Differential innate immune signalling via Ca(2+) sensor protein kinases.
Innate immunity represents the first line of inducible defence against microbial infection in plants and animals. In both kingdoms, recognition of pathogen- or microbe-associated molecular patterns (PAMPs or MAMPs, respectively), such as flagellin, initiates convergent signalling pathways involving mitogen-activated protein kinase (MAPK) cascades and global transcriptional changes to boost immunity. Although Ca(2+) has long been recognized as an essential and conserved primary mediator in plant defence responses, how Ca(2+) signals are sensed and relayed into early MAMP signalling is unknown. Using a functional genomic screen and genome-wide gene expression profiling, here we show that four calcium-dependent protein kinases (CDPKs) are Ca(2+)-sensor protein kinases critical for transcriptional reprogramming in plant innate immune signalling. Unexpectedly, CDPKs and MAPK cascades act differentially in four MAMP-mediated regulatory programs to control early genes involved in the synthesis of defence peptides and metabolites, cell wall modifications and redox signalling. Transcriptome profile comparison suggests that CDPKs are the convergence point of signalling triggered by most MAMPs. Double, triple and quadruple cpk mutant plants display progressively diminished oxidative burst and gene activation induced by the 22-amino-acid peptide flg22, as well as compromised pathogen defence. In contrast to negative roles of calmodulin and a calmodulin-activated transcription factor in plant defence, the present study reveals Ca(2+) signalling complexity and demonstrates key positive roles of specific CDPKs in initial MAMP signalling.


Erythrocyte pyrimidine 5'-nucleotidase inhibition by acute lead exposure in neonatal rats.
Inhibition by lead of erythrocyte pyrimidine 5'-nucleotidase (P5N) is thought to contribute to morphological abnormalities observed in red blood cells (RBC) of lead-exposed subjects. However, neither the mechanism of lead inhibition of P5N nor the relationship of this inhibition to blood lead levels attained in exposed subjects is known. In the present investigation, acute in vivo and in vitro lead acetate effects on erythrocyte P5N from 21-day-old rat pups were determined and were related to blood lead concentrations ascertained by atomic absorption spectrophotometry. Acute lead administration to rat pups resulted in a 16% to 21% reduction in erythrocyte P5N, with mean blood lead levels ranging from 77 to 108 micrograms/dl 24 hours later. Inhibition of erythrocyte P5N was linearly related to blood lead level (r = -0.67, P less than 0.05) following acute lead administration. Lead acetate addition to RBC preparations from 21-day-old rats resulted in concentration-dependent P5N inhibition which was comparable to that produced following acute in vivo exposure. The results indicate that acute P5N inhibition in lead-treated neonatal rats is due to noncompetitive P5N inhibition by lead. The inhibition of P5N produced by acute lead treatment is linearly related to blood lead concentrations.


[Studies on viral immunotherapy of ascitic tumors in mice. II. Preliminary studies on the mechanism of treatment of S 180 ascitic tumors in mice by PR8 strain of influenza virus].
Present paper reports on the preliminary studies of the mechanism of virus therapy. In the untreated group, after ip transplant of 7.5 X 10(5) S 180 cells into healthy mice, the number of tumor cells increased rapidly and reached 3 X 10(8) cells/ml on day 9 and the death rate of cells was under 5%, except day 1 and 2. However, in the virus treated group, the PR 8 virus was given ip 48 hours after transplant of S 180 cells. The growth rate of tumor cells was significantly suppressed (maintained at about 3 X 10(5) cells/ml) and the death rate averaged 58.6%. In the antiPR 8 antibody treated group, the antibody was given ip 24 hours after injection of virus. The number of tumor cells decreased to the average of 1.5 X 10(5) cells/ml and the death rate reached 72.8% which is comparable with the virus treated group at day 6-9 after transplant of S 180 cells, suggesting in this period the oncolysis be antibody related (ADCC). In vitro test, the death rate of the tumor cells caused by PR 8 virus was only 6.9% in 24 hours after virus infection and 7.8% after 72 hours. The increased death rate of tumor cells after virus treatment in vivo and in vitro shows that the immune system is the main factor which eliminates the tumor cells in vivo.


Effectiveness and Side Effect Profile of Stimulant Medication for the Treatment of Attention-Deficit/Hyperactivity Disorder in Youth with Epilepsy.
This clinical case series examined the effectiveness and potential side effects associated with stimulant medication for the treatment of attention-deficit/hyperactivity disorder (ADHD) in 20 youth with epilepsy. Response to stimulant medication was examined through symptom reduction on the Conners-Third Edition: Parent Rating Scale, Short Form [Conner 3-P(S)], which was administered to caregivers before initiation of treatment and following dosage titration to achieve therapeutic efficacy. Stimulant medication side effects were examined with the Side Effect Rating Scale before treatment and following dosage titration. Repeated measures mixed model approach was used to compare symptom reduction and side effects between the two time points. Repeated measures ANOVA revealed significant ADHD symptom reduction as measured by the Conner 3-P(S). Review of patient medical records and caregiver report did not reveal seizure exacerbation. Caregivers, in fact, reported fewer side effects following treatment for ADHD compared with baseline. These results contribute to growing evidence in support of the effectiveness of stimulant medication, without seizure exacerbation or medication side effects, for treatment of ADHD in youth with epilepsy.


[The interrelations of the causative agents of transmissible diseases in ixodid ticks (Ixodidae) with a mixed infection].
The data on interactions between pathogens of human diseases with natural focality in ixodid ticks (Ixodidae) with mixed infection are reviewed. Different variants of mixed infection revealed in nature and accompanied by predominantly extracellular, or both extra- and intracellular location of the agents in tick organism are considered. Natural mixed infection of ticks by different pathogens is a normal and commonly occurring phenomenon; moreover, there is no experimental evidence for the existence of any antagonistic relationships between spirochetes, rickettsiae, and piroplasms in such ticks. The absence of antagonism between different agents in vectors largely provides a relative autonomy of corresponding parasitic systems and creates conditions for coexistence of different parasitic systems in mixed natural foci.


Ultrastructural aspects and programmed cell death in the tapetal cells of Lathyrus undulatus Boiss.
Programmed cell death (PCD) in the tapetum of Lathyrus undulatus L. was analyzed based on light, fluorescence and electron microscopy to characterize its spatial and temporal occurrence. Development and processes of PCD in secretory tapetal cells of Lathyrus undulatus L. were correlated with the sporogenous cells and pollen grains. At early stages of development the tapetal cells appeared similar to pollen mother cells, structurally. Concurrent with meiosis, tapetum expanded both tangentially and radially as vacuoles increased in size. Tapetal cells most fully developed at young microspore stage. However, tapetum underwent substantial changes in cell organization including nucleus morphology monitored by DAPI. The TUNEL staining confirmed the occurrence of intra-nucleosomal DNA cleavage. In addition to nuclear degeneration which is the first hallmark of PCD other diagnostic features were observed at vacuolated microspore stage intensely; such as chromatin condensation at the periphery of the nucleus, nuclear membrane degeneration, chromatin release to the cytoplasm, vacuole collapse according to tonoplast rupture, shrinkage of the cytoplasm, the increase and enlargement of the endoplasmic reticulum cisternae and disruption of the plasma membrane. After vacuole collapse due to possible release of hydrolytic enzymes the cell components degraded. Tapetal cells completely degenerated at bicellular pollen stage.


The microscopic structure of liquid methanol from Raman spectroscopy.
The microscopic structure of liquid methanol has been systematically investigated with Raman spectroscopy in a temperature range of 15-55 degrees C. The unbonded free -OH stretching vibrational band has been observed at approximately 3660 cm(-1) in pure liquid. With the aid of depolarization measurements and theoretical calculations, four featured spectral components have been unambiguously identified and assigned to four well-defined vibrational modes of clusters in chain or ring forms. Furthermore, the cluster size distribution and its temperature dependence have been derived from the spectral fittings for the first time, which lead to the conclusion that the trimer, tetramer, and pentamer are the dominant clusters in liquid methanol, taking up more than 50% of total clusters.


Structural and dynamic properties that govern the stability of an engineered fibronectin type III domain.
Consensus protein design is a rapid and reliable technique for the improvement of protein stability, which relies on the use of homologous protein sequences. To enhance the stability of a fibronectin type III (FN3) domain, consensus design was employed using an alignment of 2123 sequences. The resulting FN3 domain, FN3con, has unprecedented stability, with a melting temperature >100°C, a ΔG(D-N) of 15.5 kcal mol(-1) and a greatly reduced unfolding rate compared with wild-type. To determine the underlying molecular basis for stability, an X-ray crystal structure of FN3con was determined to 2.0 Å and compared with other FN3 domains of varying stabilities. The structure of FN3con reveals significantly increased salt bridge interactions that are cooperatively networked, and a highly optimized hydrophobic core. Molecular dynamics simulations of FN3con and comparison structures show the cooperative power of electrostatic and hydrophobic networks in improving FN3con stability. Taken together, our data reveal that FN3con stability does not result from a single mechanism, but rather the combination of several features and the removal of non-conserved, unfavorable interactions. The large number of sequences employed in this study has most likely enhanced the robustness of the consensus design, which is now possible due to the increased sequence availability in the post-genomic era. These studies increase our knowledge of the molecular mechanisms that govern stability and demonstrate the rising potential for enhancing stability via the consensus method.


Epilepsy and Encephalopathy.
Epilepsy encompasses more than the predisposition to unprovoked seizures. In children, epileptic activity during (ictal) and between (interictal) seizures has the potential to disrupt normal brain development. The term "epileptic encephalopathy (EE)" refers to the concept that such abnormal activity may contribute to cognitive and behavioral impairments beyond that expected from the underlying cause of the epileptic activity. In this review, we survey the concept of EE across a diverse selection of syndromes to illustrate its broad applicability in pediatric epilepsy. We review experimental evidence that provides mechanistic insights into how epileptic activity has the potential to impact normal brain processes and the development of neural networks. We then discuss opportunities to improve developmental outcomes in epilepsy now and in the future. Epileptic activity in the brain poses a threat to normal physiology and brain development. Until we have treatments that reliably target and effectively treat the underlying causes of epilepsy, a major goal of management is to prevent epileptic activity from worsening developmental outcomes.


