for all rabbits except 4, each of which had mild leukopenia. Cytologic assessment of bone marrow revealed a median myeloid-to-erythroid ratio of 0.7 and 2.8 megakaryocytes/low-power field (magnification, 100X), and the median percentages of lymphocytes, plasma cells, and macrophages were 11.5%, 0.1%, and 0%, respectively. The myeloid-to-erythroid ratio was not significantly correlated with any CBC variable. On histologic evaluation of bone marrow, the cellularity ranged from 30% to 50%, there were 2.1 to 7.7 megakaryocytes/hpf (magnification, 400X), and no iron stores were visible in H&E or Prussian blue-stained specimens. CONCLUSIONS AND CLINICAL RELEVANCE Results of the present study provided contemporary preliminary guidelines for the evaluation of bone marrow in healthy laboratory rabbits.


The relationship between chronic cocaine or alcohol use and blood pressure in black men during uncomplicated tooth extraction.
The object of this study was to determine whether a history of cocaine or alcohol use is associated with blood pressure changes in patients undergoing an uncomplicated mandibular molar extraction. The blood pressure (BP) values of middle-aged (30 to 40 years of age) black men with different chronic drug histories were compared during extraction procedures. The four different groups were 1) no-drug control, (n = 10); 2) alcohol (n = 15); 3) "crack" cocaine (n = 9); and 4) cocaine (n = 22). The cocaine group's blood pressures were significantly different compared with the blood pressures within the no-drug and alcohol groups (P < .05). The cocaine group's BPs decreased throughout the procedure, and the BPs of the no-drug and alcohol groups rose during administration of the local anesthetic and extraction, and then fell. The BPs of the crack group were highly variable and not significantly different when compared with other groups. There is a paradoxical effect of chronic cocaine use on blood pressure that needs to be considered when treating such patients.


[Effect of negative hydro-aero ions on the structure and functional properties of mitochondria].
Studies were carried out of the physical mechanism of biological effect of natural stimulant of the living activity--light negative hydroaeroions. The latter are a hydroxyl separated from water ions and designated here as electrically noncompensated hydroxyl OH-. Unique effect of OH-, i.e. fast restoration and prevention of fine damage of native mitochondria (NM) at storage was revealed on mitochondria preparations by specific procedure, providing preservation of the ability of self-organization--formation of aggregated and denser packing--native mitochondria. This effect of OH- is conditioned by increased formation of native mitochondria aggregates and is concerned with better ADP phosphorylation and Ca2- release. The effect of the air current OH- is produced by water action presaturated with OH-. OH- induces in water cooperative structure formation preserved for many days, which is indicated by an increase of its heat capacity and decrease of surface tension. The principal factor in OH- effect both on mitochondria and water seems to be a decrease of local positive changes. It is of more advantage in NM water suspensions to order (structurate) NM with disordering water, which explains formation of NM stable aggregates. OH- effect supports the main function of the organism struggling with proton excess which destroys biological self-organization. Strengthened structural self-organization under the effect of OH- found in NM seems to be of universal importance for biological macromolecules and membranes and is a primary effect of OH- on the living objects.


CCR5 expression is elevated on endocervical CD4+ T cells in healthy postmenopausal women.
New HIV-1 infections are increasing in older American women largely through heterosexual transmission. Activated CD4+ T cells and CCR5 expression are linked to HIV-1 susceptibility, but whether these parameters are altered in the cervix of older women is unknown. Whole blood and in some instances endocervical brush samples were collected from healthy premenopausal (n = 22) and postmenopausal women (n = 24). Percentages of HLA-DR(DR)+CD38(38)+CD4+ T cells and HIV-1 chemokine coreceptor expression were determined by flow cytometry. Percentages of DR+38+CD4+ T cells were 6 times greater in cervix (median: 6.4%) than blood (median: 1.1%; P < 0.001) but did not differ within each compartment between premenopausal and postmenopausal women (P = 0.2). Postmenopausal women had greater percentages of CCR5+CD4+ and CCR5+DR+38+CD4+ T cells compared with premenopausal women in cervix (median: 70% vs. 42%, P = 0.005; and 80% vs. 57%; P = 0.05, respectively) and blood (medians: 22% vs. 13%, and 76% vs. 62%, respectively; P < 0.001). Postmenopausal women had more CCR5 molecules on cervical DR+38+CD4+ T cells (median: 3176) than premenopausal women (median: 1776; P = 0.02). Age and percent CCR5+CD4+ and CCR5+DR+38+CD4+ cells were linearly related in cervix (r(2) = 0.47, P < 0.001 and r(2) = 0.25, P = 0.01, respectively) and blood (r(2) = 0.20, P = 0.001 and r(2) = 0.31, P < 0.001; respectively), but confounding of age with menopause could not be excluded. Cervical CXCR4 expression did not differ substantially between premenopausal and postmenopausal women. Elevated cervical CCR5 expression in postmenopausal women may increase their risk for HIV-1 acquisition. Studies are needed to confirm whether elevated CCR5 expression confers increased HIV-1 susceptibility in postmenopausal women, and if it is related to hormonal or nonhormonal effects of aging.


