RKTG overexpression inhibits proliferation and induces apoptosis of human leukemia cells via suppression of the ERK and PI3K/AKT signaling pathways.
Raf kinase trapping to Golgi (RKTG) is reported to be a tumor suppressor in a number of solid tumors due to its negative modulation of the Ras/Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (ERK) pathways. However, the role of RKTG in the progression of leukemia remains unknown. In the present study, a human leukemia U937 cell line overexpressing RKTG was established, and the effect of RKTG on proliferation, cell cycle and apoptosis of human leukemia cells was analyzed. The results of the present study demonstrated that exogenous overexpression of RKTG significantly inhibited cell proliferation, which was accompanied by cell cycle arrest. Apoptosis assay and Hoechst staining demonstrated that the percentage of apoptotic cells in RKTG overexpressing cells was markedly increased. Furthermore, western blotting showed that RKTG overexpression significantly increased the level of cleaved caspase 3, B-cell lymphoma 2 (Bcl2)-associated X apoptosis regulator and reduced the level of Bcl-2. In addition, the activation of ERK and phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase 1 signaling pathways in human leukemia cells was also suppressed by RKTG overexpression. In conclusion, the present study demonstrated the tumor-suppressive effect of RKTG on human leukemia cells, which seem to be partially dependent on the suppression of ERK and PI3K/AKT signaling. Overexpression of RKTG may be a potential therapeutic target for the treatment of leukemia.


The therapeutic activity of 1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid monohydrate glucosamide in rheumatoid arthritis (double blind trial).
A new nonsteroidal anti-inflammatory agent, 1-(p-chlorobenzyl)-5-methylindole-3-acetic acid monohydrate glucosamide (glucametacine, Teoremac¿), was used in the treatment of a total of 39 patients including 31 cases of rheumatoid arthritis, 3 of ankylosing spondylitis, 1 of psoriatic rheumatism, 1 of chronic chondrocalcinosis and 3 of arthrosis. Teoremac was given for 14 days at a dosage of 420 mg/day. The drug was shown to be more or less active in all the patients except 4. The improvement in the various clinical parameters of rheumatoid arthritis studied was statistically significant. The side effects recorded were headache, which was severe in only 1 case, and "minor" disturbances of the gastro-intestinal tract. A double blind crossover trial was carried out in 15 patients with rheumatoid arthritis to compare the action of Teoremac (420 mg/day for 14 days) with that of indometacin (100 mg/day for 14 days). Under the conditions of the trial, the clinical findings showed Teoremac to be slightly superior to indometacin, but the difference was not significant statistically.


The Impact of Gender and Age in Obese Patients on Sternal Instability and Deep-Sternal-Wound-Healing Disorders after Median Sternotomy.
The aim of this study was to investigate the relationship between age and sex in regard to the development of deep sternal wound infections and sternal instability following median sternotomy. A propensity-score-matching analysis was conducted on 4505 patients who underwent cardiac surgery between 2009 and 2021, all of whom had a BMI of ≥30 kg/m2. A total of 1297 matched pairs were determined in the sex group, and 1449 matched pairs we determined in the age group. The distributions of sex, age, diabetes mellitus, delirium, unstable sterna, wire refixation, wire removal, superficial vacuum-assisted wound closure, deep vacuum-assisted wound closure, clamp time, bypass time, logistic EuroSCORE, and BMI were determined. The 30-day in-hospital mortality was found to be similar in the older and younger groups (8.149% vs. 8.35%, p = 0.947), and diabetes mellitus was also equally distributed in both groups. However, postoperative delirium occurred significantly more often in the older group (29.81% vs. 17.46%, p < 0.001), and there was a significantly higher incidence in men compared with women (16.96% vs. 26.91%, p < 0.001). There were no differences found in the incidence of sternum instability, fractured sternum, superficial vacuum-assisted wound closure, and deep vacuum-assisted wound closure between the age and sex groups. In conclusion, this study found that sternal instability and deep-wound-healing problems occur with equal frequency in older and younger patients and in men and women following median sternotomy. However, the likelihood of postoperative delirium is significantly higher in older patients and in men. These findings suggest that a higher level of monitoring and care may be required for these high-risk patient groups to reduce the incidence of postoperative delirium and improve outcomes following median sternotomy.


