Minimal subdermal shaving by means of sclerotherapy using absolute ethanol: a new method for the treatment of axillary osmidrosis.
Axillary osmidrosis is characterized by unpleasant odors originating from the axillary apocrine glands, resulting in psychosocial stress. The main treatment modality is apocrine gland removal. Until now, of the various surgical techniques have sometimes caused serious complications. We describe herein the favorable outcomes of a new method for ablating apocrine glands by minimal subdermal shaving using sclerotherapy with absolute ethanol. A total of 12 patients underwent the procedure. The severity of osmidrosis was evaluated before surgery. Conventional subdermal shaving was performed on one side (control group) and ablation by means of minimal subdermal shaving and absolute ethanol on the other side (study group). Postoperative outcomes were compared between the study and control groups. The length of time to removal of the drain was 1 day shorter in the study group than in the control group. There were no serious complications, such as hematoma or seroma, in either group, but flap margin necrosis and flap desquamation occurred in the control group, and were successfully managed with conservative treatment. Six months after surgery, we and our patients were satisfied with the outcomes. Sclerotherapy using absolute ethanol combined with minimal subdermal shaving may be useful for the treatment of axillary osmidrosis. It can reduce the incidence of seroma and hematoma and allow the skin flap to adhere to its recipient site. It can degrade and ablate the remaining apocrine glands and eliminate causative organisms. Furthermore, since this technique is relatively simple, it takes less time than the conventional method.


A rare giant sarcoma of the chest wall: Undifferentiated pleomorphic sarcoma.
Undifferentiated pleomorphic sarcoma or, as formerly called, malignant fibrous histiocytoma is a type of sarcoma which originates from fibroblast and histiocytic cells. It is the most common type of sarcoma among all soft tissue sarcomas in adults. Its most common site is the lower limb, followed by the upper limb and the retroperitoneum. It is rarely encountered on chest wall. In the differential diagnosis of masses on chest wall, it is important to consider undifferentiated pleomorphic sarcoma in surgical planning. In this article, we report a male case with a giant undifferentiated pleomorphic sarcoma located above the right scapula.


Informal support from black churches and the well-being of elderly blacks.
This paper explores the type of support black churches and families provide, and how that support relates to the well-being of elderly blacks. Findings indicate that the family network is perceived as more supportive than the church network, but that church support contributes to feelings of well-being. Perceptions of support from the churches and not the spiritual aspects of religion or involvement in organized religious activities were associated with well-being.


Care manager/nurse manager: a blending of roles.
Excellent clinicians often are "promoted" to management positions. Lack of involvement in patient care can lead to diminished nurse manager satisfaction, so job enrichment and enhancement must be as important as efficiency and economy as healthcare undergoes reform. A study of 314 patients from 20 DRG categories revealed a statistically significant shortened length of stay and a savings of at least $552 per care-managed patient. Satisfaction was widespread among nurses, patients and physicians and a collaborative spirit developed between nurses and physicians. The blended care manager/nurse manager role alleviates much frustration and conflict and enriches the performance of the manager.


The effect of alpha-trinositol on cholera toxin-induced hypersecretion and morphological changes in pig jejunum.
alpha-Trinositol (D-myo-inositol 1,2,6-trisphosphate, PP56) is a novel antiinflammatory drug. This study elucidates the effect of intravenous alpha-trinositol on basal and acute fluid transport and morphological changes following cholera toxin administration in pig jejunum in vivo. Using isolated jejunal tied-off loops, the fluid hypersecretory (accumulation) effect of different doses of cholera toxin was studied in pigs treated intravenously with saline added different doses (0, 4, 8, 16 and 32 mg x kg-1 x hr-1) of alpha-trinositol. Levels of alpha-trinositol, as well as stereomicroscopical, light microscopical and scanning electron microscopical morphological studies were performed. Cholera toxin evoked a dose-dependent fluid hypersecretion. Treatment with alpha-trinositol caused a dose-dependent inhibition of the cholera toxin-induced fluid hypersecretion and did not affect basal fluid absorption. The 16 mg x kg-1 x hr-1 alpha-trinositol dose gave a maximal inhibition of 36%. Morphological studies showed only minor changes following 6 hr of exposure to 20 micrograms x loop-1 cholera toxin. These changes consisted of dilation of the villus capillaries, an increase of apical membrane blebbing and a reduction of the intercellular space. Treatment with 16 mg x kg-1 x hr-1 alpha-trinositol alone did not induce any morphological changes, and did not alter the morphological changes induced by cholera toxin, which caused fluid hypersecretion and only minor acute morphological changes. In conclusion, alpha-trinositol treatment reduced cholera toxin-induced fluid hypersecretion without altering basal fluid absorption, basal morphology, or cholera toxin-induced morphological changes in pig jejunum in vivo.


Expression and partial characterization of estramustine-binding protein (EMBP) in human breast cancer and malignant melanoma.
The expression of the estramustine/estromustine-binding protein (EMBP) in human mammary cancer and malignant melanoma was examined by immunochemical methods and compared with that in endometrial and ovarian cancers. By RIA measurements, EMBP was detected in 6/17 mammary cancers (range 11.3-2,660 ng/g tissue) and 2/3 malignant melanomas (618 and 1,240 ng/g), whereas endometrial (n = 6) and ovarian (n = 3) cancers exhibited non-detectable levels. In breast cancer, EMBP-expressing tumours were all estrogen receptor-negative, suggesting an inverse correlation between EMBP and hormone responsiveness of the tumour. Biochemical characterization revealed properties of EMBP in mammary tumours and melanomas almost identical to those for EMBP purified from rat ventral prostate: i.e. surface-charge distribution by Mono Q/FPLC ion-exchange chromatography, a molecular weight of 50,000 by gel filtration, and a subunit composition by Western blot analysis under denaturing conditions. Finally, the EMBP immunoreactivity was confined to the cytoplasm of malignant cells in breast cancer and melanoma sections by immunohistochemical examination. This is the first study that demonstrates EMBP in mammary cancer and malignant melanoma. Our findings suggest that a mechanism for selective uptake of cytotoxic estramustine and estromustine is prevailing in these malignancies and that monitoring of EMBP in biopsy samples will be of value in defining patients who may benefit from Estracyt treatment.


RELATIONSHIP BETWEEN ORAL SQUAMOUS CELL CARCINOMA AND IMPLANTS (REVIEW).
In this review, we have discussed the relationships between oral squamous cell carcinoma (OSCC) and dental implants. In the last decade, dental implants have been widely used for the treatment of complete or partial edentulism. Despite the fact that they have seen incredible success and the use of dental implants increases, concerns over safety and efficiency is rising as well. The literature analysis has shown that the number of reported cases when the OSCC development is associated with peri implantitis is gradually increasing. The possibility of squamous cell carcinoma development must be considered when evaluating the peri-implantitis. We highly recommend periodic oral and radiographic examination after the implant placement. The patients with peri-implantitis that do not respond to conventional treatment methods, and the patients who have a severe or rapid progression of peri-implantitis require biopsy. The histopathological examination will aid with the differential diagnosis between peri-implantitis and OSCC, and hence, provide the correct diagnosis.


Difference in requirement of macrophage products for concanavalin A-induced production of eosinophil chemotactic factor and macrophage chemotactic factor from guinea pig lymphocytes in vitro.
Differences between the conditions for an eosinophil chemotactic factor (ECF) and macrophage chemotactic factor (MCF) production by lymphoid cells of mesenteric lymph nodes and spleen were studied in guinea pigs. If lymphoid cells were washed less than 4 hr after concanavalin A (Con A) stimulation and were cultured for an additional 24 hr, they failed to produce ECF, whereas Con A stimulation for 1 hr before washing was sufficient to stimulate them to produce MCF. Subsequently, it was shown that heat-labile soluble factors (termed ECF-PF) with potentiating activity for ECF production are produced from macrophages by 5 micrograms/ml Con A activation. When ECF-PF were added to the cell culture with 5 micrograms/ml Con A, the lymphoid cells could produce ECF even when they were washed 2 hr after Con A stimulation and were cultured for an additional 24 hr, suggesting that ECF-PF plays a critical role in the early stage of ECF production. The lymphoid cells were also able to produce ECF even when they were cultured with ECF-PF and a suboptimal dose of Con A (1 microgram/ml) for ECF production. Protein synthesis seemed to be essential for ECF-PF production. The ECF-PF activity was associated with two separated molecular fractions with m.w. of about 50,000 to 70,000 and of 10,000 to 20,000. It is thus suggested that ECF is produced from T cells by Con A stimulation under conditions which differ, at least, from those for MCF in the requirement of ECF-PF.


[Treatment of neglected and abused children and their families in the context of complicated divorce].
Coceptualisation of complicated divorce, as an escalation of systemic dysfunctioning in a highly disturbed and unbalanced system, acquires attributes of trauma-organised-system, and yields itself for therapeutic interventions. The authors comment on their experience while treating families sent by Court order in divorce custody disputes, with explicit aim of evaluating parental competence. This type of systemic dysfunction is severely affecting communication styles, family rules and norms, whereas parenting is frequently marked by tendency to repeat relational-style experienced in marital, partners' conflicts. Feelings of discontent and resentment are projected onto children, and may take form of disqualifications, rejection, discrimination or else, those feelings stemming out of personal ambition such as favoring children. Parental rivalry worsens these processes, leading to attempts of establishing inappropriate level of control over children (instrumentalisation or favorisation). Therefore, care and protection of children is inadequate and children are emotionally neglected Many of these highly disturbed families, especially those sent by Court order are engaged in a network of different social, legal and mental health institutions. Intervention plans are thus conceived and specifically tailored to suit individual families, confronting dysfunctional patterns and appealing to enhance parental responsibilities. Overcoming family crisis of complicated divorce where childresn's emotional needs are neglected is highly indicated for systemic intervening. The authors discuss their experience in treating such families and offer their questions, dilemmas and recommendations.


A miniature effusion cell for the vacuum deposition of organic solids with low vapor pressures in surface science studies.
A miniature effusion cell for the vacuum deposition of volatile organic solids with low vapor pressures has been fabricated and used in surface science studies. The effusion cell is designed to operate at up to 200 degrees C under ultrahigh vacuum (UHV) conditions. The size of this cell is so small that it is attached to the top of a transfer rod and can be introduced from a subchamber into a main UHV chamber (retrievable). In addition, the small heat capacity of this cell means rapid heating and cooling rates. The advantages of this evaporator are its simplicity of design and ease of fabrication, assembly, and operation.