Prevalence and patterns of potentially avoidable hospitalizations in the US long-term care setting.
We examined the magnitude and related costs of potentially avoidable hospitalizations including re-hospitalizations for long-stay residents in nursing homes. We conducted our investigation as a retrospective cohort study where the cohort comprised individuals who were eligible for Medicare and had spent at least 120 uninterrupted days in a nursing home in New York State between 2004 and 2007. To conduct the study, we linked the Minimum Data Set, Medicare Provider Assessment File and Provider of Service File. We defined a potentially avoidable hospitalization as one where a resident was admitted to a hospital for which the principle diagnosis was 1 of 15 ambulatory care sensitive (ACS) conditions. Although the percentage of total hospitalizations for ACS conditions declined during the study period, 20% or more of annual hospitalizations were for ACS conditions entailing Medicare payments in excess of $450 million. Approximately 40% of the residents who were hospitalized once for an ACS condition were re-hospitalized during the study period for the same or different ACS condition. During the study period, potentially avoidable hospitalizations from nursing homes were a common occurrence in New York. A substantial percentage of such hospitalizations involved residents who had been previously hospitalized, in some cases multiple times, for an ACS condition. Although the observed decline in ACS-related hospitalizations suggests improvements in nursing home care, various policy and managerial-level initiatives may be needed to ensure that nursing home residents are not exposed to a substantial risk of avoidable hospitalizations in the future.


Effectiveness of antenatal corticosteroids at term: Can we trust the data that 'inform' us?
Randomized controlled trials (RCTs) are a cornerstone for the assessment of the effectiveness of interventions. Appropriate randomization, design, sample size, statistical analyses, and conduct that reduces the risk of bias, enhance the chance they will deliver true research findings. The credibility of RCTs is difficult to assess without objective evidence of compliance with Good Clinical Practice standards. Remarkably, no mechanisms are in place both in the initial peer review process and during meta-analysis to assess these, and little guidance on how to assess data where research integrity cannot be confirmed (e.g. where data originated from a setting without established infrastructure or an era preceding current standards). We describe the case of the use of antenatal steroids. When these drugs are used in early preterm birth, their benefits outweigh the harms. However, later in pregnancy, and specifically at term, this balance is less clear. We describe that the four randomised clinical trials that inform clinical practice through the Cochrane meta-analysis, for various reasons, lack clear governance which makes it difficult to verify provenance and reliability of the data. We conclude that transparency and assessment of data credibility need to be inbuilt both at the time of publication and at the time of meta-analysis. This will drive up standards and encourage appropriate interpretation of results and the context from which they were derived.