Volumetric MR imaging of oral, maxillary sinus, oropharyngeal, and hypopharyngeal cancers: correlation between tumor volume and lymph node metastasis.
The size of the primary lesion and the lymph node metastasis are critical indicators for the patient prognosis. Here we attempted to assess the correlation between these 2 prognostic parameters in patients with oropharyngeal, hypopharyngeal, oral, or maxillary sinus cancer. We retrospectively studied 66 patients with oropharyngeal or hypopharyngeal (n = 24), oral (n = 35), or maxillary sinus (n = 7) cancer. Of these patients, 25 (10 with oral or maxillary sinus and 15 with pharyngeal cancers) had lymph node metastases. We measured the volumes of the primary lesions as sums of gadolinium-enhanced areas on fat-suppressed, spectral presaturation with inversion recovery (SPIR) T1-weighted images. Histologically confirmed metastatic nodes were mapped to the neck levels. The tumor volumes were well correlated with the clinical T-category for the primary lesions in oral, maxillary sinus, and oropharyngeal and hypopharyngeal cancers. The volumes of the oropharyngeal and hypopharyngeal cancers were significantly greater (P < .05) in patients with metastatic nodes than in patients without metastasis, whereas there was no significant correlation between the tumor volume and nodal metastasis in patients with oral or maxillary sinus cancer (Mann-Whitney U test). Furthermore, the correlation between tumor volume and the distribution of metastatic nodes in the neck was observed to be weak in patients with oral or maxillary sinus cancer. The MR image-based tumor volume measurement proved to be clinically feasible. We observed a good correlation between tumor volume and lymph node metastasis in patients with oropharyngeal or hypopharyngeal cancer but not in those with oral or maxillary sinus cancer.


A new whitefly genus and species, Aleuroparvus theae Dubey (Hemiptera: Aleyrodidae) colonising Assam tea (Camellia sinensis) and Cinnamomum bejolghota, in North-East India.
Puparia of a new whitefly genus and species, Aleuroparvus theae Dubey gen. et sp. nov. are described along with drawings, habitus and type images of habitus and types, and scanning electron microscope microphotographs. It is found infesting an economically important plant, Assam tea, Camellia sinensis (L.) (Theaceae) in Assam, and Cinnamomum bejolghota (Hamilton) (Lauraceae) in Arunachal Pradesh, India. Puparia of A. theae are dimorphic, the females being larger than males. The puparia of the new genus differ from all other genera in having smaller ventral surface, submarginal wax secreting pores and dorsal submargin separated from the dorsal disc by a submarginal ridge. The diagnostic characteristics for puparia of the new genus are compared with closely related genera, Aleuroclava Singh, Aleuropleurocelus Drews Sampson, Dialeuropora Quaintance Baker, Tetralicia Harrison and Tetraleurodes Cockerell.


Detection and quantification of protein-microtubules interactions using green fluorescent protein photoconversion.
We present an in vitro system to analyze quantitatively the interactions of green fluorescent protein (GFP)-tagged recombinant proteins with microtubules. This method relies on photoconversion of GFP and time-lapse microscopy. Specific interactions can be detected and binding kinetics can be determined rapidly and accurately. This method provides an alternative to classical in vitro microtubule-binding assays to analyze microtubule-associated proteins binding to microtubules. It has the potential to be extended to study interactions of proteins or multi-protein complexes with different biopolymers like actin microfilaments or organelle membranes.