Evolutionarily conserved function of a viral microRNA.
MicroRNAs (miRNAs) are potent RNA regulators of gene expression. Some viruses encode miRNAs, most of unknown function. The majority of viral miRNAs are not conserved, and whether any have conserved functions remains unclear. Here, we report that two human polyomaviruses associated with serious disease in immunocompromised individuals, JC virus and BK virus, encode miRNAs with the same function as that of the monkey polyomavirus simian virus 40 miRNAs. These miRNAs are expressed late during infection to autoregulate early gene expression. We show that the miRNAs generated from both arms of the pre-miRNA hairpin are active at directing the cleavage of the early mRNAs. This finding suggests that despite multiple differences in the miRNA seed regions, the primary target (the early mRNAs) and function (the downregulation of early gene expression) are evolutionarily conserved among the primate polyomavirus-encoded miRNAs. Furthermore, we show that these miRNAs are expressed in individuals diagnosed with polyomavirus-associated disease, suggesting their potential as targets for therapeutic intervention.


[Clinical and genetic analysis for activated PI3K-δ syndrome by PIK3CD gene mutation].
To analyze clinical and genetic features of activated PI3K-δ syndrome (APDS), a new form of immunodeficiency disease caused by PIK3CD gene mutation. Data of two patients diagnosed as APDS at Second Department of Respiratory Medicine of Beijing Children's Hospital Affiliated to Capital Medical University in 2015 were retrospectively reviewed. Pathogenetic genes were screened by whole exome sequencing, and identified by first generation sequencing. The identified pathogenetic genes were further verified in patients' parents. Then the gene sequencing results were analyzed. Both patients were females, aged 2 years and 4 months and 5 years respectively. The main clinical features of both cases were recurrent respiratory infections, enlargement of lymph node, hepatosplenomegaly, cytomegalovirus (CMV) or Epstein-Barr virus (EBV) viremia, decreased number of native CD4(+) T cell, inverted CD4(+) /CD8(+) T cell ratio and increased IgM. Patient 1 has decreased IgA and IgG. Patient 2 showed wide follicular hyperplasia of the airway mucosa. Both patients had de novo mutation in c. 3061G>A(E1021K)of PIK3CD gene, which was homozygous in patient 1 and heterozygous in patient 2. Both were treated with 500 mg/kg dose of gamma globulin intravenously at 4-weeks interval. Patient 1 started oral rapamycin therapy at the dose of 1 mg/(m(2)·d) and discontinued the treatment after 2 weeks. Patient 2 was given low dose of oral prednisone. The two patients were followed up for 2 months. The number of respiratory infection in both patients was decreased. Hepatosplenomegaly was subsided, while respiratory tract damage was not improved in patient 2. The clinical manifestations of APDS include recurrent respiratory tract infection, enlargement of lymph nodes, hepatosplenomegaly, and CMV or EBV infection. The immunophenotype is decreased native CD4(+) T cell, inverted CD4(+) /CD8(+) T cell ratio, increased IgM and decreased IgA/IgG for some patients. c. 3061G>A(E1021K)of PIK3CD gene is a common de novo mutation in APDS patients.


A QM/MM-based computational investigation on the catalytic mechanism of saccharopine reductase.
Saccharopine reductase from Magnaporthe grisea, an NADPH-containing enzyme in the α-aminoadipate pathway, catalyses the formation of saccharopine, a precursor to L-lysine, from the substrates glutamate and α-aminoadipate-δ-semialdehyde. Its catalytic mechanism has been investigated using quantum mechanics/molecular mechanics (QM/MM) ONIOM-based approaches. In particular, the overall catalytic pathway has been elucidated and the effects of electron correlation and the anisotropic polar protein environment have been examined via the use of the ONIOM(HF/6-31G(d):AMBER94) and ONIOM(MP2/6-31G(d)//HF/6-31G(d):AMBER94) methods within the mechanical embedding formulism and ONIOM(MP2/6-31G(d)//HF/6-31G(d):AMBER94) and ONIOM(MP2/6-311G(d,p)//HF/6-31G(d):AMBER94) within the electronic embedding formulism. The results of the present study suggest that saccharopine reductase utilises a substrate-assisted catalytic pathway in which acid/base groups within the cosubstrates themselves facilitate the mechanistically required proton transfers. Thus, the enzyme appears to act most likely by binding the three required reactant molecules glutamate, α-aminoadipate-δ-semialdehyde and NADPH in a manner and polar environment conducive to reaction.


Enhanced thermoelectric properties of selenium-deficient layered TiSe(2-x): a charge-density-wave material.
In the present work, we report on the investigation of low-temperature (300-5 K) thermoelectric properties of hot-pressed TiSe2, a charge-density-wave (CDW) material. We demonstrate that, with increasing hot-pressing temperature, the density of TiSe2 increases and becomes nonstoichiometric owing to the loss of selenium. X-ray diffraction, scanning electron microscopy, and transimission electron microscopy results show that the material consists of a layered microstructure with several defects. Increasing the hot-press temperature in nonstoichiometric TiSe2 leads to a reduction of the resistivity and enhancement of the Seebeck coefficient in concomitent with suppression of CDW. Samples hot-pressed at 850 °C exhibited a minimum thermal conductivity (κ) of 1.5 W/m·K at 300 K that, in turn, resulted in a figure-of-merit (ZT) value of 0.14. This value is higher by 6 orders of magnitude compared to 1.49 × 10(-7) obtained for cold-pressed samples annealed at 850 °C. The enhancement of ZT in hot-pressed samples is attributed to (i) a reduced thermal conductivity owing to enhanced phonon scattering and (ii) improved power factor (α(2)σ).


The susceptibility of weathered versus unweathered schist to biological colonization in the Côa Valley Archaeological Park (north-east Portugal).
This study addresses the primary and secondary bioreceptivity of schist used as a support for prehistoric rock art in the Côa Valley Archaeological Park (north-east Portugal) and provides some parameters that can be related to the risk of biologically induced schist weathering. Samples of freshly quarried and naturally weathered schist were characterized in terms of their intrinsic properties and maintained in controlled environmental conditions after inoculation with biofilm-forming cyanobacteria. The physical properties of the studied schist, as well as its abrasion pH, all varied according to the weathering degree of the samples and so did its susceptibility to colonization by biofilm-forming cyanobacteria. Complete separation between weathered and unweathered schist samples in terms of laboratory-induced photosynthetic biomass was obtained by measuring total colour change in the CIE (International Commission on Illumination) L*a*b* colour space. Weathered schist was more bioreceptive than unweathered schist, associated with increased open porosity, water saturation, capillary water and capillarity coefficient and decreased abrasion pH. In the future, it might be possible to determine the susceptibility of schist surfaces to biological colonization through evaluation of colour differences associated with the different weathering degrees presented by those surfaces prior to colonization.


Apheresis medicine state of the art in 2010: American Society for Apheresis fifth special edition of the Journal of Clinical Apheresis.
The quality of evidence supporting the use of apheresis in the treatment of individual diseases and disorders is often limited. For most diseases and disorders, randomized controlled trials of the use of apheresis have not been performed and for many, due to rarity of the condition, it is unlikely that they will ever be performed. In keeping with its vision, the American Society for Apheresis (ASFA) has created and regularly updated guidelines on the use of apheresis in the treatment of disease. These guidelines seek to summarize the literature on the use of apheresis in treating diseases, provide a critical review of this literature, and give practical guidance to apheresis practitioners. The most recent ASFA guidelines were published in 2010. This article reviews the history of the ASFA guidelines, the changes that were made in the 2010 guidelines, and future directions and plans for these guidelines. The 2010 ASFA guidelines on the use of therapeutic apheresis in clinical practice represent the state of the art in apheresis medicine in 2010.


Possible Cerebral Vasculitis in a Case with Rheumatoid Arthritis.
Cerebral rheumatoid vasculitis (CRV) is a rare, fatal, and diagnostically challenging disorder. We herein report an 81-year-old woman with a 4-year history of rheumatoid arthritis who presented with a fever, progressive disturbance of consciousness, high level of rheumatoid factor, and hypocomplementemia. The enhancement of the perforating branches in the left middle cerebral artery led us to suspect CRV. A brain biopsy could not be performed. After we intensified steroid therapy, the size of the cerebral lesions temporarily decreased. However, recurrence in the left frontal lobe occurred one month later, and the patient subsequently died. Early intensive treatments may be needed for CRV.


Solution conformation of a neuronal nicotinic acetylcholine receptor antagonist alpha-conotoxin OmIA that discriminates alpha3 vs. alpha6 nAChR subtypes.
alpha-Conotoxin OmIA from Conus omaria is the only alpha-conotoxin that shows a approximately 20-fold higher affinity to the alpha3beta2 over the alpha6beta2 subtype of nicotinic acetylcholine receptor. We have determined a three-dimensional structure of alpha-conotoxin OmIA by nuclear magnetic resonance spectroscopy. alpha-Conotoxin OmIA has an "omega-shaped" overall topology with His(5)-Asn(12) forming an alpha-helix. Structural features of alpha-conotoxin OmIA responsible for its selectivity are suggested by comparing its surface characteristics with other functionally related alpha4/7 subfamily conotoxins. Reduced size of the hydrophilic area in alpha-conotoxin OmIA seems to be associated with the reduced affinity towards the alpha6beta2 nAChR subtype.


Prevalence of diabetic retinopathy in Peruvian patients with type 2 diabetes: results of a hospital-based retinal telescreening program.
To estimate the prevalence of diabetic retinopathy (DR) in patients with type 2 diabetes and to determine any association with clinical factors. This hospital-based screening project was designed to prospectively detect the presence of DR in patients with type 2 diabetes by grading images acquired with a digital retinal camera. Of 1 311 patients screened, appropriate retinal images were obtained in 1 222 subjects (93.2%). DR was detected in 282 patients (23.1%) [95% confidence interval (CI): 20.71-25.44]; 249 patients (20.4%) (95% CI: 18.1-22.6) had nonproliferative DR and 33 (2.7%) (95% CI: 1.8-3.6) had proliferative DR. In 32 patients (11.3%), DR was unilateral. The frequency of DR was the same in both sexes. Prevalence of blindness was twice as frequent in patients with DR as in those without it (9.4% and 4.6%, respectively) (P = 0.001). The frequency of DR at diagnosis was 3.5% and it increased with the duration of diabetes. DR was more frequent in patients with arterial hypertension, macrovascular or microvascular complications, and hemoglobin A1c (HbA1c) > 7.0% and in those treated with insulin or sulfonylureas. It was less prevalent in those with HbA1c < 7.0%, with greater body mass index, and who had been treated with metformin. The prevalence of DR in these patients with type 2 diabetes was 23.1%. Nonproliferative retinopathy accounted for 77.0% of cases. Although less prevalent than in a previous report, it doubled the frequency of blindness in the people affected. A national screening DR program should be considered in order to detect this prevalent condition early and treat it in a timely fashion.