Beta-amino-butyric acid-induced resistance against necrotrophic pathogens is based on ABA-dependent priming for callose.
The non-protein amino acid beta-amino-butyric acid (BABA) protects plants against a wide range of pathogens. We have examined the effectiveness and mode of action of BABA on resistance against two necrotrophic pathogens. Treatment of Arabidopsis with BABA induced resistance against Alternaria brassicicola and Plectosphaerella cucumerina to a similar level by jasmonic acid (JA). Conversely, treatment with benzothiadiazole (BTH), a functional analogue of salicylic acid (SA), had no significant effect on the resistance against both pathogens. BABA-induced resistance against A. brassicicola and P. cucumerina was unaffected in the JA-insensitive mutant coi1-1 and the camalexin-deficient mutant pad3-1. Moreover, the expression of BABA-induced resistance was not associated with enhanced accumulation of camalexin or enhanced transcription of the JA-inducible PDF1.2 gene. The expression of BABA-induced resistance against P. cucumerina was unaffected in mutants impaired in ethylene (ET) and SA signalling, but was blocked in the abscisic acid (ABA)-deficient mutant aba1-5, the ABA-insensitive mutant abi4-1 and the callose-deficient mutant pmr4-1. Upon infection by both pathogens, BABA-treated plants showed an earlier and more pronounced accumulation of callose. Treatment with the callose-inhibitor 2-deoxy-D-glucose (2-DDG) reversed the BABA-induced resistance against A. brassicicola. Furthermore, primed callose deposition was absent in BABA-treated abi4-1 and pmr4-1 plants upon infection by P. cucumerina. Although the expression of BABA-induced resistance was not associated with enhanced transcription of the ABA-inducible RAB18 gene, application of ABA mimicked the effect of BABA on the level of callose accumulation and resistance. Hence, BABA-induced resistance against necrotrophic pathogens is based on primed callose accumulation, which is controlled by an ABA-dependent defence pathway.


[Knowledge of the municipal health managers about the National Policy on Integrative and Complementary Practices and its influence on the provision of homeopathy in the Local Unified Health System].
The social determinants of the health-disease process and the challenge of comprehensive care have led the World Health Organization to propose Complementary and Alternative Medicines to be included in health policies. In Brazil in 2006 the National Policy on Integrative and Complementary Practices (PNPIC) was published. It is a tool for the institutionalization of homeopathy in the Unified Health System (SUS). This paper analyzes the knowledge of health managers of municipalities of São Paulo on PNPIC, and its influence on homeopathic care. In 2008, the municipalities that performed homeopathic consultations from 2000 to 2007 were identified in DATASUS, managers were interviewed and the results were analyzed quantitatively and qualitatively: of the 645 municipalities, 47 had offered homeopathy and 42 of them were interviewed. Of these, 26% knew about PNPIC, 31% knew little, 41% were unaware of it. It should be stressed that those aware of it stated that they use PNPIC to: instruct the local government about homeopathy; the construction of specific legislation and the increase in homeopathic services. The conclusion is that PNPIC is unknown by health managers and those that know it use it to make known the homeopathic medical rationale and justify its application in the SUS.


The psychotic spectrum: a community-based study.
Over the last years, there has been an increasing awareness and knowledge about bipolar spectrum disorders. However, descriptive data on bipolar I disorder with psychotic features (BPI-p) in comparison with schizophrenia (SCH) and schizoaffective disorder (SA) in mental health community services are scanty in the literature. We conducted a study with the aim of assessing the prevalence, clinical characteristics and levels of functioning of SCH, SA and BPI-p in a random sample of patients with psychotic symptoms recruited in nine departments of mental health. Patients with a psychotic disorder according to their treating clinicians were assessed using the SCID and a series of questionnaires to evaluate their psychopathology and level of functioning. Patients who received a DSM-IV diagnosis of SA (N=55), SCH (N=82), or BPI-p (N=60) represented the final sample. The three diagnostic groups showed similar demographic characteristics. Independently from the diagnosis, all patients had a long duration of illness and a persistent course. Uni-variate group comparisons showed that, as compared to SCH patients, BPI-p and SA patients did better in several measures of functioning and differed in frequency of psychotic symptoms. However, a multinomial logistic regression model in which only significantly different variables were entered showed similar levels of functioning in the three groups of patients. The three groups' scores did not significantly differ on instruments that assessed dimensionally psychotic and affective symptoms during the previous month.


The membrane fluidity sensor DesK of Bacillus subtilis controls the signal decay of its cognate response regulator.
The Bacillus subtilis DesK/DesR two-component system regulates the expression of the des gene coding for the Delta5 acyl lipid desaturase. It is believed that a decrease in membrane lipid fluidity activates the DesK/DesR signal transduction cascade, which results in synthesis of the Delta5 acyl lipid desaturase and desaturation of membrane phospholipids. These newly synthesized unsaturated fatty acids then act as negative signals of des transcription, thus generating a regulatory metabolic loop that optimizes membrane fluidity. We previously suggested that DesK is a bifunctional enzyme with both kinase and phosphatase activities that could assume different signaling states in response to changes in the fluidity of membrane lipids. However, no direct experimental evidence supported this proposed model. In this study, we show that the C-terminal fragment of the DesK protein (DesKC) indeed acts as an autokinase. Addition of the response regulator DesR to phosphorylated DesKC resulted in rapid transfer of the phosphoryl group to DesR. Further, phosphorylated DesR can be dephosphorylated in the presence of DesKC, thus demonstrating that the sensor kinase has the ability to covalently modify DesR through both kinase and phosphatase activities. We also present evidence that DesKC might be locked in a kinase-dominant state in vivo and that its activities are not affected either in vivo or in vitro by unsaturated fatty acids. These findings provide the first direct evidence that the transmembrane segments of DesK are essential to sense changes in membrane fluidity and for regulating the ratio of kinase to phosphatase activities of the cytoplasmic C-terminal domain.