Intraocular pressure and ocular perfusion pressure in myopes during 21 min head-down rest.
Myopic eyes show structural differences from normal eyes and may respond differently to microgravity, increasing the risk for possible development of ocular hypertension and glaucoma on orbit. In this experiment we used head-down rest (HDR) at an angle of 15 degrees to produce hydrostatic changes similar to acute exposure to microgravity. There were 65 subjects (129 eyes) who were divided into groups characterized by refraction: emmetropes (N = 46; refraction error between -0.99 D and +0.10 D), low myopes (N = 39; > or = -1.0 D to < -3.0 D), and moderate myopes (N = 44; > or = -3.0 D to < -6.0 D). Each subject was studied resting in a horizontal position and after 1, 6, 11, 16, and 21 min of HDR. Measured variables included systolic and diastolic blood pressure (SBP and DBP, respectively), intraocular pressure (IOP), and ocular perfusion pressure (OPP). The mean values of IOP increased significantly in all eyes during HDR, with IOP peaking at 6 min. Compared to emmetropes and low myopes, moderate myopes showed a significantly greater increase in IOP and higher peak values for IOP (18.6, 18.7, and 19.8 mmHg for emmetropes, low, and moderate myopes, respectively). Mean values of OPP in moderate myopes were significantly lower than in emmetropes and low myopes during HDR. Compared with baseline, mean SBP and DBP decreased obviously in emmetropes during HDR, while changes were minimal in the other groups. Abnormal auto-regulation of ocular blood pressure in myopes of moderate and greater severity may pose a risk factor for developing ocular hypertension and possibly glaucoma when exposed to microgravity. HDR may offer a method of screening candidates for spaceflight for this risk prior to microgravity exposure.


Moderators of Sexual Recidivism as Indicator of Treatment Effectiveness in Persons With Sexual Offense Histories: An Updated Meta-analysis.
The present meta-analysis is an update of the meta-analysis by Schmucker and Lösel [Campbell Syst. Rev. 2017; 13: 1-75], which synthesized evidence on sexual recidivism as an indicator of treatment effectiveness in persons with sexual offense histories. The updated meta-analysis includes 37 samples comprising a total of 30,394 individuals with sexual offense histories, which is nearly three times the sample size reported by Schmucker and Lösel (2017: 28 samples, N = 9781). In line with Schmucker and Lösel (2017), the mean treatment effect was small with an odds ratio of 1.54 [95% CI 1.22, 1.95] (p < .001). A moderator analysis suggested three predictors of importance, i.e., risk level, treatment specialization, and author confounding. Greater treatment effectiveness was suggested in high- and medium-compared to low-risk individuals and in specialized compared to non-specialized treatments. Authors affiliated with treatment programs reported larger effectiveness than independent authors. These findings were overall in line with Schmucker and Lösel (2017), though the effects of risk level and treatment specialization were stronger in the current meta-analysis. The findings of the updated meta-analysis reinforce the evidence for the first and second principle of the Risk-Need-Responsivity model. The results may support researchers and decision-makers in interpreting the current evidence on sexual recidivism as an indicator of treatment effectiveness, and, based on that, implement and carry out informative, methodologically sound evaluations of ongoing treatment programs in persons with sexual offense histories.


Retrograde acucise endopyelotomy: is it worth its cost?
To identify patients with ureteropelvic junction (UPJ) obstruction who will benefit from endoscopic Acucise incision of the stenosis and to compare the open Hynes-Anderson pyeloplasty with this minimally invasive technique. In a prospective trial, 22 patients with primary and secondary UPJ obstruction were treated by Acucise endopyelotomy, and 18 patients were treated by Hynes-Anderson pyeloplasty. Preoperative and postoperative renal scans were used to determine the degree of obstruction and intravenous urography, ultrasound scanning, or both to assess the degree of dilation. There was a vast difference in the cure rate of the two groups: Hynes-Anderson pyeloplasty cured 94.5% of the patients, while in the Acucise group, the cure rate was only 32%. There was some improvement in another 22% of the patients, but the renal scan curve remained obstructed. The remaining 45% of patients failed to show any improvement. Acucise endopyelotomy will improve or cure only patients with good renal function and mild dilation of the pelvicaliceal system. Patients with severe dilation should be treated by Hynes-Anderson pyeloplasty.