Acto-myosin based response to stiffness and rigidity sensing.
Cells sense the rigidity of their environment and respond to it. Most studies have been focused on the role of adhesion complexes in rigidity sensing. In particular, it has been clearly shown that proteins of the adhesion complexes were stretch-sensitive, and could thus trigger mechano-chemical signaling in response to applied forces. In order to understand how this local mechano-sensitivity could be coordinated at the cell scale, we have recently carried out single cell traction force measurements on springs of varying stiffness. We found that contractility at the cell scale (force, speed of contraction, mechanical power) was indeed adapted to external stiffness, and reflected ATPase activity of non-muscle myosin II and acto-myosin response to load. Here we suggest a scenario of rigidity sensing where local adhesions sensitivity to force could be coordinated by adaptation of the acto-myosin dependent cortical tension at the global cell scale. Such a scenario could explain how spreading and migration are oriented by the rigidity of the cell environment.


Cocktail-substrate approach-based high-throughput assay for evaluation of direct and time-dependent inhibition of multiple cytochrome P450 isoforms.
Avoiding drug-drug interactions (DDIs) mediated through inhibition of cytochrome P450 (CYP) activity is highly desirable. Direct inhibition (DI) of CYP through new chemical entities (NCEs) or time-dependent inhibition (TDI) through reactive metabolites should be elucidated at an early stage of drug discovery research. In particular, TDI of CYP occurring through reactive metabolites may be irreversible and even sustained, causing far more serious DDIs for TDIs than for DIs. Furthermore, it is important to ascertain whether an NCE inhibits multiple CYP isoforms. Hence, using a cocktail-substrate approach that we previously established (in which the activity of 8 CYP isoforms is simultaneously evaluated in a single run), we evaluated the IC50 values of direct inhibitors and TDI parameters (kobs, shifted IC50, KI and kinact) of time-dependent inhibitors that affect multiple CYP isoforms. The IC50 values for 8 CYP isoforms obtained using the cocktail-substrate approach were nearly identical to values previously reported. The TDI parameters for CYP1A2, 2C9, 2C19, 2D6, and CYP3A4/5 obtained using the cocktail-substrate approach were also nearly identical to those obtained using a single-substrate approach. Thus, the cocktail-substrate approach is useful for evaluating DI and TDI in the early stages of drug discovery and development processes.


Outcome of renal allograft in patients with Henoch-Schönlein nephritis: single-center experience and systematic review.
Henoch-Schönlein nephritis (HSN) is a rare condition resulting in end-stage renal disease. Therefore, graft outcomes and recurrence rates after transplantation are not well studied. Also, the effect of donor type on graft outcome has not been evaluated thoroughly. The graft outcome and recurrence rate in 20 kidney recipients with HSN were compared with age-, sex-, and donor source-matched controls (control A, primary immunoglobulin A nephropathy; control B, other causes; 40 recipients per group). To assess the effect of donor type, we pooled our data with two previous cohort studies where donor type had been described in detail. Overall graft survival rates were 87.7% at 10 years. The overall recurrence rate of HSN was 15.4% over 10 years. Graft survival and recurrence rates in the HSN group were similar to those of control A and control B. The pooled data showed a 29.4% incidence rate for recurrent HSN. Living related donor transplantation showed a trend of higher recurrence compared with recipients with nonrelated grafts, although it was marginally significant (P=0.059). However, the graft survival rate in related-donor recipients was not inferior to that in the unrelated-donor recipients. Long-term graft survival and recurrence rates in kidney recipients with HSN were comparable to those of recipients with primary immunoglobulin A nephropathy. The type of donor did not significantly affect long-term graft survival.


The ProHance story: the making of a novel MRI contrast agent.
The four gadolinium chelates currently in clinical use as magnetic resonance imaging (MRI) contrast agents differ in two structural features: linear vs. macrocyclic cores, and ionic vs. nonionic charge types. While all are equivalent in relaxation effectiveness, the nonionic molecules have lower osmolality and viscosity and may be formulated safely at greater concentrations, and delivered confidently at greater doses and as a faster bolus. The macrocyclic molecules are more stable and show less tendency to dissociate free Gd. ProHance was conceived well over a decade ago, based upon a unique structure. It was first marketed in the USA in 1992, and was the first nonionic agent. It remains today still the only commercial MRI agent that is both macrocyclic and nonionic. To date it has been used safely in over a million patients.


Lipopolysaccharide Composition of the Wilt Pathogen, Pseudomonas solanacearum: CORRELATION WITH THE HYPERSENSITIVE RESPONSE IN TOBACCO.
In the induction of the hypersensitive response (HR) in tobacco by Pseudomonas solanacearum, the recognition between host and pathogen is thought to involve an interaction between plant lectins and bacterial lipopolysaccharide (LPS). The LPS of a series of strains of P. solanacearum were examined to determine if there are structural differences that might account for the ability or inability of these strains to induce the hypersensitive response. Analysis of the components of LPS by gas chromatography indicates a clear difference in sugar composition between the HR-inducing and non-HR-inducing strains, especially in terms of the percentage of glucose, xylose and rhamnose. Sodium dodecyl sulfate polyacrylamide gel electrophoresis shows there are two distinct kinds of LPS, differing greatly in size, which correspond to rough and smooth LPS in other systems. In addition, a phage, CH154, was isolated which lyses non-HR-inducing bacteria and which is inactivated by LPS from these bacterial strains. Therefore, differences in LPS structure correlate strongly with host recognition of Pseudomonas solanacearum.


[Health policy and social epidemiology].
Major approaches of Social epidemiology; 1) holistic, ecological approach, 2) population based approach, 3) development and life-course approach, 4) contextual multi-level approach, have stressed the importance of not only social context of health and illness, but also the population based strategy in the health interventions. Ultimately, it provides the conceptual guidelines and methodological tools to lead toward the healthy public policies; integrated efforts to improve condition which people live: secure, safe, adequate, and sustainable livelihoods, lifestyles, and environments, including housing, education, nutrition, information exchange, child care, transportation, and necessary community and personal social and health services.


Ultrastructural traits of apoptosis.
This review summarizes original and literature data on changes in the ultrastructure of major cell organelles during apoptosis obtained by transmission electron microscopy. Organelles that make the most crucial contribution to the initiation of apoptosis: plasma membrane, mitochondria, proteasomes, Golgi apparatus, and endoplasmic reticulum, were of our prime attention. The nucleus and cytoskeleton that undergo essential changes, were considered as well. Special attention was paid to the data on ultrastructural changes in the cell organelles observed recently by electron microscopic tomography and correlative microscopy, in particular, to remodeling of mitochondrial crista junctions and microtubules during the execution phase of apoptosis.


Simplified detection of hydrochlorothiazide in urine by thin-layer chromatography.
A new thin-layer chromatographic procedure for the detection of the antihypertensive/diuretic drug hydrochlorothiazide in human urine is described. The sensitivity of the method, 5 micrograms/mL, makes it useful to both the clinician interested in determining patient compliance and the toxicologist who must identify or confirm hydrochlorothiazide ingestion. The rapidity of analysis typically allows the screening of 25 urine samples within one hour.


Drug interaction between simvastatin and itraconazole in male and female rats.
Taking into account the species and sex differences in drug interactions based on the inhibition of cytochrome P450 (P450)-mediated drug metabolism, we examined whether the interaction between simvastatin and itraconazole observed in humans could also occur in rats, the most commonly used animal species for pharmacokinetic studies. Itraconazole inhibited the in vitro metabolism of simvastatin in female rat liver microsomes, but not in male rat liver microsomes. Using anti-P450 antisera, the main P450 isozyme responsible for the metabolism of simvastatin was identified as CYP3A in female rats and CYP2C11 in male rats. Therefore, the sex difference in the inhibition of simvastatin metabolism by itraconazole seems to be caused by a difference in the P450 isozymes responsible for the metabolism of simvastatin in male and female rats and the different ability of itraconazole to inhibit CYP3A and CYP2C11. In addition, the effect of itraconazole on the pharmacokinetics of simvastatin in rats was also investigated. The area under the curve value of simvastatin was increased approximately 1.6-fold by the concomitant use of itraconazole (50 mg/kg) in female rats, whereas in male rats, itraconazole had no effect. In conclusion, it was found that the results obtained in male rats did not reflect the results in humans as far as the inhibition of simvastatin metabolism by itraconazole was concerned. The P450 isozymes involved in the metabolism of drugs should be taken into consideration when rats are used as a model animal for humans in the investigation of drug interactions.


[Broad use of laparoscopic cholecystectomy in the teaching clinic. Experiences and results of 300 operations].
Laparoscopic cholecystectomy (LC) was integrated early in surgical training according to the concept "observe, assist and then operate under the assistance of an experienced surgeon". 300 LC's were performed by 27 different surgeons (8 board certified surgeons, 19 residents in the year 2-6 of training). 60.3% of all LC's and 73% of LC's performed for acute cholecystitis were done by residents. Our results including an overall complication rate of 5.3% shows, that LC can be performed by residents without additional complications or unacceptable length of operations, provided the threshold for conversion is low and the surgeon is assisted by an experienced laparoscopist. We therefore suggest that the early integration of LC in surgical training is justified.


Eosinophilic gastritis; an unusual and overlooked cause of chronic abdominal pain.
Eosinophilic gastritis is an extremely rare disorder. The disease is associated with eosinophilic infiltration of various layers of gastrointestinal tract along with significant peripheral eosinophilia and increased Immunoglobulin E (IgE). We report a case of 37 year old Saudi male who presented with chronic non-specific upper abdominal pain. On initial workup, the diagnosis was missed. However the diagnosis was established after subsequent work up in Gastroenterology clinic. Our case demonstrates that patients with uncharacteristic abdominal pain who are unresponsive to conventional treatment, rare illnesses like eosinophilic gastritis should be considered. We also aim to review the clinicopathological features, differential diagnosis and various treatment options of this disorder. To the best of our knowledge, this disease has not been previously reported from Saudi Arabia.