GM-CSF increases mucosal and systemic immunogenicity of an H1N1 influenza DNA vaccine administered into the epidermis of non-human primates.
The recent H5N1 avian and H1N1 swine-origin influenza virus outbreaks reaffirm that the threat of a world-wide influenza pandemic is both real and ever-present. Vaccination is still considered the best strategy for protection against influenza virus infection but a significant challenge is to identify new vaccine approaches that offer accelerated production, broader protection against drifted and shifted strains, and the capacity to elicit anti-viral immune responses in the respiratory tract at the site of viral entry. As a safe alternative to live attenuated vaccines, the mucosal and systemic immunogenicity of an H1N1 influenza (A/New Caledonia/20/99) HA DNA vaccine administered by particle-mediated epidermal delivery (PMED or gene gun) was analyzed in rhesus macaques. Macaques were immunized at weeks 0, 8, and 16 using a disposable single-shot particle-mediated delivery device designed for clinical use that delivers plasmid DNA directly into cells of the epidermis. Significant levels of hemagglutination inhibiting (HI) antibodies and cytokine-secreting HA-specific T cells were observed in the periphery of macaques following 1-3 doses of the PMED HA DNA vaccine. In addition, HA DNA vaccination induced detectable levels of HA-specific mucosal antibodies and T cells in the lung and gut-associated lymphoid tissues of vaccinated macaques. Importantly, co-delivery of a DNA encoding the rhesus macaque GM-CSF gene was found to significantly enhance both the systemic and mucosal immunogenicity of the HA DNA vaccine. These results provide strong support for the development of a particle-mediated epidermal DNA vaccine for protection against respiratory pathogens such as influenza and demonstrate, for the first time, the ability of skin-delivered GM-CSF to serve as an effective mucosal adjuvant for vaccine induction of immune responses in the gut and respiratory tract.


Exclusive mutations related to isoniazid and ethionamide resistance among Mycobacterium tuberculosis isolates from Korea.
The single base change at the 94th codon of inhA has been referred to as the event that confers resistance on the drugs isoniazid (INH) and ethionamide (ETH) in Mycobacterium smegmatis and M. bovis. From this observation, it has been anticipated that some of the INH-resistant clinical isolates of M. tuberculosis would carry missense mutations in the same region of the gene. However, few polymorphisms have been identified in this region among INH-resistant isolates. To understand the molecular basis for M. tuberculosis resistance to INH and ETH. The sequence polymorphism at the 94th codon of inhA among M. tuberculosis isolates from Korea was analyzed by polymerase chain reaction (PCR) cloning and sequence analysis. No nucleotide change at the 94th codon of inhA was detected in any of the 24 INH-resistant isolates analyzed in this study. On the other hand, a point mutation was found exclusively at the regulatory region flanking a putative ribosome-binding site of the inhA locus in 14 isolates. Interestingly, all the mutations were of the same kind, which substitutes C to T. Among 14 isolates, 12 were resistant to INH as well as to ETH, while two were resistant to INH only. It seems that mutations previously found at the 94th codon of inhA have no particular relationship with the mechanism involved in the resistance of M. tuberculosis to INH and/or ETH. On the other hand, the resistance mechanism of M. tuberculosis to INH/ETH may involve an altered level of InhA, an expression which may have been influenced by the sequence change in the regulatory region of the inhA locus.


Solitary vertebral metastasis of primary clear cell carcinoma of the liver: a case report and review of literature.
Primary clear cell carcinoma of liver (PCCCL) is an uncommon variant of primary hepatocellular carcinoma. Though the literature describes a better prognosis in relation to the proportion of clear cells in the tumour when compared to the other variants, there is no general consensus in the management due to its rarity and unclear clinicopathological and prognostic factors. There is dearth of evidence with regard to the metastasizing nature of PCCCL and its management. In addition, the management of recurrent spinal tumours both primary and metastatic is not clear as the available evidence is mostly based on case reports. We describe an unusual presentation of PCCCL with solitary spinal metastasis and further complicated by tumour recurrence in a 71-year-old male. Such presentation has never been described before. He presented with low back pain and incomplete neurological deficits involving both lower limbs. On detailed evaluation, he was found to have a solitary metastasis at L3 vertebra secondary to PCCCL. He underwent radical excision of tumour and reconstruction for the solitary metastasis at L3 vertebral body and trans arterial chemo embolisation (TACE) for the hepatic lesion. Pt was asymptomatic until 9 months post operatively when he developed tumour recurrence at L3 vertebra. Patient subsequently underwent 2 stage palliative surgery followed by radiotherapy and chemotherapy. At his latest follow-up (1 year), the patient's overall general condition has improved with residual neurological deficits in the lower limb. PCCCL is a rare type of hepatocellular carcinoma which can present as "solitary metastasis" to the spine. Although the literature suggests a good prognosis for this histological type, this case did not have a good outcome. In addition to providing information for the management of similar cases in the future, this case report highlights that every patient has to be managed on a case-by-case basis.


Association between volume and charges for most frequently performed ambulatory and nonambulatory surgery for bladder cancer. Is more cheaper?
We investigated the relationship between provider volume and charges for transurethral bladder tumor resection (TURBT) and radical cystectomy in patients with bladder cancer. The National Inpatient Sample (1988 to 1999) of the Health Care Utilization Project, and State Ambulatory Surgery Databases for Wisconsin and Florida (2000 data set) were used for analysis. All patients with bladder cancer who had undergone radical cystectomy or TURBT as the principal procedure were identified. Hospitals and surgeons were categorized into terciles of volume based on the average number performed per year. The average hospital charge per discharge/procedure corrected to 2000 levels was calculated. One-way ANOVA with the Bonferroni correction was used to compare charges between different volume levels. A total of 13,498 patients who underwent radical cystectomy and 5,954 who underwent TURBT were included in the analysis. Charges for radical cystectomy were 5,648 USD lower at high volume hospitals than at low volume hospitals (p <0.001). High volume surgeons were 2,976 USD less expensive than low volume surgeons (p =0.054). For TURBT total hospital charges at high volume hospitals were 1,013 USD more than at low volume hospitals (p <0.0001), while average total hospital charges for procedures performed by high volume surgeons were 919 USD less compared to low volume surgeons (p <0.0001). High risk inpatient procedures for bladder cancer such as cystectomy, which are more influenced by systems of care, are less expensive to perform at high volume centers. Lower risk ambulatory procedures for bladder cancer, such as TURBT, which are not influenced by systems of care, may be more cost efficiently performed by high volume surgeons at low volume centers.


Psychological resilience in young and older adults.
The goal of the current study was to investigate psychological resilience in the older adults (>64 years) compared with that of the young ones (<26 years). Questionnaire measures of depression, hopelessness, general health and resilience were administered to the participants. The resilience measure comprised three sub-scales of social support, emotional regulation and problem solving. The older adults were the more resilient group especially with respect to emotional regulation ability and problem solving. The young ones had more resilience related to social support. Poor perceptions of general health and low energy levels predicted low levels of resilience regardless of age. Low hopelessness scores also predicted greater resilience in both groups. Experiencing higher levels of mental illness and physical dysfunction predicted high resilience scores especially for the social support resilience scale in the older adults. The negative effects of depression on resilience related to emotional regulation were countered by low hopelessness but only in the young adults. These results highlight the importance of maintaining resilience-related coping skills in both young and older adults but indicate that different psychological processes underlie resilience across the lifespan.


Effects of orlistat combined with enzalutamide and castration through inhibition of fatty acid synthase in a PC3 tumor-bearing mouse model.
Androgen deprivation therapy (ADT) is one of the typical treatments used for patients with prostate cancer (PCa). ADT, however, may fail when PCa develops castration-resistance. Fatty acid synthase (FASN), a critical enzyme involved in fatty acid synthesis, is found to be up-regulated in PCa. Since enzalutamide and ADT are frequently used for the treatment of PCa, the present study aimed to unravel the underlying mechanism of combination of orlistat, an FASN inhibitor, and enzalutamide using PC3 cell line; and orlistat and castration in PC3 tumor-bearing animal model. Cytotoxicity was determined by AlamarBlue assay. Drug effects on the cell cycle and protein expressions were assayed by the flow cytometry and Western blot. Electromobility shift assay was used to evaluate the NF-κB activity. The tumor growth delay, expressions of the signaling-related proteins, and histopathology post treatments of orlistat and castration were evaluated in PC3 tumor-bearing mouse model. The results showed that orlistat arrested the PC3 cells at the G1 phase of the cell cycle and enhanced the cytotoxic effects of enzalutamide synergistically. Pretreatment with orlistat combined with castration inhibited the tumor growth significantly compared with those of castration and orlistat treatments alone in PC3 tumor-bearing mice. Combination treatment reduced both FASN and NF-κB activities and their downstream effector proteins. The present study demonstrated the synergistic effects of orlistat combined with enzalutamide in vitro and castration in vivo on human PCa.


Development and validation of a prognostic score during tuberculosis treatment.
Death under care is a major challenge for tuberculosis (TB) treatment programs. We derived and validated a simple score to predict mortality during tuberculosis treatment in high endemicity areas. We used data for patients aged ≥15 years, diagnosed and treated for tuberculosis at the Yaounde Jamot Hospital between January 2012 and December 2013. Baseline characteristics associated with mortality were investigated using logistic regressions. A simple prognosis score (CABI) was constructed with regression coefficients for predictors in the final model. Internal validation used bootstrap resampling procedures. Models discrimination was assessed using c-statistics and calibration assessed via calibration plots and the Hosmer and Lemeshwow (H-L) statistics. The optimal score was based on the Youden's index. A total of 2250 patients (men 57.2%) with a mean age of 35.8 years were included; among whom 213 deaths (cumulative incidence 9.5%) were recorded. Clinical form of tuberculosis (C), age (A, years), adjusted body mass index (B, BMI, kg/m2) and status for HIV (Human immunodefiency virus) infection (I) were significant predictors in the final model (p < 0.0001) which was of the form Death risk = 1/(1 + e - (-1.3120 + 0.0474 ∗ age - 0.1866 ∗ BMI + 1.1637 (if smear negative TB) + 0.5418(if extra - pulmonary TB) + 1.3820(if HIV+))). The c-statistic was 0.812 in the derivation sample and 0.808 after correction for optimism. The calibration was good [H-Lχ2 = 6.44 (p = 0.60)]. The optimal absolute risk threshold was 4.8%, corresponding to a sensitivity of 81% and specificity of 67%. The preliminary promising findings from this study require confirmation through independent external validation studies. If confirmed, the model derived could facilitate the stratification of TB patients for mortality risk and implementation of additional monitoring and management measures in vulnerable patients.