Validation of PREDICT Version 2.2 in a Retrospective Cohort of Indian Women With Operable Breast Cancer.
Online prediction models that use known prognostic factors in breast cancer (BC) are routinely used to assist in decisions for adjuvant therapy. PREDICT Version 2.2 (P2.2) is one such online tool, which uses tumor size, lymph node involvement, grade, age, hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, and Ki67. We performed an external validation in a retrospective cohort of patients treated at a tertiary center in India. Women with operable BC between 2008 and 2016 with nonmetastatic, T1-T2 invasive, and HER2 receptor-negative BC and with available 5-year overall survival (OS) data were selected. Median predicted 5-year OS rates were used to calculate predicted events for the whole cohort and subgroups. The chi-square test was used to evaluate the goodness of fit of the tool. Of 11,760 cases registered between 2008 and 2016, 2,783 (23.66%) eligible patients with a median age of 50 (26-70) years and a median pT size of 2.5 (0.1-5) cm, 2,037 (73.19%) with grade 3 tumors, 1,172 (42.11%) with node-positive disease, 817 (29.35%) with triple-negative breast cancer, and 1,966 (70.64%) with HR-positive BC were included in the analysis. The observed 5-year OS and predicted 5-year OS in the whole cohort were 94.8% and 90.00%, respectively, with an absolute difference of 4.8% (95% CI, 3.417 to 6.198, P < .001). The observed 5-year OS and predicted 5-year OS were also different in various subgroups. PREDICT version 2.2 overestimated the number of deaths, with lower predicted 5-year OS compared with the observed value, in this retrospective Indian cohort. The reasons for this discrepancy could be differing biologic characteristics and possible selection bias in our cohort. We recommend a prospective validation of PREDICT in Indian patients and advocate caution in its use until such validation is achieved.


Developing a Toolbox of Antibodies Validated for Array Tomography-Based Imaging of Brain Synapses.
Antibody-based imaging techniques rely on reagents whose performance may be application-specific. Because commercial antibodies are validated for only a few purposes, users interested in other applications may have to perform extensive in-house antibody testing. Here we present a novel application-specific proxy screening step to efficiently identify candidate antibodies for array tomography (AT), a serial section volume microscopy technique for high-dimensional quantitative analysis of the cellular proteome. To identify antibodies suitable for AT-based analysis of synapses in mammalian brain, we introduce a heterologous cell-based assay that simulates characteristic features of AT, such as chemical fixation and resin embedding that are likely to influence antibody binding. The assay was included into an initial screening strategy to generate monoclonal antibodies that can be used for AT. This approach simplifies the screening of candidate antibodies and has high predictive value for identifying antibodies suitable for AT analyses. In addition, we have created a comprehensive database of AT-validated antibodies with a neuroscience focus and show that these antibodies have a high likelihood of success for postembedding applications in general, including immunogold electron microscopy. The generation of a large and growing toolbox of AT-compatible antibodies will further enhance the value of this imaging technique.Significance StatementArray tomography (AT) is a powerful volume microscopy technique for high-dimensional analysis of complex protein populations in cells and organelles, including synapses. AT involves the use of ultrathin serial sections embedded in resin and subjected to multiple rounds of immunofluorescence antibody (Ab) labeling and imaging. AT relies on antibody-based detection of proteins but because commercial antibodies are typically validated for other applications they often fail for AT. To identify antibodies with high probability of success in AT we developed a novel screening strategy and used this to create a comprehensive database of AT-validated antibodies for neuroscience.