Evaluation of Meibomian Gland Dysfunction and Local Distribution of Meibomian Gland Atrophy by Non-contact Infrared Meibography.
The main purpose of this study was to investigate the relationship between Meibomian gland atrophy (meiboscore) and Meibomian gland expressibility. In addition, the local distribution of Meibomian gland loss was analyzed. A retrospective analysis of 128 patients (92 women and 36 men, 57 ± 17 years) from our dry eye clinic was performed. Infrared meibography was performed using the Keratograph 5 M (Oculus, Wetzlar, Germany) and evaluated with a scoring system introduced by Arita et al. A significant inverse correlation between Meibomian gland atrophy measured by meibography and expressible Meibomian glands (r = -0.197, p = 0.003) as well as between meiboscore and TBUT (r = -0.1615, p = 0.012) was found. There also was a significant correlation between the total meiboscore and the age (r = 0.33, p < 0.0001). We could find a strong and highly significant correlation between the total meiboscore and the individual meiboscore of the upper eyelid (r = 0.905, p < 0.0001) and the lower eyelid (r = 0.892, p < 0.0001). There was no significant difference of Meibomian gland atrophy between the individual thirds of the upper eyelid, but for the lower eyelid, we could find a higher degree of Meibomian gland atrophy in the nasal third compared with the middle and the temporal third (Dunn's post hoc test, p < 0.0001). Meibomian gland atrophy seems to be not constant over the tarsal plate but the examination of the lower tarsus might be sufficient in most of the cases. The correlation of the meiboscore with functional dry eye parameters suggest that in patients with detectable Meibomian gland atrophy there is also an impaired Meibomian gland function. However, meibography seems not to be sufficient as a single test for the diagnosis of MGD. For the future larger, prospective studies are needed to confirm these results and further evaluate the potential of meibography in the diagnosis of MGD.


Co-occurrence of AIDS and tuberculosis: results of a database "match" and investigation.
To conduct a match between the AIDS and Tuberculosis (TB) Registries in Philadelphia. Database extracts for the year 1993 were prepared manually and matched by name, birth date, and social security number. Reported cases not matching with those on the primary registry were investigated. Proportion levels of comorbidity were calculated. Predictors of comorbidity were evaluated separately for the TB sample and for the AIDS sample. The proportion of comorbid patients with AIDS alive at midyear was 4.7%; 17.1% of TB cases were also HIV-positive. Twenty-three percent of AIDS cases were falsely reported as having active TB; the false-positive rate in TB Control for HIV seropositivity was 4.2%. Having public or no health insurance, injection drug use (IDU) or heterosexual risk background (HET), and being nonwhite and female were significant predictors of active TB in persons with AIDS. A registries' data match can provide useful information and result in improved validity for both registries. Although women with AIDS initially appeared to have a higher risk of having active TB, additional parallel analyses suggested that this effect was primarily the result of the 1993 expansion of the definition of AIDS.


Central line associated bloodstream infection caused by Kodamaea ohmeri in a young child.
Kodamaea ohmeri, a yeast frequently mistaken for Candida, has emerged in recent years as an opportunistic fungal pathogen, showing a predilection towards patients with immunosuppression, or those with long-term central venous access. This report describes a central line associated bloodstream infection (CLABSI) due to K. ohmeri, in a young child, which was successfully treated. The patient is a 5-year-old male with a history of short gut syndrome, and total parenteral nutrition (TPN) dependence who presented to the emergency room with a two-day history of productive-cough, rhinorrhea, and fever. Antibiotic therapy was initiated with cefepime and vancomycin for suspected CLABSI. However, within the first twenty-four hours of his admission, his initial blood culture from his central venous catheter became positive for yeast so fluconazole was added due to suspicion of candidemia. During his admission, his initial central line and peripheral blood culture were later speciated as Kodamaea ohmeri, with susceptibilities to fluconazole (MIC: 4 μg/mL) and micafungin (MIC: 0.125 μg/mL). After evaluating the susceptibilities, he was transitioned to micafungin. This case report further acknowledges that while rare, K. ohmeri is an emerging pathogen that has the potential to be life threatening if not accurately identified and treated with the optimal, empiric antifungal therapy. Due to potentially high mortality and antifungal resistance, this yeast species should be on the differential in patients that present with a central venous catheter and/or other underlying risk factors. Favorable outcomes can be achieved by removing indwelling catheters and administering optimal antifungal therapy.


Neuropsychiatric effects of guanfacine in children with mild tourette syndrome: a pilot study.
The objective of this study was to evaluate the neuropsychiatric effects of the alpha-2a adrenergic agonist guanfacine in children with Tourette syndrome (TS). Twenty-four children with TS participated in a 4-week, double-blind, placebo-controlled study of guanfacine. Tic severity, neuropsychologic functioning, and parent ratings of behavior were evaluated pre- and post-treatment. The sample had mild tic severity and subtle neuropsychologic dysfunction pretreatment. Post-treatment, patients receiving guanfacine were rated by parents as significantly improved (compared to placebo) on one measure of executive function (parent-rated metacognition). Improvement on tic severity, performance-based neuropsychologic measures, and all other parent ratings were not significantly better than placebo. At a moderate dose and short-term treatment duration, guanfacine did not provide significant neuropsychiatric benefits in this group of children with mild TS.


Adoption of azygos, hemiazygos, and dartos.
Exceptions to the anatomical nomenclature rule that names must be in proper Latin include a few terms that contain borrowed Greek adjectives that are not declined like Latin words. Adoption of these adjectives into Latin would change about a half-dozen terms, e.g., vena azyga, vena hemiazyga, and fascia darta. The anatomical nomenclature rules apply only to the Latin terms, so there is no requirement to alter the way azygos, hemiazygos, and dartos are used in equivalent terms in other languages. Clin. Anat. 30:450-451, 2017. © 2017 Wiley Periodicals, Inc.


[Knowledge of patients from the rural environment on the risk factors and prevention of cardiovascular diseases].
Cardiovascular diseases (CVDs) are the leading cause of death in Poland. The aim of the study was to assess the knowledge of patients from the rural environment on the risk factors and prevention CVDs. In the period from January to February 2006. one hundred and twenty patients [69 (57.5%) females and 51 (42.5%) males] from Primary Care Practice in Zabłudow living in rural areas in the vicinity of Białystok were interviewed using questionnaires developed by the authors of the work. It contained questions on demographic data (gender, age, education and residence), health status and level of knowledge about risk factors and prevention CVDs. The vast majority of patients had a thorough understanding of risk factors CVDs. The least known factor is diabetes--just as the second test (55.8%) believe that it contributes to the formation of CVDs. As prophylaxis 77.5% of respondents reported a diet low in salt, and 75%--regular physical activity. Advancing our knowledge about the disease as an existing preventive recognized 70.8% of respondents. Comparing knowledge of patients with the knowledge of healthy CVDs participating in the survey stated that they know more about risk factors and prevention CVDs than the differences are statistically significant (p < 0.05). Better educated person knows more about risk factors and prevention of CVDs than the less educated people. These differences were statistically significant (p < 0.05). Examined patients living in rural areas have a wide knowledge on risk factors and prevention CVDs. This applies especially to people with higher education or with known cardiovascular diseases. People with lower education require more attention and education. Emphasis should be given to promoting information on the impact of diabetes on the development of CVDs.


Activation of dendritic cells: translating innate into adaptive immunity.
Innate recognition of infection in vertebrates can lead to the induction of adaptive immune responses through activation of dendritic cells (DCs). DCs are activated directly by conserved pathogen molecules and indirectly by inflammatory mediators produced by other cell types that recognise such molecules. In addition, it is likely that DCs are activated by poorly characterised cellular stress molecules and by disturbances in the internal milieu. The multiplicity of innate pathways for DC activation may have evolved to ensure that any signs of infection are detected early, before overwhelming pathogen replication. Understanding which of these signs are both necessary and sufficient to convert DCs into the immunostimulatory antigen-presenting cells that prime appropriate effector T cells may hold the key to improved strategies for vaccination and immunotherapy.


In vivo effects of microinjected alkaline phosphatase and its low molecular weight substrates on the first meiotic cell division in Xenopus laevis oocytes.
Xenopus laevis oocytes were microinjected with low molecular weight phosphoesters such as 2-glycerophosphate, phosphotyrosine, phosphoserine, phosphothreonine, 4-nitrophenyl phosphate, and orthophosphate. These compounds were able to induce a considerable reduction in the time course of progesterone-induced maturation, with 2-glycerophosphate being the most effective. The basal level of cAMP and its drop during maturation were not affected by the microinjection of 2-glycerophosphate. The injection of alkaline phosphatase (EC 18.104.22.168.) from calf intestine at a low concentration (10 ng per oocyte) was able to decrease or abolish the effect of 2-glycerophosphate. At higher concentration (25 ng per oocyte) this enzyme totally blocked progesterone- or maturation-promoting factor-induced maturation. Alkaline phosphatase might behave in vivo as a phosphoprotein phosphatase active towards phosphotyrosine-containing proteins. In addition, our results indicate that phosphate or phosphoester-containing buffers should be avoided in the course of maturation-promoting factor purification.


Chronic psychosocial stress exposes Alzheimer's disease phenotype in a novel at-risk model.
Because of the extensive individual variations in the time of onset and severity of the prevalent sporadic form of Alzheimer's disease (AD), a patient-related external factor must be assumed to play a significant role in the development of the disease. Since stress is increasingly recognized as an external factor in the development of AD, a number of labs, including this lab, have shown that chronic stress or corticosterone administration worsens the AD phenotype in both transgenic and non-transgenic models of the disease. Recently we develop a novel at-risk model that correlates with seemingly normal individuals who are predisposed to develop AD. This review is a summarized recount of the findings we have reported on the effect of chronic psychosocial stress in this at-risk model of AD. Behavioral (learning and memory tests), electrophysiological and molecular findings indicated that even mild chronic psychosocial stress clearly transforms this seemingly normal rat model to a full-fledge AD phenotype.


The association of CD18 alleles with anti-myeloperoxidase subtypes of ANCA-associated systemic vasculitides.
Wegener granulomatosis (WG), microscopic polyangiitis (MP), and Churg Strauss syndrome (CSS) are rare systemic autoimmune disorders. Common features are anti-neutrophil cytoplasmic antibodies (ANCA) in patient sera. Whereas WG patients show mainly anti-proteinase 3 ANCA, MP and CSS patients typically present anti-myeloperoxidase (MPO) ANCA. ANCA play an important role in the pathogenesis in the vessel wall by activating polymorphonuclear cells (PMN) and increased adhesivity between PMN and endothelial cells via adhesion molecules. Here we investigated major adhesion molecules as predisposition factors via common polymorphisms in or in the vicinity of the candidate genes ICAM-1, e-selectin, PLAUR, CD11b, and CD18. A restriction fragment-length polymorphism in exon 11 of the CD18 gene was associated with MPO-ANCA(+) systemic vasculitis. Our data indicate that a common variant of the CD18 gene confers increased risk for CSS and MP, supporting that genetic factors are involved in the etiology and pathogenesis of ANCA-associated systemic vasculitides.