Remodelling of bone around intramedullary stems in growing patients.
The remodelling of bone around intramedullary cemented stems, used for the fixation of massive distal femoral replacements in young patients, has been studied. Several types of remodelling have been identified, and this is common to all of the retrieved specimens that have been in situ for periods of 6 to 18 months. Transection of cortical bone and the insertion of a massive prosthesis leads to (a) the formation of a pedicle of bone or bony bridge that grows from the transection site over the shaft of the prosthesis, (b) bone resorption at the transection site, (c) the development of an inner porotic cortex surrounding the intramedullary stem and subperiosteal bone formation, and (d) a shell of bone around the acrylic cement. The tibial component that allows continued growth of the proximal tibial physis consists of a press fit metallic plateau with a stem that slides into an ultra-high-molecular-weight polyethylene sleeve inserted below the growth plate. A sclerotic layer of bone forms adjacent to a soft-tissue interface around both the sleeve and the metallic component. Remodelling of bone around intramedullary stems is attributed either to a redeveloping blood supply or to load adaptive changes.


Association between B7-H1 expression and bladder cancer: a meta-analysis.
B7 homolog 1 (B7-H1), which is also known as programmed death-L1, is an important member of the B7/CD28 costimulatory factor superfamily, which are emerging as important mediators of various host immune responses. B7-H1 is differentially expressed in various cell subsets and to different extents in human and murine cells. Human B7-H1 is constitutively expressed at low levels in dendritic cells and activated T cells (compared with high expression in activated murine T cells) and is highly expressed in monocytes and tumor cells. We conducted a meta-analysis to explore the association between B7-H1 expression and bladder cancer risk. Two groups were examined, including 352 bladder cancer cases and 60 healthy controls. Meta-analysis results revealed that B7-H1 expression is positively associated with bladder cancer and is strongly associated with the clinical stage of bladder cancer. However, no significant difference was found with respect to gender and the pathological grade of bladder cancer.


Surgical treatment of recurring preauricular sinus: supra-auricular approach.
Congenital preauricular sinus is a malformation of the preauricular soft tissues with an incidence ranging between 0.1 and 0.9% in Europe and the United States. It presents a high risk of recurrence when treated by a standard surgical technique (simple sinectomy), the incidence of which is reported to be between 19% and 40%. The supra-auricular approach, proposed by Prasad et al. in 1990, is easier to perform and presents a lower recurrence risk. Personal experience is presented in the treatment of congenital preauricular sinus with the supra-auricular approach as first choice or in the case of recurrence following previous standard surgery. This report includes a short review of the literature in order not only to focus on the supra-auricular approach and check the efficacy as far as concerns reduction of recurrence risk but also to contribute to a more widespread use of this method.


DMBT1 confers mucosal protection in vivo and a deletion variant is associated with Crohn's disease.
Impaired mucosal defense plays an important role in the pathogenesis of Crohn's disease (CD), one of the main subtypes of inflammatory bowel disease (IBD). Deleted in malignant brain tumors 1 (DMBT1) is a secreted scavenger receptor cysteine-rich protein with predominant expression in the intestine and has been proposed to exert possible functions in regenerative processes and pathogen defense. Here, we aimed at analyzing the role of DMBT1 in IBD. We studied DMBT1 expression in IBD and normal tissues by quantitative reverse transcription-polymerase chain reaction, immunohistochemistry, and mRNA in situ hybridization. Genetic polymorphisms within DMBT1 were analyzed in an Italian IBD case-control sample. Dmbt1(-/-) mice were generated, characterized, and analyzed for their susceptibility to dextran sulfate sodium-induced colitis. DMBT1 levels correlate with disease activity in inflamed IBD tissues. A highly significant fraction of the patients with IBD displayed up-regulation of DMBT1 specifically in the intestinal epithelial surface cells and Paneth cells. A deletion allele of DMBT1 with a reduced number of scavenger receptor cysteine-rich domain coding exons is associated with an increased risk of CD (P = .00056; odds ratio, 1.75) but not for ulcerative colitis. Dmbt1(-/-) mice display enhanced susceptibility to dextran sulfate sodium-induced colitis and elevated Tnf, Il6, and Nod2 expression levels during inflammation. DMBT1 may play a role in intestinal mucosal protection and prevention of inflammation. Impaired DMBT1 function may contribute to the pathogenesis of CD.


[Levels of fraction I and VW antigens in cultures of the plague microbe grown on yeast-casein, yeast-Hottinger broth and yeast-sunflower oil cake media].
The content of fraction 1 and VW-antigens in Y. pestis cultures grown in different media (yeast-casein medium, yeast medium with Hottinger digest, and yeast medium with sunflower-seed protein) was studied over the course of their growth by means of the antibody neutralization and microprecipitation in agar tests. The media under study were not inferior to the casein sulfuric hydrolysate-based medium used for control in their capacity for ensuring the synthesis of VW-antigens. The maximum accumulation of fraction 1 was observed in yeast medium with sunflower-seed protein. In all media the maximum content of fraction 1 was registered on day 3 of cultivation, and the maximum accumulation of VW-antigens on days 8-9 of incubation at 37 degrees C. The data obtained in this study make it possible to regard fraction 1 and VW-antigens as the secondary metabolites of Y. pestis.


Chronic lymphocytic leukemia: long-lasting remission with combination of cyclophosphamide, somatostatin, bromocriptine, retinoids, melatonin, and ACTH.
The usual, initial therapy of patients with chronic lymphocytic leukemia (CLL) involves alkylating agents, corticosteroids, purine analogs, and monoclonal antibodies. The combination of these agents may lead to high complete and overall response rates, but all patients inevitably relapse, and median progression-free survival varies between 16 and 48 months. Further, these treatments present the risk of myelosuppression and infection, so that some of the combination regimens require antibiotic, antiviral, and antimycotic prophylaxis during and after their administration. We treated 4 patients with previously untreated progressive stage I Rai CCL, with a combination of cyclophosphamide, somatostatin, bromocriptine, retinoids, melatonin, and ACTH. All the patients had partial remission after 2 months and continued treatment, which was gradually reduced if lymphocyte count fell below 4000/microL. No patients had disease recurrence, and progression-free survival has not yet been reached (125, 121, 73, and 21 months, respectively). Toxicity was absent, and patients underwent the treatment at home, while carrying out their normal activities.


Bermudagrass mite (Acari: Eriophyidae) infestation worsens in response to increasing nitrogen fertility and decreasing irrigation volume but not mowing height.
Severe bermudagrass mite (Aceria cynodoniensis Sayed) infestation stunts turfgrass growth and reduces the aesthetic and recreational value of managed bermudagrass. Management practices, such as fertilization, mowing, and irrigation, may impact bermudagrass mite infestation and damage, but empirical evidence is lacking. Two 20 wk experiments were conducted with potted bermudagrass in a greenhouse or nursery to evaluate the effect of varying nitrogen rates (0, 24.5, or 49 kg N/ha), mowing heights (1.3, 2.5, 3.8, or 5 cm), and irrigation rates (60%, 100%, or 140% evapotranspiration [ET] rate) on the densities of witch's brooms (i.e., stunted and deformed terminals symptomatic of infestation) and bermudagrass mites. Increasing nitrogen fertility from 0 to 49 kg N/ha increased witch's broom and bermudagrass mite densities by 292% and 339%, respectively. Bermudagrass fertilized with nitrogen maintained higher turf quality than unfertilized grass despite greater mite damage. Decreasing irrigation from 140% to 60% of the ET rate also increased witch's broom densities by 124%. Mowing height did not consistently affect witch's broom or mite densities. Witch's broom and mite densities were positively correlated and followed a general trend with greater densities in April-August and a decline in densities in August-October. These findings suggest that nitrogen fertilization and water stress influence bermudagrass mite damage. Thus, limiting nitrogen fertilization to a level necessary to maintain turfgrass health and quality (0.5 kg N/ha) and minimizing turfgrass water stress can complement current chemical control strategies as part of an integrated pest management program.


A rare case of conjunctival malignant melanoma with orbital invasion.
Conjunctival malignant melanoma is a rare ocular malignancy most commonly affecting mostly the elderly population. It is a pigmented lesion which canarise from primary acquired melanosis, de novo or from preexisting nevus. A 63 year old male presented with a chief complaints rapidly increasing mass in the left eye for two months following trauma with a wooden stick. He had preexisting nevus in the same eye. His best corrected visual acuity was 6/12 in right eye and 1/60 left eye respectively. Slit lamp biomicroscopy examination showed 4 cm x 4 cm pigmented mass in the nasal bulbar and inferior palpebral conjunctiva causing mechanical ectropion of the lower lid with keratinization of palpebral conjunctiva. Incisionalbiopsy of conjunctiva showed malignant melanoma. On computed tomography, there was expansion of bony orbit. Considering all the findings, exenteration of the left orbitwas done. Histopathological report of exenterated mass was suggestive of malignantmelanoma of conjunctiva. Conjunctival melanoma is a rare malignant tumor of eye which has high metastasis rate and the treatment option is surgery with adjuvant therapy.


Late Retrograde Migration of a Left Subclavian Artery Chimney Stent-Graft Into the Innominate Artery.
To report an uncommon case of chimney stent-graft migration in the aortic arch. A 29-year-old man presented with chronic left arm hyposthenia after late displacement and thrombosis of a left subclavian artery (LSA) chimney graft that migrated retrogradely into the innominate artery 2 years after deployment. The self-expanding LSA chimney was placed during a redo procedure to repair a pseudoaneurysm and type I endoleak after an index emergency thoracic endovascular aortic repair for traumatic aortic rupture 1 year earlier. The patient was successfully treated in an elective procedure via a median sternotomy, with arch aortotomy under circulatory arrest to remove the proximal end of the thrombosed chimney graft from the ostium of the innominate trunk. Three months later, a left carotid-to-subclavian bypass was performed to restore flow to the left arm. Migration of the proximal end of an overly long chimney graft that moved freely in the aortic arch exposed the patient to a high risk of stroke and death. Because of the high-risk situation, open repair under circulatory arrest was elected to remove the proximal end of the chimney graft, with no major complications.