Silage maize as a potent candidate for sustainable animal husbandry development-perspectives and strategies for genetic enhancement.
Maize is recognized as the queen of cereals, with an ability to adapt to diverse agroecologies (from 58oN to 55oS latitude) and the highest genetic yield potential among cereals. Under contemporary conditions of global climate change, C4 maize crops offer resilience and sustainability to ensure food, nutritional security, and farmer livelihood. In the northwestern plains of India, maize is an important alternative to paddy for crop diversification in the wake of depleting water resources, reduced farm diversity, nutrient mining, and environmental pollution due to paddy straw burning. Owing to its quick growth, high biomass, good palatability, and absence of anti-nutritional components, maize is also one of the most nutritious non-legume green fodders. It is a high-energy, low-protein forage commonly used for dairy animals like cows and buffalos, often in combination with a complementary high-protein forage such as alfalfa. Maize is also preferred for silage over other fodders due to its softness, high starch content, and sufficient soluble sugars required for proper ensiling. With a rapid population increase in developing countries like China and India, there is an upsurge in meat consumption and, hence, the requirement for animal feed, which entails high usage of maize. The global maize silage market is projected to grow at a compound annual growth rate of 7.84% from 2021 to 2030. Factors such as increasing demand for sustainable and environment-friendly food sources coupled with rising health awareness are fueling this growth. With the dairy sector growing at about 4%-5% and the increasing shortage faced for fodder, demand for silage maize is expected to increase worldwide. The progress in improved mechanization for the provision of silage maize, reduced labor demand, lack of moisture-related marketing issues as associated with grain maize, early vacancy of farms for next crops, and easy and economical form of feed to sustain household dairy sector make maize silage a profitable venture. However, sustaining the profitability of this enterprise requires the development of hybrids specific for silage production. Little attention has yet been paid to breeding for a plant ideotype for silage with specific consideration of traits such as dry matter yield, nutrient yield, energy in organic matter, genetic architecture of cell wall components determining their digestibility, stalk standability, maturity span, and losses during ensiling. This review explores the available information on the underlying genetic mechanisms and gene/gene families impacting silage yield and quality. The trade-offs between yield and nutritive value in relation to crop duration are also discussed. Based on available genetic information on inheritance and molecular aspects, breeding strategies are proposed to develop maize ideotypes for silage for the development of sustainable animal husbandry.


Light microscopic morphology of viral hepatitis.
The histopathology of acute and chronic infections associated with viral hepatitis is reviewed and illustrated. Particular attention is directed to changes that help to differentiate chronic persistent from chronic active viral hepatitis. Features that help to identify the intravenous drug abuser who has hepatitis, whether acute or chronic, include the presence of particulate birefringent material (usually talc) in reticuloendothelial cells, as well as tissue eosinophilia. Ground-glass hepatocytes are characteristic of the HBAg carrier. They may be present in chronic persistent and chronic active hepatitis and in cirrhotic livers with or without hepatocellular carcinoma. Ground-glass cells which contain the surface component of the HBAg, can be stained specifically by a number of stains that include aldehyde fuchsin and orcein. The cirrhotic liver of the HBAg-seropositive patient may show liver-cell dysplasia, a premalignant change.


[Vagal nerve stimulation in children with drug-resistant epilepsy].
To evaluate the clinical efficacy and side effects of vagal nerve stimulation (VNS) in Norwegian children with difficult-to-treat epilepsy. We have performed an open retrospective study of 60 children with pharmaco-resistant epilepsy who had a VNS implantation between October 1996 and May 2003. The effects and side effects of VNS were evaluated on the basis of the medical records and a questionnaire filled in by the patients and/or their relatives. Forty-six patients (77%), 25 females and 21 males, aged 4-16 years at the time of implantation, filled in the questionnaire. All patients had tried > or = 6 antiepileptic drugs prior to the implantation. Five of them had undergone resective epilepsy surgery. After a mean of 2.5 years of follow up, 33 patients (72 %) reported positive effects of VNS. Twenty-nine patients (63%) reported decreased seizure frequency and/or less severe seizures, 20 (43%) achieved > or = 50 % seizure reduction, but only two became seizure free. Sixteen (35%) experienced a shorter and milder postictal phase. In 10 patients (22%) the need of diazepam treatment to terminate seizures was considerably reduced. Twenty-eight of the children (61%) experienced a positive effect of magnet activation. Twenty-three patients (50%) reported minor and waning side effects. Because most of the patients (32) had their antiepileptic medication changed after the implantation, the results should be interpreted with caution. A majority of the patients (72%) reported positive effects on seizure frequency and/or epilepsy-related symptoms. The side effects were modest. Our findings support previous reports about VNS being an effective additional treatment in children with refractory epilepsy.