Experimental results using nafamostat mesilate as anticoagulant during extracorporeal lung assist for 24 hours in dogs.
We report on the experimental application of nafamostat mesilate (NM, 6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulfonate, FUT), a new anticoagulant, to extracorporeal lung assist (ECLA) with an artificial membrane lung. Venovenous ECLA, from the jugular vein to the femoral vein, was performed with a hollow-fiber membrane lung at a blood flow rate of approximate 82 ml kg-1 min-1 for 24 h in 7 dogs under anesthesia and hypoventilation. Heparin (10 U ml-1 in a priming lactated Ringer solution of 140 ml, and 200 U kg-1) was administered before blood access cannulation. After start of ECLA, however, no heparin was used, and nafamostat mesilate was continuously infused into the drainage line of the bypass circuit to control activated coagulation time (ACT) at about 150 to 200 s. To maintain the prolonged ACT, 8.0 +/- 1.7 mg kg-1 h-1 of NM was required. Arterial blood pressure and pulse rate decreased significantly. Though fibrin monomer test revealed hypercoagulability after 6 h of ECLA, platelet counts did not significantly decrease. Total blood loss remained less than 40 g. The artificial membrane lung sustained a good gas exchange and low flow resistance throughout ECLA. Macroscopic examination revealed small spotty thrombi in the artificial lung but no major pathologic changes of the visceral organs in the all dogs at autopsy. High-dose NM administration could control blood coagulation and decrease blood loss during ECLA for 24 h without deterioration of the artificial lung and systemic complication other than mild hypotension and bradycardia.


Investigation of the tissue equivalence of gels used for NMR dosimetry.
The transition of Fe2+ to Fe3+ in Fricke solution after irradiation results in a change of NMR proton relaxation times in agarose gels which can be used for the dosimetry of ionizing radiation. The main advantage of this system is the possibility of observing dose distributions in 3 dimensions in a medium which is supposed to be tissue equivalent. The aim of the present study was to quantify parameters which determine the tissue equivalence of NMR dosimetry gels. Electron densities and effective atomic numbers were calculated for gels with varying iron, sulphur and agarose concentration. The Hounsfield CT numbers so derived agree well with the CT numbers measured on a clinical CT scanner (effective photon energy 70.7 keV). The Hounsfield CT number of 7.2 +/- 1.5 (n = 9) measured for a 1.5% agarose gel doped with 0.5 mM ammonium ferrous sulphate and 125 mM sulphuric acid compares well with the calculated one of 8 +/- 5. Relaxation times were measured from a series of MR images obtained on a 1.5 T clinical MR scanner. The observed change in 1/T1 of the gel with dose was found to be linear up to 10 Gy (0.084 s-1 Gy-1). No difference in dose response for 10 Gy delivered by four different superficial radiation qualities (HVT = 1.4-7.5 mm Al) could be observed. These findings and the calculated effective atomic number of 7.46 demonstrate the close tissue equivalence of this agarose gel which makes it an ideal tool for the investigation of low energy therapeutic x-rays.


Preparation and properties of Vibrio cholerae antifimbrial antibody.
The presence of fimbriae on the Vibrio cholerae strains used was assessed by pellicle formation, haemagglutination activity and electron microscopy. Fimbrial suspensions were prepared by shearing them off the organisms, then separating them from other components by absorbing them on to rabbit red blood cells. Rabbits were then immunized with the fimbrial-red cell suspensions and the antibodies evoked were titrated by haemagglutination inhibition, agglutination, vibriocidal and immobilization techniques.


Level of spinal anesthesia can be predicted by the cerebrospinal fluid pressure difference between full-flexed and non-full-flexed lateral position.
We studied whether cerebrospinal fluid pressure difference between full-flexed and non-full-flexed lateral position (dP) influences the spread of intrathecally (i.e., spinal) administered anesthetic solution (SSA). Forty-two women, 18-60 yr old, who underwent gynecologic surgery under spinal anesthesia were enrolled in the study. They were divided into two groups (group 1: less than 40 yr old, group 2: greater than or equal to 40 yr old). Before spinal anesthetic injection, we measured the pressure difference produced by postural change from the right lateral decubitus position (non-full-flexed) for needle insertion at the L2-3 interspace to a full-flexed lateral decubitus position with a spinal needle in place. After they returned to the non-full-flexed lateral position, 14 mg of plain tetracaine in 10% dextrose solution (2.8 mL) was injected intrathecally in each patient. Pressure differences had a significant correlation with the cephalad levels of spinal anesthesia in each group; the larger pressure difference was associated with a larger SSA. The relationship was stronger in the younger group (correlation coefficients, 0.82 and 0.63; P-values less than 0.01 in groups 1 and 2, respectively). Three patients in group 1 developed T-2 anesthesia, whereas no one in group 2 did (P less than 0.01), and their pressure difference values ranged from 12 to 16 cm H2O, substantially larger than those of the other patients in group 1. Five patients in group 2 developed T-3 anesthesia, whereas no patient in group 1 (P less than 0.01) did, and their pressure differences were not essentially larger than those of the rest in the same group. The authors conclude that pressure differences correlated with the SSA, although the mechanism remains to be clarified. It seems possible to predict which patient in the younger patient group may develop unintentional high spinal anesthesia (T-3 or higher) by measuring pressure differences.


[Transdermal nitroglycerin systems with continuous and discontinuous drug release. A comparison of the anti-ischemic and hemodynamic acute and long-term effects].
The anti-ischaemic and haemodynamic effects of two transdermal nitroglycerin systems, each offering 15 mg of nitroglycerine, the first giving continuous release (group 1) and the other discontinuous release (group 2), were compared in 30 men (mean age 56.5 [33-70] years) with coronary heart disease confirmed by angiography. Resting and exercise haemodynamics together with the degree of exercise-induced ST segment depression were measured on the first day, before and two hours after application of the plaster. After one week's therapy these measurements were repeated 24 hours after the application of the plaster on the previous day and two hours after the last application. Two hours after the first application both groups showed significant reduction (P less than 0.01) in exercise-induced ST segment depression (group 1: -60%, group 2: -50%) and in mean pulmonary artery pressure during exercise (group 1: -10%; group 2: -7%). After one week's therapy the reduction in exercise-induced ST segment depression was still significant in group 1 (-60%; P less than 0.01), but in group 2 (-30%) it was no longer significant. After one week had passed there was no longer any significant reduction in mean pulmonary artery pressure in either group (group 1: -6%; group 2: 0%). The acute anti-ischaemic and haemodynamic efficacy of both transdermal nitroglycerin systems was hence comparable; however, the emergence of nitrate tolerance during long-term use was not prevented even by phased release of the drug.


Phosphatase inhibitor, sodium stibogluconate, in combination with interferon (IFN) alpha 2b: phase I trials to identify pharmacodynamic and clinical effects.
Since sodium stibogluconate (SSG) inhibited phosphatases including SHP-1 and augmented anti-tumor actions of IFN-α2b in vitro and in mice, two Phase I trials of SSG/IFN-α2b combination were undertaken to evaluate safety and target inhibition. Escalating doses of SSG (200-1200 mg/m2) and fixed doses of IFN-α2b (3x106 units/m2) with or without chemotherapy (dacarbazine, vinblastine, cisplatin) were evaluated for side effects and impact on SHP-1 phospho-substrates and IFNα-stimulated-genes (ISGs) in peripheral blood in 40 patients with metastatic melanoma, soft tissue sarcomas, gastrointestinal stromal tumors, and breast or colorectal carcinomas who did not have other established treatment options. Common adverse events were bone marrow suppression, fatigue, gastrointestinal upset, and asymptomatic lipase elevation (n=13); the latter was dose related and mostly after 10d of SSG/IFN-α2b in combination. Levels of SHP-1 substrates (pSTAT1, pSTAT3, pLck and pSlp76) were increased (up to 3x) in peripheral blood cells following SSG with no potentiation by combination with IFN-α2b. Representative ISGs in peripheral blood were induced after IFN-α2b at 4 and 24 hrs with selective modulations by combination. The median time on trials was 2.3 months (10-281d) with no objective regression of disease. Alive at 1y were 17/40 (43%) patients and after 2y were 8/40 (20%) following treatment initiation. These data demonstrate that SSG impacted signal molecules consistent with PTP inhibition and was tolerated in combination with IFN-α2b. Phase II investigations of SSG could safely utilize doses of up to 1200 mg/m2 of SSG for up to 10d alone or in combination with IFN-α2b with or without chemotherapy.


[The effects of personal relationships on facial displays].
Previous studies have suggested that facial displays in the presence of others are influenced by the relationship with accompanying persons. In these studies, subjects participated with friends or strangers, without any focus on social interactions between partners. In the current study, pairs of friends or strangers viewed film clips expected to elicit positive and negative affects; the control group participated without partners. We measured synchronous smiles between partners as a social interactive display, in addition to the duration and the frequency of smiles and frowns. Subjective emotion and social motive were also measured. Smiles were facilitated by the presence of a friend than a stranger or the condition of lone participation, regardless of stimulus valence. Synchronous smiles and the communication motive were also enhanced with a friend than with a stranger. These results suggested that the expression of smiles was facilitated by the communication motive and social interactions between partners.