The FRAX tool in French women: How well does it describe the real incidence of fracture in the OFELY cohort?
The FRAX tool estimates an individual's fracture probability over 10 years from clinical risk factors with or without bone mineral density (BMD) measurement. The aim of our study was to compare the predicted fracture probabilities and the observed incidence of fracture in French women during a 10-year follow-up. The probabilities of fracture at four major sites (hip, clinical spine, shoulder, or wrist) and at the hip were calculated with the FRAX tool in 867 women aged 40 years and over from the Os des Femmes de Lyon (OFELY) cohort.The incidence of fracture was observed over 10 years. Thus 82 women sustained 95 incident major osteoporotic (OP) fractures including 17 fractures at the hip. In women aged at least 65 years (n = 229), the 10-year predicted probabilities of fracture with BMD were 13% for major OP fractures and 5% for hip fractures, contrasting with 3.6% and 0.5% in women younger than 65 years (p < .0001). The predicted probabilities of both major OP and hip fractures were significantly higher in women with osteoporosis (n = 77, 18% and 10%) and osteopenia (n = 390, 6% and 2%) compared with women with normal BMD (n = 208, 3% and <1%; p < .0001. The predicted probabilities of fracture were two and five times higher in women who sustained an incident major OP fracture and a hip fracture compared with women who did not (p < .0001). Nevertheless, among women aged at least 65 years with low BMD values (T-score < or = -1; n = 199), the 10-year predicted probability of major OP fracture with BMD was 48% lower than the observed incidence of fractures (p < .01). A 10-year probability of major OP fracture higher than 12% identified more women with incident fractures than did BMD in the osteoporotic range (p < .05). In French women from the OFELY cohort, the observed incidence of fragility fractures over 10 years increased with age following a pattern similar to the predicted probabilities given by the FRAX tool. However, in women aged at least 65 years with low BMD, the observed incidence of fractures was substantially higher than the predicted probability.


Role of HDAC6-STAT3 in immunomodulatory pathways in Colorectal cancer cells.
Colorectal cancer (CRC) is one of the most common malignant neoplasms and the second leading cause of death from tumors worldwide. Therefore, there is a great need to study new therapeutical strategies, such as effective immunotherapies against these malignancies. Unfortunately, many CRC patients do not respond to current standard immunotherapies, making it necessary to search for adjuvant treatments. Histone deacetylase 6 (HDAC6) is involved in several processes, including immune response and tumor progression. Specifically, it has been observed that HDAC6 is required to activate the Signal Transducer and Activator of Transcription 3 (STAT3), a transcription factor involved in immunogenicity, by activating different genes in these pathways, such as PD-L1. Over-expression of immunosuppressive pathways in cancer cells deregulates T-cell activation. Therefore, we focused on the pharmacological inhibition of HDAC6 in CRC cells because of its potential as an adjuvant to avoid immunotolerance in immunotherapy. We investigated whether HDAC6 inhibitors (HDAC6is), such as Nexturastat A (NextA), affected STAT3 activation in CRC cells. First, we found that NextA is less cytotoxic than the non-selective HDACis panobinostat. Then, NextA modified STAT3 and decreased the mRNA and protein expression levels of PD-L1. Importantly, transcriptomic analysis showed that NextA treatment affected the expression of critical genes involved in immunomodulatory pathways in CRC malignancies. These results suggest that treatments with NextA reduce the functionality of STAT3 in CRC cells, impacting the expression of immunomodulatory genes involved in the inflammatory and immune responses. Therefore, targeting HDAC6 may represent an interesting adjuvant strategy in combination with immunotherapy.


Resting-State EEG Signal for Major Depressive Disorder Detection: A Systematic Validation on a Large and Diverse Dataset.
Major depressive disorder (MDD) is a global healthcare issue and one of the leading causes of disability. Machine learning combined with non-invasive electroencephalography (EEG) has recently been shown to have the potential to diagnose MDD. However, most of these studies analyzed small samples of participants recruited from a single source, raising serious concerns about the generalizability of these results in clinical practice. Thus, it has become critical to re-evaluate the efficacy of various common EEG features for MDD detection across large and diverse datasets. To address this issue, we collected resting-state EEG data from 400 participants across four medical centers and tested classification performance of four common EEG features: band power (BP), coherence, Higuchi's fractal dimension, and Katz's fractal dimension. Then, a sequential backward selection (SBS) method was used to determine the optimal subset. To overcome the large data variability due to an increased data size and multi-site EEG recordings, we introduced the conformal kernel (CK) transformation to further improve the MDD as compared with the healthy control (HC) classification performance of support vector machine (SVM). The results show that (1) coherence features account for 98% of the optimal feature subset; (2) the CK-SVM outperforms other classifiers such as K-nearest neighbors (K-NN), linear discriminant analysis (LDA), and SVM; (3) the combination of the optimal feature subset and CK-SVM achieves a high five-fold cross-validation accuracy of 91.07% on the training set (140 MDD and 140 HC) and 84.16% on the independent test set (60 MDD and 60 HC). The current results suggest that the coherence-based connectivity is a more reliable feature for achieving high and generalizable MDD detection performance in real-life clinical practice.


The administration of PRN medication by mental health nurses.
The use of PRN or 'as required' medication by mental health nurses is an important, yet little explored aspect of psychiatric inpatient care. In a survey of 100 inpatients in Canada (Craven et al. 1987), it was reported that 88% had been prescribed PRN medication. The most frequently administered drugs were antipsychotics, anticholinergics, and benzodiazepines. Similar results were found in a study by Walker (1991). Craven et al. (1987) also highlight that people over the age of 50 are more likely to be given PRN medication, and suggest that gender and legal status do not influence administration. Vitello et al. (1991), in a study of factors affecting the administration of PRN medication on a children's psychiatric unit, demonstrated that 91% of administrations were given orally (compared to 9% via intramuscular injection); however it is unclear if this finding can be generalized to an adult psychiatric setting. Mental health nurses' reasons for administering PRN medication have not been examined.


IFI16 filament formation in salivary epithelial cells shapes the anti-IFI16 immune response in Sjögren's syndrome.
IFN-inducible protein 16 (IFI16) is an innate immune sensor that forms filamentous oligomers when activated by double-stranded DNA (dsDNA). Anti-IFI16 autoantibodies occur in patients with Sjögren's syndrome (SS) and associate with severe phenotypic features. We undertook this study to determine whether the structural and functional properties of IFI16 play a role in its status as an SS autoantigen. IFI16 immunostaining in labial salivary glands (LSGs) yielded striking evidence of filamentous IFI16 structures in the cytoplasm of ductal epithelial cells, representing the first microscopic description of IFI16 oligomerization in human tissues, to our knowledge. Transfection of cultured epithelial cells with dsDNA triggered the formation of cytoplasmic IFI16 filaments with similar morphology to those observed in LSGs. We found that a majority of SS anti-IFI16 autoantibodies immunoprecipitate IFI16 more effectively in the oligomeric dsDNA-bound state. Epitopes in the C-terminus of IFI16 are accessible to antibodies in the DNA-bound oligomer and are preferentially targeted by SS sera. Furthermore, cytotoxic lymphocyte granule pathways (highly enriched in the SS gland) induce striking release of IFI16•dsDNA complexes from cultured cells. Our studies reveal that IFI16 is present in a filamentous state in the target tissue of SS and suggest that this property of DNA-induced filament formation contributes to its status as an autoantigen in SS. These studies highlight the role that tissue-specific modifications and immune effector pathways might play in the selection of autoantigens in rheumatic diseases.


Acute and chronic benign ulcers of the rectum.
In managing 21 patients with benign ulcers of the rectum, there were seven patients with acute bleeding ulcers and two with acute rectal necrosis. Acute, bleeding ulcers of the rectum are associated with serious illness or injury, similar to those thought to cause stress ulcers of the stomach and duodenum. Rectal prolapse, complete or incomplete, is the condition most commonly associated with chronic, benign ulcers of the rectum. Repair of the rectal prolapse was successful treatment. Two patients had a tight muscular stenosis at the anorectal ring. This appeared to be a causative factor as complete healing occurred after myotomy.


Diagnostic accuracy of quantitative real-time PCR assay versus clinical and Gram stain identification of bacterial vaginosis.
The purpose of this investigation was to determine the diagnostic accuracy of quantitative real-time polymerase chain reaction (PCR) assay in diagnosing bacterial vaginosis versus the standard methods, the Amsel criteria and the Nugent score. The Amsel criteria, the Nugent score, and results from the molecular tool were obtained independently from vaginal samples of 163 pregnant women who reported abnormal vaginal symptoms before 20 weeks gestation. To determine the performance of the molecular tool, we calculated the kappa value, sensitivity, specificity, and positive and negative predictive values. Either or both of the Amsel criteria (≥3 criteria) and the Nugent score (score ≥7) indicated that 25 women (15%) had bacterial vaginosis, and the remaining 138 women did not. DNA levels of Gardnerella vaginalis or Atopobium vaginae exceeded 10(9) copies/mL or 10(8) copies/mL, respectively, in 34 (21%) of the 163 samples. Complete agreement between both reference methods and high concentrations of G. vaginalis and A. vaginae was found in 94.5% of women (154/163 samples, kappa value = 0.81, 95% confidence interval 0.70-0.81). The nine samples with discordant results were categorized as intermediate flora by the Nugent score. The molecular tool predicted bacterial vaginosis with a sensitivity of 100%, a specificity of 93%, a positive predictive value of 73%, and a negative predictive value of 100%. The quantitative real-time PCR assay shows excellent agreement with the results of both reference methods for the diagnosis of bacterial vaginosis.


Primary duodenal follicular lymphoma: 6-years complete remission after combined radio-immunotherapy.
Primary gastrointestinal lymphoma (PGL) is known to account for 40% of all extranodal non-Hodgkin's lymphomas (NHLs) and between 4% to 12% of all NHLs. The small intestine is the site of presentation in 20-30% of cases, with the terminal ileum usually involved. Duodenal localizations have always been thought to be rare, but are presently growing in incidence. We herein report on a case of Stage IV primary duodenal FCL, located to the second portion of the duodenum with concomitant minimal bone marrow involvement. The patient was frontline approached with a conservative combined modality treatment consisting of 4 weekly infusions of the chimeric human-murine IgG1 mono-clonal antibody against the B-cell surface antigen CD-20, Rituximab (375 mg/m2) and consolidation 3D conformal external beam radiotherapy up to a total dose of 36 Gy given into 20 fractions to the involved duodenal portion. Six years after treatment has been completed, the patient is free from disease with no treatment-related toxicity.