Reconstruction of extended orbital floor fracture using an implantation method of gamma-shaped porous polyethylene.
The conventional surgical method for reconstructing orbital floor fractures involves restoration of orbital continuity by covering an onlay with a thin material under the periorbital region. However, in large orbital floor fractures, the implant after inserting is often dislocated, leading to malposition. This study aimed to propose a novel implanting method and compare it with existing methods. Among patients who underwent surgery for large orbital floor fractures, 24 who underwent the conventional onlay implanting method were compared with 21 who underwent the novel γ implanting method that two implant sheets were stacked and bent to resemble the shape of the Greek alphabet γ. When inserting a γ-shaped implant, the posterior ledge of the orbital floor was placed between the two sheets and the bottom sheet was impacted onto the posterior wall of the maxilla to play a fixative role while the top sheet was placed above the residual orbital floor to support orbital contents. Wilcoxon signed-rank test and Mann-Whitney U test were used for data analyses. Compared to the conventional onlay method, the gamma method resulted in better restoration of orbital contents, better improvement of enophthalmos, and fewer revision surgeries. Achieving good surgical outcomes for extended orbital floor fractures is known to be difficult. However, better surgical outcomes could be obtained by using the novel implantation method of impacting a γ-shaped porous polyethylene posteriorly.


Review of the Southeast Asian species of the Aenictus javanus and Aenictus philippinensis species groups (Hymenoptera, Formicidae, Aenictinae).
The Southeast Asian species of the Aenictus javanus and Aenictus philippinensis groups are revised. Six species (four named and two new species) of the Aenictus javanus group occurring in this area are: Aenictus doydeei Jaitrong & Yamane, 2011, Aenictus duengkaei Jaitrong & Yamane, sp. n., Aenictus javanus Emery, 1896, Aenictus longinodus Jaitrong & Yamane, sp. n., Aenictus nishimurai Terayama & Kubota, 1993, and Aenictus piercei Wheeler & Chapman, 1930. Four species (three named and one new species) are recognized in the Aenictus philippinensis group: Aenictus pangantihoni Zettel & Sorger, 2010, Aenictus philippinensis Chapman, 1963, Aenictus punctatus Jaitrong & Yamane, sp. n., and Aenictus rabori Chapman, 1963. Aenictus piercei is removed from the members of the Aenictus piercei group sensu Jaitrong and Yamane (2011) and transferred to the Aenictus javanus group. Lectotypes and paralectotypes are designated for Aenictus piercei and Aenictus rabori. Size variation occurs among individuals from single colonies of the Aenictus javanus group, while the workers in the Aenictus philippinensis group are clearly monomorphic.


Identification of calmodulin activity in purified retroviruses.
Several viruses have been shown to require calcium for their function, and to bind calcium at specific sites. However, the nature of the calcium binding molecule on viruses has not been established. One possibility is the ubiquitous calcium-binding protein calmodulin. Our studies were designed to determine whether feline leukemia virus contained calmodulin. Accordingly, we tested purified feline leukemia virus for the presence of calmodulin-like activity. The virus, like authentic calmodulin, activated cyclic AMP phosphodiesterase. The ability of the virus to activate the enzyme was blocked in the presence of the known calmodulin inhibitors trifluoperazine and W-7. This indirect evidence for the presence of calmodulin was confirmed by radioimmunoassay. Several other retroviruses were also tested using radioimmunoassay and found to contain calmodulin. Our results indicate that the calcium binding site in retroviruses may be calmodulin.


Why worry about awareness in choice problems? Econometric analysis of screening for cervical cancer.
The decision to undertake a screening test is conditional upon awareness of screening. From an econometric perspective there is a potential selection problem, if no distinction is made between aware and unaware non-screeners. This paper explores this problem through analysis of the determinants of cervical screening in Australia. Cervical cancer is one of the most preventable and curable forms of cancer. Since 1991 there has been a concerted effort in Australia to recommend and encourage women to have Pap smears every two years. The success of this program can be partly gauged by exploring the determinants of screening for cervical cancer. Using unit record data from the 1995 National Health Survey, an econometric model is developed for whether women have ever screened or not. A proportion of women in the sample contend that they have never heard of a Pap test. The analysis characterizes this group of women and accounts for their presence in the modelling. The paper demonstrates failing to model awareness can result in inconsistent parameter estimates even when the degree of censoring in the sample is relatively small.