Constraint-induced therapy with trunk restraint for improving functional outcomes and trunk-arm control after stroke: a randomized controlled trial.
Studies have suggested that constraint-induced therapy combined with trunk restraint (CIT-TR) improves arm movement and reduces trunk compensation. Whether participants who receive CIT-TR can translate the benefits to real-life circumstances awaits further investigation. The effects of distributed CIT-TR (dCIT-TR) on motor function, daily function, quality of life (QOL), and arm-trunk control were investigated. The study was a single-blind, randomized controlled trial. The study took place at 4 hospitals. Participants were 57 people who had had a stroke 6 to 55 months earlier. Participants received a dose-matched intervention (2 hours per day, 5 days per week, for 3 weeks) of dCIT-TR, distributed constraint-induced therapy (dCIT), or control therapy. The Action Research Arm Test (ARAT), Motor Activity Log, Frenchay Activities Index (FAI), and Stroke Impact Scale (SIS) were used to evaluate motor function, daily function, and QOL. Data for reaching kinematics were recorded. Participants receiving dCIT-TR and dCIT exhibited higher overall scores on the ARAT, FAI, and hand function domain of the SIS and better quality of movement and larger amount of use (of the affected arm) on the Motor Activity Log than participants in the control group. Participants receiving dCIT-TR further demonstrated greater improvements on the ARAT grip subscale and FAI outdoor activities scale than participants receiving dCIT or participants in the control group. However, participants receiving dCIT showed greater improvements on the strength domain of the SIS after training than participants receiving dCIT-TR or participants in the control group. Limitations Research with a larger sample size is needed. Participants who received dCIT-TR were able to translate gains in arm-trunk control into functional performance and QOL, specifically in grip function and outdoor activities. A long-term study to examine the recovery course for force output may be needed to evaluate people's perception of less improvement in strength after dCIT-TR.


The choking game: physician perspectives.
The goal was to assess awareness of the choking game among physicians who care for adolescents and to explore their opinions regarding its inclusion in anticipatory guidance. We surveyed 865 pediatricians and family practitioners. The survey was designed to assess physicians' awareness of the choking game and its warning signs, the suspected prevalence of patients' participation in the activity, and the willingness of physicians to include the choking game in adolescent anticipatory guidance. Information on the general use of anticipatory guidance also was collected. The survey was completed by 163 physicians (response rate: 21.8%). One-hundred eleven (68.1%) had heard of the choking game, 68 of them (61.3%) through sources in the popular media. General pediatricians were significantly more likely to report being aware of the choking game than were family practitioners or pediatric subspecialists (P = .004). Of physicians who were aware of the choking game, 75.7% identified >or=1 warning sign and 52.3% identified >or=3. Only 7.6% of physicians who were aware of the choking game reported that they cared for a patient they suspected was participating in the activity, and 2 (1.9%) reported that they include the choking game in anticipatory guidance for adolescents. However, 64.9% of all respondents agreed that the choking game should be included in anticipatory guidance. Close to one third of physicians surveyed were unaware of the choking game, a potentially life-threatening activity practiced by adolescents. Despite acknowledging that the choking game should be included in adolescent anticipatory guidance, few physicians reported actually discussing it. To provide better care for their adolescent patients, pediatricians and family practitioners should be knowledgeable about risky behaviors encountered by their patients, including the choking game, and provide timely guidance about its dangers.


Chicken egg antibodies for prophylaxis and therapy of infectious intestinal diseases. V. In vivo studies on protective effects against Escherichia coli diarrhea in pigs.
A field study and a controlled infection trial showed the protective effect of egg yolk lyophilisate and whole egg lyophilisate against enterotoxic E. coli germs. The lyophilisates were gained from eggs of hens immunized against pilus antigen of porcine-enterotoxic E. coli. In a first field study using egg yolk antibodies, 92% of 299 diarrhea affected piglets were cured. In a further field study diarrhea affected piglets were cured after 3 days by application of egg yolk lyophilisate from immunized hens. Piglets treated only with egg yolk of not immunized hens showed no signs of recovery. The infection trial showed, that whole egg lyophilisate of immunized hens was as successful as a common antibiotic therapy in curing piglets, orally infected with 5 x 10(10) E. coli/feeding and animal. The present data show that chicken egg antibodies can be used for treatment of infectious diarrheal diseases in young animals. So far they represent a good alternative to the common used antibiotic therapy.


Physiological responses to catecholamine infusions in type A and type B men.
To determine whether there are basic biological differences between Type A and Type B men, we compared hemodynamic, electrophysiologic and neuroendocrine responses to equipotent doses of isoproterenol (ISO) and norepinephrine (NE) in 10 Type A and 10 Type B men ages 18 to 29. Results showed equal hemodynamic and neuroendocrine responses to graded ISO doses in Type A and Type B individuals. In contrast, Type A men showed a more prolonged decrease in electrocardiographic T-wave amplitude (TWA) than did Type B men. Post hoc analyses of the correlates of TWA recovery during high-dose ISO infusion provide preliminary evidence for a more robust parasympathetic antagonism of sympathetic nervous system effects in Type B men, especially those with low scores on the Cook-Medley Ho scale. These findings suggest that, in addition to cognitively mediated increases in sympathetic nervous system reactivity, Type As may also be placed at increased risk of developing coronary heart disease by reduced levels of parasympathetic antagonism of sympathetic effects.


[Epidemiology of malignant liver tumors].
Interpretation of descriptive statistics on liver cancer is affected by misclassification problems, evolving diagnostic procedures and changes in international classifications. Chronic infection with virus B and aflatoxin are major determinants for liver cancer in high-risk areas. In low and intermediate risk areas, including Italy, alcohol and cirrhosis are the most important risk factors. Preventive measures are neonatal vaccination against hepatitis B, reduction in aflatoxin contamination of foods, alcohol and tobacco consumption. Screening programs cannot be recommended as a measure of public health, particularly in western countries.


Developing a Low-Cost Force Treadmill via Dynamic Modeling.
By incorporating force transducers into treadmills, force platform-instrumented treadmills (commonly called force treadmills) can collect large amounts of gait data and enable the ground reaction force (GRF) to be calculated. However, the high cost of force treadmills has limited their adoption. This paper proposes a low-cost force treadmill system with force sensors installed underneath a standard exercise treadmill. It identifies and compensates for the force transmission dynamics from the actual GRF applied on the treadmill track surface to the force transmitted to the force sensors underneath the treadmill body. This study also proposes a testing procedure to assess the GRF measurement accuracy of force treadmills. Using this procedure in estimating the GRF of "walk-on-the-spot motion," it was found that the total harmonic distortion of the tested force treadmill system was about 1.69%, demonstrating the effectiveness of the approach.


Management of early-stage cervical carcinoma by modified (Type II) radical hysterectomy.
. Surgical management of cervical carcinoma by radical hysterectomy has been proven a highly effective method in treating early-stage disease. The purpose of this study was to evaluate the efficacy and safety of modified (Type II) radical hysterectomy for the treatment of early-stage (I-IIA) cervical carcinoma. A retrospective analysis of data on 435 patients with cervical carcinoma who were managed by modified radical hysterectomy was performed. In 145 cases a multimodal approach was used due to the presence of one or more risk factors such as lymph node metastasis, CLS involvement, bulky tumor, and exocervical extension of disease. Preoperative irradiation was offered to 62 patients, whereas adjuvant irradiation was offered to 101 patients. The mean age of the patients was 42.5 years. The majority of the patients had squamous cell cancer (81.6%). The patients were clinically staged as IA (3.2%), IB (86.7%), and IIA (10.1%). Positive pelvic lymph nodes were noted in 65 patients (14.9%). Operative morbidity was minimal, whereas adjuvant radiation treatment had no impact on the disease but caused genitourinary morbidity in terms of ureteral stricture and postoperative bladder dysfunction (P < 0.001). The overall 5-year survival was 88.7%. The most significant predictors related to 5-year survival were nodal metastasis (P < 0.001), adenomatous histology (P < 0.001), lesion size (P < 0.001), and CLS involvement (P = 0.004). Adjuvant radiation resulted in better local pelvic control of the disease. The results of our study support the concept that less radical procedures could be effectively applied to early-stage cervical carcinoma 4 cm or smaller with optimal surgical margins.


Sarcomatous Change of Cerebellopontine Angle Ependymoma Following Radiosurgery: A Case Report.
Sarcomatous change in ependymal tumors is rare and has been poorly described. We report on a cerebellopontine angle lesion that demonstrated rapid progression two years after radiosurgery in a 73-year-old female patient. Histopathological diagnosis at clinical progression showed an ependymoma with sarcomatous change ("ependymosarcoma") that was believed to be due to radiation. The patient underwent a complex tumor resection without complications using an exhaustive multi-modal neuromonitoring paradigm throughout the dissection and resection of the tumor. Given the limited available data on these rare tumors, we review their presentation, imaging, and histopathology in the context of the previous literature, and also discuss the management of these lesions in the cerebellopontine angle.


High-affinity monomeric 67-kD laminin receptors and prognosis in pancreatic endocrine tumours.
Cell-surface high-affinity monomeric 67-kD laminin receptors have been proposed to promote the invasion and metastasis of a variety of tumours, but there are, as yet, no data regarding the expression of these molecules in pancreatic endocrine tumours (PETs). The prognosis of these very rare tumours is problematic and the only irrefutable evidence of their malignancy still continues to be the occurrence of local invasion and metastases. In this retrospective investigation, 34 functioning and 48 non-functioning sporadic PETs were evaluated for the expression of the MLuC5 monoclonal antibody, which specifically recognizes the 67-kD laminin receptors. Laminin receptors were found in 42/82 cases (51 per cent) and their expression was associated with metastatic disease (P < 0.001), high proliferative activity expressed by a Ki-67 index above 5.0 per cent (P < 0.001), absence of progesterone receptors (P = 0.013), immunoreactivity for hormones other than insulin (P < 0.001), a tumour diameter more than 3.0 cm (P = 0.001), and a fatal clinical outcome (P < 0.001). Laminin receptors were also expressed by most metastatic foci and all intravascular emboli of tumour cells. Positivity for laminin receptors was associated with shorter survival in functioning (P = 0.026) and non-functioning (P = 0.042) tumours, as well as in the whole series of pancreatic endocrine tumours (P < 0.001). On multivariate analysis, laminin receptor expression was not an independent prognostic factor, while a Ki-67 index above 5.0 per cent was the most powerful predictor of survival. However, the association of laminin receptor expression and Ki-67 index could identify a group of malignant PETs with low proliferative activity characterized by an intermediate prognosis. In conclusion, these data suggest that monomeric laminin receptors may play a role in the invasion and metastasis of PETs and that their expression may be an additional prognostic factor, along with proliferative activity.