Psychological causes of autobiographical amnesia: A study of 28 cases.
Autobiographical amnesia is found in patients with focal or diffuse brain damage ("organic amnesia"), but also without overt brain damage (at least when measured with conventional brain imaging methods). This last condition is usually named dissociative amnesia at present, and was originally described as hysteria. Classically and traditionally, dissociative amnesia is seen as a disorder that causes retrograde amnesia in the autobiographical domain in the aftermath of incidents of major psychological stress or trauma. In the present study one of the probably largest published collections of patients (28) with psychogenically caused autobiographical amnesia, who were assessed with comprehensive neuropsychological tests, will be described and documented in order to identify variables which are central for the occurrence of dissociative amnesia. The presented cases demonstrate that autobiographical amnesia without direct brain damage can have very mixed clinical presentations, causes and consequences. The described cases of psychogenic amnesia are clustered according to a number of manifestations and features, which include a reduced effort to perform cognitively at a normal level, a forensic background, anterograde (instead of retrograde) autobiographical amnesia, the fugue condition, concurrent somatic diseases, and their appearance in childhood and youth. It is concluded that autobiographical amnesia of a psychogenic origin may occur within a variety of symptom pictures. For all patients, it probably serves a protective function by offering them a mechanism to exit a life situation which appears to them unmanageable or adverse.


Purification and some kinetic properties of rat liver glucosamine synthetase.
1. Glucosamine synthetase (l-glutamine-d-fructose 6-phosphate aminotransferase, EC 188.8.131.52) was purified about 300-fold from rat liver by two techniques. One procedure utilized the protective action of fructose 6-phosphate and gave a relatively stable preparation, the other yielded an unstable enzyme (half-life of about 20h), free of contaminant activities, on which kinetic experiments were performed. Although the properties of the two preparations showed slight differences, the unstabilized form could be converted into the stabilized form. 2. During preparation the enzyme retained its sensitivity to the feedback inhibitor, UDP-N-acetylglucosamine. 3. The reversibility of the enzyme-catalysed reaction could not be demonstrated. There was no apparent requirement for a cofactor. 4. The pH optimum was at 7.5, at which pH the reaction obeyed a Ping Pong Bi Bi rate equation. At pH values outside the range 6.9-7.6 and at temperatures below 29 degrees C the velocity was described by an ordered Bi Bi rate equation. 5. The molecular weight of the enzyme, determined by two procedures, was 360000-400000. 6. The aminotransferase was unable to utilize ammonia as a substrate.


Feedback control of polyketide metabolism during tylosin production.
Tylosin is produced by Streptomyces fradiae via a combination of polyketide metabolism and synthesis of three deoxyhexose sugars, of which mycaminose is the first to be added to the polyketide aglycone, tylactone (protylonolide). Previously, disruption of the gene (tylMII) encoding attachment of mycaminose to the aglycone unexpectedly abolished accumulation of the latter, raising the possibility of a link between polyketide metabolism and deoxyhexose biosynthesis in S. fradiae. However, at that time, it was not possible to eliminate an alternative explanation, namely, that downstream effects on the expression of other genes, not involved in mycaminose metabolism, might have contributed to this phenomenon. Here, it is shown that disruption of any of the four genes (tylMI--III and tylB) specifically involved in mycaminose biosynthesis elicits a similar response, confirming that production of mycaminosyl-tylactone directly influences polyketide metabolism in S. fradiae. Under similar conditions, when mycaminose biosynthesis was specifically blocked by gene disruption, accumulation of tylactone could be restored by exogenous addition of glycosylated tylosin precursors. Moreover, certain other macrolides, not of the tylosin pathway, were also found to elicit qualitatively similar effects. Comparison of the structures of stimulatory macrolides will facilitate studies of the stimulatory mechanism.