Usefulness of Left Atrial Emptying Fraction to Predict Ventricular Arrhythmias in Patients With Implantable Cardioverter Defibrillators.
Impaired left atrial emptying fraction (LAEF) is an important predictor of mortality in patients with heart failure. As it may reflect increased LV wall stress, it might predict ventricular arrhythmia (VA) specifically. This study evaluated the predictive value of LAEF assessed with cardiovascular magnetic resonance (CMR) imaging with respect to appropriate device therapy (ADT) for VA and compared its role with CMR assessed scar size and other risk factors. In total, 229 patients (68% male, 63 ± 10 years, 61% ischemic cardiomyopathy) with LV ejection fraction ≤35% who underwent CMR and implantable cardioverter defibrillator (ICD) implantation for primary prevention in 2005 to 2012 were included. CMR was used to quantify LV volumes and function. LV scar size was quantified when late gadolinium enhancement was available (n = 166). Maximum and minimum left atrial volumes and LAEF were calculated using the biplane area-length method. The occurrence of ADT and mortality was assessed during a median follow-up of 3.9 years. Sixty-two patients (27%) received ADT. Univariable Cox analysis showed that male gender, creatinine level, minimum left atrial volume, LAEF, and total scar size were significant predictors of ADT. In multivariable Cox analysis, LAEF (hazard ratio 0.75 per 10%, p <0.01), and scar size (hazard ratio 1.03 per g, p = 0.03) remained the only independent predictors of ADT. Patients with both LAEF > median and scar size < median were at low risk (13% ADT at 5 years), whereas those with LAEF < median and scar size > median experienced 40% ADT at 5 years (log-rank p = 0.01). In conclusion, LAEF independently predicts ADT in patients with primary prevention ICDs. Combined assessment of LAEF and scar size identifies a group with low risk of ADT. Therefore, LAEF assessment could assist in risk stratification for VA to select patients with the highest benefit from ICD implantation.


Disability and masculinity in South African autosomatography.
This article examines the representation of disability by disabled black South African men as portrayed in two texts from the autosomatography genre, which encompasses first-person narratives of illness and disability. Drawing on extracts from Musa E. Zulu's The language of me and William Zulu's Spring will come, the article argues that physical disability affects heteronormative concepts of masculinity by altering the body, which is the primary referent for the construction and performance of hegemonic masculinity. In ableist contexts, the male disabled body may be accorded labels of asexuality. This article therefore reveals how male characters with disabilities reconstruct the male self by both reintegrating themselves within the dominant grid of masculinity and reformulating some of the tenets of hegemonic masculinity.


Low vs. high fidelity: the importance of 'realism' in the simulation of a stone treatment procedure.
Simulation training for stone surgery is now increasingly used as part of training curricula worldwide. A combination of low and high fidelity simulators has been used with varying degrees of 'realism' provided by them. In this review, we discuss low and high fidelity simulators used for ureteroscopy (URS) and percutaneous nephrolithotomy (PCNL) stone procedures with their advantages, disadvantages and future direction for endourological simulation surgery. The final goal will be to understand whether or not 'realism' has to be considered as a critical element in simulation for this field. There is a wide range of simulators available for URS and PCNL training ranging from basic bench-type model to advanced virtual reality and cadaveric models, all providing various levels of realism. Although basic models might be more useful to novices, advanced models allow for complex and more realistic simulation training. With a wide variety of simulators now available and given the latest novelties in modular training curriculums, combination of low and high fidelity simulators that provide a realistic and cost-effective option seems to be the way forward. It is unavoidable that simulators will play an increasing role in endourological training.


Evaluation of Nephroprotective Efficacy of Hypoxic Preconditioning in Patients Undergoing Coronary Artery Bypass Surgery.
Nonpulsatile blood flow plays an important role in the pathogenesis of renal dysfunction in patients with extracorporeal circulation. In our opinion, hypoxic preconditioning (HP) can be used to protect kidneys from postsurgical dysfunction. The aim of this study was to evaluate nephroprotective efficacy of HP in myocardial revascularization with extracorporeal circulation. The randomized, controlled trial was performed in 63 patients undergoing coronary artery bypass grafting (CABG). Thirty-three patients were subjected to HP during CABG; 30 patients were included in the comparison group. All patients underwent dynamic renal scintigraphy with (99m)Тc-diethylenetriaminepentaacetic acid and were subjected to measuring the concentration of lipocalin in blood serum before and after CABG. After CABG, the mean values of the total glomerular filtration rate (GFR) and GFR for each kidney significantly decreased only in patients of the comparison group. Significant increases in the concentration of serum neutrophil gelatinase-associated lipocalin occurred 5 h after surgery both in the group with HP (70.65 ± 46.71 to 127.58 ± 98.46 ng/ml) and in the comparison group (65.01 ± 38.64 to 171.65 ± 89.91 ng/ml). At the same time, the mean difference values between pre- and postoperative lipocalin levels were 56.94 ± 51.75 ng/ml in the study group and 106.64 ± 51.27 ng/ml in the comparison group; these differences were highly statistically significant (р = 0.004). The results of our study showed that (i) HP exerts nephroprotection in patients undergoing on-pump CABG, and (ii) determination of the lipocalin-2 level can be used for early diagnosis of acute kidney injury in cardiac surgery patients.


Effects of lignin, cellulose, hemicellulose, sucrose and monosaccharide carbohydrates on soybean physical stem strength and yield in intercropping.
Soybean (Glycine max L.) has been extensively cultivated in maize-soybean relay intercropping systems in southwest China. However, during the early co-growth period, soybean seedlings suffer from severe shading by maize resulting in lodging and significant yield reduction. The purpose of the present research was to investigate the reasons behind severe lodging and yield loss. Therefore, four different soybean genotypes (B3, B15, B23, and B24) having different agronomic characteristics were cultivated in intercropping and monocropping planting patterns. The results showed that under different planting patterns, the stem resistance varied among genotypes (P < 0.01). The lodging resistance index of B3, B15, B23, and B24 genotypes was 70.9%, 60.5%, 65.2%, and 57.4%, respectively, under intercropping, among which the B24 genotype was less affected by the shade environment as there was little decrease in the lodging resistance index of this genotype under intercropping. The lignin content of B23 and B24 was significantly higher than that of B3 and B15 under both planting patterns. Under intercropping, the hemicellulose content of B23 and B24 stems was significantly higher than that of B3 and B15. Compared to the monocropping, the content of mannose in the structural carbohydrate of soybean stems was decreased in all genotypes except B23, but the difference was not significant. The content of xylose in the structural carbohydrate of soybean stems was significantly higher than that in B3 and B15. Mannose content showed no significant difference among genotypes. The arabinose content of B24 was significantly higher than that of B3, B15, and B23. The effective pod number, seed number per plant, seed weight per plant and yield of soybean plants were significantly decreased under intercropping. Conclusively, manipulation of structural and nonstructural carbohydrate rich soybean genotypes in intercropping systems could alleviate the yield loss due to lodging.


Comparison of PCR-RFLP with 21-plex PCR and rDNA Sequencing for Identification of Clinical Yeast Isolates.
Non-albicans Candida species and other rare yeasts have emerged as major opportunistic pathogens in fungal infections. Identification of opportunistic yeasts in developing countries is mainly performed by phenotypic assay, which are time-consuming and prone to errors. The aim of the present study was to evaluate PCR-RFLP as a routinely used identification technique for the most clinically important Candida species in Iran and make a comparison with a novel multiplex PCR, called 21-plex PCR. One hundred and seventy-three yeast isolates from clinical sources were selected and identified with sequence analysis of the D1/D2 domains of rDNA (LSU rDNA) sequencing as the gold standard method. The results were compared with those obtained by PCR-RFLP using MspI restriction enzyme and the 21-plex PCR. PCR-RFLP correctly identified 93.4% of common pathogenic Candida species (C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, and P. kudriavsevii (= C. krusei)) and was able to identify 45.5% of isolates of the uncommon yeast species compared to the D1/D2 rDNA sequencing. Compared with PCR-RFLP, all common Candida species and 72.7% of uncommon yeast species were correctly identified by the 21-plex PCR. The application of the 21-plex PCR assay as a non-sequence-based molecular method for the identification of common and rare yeasts can reduce turnaround time and costs for the identification of clinically important yeasts and can be applied in resource-limited settings.


Bacteriocins and other bioactive substances of probiotic lactobacilli as biological weapons against Neisseria gonorrhoeae.
In the search of new antimicrobial agents against Neisseria gonorrhoeae, the bacteriocins-producing probiotic lactobacilli deserve special attention. The inhibitory effects of biosubstances such as organic acids, hydrogen peroxide and each bacteriocin-like inhibitory substance (BLIS) L23 and L60 on the growth of different gonococcal strains were investigated. Different non-treated and treated cell-free supernatants of two probiotic lactobacilli containing these metabolites were used. The aims of this work were (i) to evaluate the antimicrobial activity of the biosubstances produced by two probiotic lactobacilli, estimating the proportion in which each of them is responsible for the inhibitory effect, (ii) to define their minimum inhibitory concentrations (MICs) and, (iii) to determine the potential interactions between these biosubstances against N. gonorrhoeae. The main antimicrobial metabolites were the BLIS-es L23 and L60 in comparison with other biosubstances. Proportionally, their contributions to the inhibition on the gonococcal growth were 87.28% and 80.66%, respectively. The MIC values of bacteriocins were promising since these substances, when diluted, showed considerable inhibitory activity for all gonococci. In the interaction between bacteriocins, 100% of synergism was found on the gonococcal growth. In summary, this study indicates that both L23 and L60 could potentially serve to design new bioproducts against N. gonorrhoeae.


Effect of Haemophilus somnus on nitric oxide production and chemiluminescence response of bovine blood monocytes and alveolar macrophages.
Haemophilus somnus is able to survive and multiply in bovine blood monocytes (BBM) and alveolar macrophages (BAM), but the mechanisms used by H. somnus to evade killing mechanisms of bovine mononuclear phagocytes are not completely understood. To study the bactericidal ability of bovine mononuclear phagocytes following interaction with H. somnus, in vitro assay systems were developed to detect the luminol-dependent chemiluminescence response (LDCL) and nitric oxide (NO) production of BBM and BAM. Live logarithmically growing or stationary phase H. somnus inhibited the LDCL of BBM and BAM costimulated with opsonized Staphylococcus aureus. Inhibition of the LDCL response of BBM and BAM was not mediated by live H. somnus opsonized with hyperimmune serum, or by killed bacteria. H. somnus stimulated both BBM and BAM to produce NO at levels comparable with Escherichia coli lipopolysaccharide. While NO was being produced, viable H. somnus could still be isolated from the cell cultures. The ability of H. somnus to inhibit LDCL of both BBM and BAM, and resistance to NO killing may be an important mechanism that contributes to survival of the organism following ingestion by bovine mononuclear phagocytes.


Growth of factor-dependent hemopoietic precursor cell lines.
Cell lines have been produced from long-term cultures of mouse bone marrow that require a factor, present in WEHI-3 conditioned medium (CM) or in spleen CM, for their sustained growth. The cell lines were obtained from nonvirus-treated cultures, are nonleukemic, maintain a normal karyotype, and form colonies showing granulocyte maturation when plated in soft agar. Granulocyte/macrophage (GM) colony-stimulating factor is not the inductive moiety involved in the maintenance of proliferation of these cells. It is suggested that the cell lines represent a self-renewing population of cells ancestral to GM colony-forming cells, which may be responding to a hitherto unrecognized regulator.