Humidity-Induced Phase Transitions of Surfactants Embedded in Latex Coatings Can Drastically Alter Their Water Barrier and Mechanical Properties.
Latex coatings are environmentally friendly i.e., they are formed from aqueous polymer dispersions, are cheap to produce and provide exceptional mechanical properties. Therefore, they are ubiquitous and can be found in a wide range of different applications such as paints and varnishes, pressure-sensitive adhesives, textiles, construction materials, paper coatings and inks. However, they also have weaknesses and their surfactant content is among them. Surfactants are often needed to stabilize polymer particles in the aqueous latex dispersions. These surfactants also form part of the coatings formed from these dispersions, and it is well-known that they can lower their performance. This work further explores this aspect and focuses on the role that embedded surfactant domains play in the response of latex coatings to humid environments. For this purpose, we made use of several experimental techniques where humidity control was implemented: quartz crystal microbalance with dissipation, atomic force microscopy and differential scanning calorimetry. By means of this multimethodological approach, we report that surfactants embedded in latex coatings can undergo humidity-induced transitions towards more hydrated and softer phases, and that this results in a drastic decrease of the mechanical and water barrier properties of the whole coatings. Subsequently, this work highlights the potential of taking into account the phase behavior of surfactants when choosing which ones to use in the synthesis of latex dispersions as this would help in predicting their performance under different environmental conditions.


Chromoblastomycosis Caused by Phialophora richardsiae.
Chromoblastomycosis is a chronic fungal disease of the skin and subcutaneous tissues caused by a group of dematiaceous (black) fungi. The most common etiologic agents are Fonsecaea pedrosoi and Cladophialophora carrionii, both of which can be isolated from plant debris. The infection usually follows traumatic inoculation by a penetrating thorn or splinter wound. Several months after the injury, painless papules or nodules appear on the affected area; these papules then progress to scaly and verrucose plaques. We report a case of chromoblastomycosis caused by Phialophora richardsiae, which has been rarely associated with chromoblastomycosis. The case involved a 43-year-old male, who for the past 2 months had noted an erythematous, pustulous plaque that was somewhat dark brown in color on his right shin; the plaque also had intermittent purulent discharge and crust formation. On histopathological examination, chronic granulomatous inflammation and sclerotic cells were seen. The tissue fungus culture grew out the typical black fungi of P. richardsiae, which was confirmed by polymerase chain reaction. The patient has been treated with a combination of terbinafine and itraconazole for 3 months with a good clinical response.


Beyond humanization and de-immunization: tolerization as a method for reducing the immunogenicity of biologics.
Immune responses to some monoclonal antibodies (mAbs) and biologic proteins interfere with their efficacy due to the development of anti-drug antibodies (ADA). In the case of mAbs, most ADA target 'foreign' sequences present in the complementarity determining regions (CDRs). Humanization of the mAb sequence is one approach that has been used to render biologics less foreign to the human immune system. However, fully human mAbs can also drive immunogenicity. De-immunization (removing epitopes) has been used to reduce biologic protein immunogenicity. Here, we discuss a third approach to reducing the immunogenicity of biologics: introduction of Treg epitopes that stimulate Treg function and induce tolerance to the biologic protein. Supplementing humanization (replacing xeno-sequences with human) and de-immunization (reducing T effector epitopes) with tolerization (introducing Treg epitopes) where feasible, as a means of improving biologics 'quality by design', may lead to the development of ever more clinically effective, but less immunogenic, biologics.


Differential light-dependent regulation of soybean nodulation by papilionoid-specific HY5 homologs.
Legumes have evolved photosynthesis and symbiotic nitrogen fixation for the acquisition of energy and nitrogen nutrients. During the transition from heterotrophic to autotrophic growth, blue light primarily triggers photosynthesis and low soil nitrogen induces symbiotic nodulation. Whether and how darkness and blue light influence root symbiotic nodulation during this transition is unknown. Here, we show that short-term darkness promotes nodulation and that blue light inhibits nodulation through two soybean TGACG-motif-binding factors (STF1 and STF2), which are Papilionoideae-specific transcription factors and divergent orthologs of Arabidopsis ELONGATED HYPOCOTYL 5 (HY5). STF1 and STF2 negatively regulate soybean nodulation by repressing the transcription of nodule inception a (GmNINa), which is a central regulator of nodulation, in response to darkness and blue light. STF1 and STF2 are not capable of moving from the shoots to roots, and they act both locally and systemically to mediate darkness- and blue-light-regulated nodulation. We further show that cryptochromes GmCRY1s are required for nodulation in the dark and partially contribute to the blue light inhibition of nodulation. In addition, root GmCRY1s mediate blue-light-induced transcription of STF1 and STF2, and intriguingly, GmCRY1b can interact with STF1 and STF2 to stabilize the protein stability of STF1 and STF2. Our results establish that the blue light receptor GmCRY1s-STF1/2 module plays a pivotal role in integrating darkness/blue light and nodulation signals. Furthermore, our findings reveal a molecular basis by which photosensory pathways modulate nodulation and autotrophic growth through an intricate interplay facilitating seedling establishment in response to low nitrogen and light signals.


[Images of population potential in Europe].
"The paper proposes an evaluation of relative locations in Europe circa 1990, based on a new, probabilistic, formulation of the concept of population potential. The location of centres and peripheries, as highlighted by potential, varies according to the geographical importance of exchanges and the permeability of national boundaries. An extremely stable overall pattern emerges from two analyses, the one retrospective--using data for 1960--and the other prospective--based on the distribution of young people today--: regions with a high potential are located in concentric circles around the axis formed by the Rhine, not in the peripheral regions of Europe where population growth is higher." (SUMMARY IN ENG)


Potential preventive effect of carvacrol against diethylnitrosamine-induced hepatocellular carcinoma in rats.
Antioxidants are one of the key players in tumorigenesis, several natural and synthetic antioxidants were shown to have anticancer effects. The aim of the present study is to divulge the chemopreventive nature of carvacrol during diethylnitrosamine (DEN)-induced liver cancer in male wistar albino rats. Administration of DEN to rats resulted in increased relative liver weight and serum marker enzymes aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and gamma glutamyl transpeptidase (γGT). The levels of lipid peroxides elevated (in both serum and tissue) with subsequent decrease in the final body weight and tissue antioxidants like superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx), and glutathione reductase (GR). Carvacrol supplementation (15 mg/kg body weight) significantly attenuated these alterations, thereby showing potent anticancer effect in liver cancer. Histological observations and transmission electron microscopy studies were also carried out, which added supports to the chemopreventive action of the carvacrol against DEN-induction during liver cancer progression. These findings suggest that carvacrol prevents lipid peroxidation, hepatic cell damage, and protects the antioxidant system in DEN-induced hepatocellular carcinogenesis.


Polymorphisms of genes involved in innate immunity: association with preterm delivery.
An altered inflammatory activity due to functionally relevant polymorphisms of the innate immune system may influence pathways leading to labour and, therefore, impact on the frequency of preterm birth. We examined five polymorphisms of the innate immune system in a large cohort of preterm very-low-birth-weight (VLBW, n = 909) and term-born infants (n = 491) and their mothers (n = 747). The primary outcome was preterm versus term birth. Frequencies of polymorphisms in mothers of term-born infants versus mothers of VLBW infants and term infants versus preterm VLBW infants (singletons) are given. Homozygous CD14-159T: 18.5 versus 21.8% (mothers) and 19.6 versus 21.2% (infants). Homozygous interleukin IL-6-174G: 28.8 versus 38% (P = 0.018, mothers) and 30 versus 32.7% (infants). Homozygous or heterozygous nuclear oligomerization domain NOD2-3020insC: 6.9 versus 6.1% (mothers) and 5.7 versus 5.1% (infants). Heterozygous or homozygous toll-like-receptor TLR2-Arg753Gln: 6.9 versus 6.1% (mothers) and 5.7 versus 5.1% (infants). Homozygous or heterozygous TLR4-896G: 8.1 versus 11.5% (mothers) and 11.6 versus 10.5% (infants). Although the homozygous maternal IL-6-174G genotype was found to be independently associated with preterm delivery in multivariate regression analysis, the incidence of intrauterine infection was not significantly increased in mothers of preterm VLBW-infants, carrying this or other polymorphisms of the innate immune system. The overall influence of the investigated polymorphisms on the development of preterm delivery seems moderate, since only the maternal IL6-174G genotype was associated with preterm birth and none of the polymorphisms were associated with intrauterine infection as the cause of preterm birth.


Genome Sequencing Identifies Previously Unrecognized Klebsiella pneumoniae Outbreaks in Neonatal Intensive Care Units in the Philippines.
Klebsiella pneumoniae is a critically important pathogen in the Philippines. Isolates are commonly resistant to at least 2 classes of antibiotics, yet mechanisms and spread of its resistance are not well studied. A retrospective sequencing survey was performed on carbapenem-, extended spectrum beta-lactam-, and cephalosporin-resistant Klebsiella pneumoniae isolated at 20 antimicrobial resistance (AMR) surveillance sentinel sites from 2015 through 2017. We characterized 259 isolates using biochemical methods, antimicrobial susceptibility testing, and whole-genome sequencing (WGS). Known AMR mechanisms were identified. Potential outbreaks were investigated by detecting clusters from epidemiologic, phenotypic, and genome-derived data. Prevalent AMR mechanisms detected include blaCTX-M-15 (76.8%) and blaNDM-1 (37.5%). An epidemic IncFII(Yp) plasmid carrying blaNDM-1 was also detected in 46 isolates from 6 sentinel sites and 14 different sequence types (STs). This plasmid was also identified as the main vehicle of carbapenem resistance in 2 previously unrecognized local outbreaks of ST348 and ST283 at 2 different sentinel sites. A third local outbreak of ST397 was also identified but without the IncFII(Yp) plasmid. Isolates in each outbreak site showed identical STs and K- and O-loci, and similar resistance profiles and AMR genes. All outbreak isolates were collected from blood of children aged < 1 year. WGS provided a better understanding of the epidemiology of multidrug resistant Klebsiella in the Philippines, which was not possible with only phenotypic and epidemiologic data. The identification of 3 previously unrecognized Klebsiella outbreaks highlights the utility of WGS in outbreak detection, as well as its importance in public health and in implementing infection control programs.