Assessment of quality of life in Saudi patients with vitiligo in a medical school in Qassim province, Saudi Arabia.
To determine the quality of life in Saudi patients with vitiligo and to detect the variables that could influence it by using the Dermatology Life Quality Index (DLQI). One hundred and nine Saudi vitiligo patients were recruited from Qassim Medical College clinics between November 2004 and September 2006. We included 61 males, 48 females with an age range of 18 to 47 years, and a mean of 26.94 (SD +/- 9.73) years. Quality of life was evaluated using DLQI questionnaire and related to variables as age, gender, marital status, and extent of cutaneous involvement. Family history of vitiligo in first degree relatives was positive in 27.5%. The mean DLQI for all cases was 14.72 (SD +/-5.173) that showed no statistical difference between males and females. Patients on light therapy and with generalized vitiligo had significantly higher DLQI scores than patients on topical treatments and localized cutaneous involvement. Women are more embarrassed and self-conscious on the disease with more impairment of their social life, personal relationships, sexual activities, and more influenced in their choice of clothing than men. Vitiligo is associated with severe impairment of quality of life among Saudi patients. Dermatologists should pay careful attention to the psychosocial impact of vitiligo in the patients' life. Involvement of psychologist and even psychiatrist should be an essential part in the management of these cases.


Inclusion of alkyl nitriles by tetra-armed cyclens with styrylmethyl groups.
Synthesis of tetra-armed cyclens (2a-2e), with substituted styrylmethyl groups as side-arms, and their Ag+ complexes is reported. The Ag+ complex with a tetra styrylmethyl-armed cyclen (2a) incorporates alkyl nitriles in a pseudo-cavity formed by the four styrylmethyl side-arms. This prompted us to apply this system to the determination of the absolute configurations of chiral nitriles with low [α]D and low circular dichroism (CD) intensity. In the CD spectra of the 2a/Ag+ complex, (S)- and (R)-G1 did not show a specific Cotton effect, while when chiral nitriles were added to the 2a/Ag+ complex, drastic spectral changes were observed. The (S)-G1@2a/Ag+ system exhibited first a negative and then a positive Cotton effect, whereas the (R)-G1@2a/Ag+ system showed the mirror image of the Cotton effect of (S)-G1@2a/Ag+. We have, therefore, demonstrated a new technique for determining the absolute configurations of weak optical rotation molecules using the Ag+ complex with 2a.


Individual household water supplies as a control measure against Schistosoma mansoni. A study in rural St Lucia.
As part of a programme to evaluate single control measures for reducing the transmission of Schistosoma mansoni, household water supplies were installed in 5 rural settlements in the Riche Fond Valley of St Lucia. About 2 000 persons who previously were dependent on rivers and streams are now receiving safe water at their homes. The systems provide useful design data on individual water requirements in rural areas. This experience suggests that future rural water systems can be designed more economically and efficiently by using consumption rates that are closer to the actual requirements and by eliminating water wastage at the taps.


Comparative genomics of the genus Roseburia reveals divergent biosynthetic pathways that may influence colonic competition among species.
Roseburia species are important denizens of the human gut microbiome that ferment complex polysaccharides to butyrate as a terminal fermentation product, which influences human physiology and serves as an energy source for colonocytes. Previous comparative genomics analyses of the genus Roseburia have examined polysaccharide degradation genes. Here, we characterize the core and pangenomes of the genus Roseburia with respect to central carbon and energy metabolism, as well as biosynthesis of amino acids and B vitamins using orthology-based methods, uncovering significant differences among species in their biosynthetic capacities. Variation in gene content among Roseburia species and strains was most significant for cofactor biosynthesis. Unlike all other species of Roseburia that we analysed, Roseburia inulinivorans strains lacked biosynthetic genes for riboflavin or pantothenate but possessed folate biosynthesis genes. Differences in gene content for B vitamin synthesis were matched with differences in putative salvage and synthesis strategies among species. For example, we observed extended biotin salvage capabilities in R. intestinalis strains, which further suggest that B vitamin acquisition strategies may impact fitness in the gut ecosystem. As differences in the functional potential to synthesize components of biomass (e.g. amino acids, vitamins) can drive interspecies interactions, variation in auxotrophies of the Roseburia spp. genomes may influence in vivo gut ecology. This study serves to advance our understanding of the potential metabolic interactions that influence the ecology of Roseburia spp. and, ultimately, may provide a basis for rational strategies to manipulate the abundances of these species.