Cognitive and affective theory of mind in Korsakoff's syndrome.
Korsakoff's syndrome (KS) is a chronic neuropsychiatric disorder characterised by severe anterograde amnesia and executive deficits. Theory of Mind (ToM) is the capacity to represent others' mental states such as their knowledge, thoughts, feelings, beliefs, and intentions in order to explain and predict their behaviour. Surprisingly this topic has received hardly any attention in research on KS, although the severity of behavioural problems in KS suggest possible ToM difficulties. The aim of the present study was therefore to assess whether cognitive and affective ToM are impaired in patients with KS. We examined 21 KS patients and 21 age- and gender-matched healthy controls on three standardised tests that assess cognitive and affective ToM, including the subtests of the mini-Social Cognition and Emotional Assessment battery and a specialised version of the Sally-Anne Test. KS patients showed largely impaired cognitive and affective ToM compared to healthy controls, as reflected in large effect sizes on both cognitive and affective ToM tests. Executive deficits explained problems in emotion recognition, but not other ToM aspects. KS patients have large impairments in both cognitive and affective aspects of social cognition. Their ability to recognise emotions, take the perspective of others, and understand socially awkward situations is vastly compromised. The impairments in ToM functioning are to a large degree functionally discrepant from executive disorders that are commonly present in KS. This study therefore highlights the importance to properly index ToM functioning in neuropsychological assessments for individuals with a possible KS diagnosis.


Methodology of a new inflammatory arthritis registry: TReasure
The TReasure registry, created in 2017, is an observational multicenter cohort that includes inflammatory arthritis patients. This article reviews the methodology and objectives of the TReasure registry established to collect data from rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients. Fifteen rheumatology centers in Turkey will contribute data to the TReasure database. The actual proprietor of the database is the Hacettepe Rheumatology Association (HRD) and Hacettepe Financial Enterprises. Pharmaceutical companies that operate in Turkey (in alphabetical or er), Abbvie, Amgen, BMS, Celltrion Healthcare, Novartis, Pfizer, Roche, and UCB, support the TReasure registry. TReasure is a web-based database to which users connect through a URL (https://www.trials-network.org/treasure) with their unique identifier and passwords provided for data entry and access. TReasure records demographic and clinical features, comorbidities, radiology and laboratory results, measures of disease activity, and treatment data. TReasure will provide us with various types of data, such as a cross-sectional view of the current nationwide status of the patients currently receiving these treatments, and retrospective data as much as allowed by the participating centers' records. Finally, a high-quality prospective dataset will be built over the ensuing years from patients with a new diagnosis of RA or SpA.


Efficacy of TeachTown: Basics computer-assisted intervention for the Intensive Comprehensive Autism Program in Los Angeles Unified School District.
Computer Assisted Instruction (CAI) has shown increased popularity recently and there are many studies showing promise for this approach for children with Autism Spectrum Disorders (ASD). However, there are no between-subject studies to date assessing the efficacy of CAI with this population. In this study, 47 preschool and K-1 students in ASD classrooms participated from Los Angeles Unified School District. TeachTown: Basics, a CAI program which also includes supplementary off-computer activities, was implemented over 3 months for approximately 20 minutes per day on the computer and 20 minutes per day in supplementary TeachTown: Basics activities. Compared to the students in the control group, the TeachTown: Basics students showed more improvement overall on language and cognitive outcome measures. In addition, students who used TeachTown: Basics demonstrated significant progress overall in the software and those students who used the program for more time demonstrated larger gains within the software and in outcome measures. Although not conclusive, these findings offer possibilities for the use of CAI for remediating many deficits for children with ASD and other special needs. In addition, CAI may offer solutions to schools and parents with insufficient funds for more expensive treatments.


Molecular and immunological characterization of shellfish allergens.
Shellfish (crustaceans and mollusks) have long been known as a common cause of allergic reactions to food. Like other food allergies, the allergic reactions to shellfish involve IgE-mediated Type I hypersensitivity. Biochemical and molecular studies have documented the major shrimp allergen is the muscle protein tropomyosin. Subsequent molecular cloning studies on lobsters and crabs have characterized this protein as the common allergen in crustaceans. There has also been strong immunological evidence that tropomyosin is a cross-reactive allergen among crustaceans and mollusks. This is further confirmed by recent studies on the identification of allergens in squid and abalone. The advances in the characterization of shellfish allergens will not only enhance our understanding on the physiological basis of shellfish allergy but also lay the groundwork for the development of diagnostic and therapeutic design in food allergies.


Design and analysis of keratoconus tissue microarrays.
The aim was to produce 2 tissue microarrays (TMAs) for keratoconus (KC) corneas and to evaluate the expression of stress-related markers, epidermal growth factor receptor (EGFR), and 8-oxo-2'-deoxyguanosine (8-OHdG), in KC corneas. The corneal buttons of 66 patients with KC were included in both TMAs; 10 Fuchs endothelial corneal dystrophy (FECD), 20 normal autopsy corneas, and 32 nonocular tissue cores served as controls. The expression of immunolabeling for EGFR and 8-OHdG in KC corneas was compared with those of the controls by TMAJ software using an H-score index. To further interpret our findings, pig eyes under different preservation conditions were stained for the same markers. With 2 TMAs, we designed an effective model to investigate KC corneas at the protein level. The EGFR in epithelial cells showed significant upregulation in KC specimens compared with that in FECD controls (P = 0.009), and this was also higher in autopsy controls compared with that in KC corneal samples (P = 0.0002). The 8-OHdG in epithelial cells was elevated in KC samples compared with that in the FECD specimens (P = 0.03), whereas autopsy controls showed higher levels compared with those shown by the KC corneal samples (P < 0.0001). Immunohistochemical staining intensities for both markers in pig corneas correlated with increased time to fixation. TMAs simultaneously enable efficient, high-throughput analysis of tissue samples. The upregulation of EGFR and 8-OHdG protein levels in KC epithelium compared with FECD controls implicates oxidative stress in KC corneas. The expression of these stress markers is increased depending on the time to preservation, which may explain the increased levels of these markers in autopsy control corneas.


Aqueous solution speciation of Fe(III) complexes with dihydroxamate siderophores alcaligin and rhodotorulic acid and synthetic analogues using electrospray ionization mass spectrometry.
Aqueous solutions of Fe3+ complexes of cyclic (alcaligin) and linear (rhodotorulic acid) dihydroxamate siderophores and synthetic linear eight-carbon-chain and two-carbon-chain dihydroxamic acids ([CH3N(OH)C=O)]2(CH2)n; H2Ln; n = 2 and 8) were investigated by electrospray ionization mass spectrometry (ESI-MS). Information was obtained relevant to the structure and the speciation of various Fe(III)-dihydroxamate complexes present in aqueous solution by (1) comparing different ionization techniques (ESI and FAB), (2) altering the experimental parameters (Fe3+/ligand ratio, pH, cone voltage), (3) using high-stability hexacoordinated Fe(III) siderophore complex mixtures (ferrioxamine B/ferrioxamine E) as a calibrant to quantify intrinsically neutral (H+ clustered or protonated) and intrinsically charged complexes, and (4) using mixed-metal complexes containing Fe3+, Ga3+, and Al3+. These results illustrate that for all dihydroxamic acid ligands investigated multiple tris- and bis-chelated mono- and di-Fe(III) species are present in relative concentrations that depend on the pH and Fe/L ratio.


Diagnostic yield, safety, and impact of transbronchial lung biopsy in mechanically ventilated, critically ill patients: a retrospective study.
Pulmonary infiltrates of variable etiology are one of the main reasons for hypoxemic respiratory failure leading to invasive mechanical ventilation. If pulmonary infiltrates remain unexplained or progress despite treatment, the histopathological result of a lung biopsy could have significant impact on change in therapy. Surgical lung biopsy is the commonly used technique, but due to its considerable morbidity and mortality, less invasive bronchoscopic transbronchial lung biopsy (TBLB) may be a valuable alternative. Retrospective, monocentric, observational study in mechanically ventilated, critically ill patients, subjected to TBLB due to unexplained pulmonary infiltrates in the period January 2014 to July 2019. Patients' medical records were reviewed to obtain data on baseline clinical characteristics, modality and adverse events (AE) of the TBLB, and impact of the histopathological results on treatment decisions. A multivariable binary logistic regression analysis was performed to identify predictors of AE and hospital mortality, and survival curves were generated using the Kaplan-Meier method. Forty-two patients with in total 42 TBLB procedures after a median of 12 days of mechanical ventilation were analyzed, of which 16.7% were immunosuppressed, but there was no patient with prior lung transplantation. Diagnostic yield of TBLB was 88.1%, with AE occurring in 11.9% (most common pneumothorax and minor bleeding). 92.9% of the procedures were performed as a forceps biopsy, with organizing pneumonia (OP) as the most common histological diagnosis (54.8%). Variables independently associated with hospital mortality were age (odds ratio 1.070, 95%CI 1.006-1.138; p = 0.031) and the presence of OP (0.182, [0.036-0.926]; p = 0.040), the latter being confirmed in the survival analysis (log-rank p = 0.040). In contrast, a change in therapy based on histopathology alone occurred in 40.5%, and there was no evidence of improved survival in those patients. Transbronchial lung biopsy remains a valuable alternative to surgical lung biopsy in mechanically ventilated critically ill patients. However, the high diagnostic yield must be weighed against potential adverse events and limited consequence of the histopathological result regarding treatment decisions in such patients.


[Vaccinology update for 2008: what's new in Switzerland?].
Immunization against HPV is now both recommended and reimbursed within the base medical insurance. The epidemiological data and the behavior of adolescents indicate that HPV immunization should be completed by the 15th birthday, catch-up being transiently recommended until the 20th birthday. The immunization against chickenpox of healthy children < 11 years remains non recommended, 2 vaccine doses being however recommended for high-risks children and adults. Hepatitis A vaccination is finally also reimbursed for high-risk patients - except for travelers. Finally, the WHO certified www.infovac.ch website now displays in French and German all information related to vaccine-preventable diseases and immunizations recommended in Switzerland, for both the professionals and the public. A source of information to be recommended without hesitation!