Development of Novel PSMA Ligands for Imaging and Therapy with Copper Isotopes.
Prostate-specific membrane antigen (PSMA)-binding tracers have been shown to be promising agents for the specific targeting of prostate tumors. On labeling with the short-lived isotopes 18F and 68Ga, excellent molecular imaging performance is achieved. This potential could be further exploited using long-lived isotopes. Because of the favorable half-life of 64Cu, tracers labeled with this PET nuclide could solve logistic problems. Moreover, this isotope provides a theranostic pair with the therapeutic copper isotope 67Cu. Hence, 9 novel tracers that combine dedicated copper chelators with the PSMA-specific urea-based binding motif were developed. Methods: The precursors were obtained by solid-phase synthesis. The purity and molecular weight of the PSMA ligands were confirmed by high-performance liquid chromatography and liquid chromatography-mass spectrometry. The compounds were labeled with 64Cu, with a radiolabeling yield of more than 99%. Competitive cell binding assays and internalization assays were performed with C4-2 cells, a subline of the PSMA-positive cell line LNCaP (human lymph node carcinoma of the prostate). In vitro serum stability, the stability of 64Cu-CA003 in blood, and the in vivo fate of neat 64Cu-chloride or 64Cu-CA003 were determined to prove whether the stability of the radiolabeled compounds is sufficient to ensure no significant loss of copper during the targeting process. For PET imaging and biodistribution studies, a C4-2 tumor-bearing mouse model was used. Results: The radiolabeled 64Cu-PSMA ligands showed high serum stability. All PSMA ligands showed high inhibition potencies, with equilibrium inhibition constants in the low nanomolar range. 64Cu-CA003 and 64Cu-CA005 showed high internalization ratios (34.6% ± 2.8 and 18.6% ± 4.4, respectively). Both the in vitro serum stability determination and the in vivo characterization of the main radiolabeled compounds confirmed that, except for 64Cu-PSMA-617, all compounds showed high serum stability within the observation period of 24 h. Small-animal PET imaging demonstrated high tumor uptake within 20 min. Organ distribution studies confirmed high specific uptake in the tumor, with 30.8 ± 12.6 percentage injected dose (%ID)/g at 1 h after injection. Rapid clearance from the kidneys was observed-a decrease from 67.0 ± 20.9 %ID/g at 1 h after injection to 7.5 ± 8.51 %ID/g at 24 h after injection (in the case of CA003). The performance of CA003, the compound with the best preclinical properties, was assessed in a first patient. In line with its preclinical data, PET imaging resulted in clear visualization of the cancer lesions, with high contrast. Conclusion: The 64Cu-labeled PSMA ligands are promising agents to target PSMA and visualize PSMA-positive tumor lesions as shown in preclinical evaluation by small-animal PET studies, organ distribution, and a patient application. Most importantly, the images obtained at 20 h enabled delineation of unclear lesions, showing that the compounds fulfill the prerequisite for dosimetry in the course of therapy planning with 67Cu. Thus, we suggest clinical use of copper-labeled CA003 for diagnostics and radiotherapy of prostate cancer.


Use of strain typing to provide evidence for specific interventions in the transmission of VTEC O157 infections.
Transmission of verocytotoxin (VT)-producing Escherichia coli (VTEC) occurs by three main routes. These comprise food- or water-borne infections, acquisition of disease by direct or indirect contact with animals and person-to-person spread. Phenotypic typing of VTEC belonging to serogroup O157 is achieved by phage typing and identification of VT type. These properties quickly provide evidence for the linkage of human cases and their association to potential sources. DNA-based subtyping methods such as pulsed field gel electrophoresis (PFGE) are generally required to increase discrimination of VTEC O157 strains so that the spread of specific strains can be monitored. Phenotypic and DNA-based methods were used in the investigation of 85 general outbreaks of VTEC O157 infection between 1995 and 1999. Results were used in conjunction with epidemiological data to provide direct or indirect evidence for the likely route of transmission. Detailed strain fingerprinting identified specific food vehicles and reservoirs of infection in animals. Typing supported the implementation of measures to control the spread of infection that included pasteurisation orders, product withdrawal, temporary closure of retail premises and open farms and the introduction of HACCP-based working practices. In outbreaks involving widely distributed foods, DNA-based examination of apparently sporadic isolates with the same phage and VT type as outbreak strains was performed to identify additional potential outbreak cases and estimate the spread of infection. Strain typing was applied in outbreaks in nurseries and other institutions to monitor person-to-person spread, including careers and their families and to assess the involvement of community cases occurring at the same time. Rapid exchange of epidemiological, microbiological and typing data will be increasingly important in investigation of VTEC O157 outbreaks.


Whey Protein Isolate-Xylose Maillard-Based Conjugates with Tailored Microencapsulation Capacity of Flavonoids from Yellow Onions Skins.
The objective of this study is to encapsulate flavonoids from yellow onion skins in whey protein isolates (WPI) and xylose (X), by Maillard-based conjugates, as an approach to improve the ability to entrap flavonoids and to develop powders with enhanced antioxidant activity. WPI (0.6%, w/v) was conjugated to X (0.3%, w/v) through the Maillard reaction at 90 °C for 120 min, in the presence of a flavonoid-enriched extract. Two variants of powders were obtained by freeze-drying. The glycation of WPI allowed a better encapsulation efficiency, up to 90.53 ± 0.29%, corresponding to a grafting degree of 30.38 ± 1.55%. The molecular modelling approach was used to assess the impact of X interactions with α-lactalbumin and β-lactoglobulin on the ability of these proteins to bind the main flavonoids from the yellow onion skins. The results showed that X might compete with quercetin glucosides to bind with α-lactalbumin. No interference was found in the case of β-lactoglobulin. The microstructural appearance of the powders revealed finer spherosomes in powder with WPI-X conjugates via the Maillard reaction. The powders were added to nachos, followed by a phytochemical characterization, in order to test their potential added value. An increase in antioxidant activity was observed, with no significant changes during storage.


Evaluation of antimicrobial therapy management of 120 consecutive patients with secondary peritonitis.
To evaluate antimicrobial therapy management of secondary peritonitis in a University Hospital. All patients admitted to the intensive care unit of the University Hospital of Nîmes from 1 January 1997 to 31 July 1999 with a diagnosis of secondary peritonitis were retrospectively included. Patients' medical records were collected from the data recordings of the Department of Critical Care and Emergency and the Departments of Surgery. Acute Physiology and Chronic Health Evaluation II (APACHE II) was calculated for each patient at the time of admission. Antimicrobial treatment management before and after the diagnosis of peritonitis was studied. One hundred and twenty patients were included. Results concerning mortality, aetiology of peritonitis and microbiological data were in accordance with previous studies. APACHE II score (P = 0.005), age (P = 0.002), presence of Enterococcus in the peri-operative samples (P = 0.02) and period between diagnosis and surgery (P = 0.04) were predictive of death within 30 days after diagnosis of peritonitis. No significant difference was shown in the mortality rate in patients whose post-operative antibiotic treatment was changed following results of intra-operative peritoneal cultures versus patients having inappropriate treatment (P = 0.96). The same observations were noted for anti-enterococcal treatment. This study emphasizes the importance of prompt surgical treatment and shows the modest impact of adapting antibiotic treatment. The morbidity and mortality associated with the presence of Enterococcus, which was not influenced by antibiotic treatment, would seem to suggest the pro-inflammatory role of Enterococcus. However, prospective randomized studies are needed to evaluate the real contribution of enterococcal antibiotic coverage in this context.


The impact of multiple types of child maltreatment on subsequent risk behaviors among women during the transition from adolescence to young adulthood.
The purpose of this study was to investigate how different types of child maltreatment, independently and collectively, impact a wide range of risk behaviors that fall into three domains: sexual risk behaviors, delinquency, and suicidality. Cumulative classification and Expanded Hierarchical Type (EHT) classification approaches were used to categorize various types of maltreatment. Data were derived from Wave III of the National Longitudinal Study of Adolescent Health (Add Health). Our sample consisted of White, Black, Hispanic, and Asian females ages 18 to 27 (n = 7,576). Experiencing different kinds of maltreatment during childhood led to an extensive range of risk behaviors within the three identified domains. Women experiencing sexual abuse plus other maltreatment types had the poorest outcomes in all three domains. These findings illustrate that it may no longer be appropriate to assume that all types of maltreatment are equivalent in their potential contribution to negative developmental sequelae.


SPECT analysis of a new implant surface: a human preliminary report.
Several recent medical reports have focused attention on the possible application of skeletal scintigraphy imaging in odontostomatology. The aim of the present report was to assess the influence of a new implant surface on peri-implant osteoblastic activity through bone scintigraphy. Implants were placed in one healthy subject. A nuclear medicine investigation with single-photon emission-computed tomography (SPECT) was performed at 30 and 90 days after implant placement. The study was completed with acquisition of planar images of the skull in an anterior view and the use of regions of interest (ROIs) of the same size in the area corresponding to new surfaces implants and in the opposite maxilla (at the control sites). Count density ratios (counts/pixel) obtained from each ROI were used for a quantitative/relative assessment. Tomographic images were evaluated with a qualitative method. Routine planar methodology provided a direct measure of cellular activity of the examined areas. The difference in count density ratio registered from the same ROI between the first and the second scintigraphy revealed the course of peri-implant osteoblastic activity, which was very high in the first month and then declined during subsequent months. In spite of the small number of involved patients, the results obtained from this pilot study suggest that nuclear medicine investigation held advantages in oral implantology to clarify those aspects still unknown dealing with osteoblastic activity.


Paclitaxel and platinum chemotherapy for malignant mixed müllerian tumors of the ovary.
Malignant mixed müllerian tumor (MMMT) of the ovary is a rare tumor with a dismal prognosis. The most effective therapy is unknown. The current study was undertaken to characterize a group of patients treated as if they had aggressive epithelial ovarian tumors, with cytoreductive surgery and combination paclitaxel/platinum chemotherapy. Retrospective analysis of data obtained from tumor registry and hospital records of cases of malignant mixed müllerian tumor between January 1, 1992 and January 1, 2000 treated at the Massachusetts General Hospital, Brigham and Women's Hospital, and University of Vermont was performed. Only patients treated with combination paclitaxel and platinum therapy were included in the analysis. Data were collected regarding cytoreduction, response to chemotherapy, disease-free interval, and survival. Fifty-five patients were identified with MMMT. Twenty-eight patients with a clearly ovarian primary had received treatment with combination paclitaxel and platinum. Paclitaxel and carboplatin was given as second-line therapy in 2 patients who had chemoresponsive but incurable disease; the remaining patients were treated with paclitaxel and platinum therapy as first-line therapy. These 28 patients had a median (range) age of 66 (46-84 years) and stage was I in 2 patients, II in 3, III in 18, and IV in 5. Treatment was generally well tolerated. Sixteen patients of 26 treated with paclitaxel and platinum as first-line therapy achieved a complete clinical response (55%) and 6 patients achieved partial response for a total response rate of 72%. Optimal cytoreduction was associated with increased time to recurrence (P = 0.001) but not with survival. Overall median survival for the 28 patients is 27.1 months. Although treatment fails many patients, a minority of patients with MMMT in this highly selected population do unexpectedly well. An aggressive approach with surgery and combination paclitaxel-platinum chemotherapy appears to offer very effective therapy.