Nucleation and structural growth of cluster crystals.
We study the nucleation of crystalline cluster phases in the generalized exponential model with exponent n = 4. Due to the finite value of this pair potential for zero separation, at high densities the system forms cluster crystals with multiply occupied lattice sites. Here, we investigate the microscopic mechanisms that lead to the formation of cluster crystals from a supercooled liquid in the low-temperature region of the phase diagram. Using molecular dynamics and umbrella sampling, we calculate the free energy as a function of the size of the largest crystalline nucleus in the system, and compare our results with predictions from classical nucleation theory. Employing bond-order parameters based on a Voronoi tessellation to distinguish different crystal structures, we analyze the average composition of crystalline nuclei. We find that even for conditions where a multiply occupied fcc crystal is the thermodynamically stable phase, the nucleation into bcc cluster crystals is strongly preferred. Furthermore, we study the particle mobility in the supercooled liquid and in the cluster crystal. In the cluster crystal, the motion of individual particles is captured by a simple reaction-diffusion model introduced previously to model the kinetics of hydrogen bonds.


Estimation of Total and Inorganic Arsenic Intake from the Diet in Korean Adults.
Arsenic (As) is a major environmental pollutant and a known human carcinogen that is widely distributed in the air, soil, and water. General population is mainly exposed to As through drinking water and food from the contaminated water and soil. Arsenic in drinking water is generally well controlled now. This study was performed to estimate total and inorganic As intake and to determine the major contributing source in the Korean adult diet. The study subjects were 2117 healthy adults (922 males and 1195 females) who had not been occupationally exposed to As. Total dietary intake was studied using the 24-h recall method, which included 138 specific food items. The estimates of total As and inorganic As intake were based on total and inorganic As contents in each food item consumed during the last 24 h. Daily dietary intake was estimated to be 1373.6 g. Total As intake was estimated to be 145.4 µg As/day. Total dietary As intake was correlated with consumption of fish/shellfish, seaweeds, and grains. Approximately 87% of total dietary As intake was attributed to seafood, such as 105.5 µg As/day from fish/shellfish and 20.5 µg As/day from seaweeds. Inorganic As intake was estimated to be 10.4 µg As per day. Inorganic As intake was mainly provided by grains (6.4 µg As/day), followed by seaweeds and fish/shellfish. Our results indicate that seafood and grains are the main As dietary sources in Korean adults and that dietary As exposure may be associated with individual dietary habits and environmental As contamination among countries.


Reconstruction of the breast following radical mastectomy.
A method of reconstruction of the breast following radical mastectomy is presented. The technique involves the use of an individually made Silastic prosthesis inserted three to six months after the mastectomy. A new simple method of nipple reconstruction is described, and the total restoration can be achieved in one operation. It is suggested that reconstruction of the breast be considered more frequently in patients subjected to mastectomy.


Thalamic deep brain stimulation for tremor-predominant Parkinson's disease.
Determine the long-term efficacy of thalamic deep brain stimulation (DBS) for treatment of tremor among individuals with tremor-predominant Parkinson's disease (PD).Design. Longitudinal, unblinded assessment of tremor and activities of daily living (ADL) at baseline (pre-surgical), and post-operative intervals of 1, 3, and 12 months, and annually thereafter up to 3 years. A clinical series of 19 individuals undergoing placement of a DBS system for treatment of PD-related tremor. A battery of subjective and objective measures of tremor was completed at planned pre- and post-operative intervals. Stimulation was associated with significant improvement on subjective and objective measures of ADL performance, midline tremor, and contralateral upper and lower extremity tremor, including parkinsonian resting and action tremors, over the follow-up period. Ipsilateral tremor showed little or no effect of stimulation after the first 3 months. Antiparkinsonian medication use and stimulation parameters showed little or no change over the course of follow-up. About half (53%) of all individuals reported at least one side effect, generally mild, during the follow-up period, with paresthesias and dysarthria being the most common. A total of two leads required replacement due to (1) infection, and (2) adverse side effects (i.e. burning and tingling with stimulation). DBS is associated with stable tremor control in PD. Side-effects are typically easily managed with stimulation adjustments, although in some cases lead replacement may be required.


Evaluation of the neuroprotective effects of anti-inflammatory drugs in experimental spinal cord damage.
In this study, we aimed to investigate the effectiveness of etofenamate and compare it with methyl prednisolone in the experimental spinal cord trauma model. A total of 31 Wistar Albino rats weighed between 220 and 270 gr were used in this study. The rats were divided into three groups as the control; posttraumatic normal saline (NS), trauma + E; posttraumatic etofenamate; and trauma + methylprednisolone, posttraumatic methylprednisolone. All medications were given into the peritoneum. Six hours after trauma and drug administration, approximately 2 cm of cord segment in the area subjected to dorsal laminectomy was dissected from the dura spinal cord and removed. The samples were histopathologically examined. In this study, significant differences were found both between trauma + NS and trauma + methylprednisolone, and between trauma NS and trauma + etofenamate, and trauma + methylprednisolone and trauma + etofenamate groups according to the Ivan Damjanov criteria and in terms of petechial hemorrhage, diffuse bleeding, loss in the regulation of grey and white matters, edema, necrosis, and cystic degeneration findings. According to the Ivan Damjanov criteria, trauma + NS group was found as Grades 2-3, trauma + etofenamate group as Grade 1, and trauma + methylprednisolone as Grades 1-2. Neuroprotective effect of etofenamate was found to be stronger than that of methyl prednisolone in rats with induced posttraumatic spinal cord damage (Tab. 4, Ref. 24). Keywords: etofenamate, methylprednisolone, spinal trauma, rats.


Relationship between foot type, foot deformity, and ulcer occurrence in the high-risk diabetic foot.
We hypothesized an association between foot type, foot deformity, and foot ulceration and conducted an analysis of a well-characterized, high-risk diabetic population of 398 subjects. The average age was 62 years of age and 74% of the study population were males. Foot-type distributions were 19.5% pes cavus (high arch), 51.5% neutrally aligned (normal arch), and 29.0% pes planus (low arch). We quantified the presence of hallux valgus (23.9%), hammer/claw toes (46.7%), and hallux limitus (24.4%). A significant association was found between foot type and hallux valgus (p = 0.003); pes planus feet had the highest prevalence as compared with neutrally aligned feet (odds ratio [OR] = 2.43, p = 0.0006). Foot type was also significantly associated with fixed hammer/claw toes (p = 0.01); pes cavus feet had the highest prevalence as compared with neutrally aligned feet (OR = 3.89, p = 0.001). Foot type was also significantly associated with hallux limitus (p = 0.006) with pes planus feet having the highest prevalence as compared with neutrally aligned feet (OR = 2.19, p = 0.003). However, foot type was not significantly related to any ulcer outcome (p = 0.7). Fixed hammer/claw toes (OR = 3.91, p = 0.003) and hallux limitus (OR = 3.02, p = 0.006) were associated with increased risk of any ulcer occurrence. This study affirms that foot type and foot deformity are related and that foot deformities are associated with ulcer occurrence.


Assessment of the Tear Film Lipid Layer Thickness after Cataract Surgery.
To evaluate changes in the tear film lipid layer thickness (LLT) after cataract surgery and the effects of cataract surgery on dry eye syndrome (DES) and meibomian gland dysfunction (MGD). LLT measurements obtained using the LipiView interferometer, tear break-up time (TBUT) measurements, Schirmer's tests, Oxford staining scores, lid margin and meibomian gland findings, and the Ocular Surface Disease Index (OSDI) questionnaire scores were evaluated before and one and three months after cataract surgery. Forty-three eyes (43 patients) were included. LLT was significantly thinner one month after surgery than at baseline (P = 0.004). TBUT was significantly shorter at both one (P < 0.001) and three (P < 0.001) months after surgery than at baseline. OSDI scores were significantly higher (P < 0.001) and the meibum quality was significantly poorer (P = 0.001) at one month after surgery than at baseline. TBUT was significantly and positively correlated with LLT (r = 0.29, P < 0.001), while the OSDI (r = -0.38, P < 0.001) and Oxford staining (r = -0.30, P = 0.001) scores and the meibum quality (r = -0.21, P = 0.01) were significantly and negatively correlated with LLT. The tear film LLT was significantly thinner and DES and MGD parameters showed deterioration after cataract surgery. In addition, LLT was significantly correlated with DES and MGD parameters. These results suggest that clinicians should consider the tear film lipid layer while managing the exacerbation of DES after cataract surgery.


Form-to-expectation matching effects on first-pass eye movement measures during reading.
Recent Electroencephalography/Magnetoencephalography (EEG/MEG) studies suggest that when contextual information is highly predictive of some property of a linguistic signal, expectations generated from context can be translated into surprisingly low-level estimates of the physical form-based properties likely to occur in subsequent portions of the unfolding signal. Whether form-based expectations are generated and assessed during natural reading, however, remains unclear. We monitored eye movements while participants read phonologically typical and atypical nouns in noun-predictive contexts (Experiment 1), demonstrating that when a noun is strongly expected, fixation durations on first-pass eye movement measures, including first fixation duration, gaze duration, and go-past times, are shorter for nouns with category typical form-based features. In Experiments 2 and 3, typical and atypical nouns were placed in sentential contexts normed to create expectations of variable strength for a noun. Context and typicality interacted significantly at gaze duration. These results suggest that during reading, form-based expectations that are translated from higher-level category-based expectancies can facilitate the processing of a word in context, and that their effect on lexical processing is graded based on the strength of category expectancy.


Highly efficient transduction of human monocyte-derived dendritic cells with subgroup B fiber-modified adenovirus vectors enhances transgene-encoded antigen presentation to cytotoxic T cells.
The efficiency of dendritic cells (DC) as immunotherapeutic vaccines critically depends on optimal delivery of target Ags. Although DC modified by subgroup C type 5 recombinant adenoviruses (rAd5) provide encouraging results, their clinical application is hampered by the need for high viral titers to achieve sufficient gene transfer, due to the lack of the Ad5 fiber receptor. We now demonstrate that rAd5 carrying subgroup B Ad fibers are up to 100-fold more potent than classical rAd5 for gene transfer and expression in human DC, rAd5 with a type 35 fiber (rAd5F35) being the most efficient vector. This improvement relates to a greater and faster virus entry and to an increased transgene expression especially following DC maturation. Furthermore, these new vectors possess enhanced synergistic effects with other activation signals to trigger DC maturation. Consequently, rAd5F35-infected DC engineered to express the gp100 melanoma-associated Ag largely exceed rAd5-infected DC in activating gp100-specific CTL. Finally, the DC infection pattern of rAd5F35 is fully conserved when DC are in the vicinity of primary skin-derived fibroblasts, suggesting this vector as a candidate for in vivo targeting of DC. Thus, subgroup B fiber-modified rAd5 constitute a major breakthrough in the exploitation of ex vivo rAd-targeted DC as clinically relevant vaccines and may also be suitable for in vivo genetic modification of DC.


Scarring trachoma is associated with polymorphism in the tumor necrosis factor alpha (TNF-alpha) gene promoter and with elevated TNF-alpha levels in tear fluid.
Tumor necrosis factor alpha (TNF-alpha) may play a central role in the disease pathogenesis which occurs as a consequence of chlamydial infection. To investigate the importance of TNF-alpha gene promoter polymorphisms and TNF-alpha levels in tear fluid in scarring trachoma, a large matched-pair case-control study was performed in The Gambia. The -308A allele was present in a higher proportion of patients (28.4%) than controls (18.4%), with an increasing association for homozygotes (chi2 for trend, P = 0.032; allele frequency, 0.163 in patients and 0.099 in controls; chi2, P = 0.025). For the -238A allele, the association was similar but not significant. The disease association was highly significant when the number of either -308A or -238A sites in an individual was considered (P = 0.003). TNF-alpha promoter alleles are tightly linked to some HLA class I and II alleles, but multivariate analysis confirmed that the disease associations were independent of HLA, although a class I allele, A*6802, is also associated with disease. TNF-alpha was more frequently detected in tear samples from patients (27.6%) than from controls (15.9%), increasingly so for higher levels of detectable TNF-alpha (P = 0.015). Among patients, detectable TNF-alpha in tears was highly associated with the presence of ocular chlamydial infection (P < 0.001). The results indicate that TNF-alpha plays a major role in the tissue damage and scarring which occurs as a consequence of Chlamydia trachomatis infection.


Annual report of the Committee on Gynecologic Oncology, the Japan Society of Obstetrics and Gynecology: Annual Patient Report for 2018 and Annual Treatment Report for 2013.
To provide information including the trend of gynecological malignancies in Japan, we hereby present the Annual Patient Report for 2018 and the Annual Treatment Report for 2013, on the outcomes of patients who started treatment in 2013. The Japan Society of Obstetrics and Gynecology maintains an annual tumor registry, where information on gynecological malignancies from various participating institutions is gathered. The data of patients whose treatment with gynecologic malignancies was initiated in 2018 were analyzed retrospectively. Survival of the patients who started treatment with cervical, endometrial, and ovarian cancer in 2013 was analyzed by using the Kaplan-Meier, log-rank, and Wilcoxson tests. Treatment was initiated in 2018 for 7304 patients with cervical cancer; 11 230 with endometrial cancer; 7031 with ovarian, tubal, and peritoneal cancer; 2072 with ovarian borderline tumors; and with the others (222 vulvar cancer, 159 vaginal cancer, 413 uterine sarcoma, 54 uterine adenosarcoma, and 135 trophoblastic diseases). This clinicopathological information was summarized as the Patient Annual Report. The 5-year survival rates of the patients with cervical cancer were 93.1%, 75.9%, 59.1%, and 31.2% for Stages I, II, III, and IV, respectively. The 5-year survival rates for the patients with endometrial cancer were 94.1%, 89.2%, 73.6%, and 25.8% for Stages I, II, III, and IV, respectively. The 5-year survival rates for the patients with ovarian cancer (surface epithelial-stromal tumors) were 89.7%, 76.8%, 49.1%, and 32.4% for Stages I, II, III, and IV, respectively. The annual report is important to provide knowledge on gynecological malignancy trends in Japan.


Surface proteins and fibrinolytic activity of cultured mammalian cells.
Surface proteins and fibrinolysis were investigated in a variety of cell types. A large external transformation-sensitive protein was demonstrated by lactoperoxidase-catalyzed iodination. Electron microscope autoradiography confirmed that the technique labeled surface material only. The protein was present in explants of normal tissues was well as in nontumor-producing cultured cell lines. It was not lost during long-term culture. Neoplastic transformation in vitro, whether spontaneous or induced by a chemical carcinogen or virus, led to the loss of the material in most but not all cases. The protein was also absent from many but not all spontaneous and induced tumors of the different types tested. Elevated fibrinolytic activity was demonstrated in a number of normal tissues and non-tumor-producing cell lines. It was also present in most sarcomas but absent from most carcinomas that we have examined, except for a cell line from a well-differentiated bladder tumor. The correlation between absence of large external transformation-sensitive protein and fibrinolysis was examined, and it was found that activation of plasminogen was not sufficient to cause the absence of this surface protein.


Is SHORT syndrome another phenotypic variation of PITX2?
Even though responsible genetic loci and mode of inheritance for the Rieger syndrome have been well established, the mode of inheritance and the genetic basis for SHORT syndrome are still uncertain. The purpose of this paper is to document a familial translocation of t(1;4)(q31.2;q25), in a mother and her son manifesting Rieger syndrome with polycystic ovaries and SHORT syndrome, respectively. It is suggested that these two syndromes may be different expressions of the same gene, PITX2, localized at 4q25. Our patient is the second with the association of Rieger syndrome and polycystic ovaries, and thus this may not be coincidental, moreover insulin resistance-related phenotypes, such as lipodystrophy and polycystic ovaries, can be major component of syndromes with Rieger eye malformation.


Miconazole nitrate compared with chlordantoin in the treatment of vaginal candidiasis.
In a double-blind study of the treatment of vaginal candidiasis, miconazole nitrate gave a cure-rate of 88 per cent. (29 out of 33) compared with 58 per cent. (21 out of 36) using chlordantoin. Although approximately two-thirds of the patients who responded did so to a 10-day course of treatment, the different rates of cure with these preparations at this stage were not statistically significant. However, when a second course of treatment was given to those women who still had proven candidiasis, the overall cure-rate with miconazole was significantly greater than that with chlordantoin.


Macronutrient intake of dogs, self-selecting diets varying in composition offered ad libitum.
The diet of the domestic dog has changed significantly from that of its wolf ancestor, with to date only two studies having examined macronutrient self-selection in dogs. Whilst the first focused solely on protein intake, determining an intake of 30% metabolisable energy (ME), the second investigated dietary protein, fat and carbohydrate (PFC), indicating an intake ratio of 30:63:7% by energy. This study's aim was to further elucidate macronutrient intake by providing greater macronutrient range, energy content, and to investigate over a longer duration than previous studies. Fifteen adult dogs were given access to three wet diets providing 500% of daily ME, twice daily over 10 days. The diets were nutritionally complete and formulated using the same four ingredients in different proportions to supply high levels of protein (58% ME), fat (86% ME) or carbohydrate (54% ME). Overall fat and carbohydrate consumption significantly declined from 6,382 to 917 kcals per day (p < 0.001) and 553 to 214 kcals day-1 (p < .01) respectively. Protein intake, however, remained constant over the study and ranged from 4,786 to 4,156 kcals day-1 . Such results impacted on percentage total energy intake, with fat decreasing from 68% to 52% (p < .001) and protein increasing from 29% to 44% (p < .01). Our findings suggest that dogs still possess a "feast or famine" mentality, wherein energy dense fat is prioritised over protein initially. With continued feeding over 10 days, a transition to a more balanced energy contribution from both macronutrients is evident. The study also shows that given the option, dogs do not select carbohydrate to be a significant portion of the diet. The health implications of such dietary selection are of interest.


Effects Of Excessive Screen Time During Online Teaching On The Physical And Mental Health Of Medical And Dental Students.
To assess the effects of excessive screen time on the health of medical and dental students due to online teaching during the COVID-19 pandemic. It was a descriptive cross-sectional study, conducted in Bahria University of Health Sciences from June 2022 to September 2022 after getting ethical approval. A total of 200 students who attended online teaching modules for at least one year through online teaching Apps, were included. A structured questionnaire was distributed using google forms. The results revealed that factors including strain on the eyes, restlessness, declined academic performance and exercise during lockdown, along with feeling connected as a group had a significant association with increased screen time. Excessive screen time has various adverse effects on the physical and mental health of medical and dental students. For improving students' physical and mental health during online teaching we need to change teaching strategies and support the introduction of flipped classroom.


Pain Management and Opioid Free Treatment Order Sets: An Evolving Role for Pharmacists.
Over the past twenty five years, significant changes to the assessment and treatment of pain have occurred. In the 1990s, the identification of "pain as the fifth vital sign" impacted how providers assessed and treated pain. Now, with the opioid epidemic and recommendations from multiple organizations to remove pain as the fifth vital sign, the practice of pain management is changing again. Despite these changes, pain is still a common condition many patients experience. It is estimated about 50% of older adults in the community report daily pain, and there is an increased prevalence of pain in the facility setting, with 45-80% of residents reporting chronic pain impacting their quality of life. With the growing number of older adults in the United States, pharmacists working with geriatric patients need to be familiar with the treatment of pain and new approaches that are being utilized.


Early outcomes of transcatheter versus surgical aortic valve implantation in patients with bicuspid aortic valve stenosis.
Limited information is available on outcomes in patients with bicuspid aortic valve (BAV) stenosis undergoing transcatheter aortic valve implantation (TAVI) compared with surgical aortic valve replacement (SAVR), as pivotal randomised trials excluded patients with BAV pathology due to anatomic complexity. The aim of the study was to compare early outcomes between TAVI and SAVR in patients with BAV stenosis. We queried the Nationwide Readmission Database (NRD) between 2016 and 2018 to identify adults who underwent TAVI or SAVR for BAV stenosis. The study's primary outcome was in-hospital mortality. Secondary outcomes were 30-day and six-month major adverse cardiovascular events (MACE). We matched both cohorts using propensity score matching, and applied logistic and Cox-proportional hazard regression to compute the odds ratio (OR), the hazard ratio (HR), and the 95% confidence interval (CI). Out of 17,068 patients with BAV stenosis, 1,629 (9.5%) patients underwent TAVI and 15,439 (90.5%) underwent SAVR. After propensity score matching (PSM), we found 1,393 matched pairs. Of the matched pairs, 848 had complete six-month follow-ups. In the PSM cohort, TAVI was associated with reduced in-hospital mortality (0.7% vs 1.8%, OR: 0.35, 95% CI: 0.13-0.93; p=0.035), and a similar rate of MACE at 30 days (1% vs 1.5%, OR: 0.65, 95% CI: 0.27-1.58; p=0.343) and at six months (4.2% vs 4.9%, HR 0.86, 95% CI: 0.44-1.69; p=0.674), compared with SAVR. In the propensity score-matched cohort, TAVI was associated with reduced odds of in-hospital mortality and a similar risk of 30-day and six-month MACE, supporting the feasibility of TAVI in BAV patients without a need for concurrent aortic root repair.