Common variable immunodeficiency presenting in a man with recurrent pneumonia caused by Staphylococcus lugdunensis.
Common variable immunodeficiency (CVID) refers to a group of disorders where differentiation and maturation of B cells into plasma cells are affected, leading to decreased or defective immunoglobulin production and subsequent immunodeficiency. Symptoms may present at any age between 5 and 72 years, although more severe forms often manifest earlier in life. Milder forms may not be detected. We present an intriguing case of a 69-year-old man presenting with recurrent pneumonia caused by a rare organism Staphylococcus lugdunensis, eventually determined to be caused by CVID. The patient had a good clinical outcome after receiving immunoglobulin replacement therapy.


Influence of multi-step etch-and-rinse versus self-etch adhesive systems on the post-operative sensitivity in medium-depth carious lesions: An in vivo study.
To evaluate the influence of a three-step etch-and-rinse versus a two-step self-etch adhesive system on immediate post-operative sensitivity. In total, 204 subjects with one posterior tooth affected by a primary carious lesion were recruited. The subjects were randomly divided into two groups, based on the two multi-step adhesive systems used: Group A (All Bond 3) and Group B (Clearfil Protect Bond). The same skilled operator carried out the restorations using a nano-hybrid composite (Venus Diamond) in oblique stratification. Each increment was light-cured for 20 seconds with a LED lamp (Translux Power Blue). Subjects received a three-level thermal sensitivity questionnaire for post-operative sensitivity ratings. The evaluations were recorded daily for 7 days. Scores were analyzed using the McNemar test and postoperative trends were analyzed with the Friedman test (P < 0.05). All (100%) enrolled subjects completed the follow-up visits. There was no statistically significant difference between the two groups in post-operative sensitivity trends. In both groups, increased post-operative sensitivity was found at D1, which then decreased significantly during the observation period. The results of this in vivo study showed that both of the tested adhesives, etch-and-rinse or self-etch, provided effective dentin sealing, preventing subjects from experiencing post-operative sensitivity in the treatment of medium-depth cavities.


Epithelial to mesenchymal transition is a determinant of sensitivity of non-small-cell lung carcinoma cell lines and xenografts to epidermal growth factor receptor inhibition.
Treatment of second- and third-line patients with non-small-cell lung carcinoma (NSCLC) with the epidermal growth factor receptor (EGFR) kinase inhibitor erlotinib significantly increased survival relative to placebo. Whereas patient tumors with EGFR mutations have shown responses to EGFR inhibitors, an exclusive role for mutations in patient survival benefit from EGFR inhibition is unclear. Here we show that wild-type EGFR-containing human NSCLC lines grown both in culture and as xenografts show a range of sensitivities to EGFR inhibition dependent on the degree to which they have undergone an epithelial to mesenchymal transition (EMT). NSCLC lines which express the epithelial cell junction protein E-cadherin showed greater sensitivity to EGFR inhibition in vitro and in xenografts. In contrast, NSCLC lines having undergone EMT, expressing vimentin and/or fibronectin, were insensitive to the growth inhibitory effects of EGFR kinase inhibition in vitro and in xenografts. The differential sensitivity of NSCLC cells with epithelial or mesenchymal phenotypes to EGFR inhibition did not correlate with cell cycle status in vitro or with xenograft growth rates in vivo, or with total EGFR protein levels. Cells sensitive to EGFR inhibition, with an epithelial cell phenotype, did exhibit increased phosphorylation of EGFR and ErbB3 and a marked increase in total ErbB3. The loss of E-cadherin and deregulation of beta-catenin associated with EMT have been shown to correlate with poor prognosis in multiple solid tumor types. These data suggest that EMT may be a general biological switch rendering non-small cell lung tumors sensitive or insensitive to EGFR inhibition.


Designed Long-Lived Emission from CdSe Quantum Dots through Reversible Electronic Energy Transfer with a Surface-Bound Chromophore.
The size-tunable emission of luminescent quantum dots (QDs) makes them highly interesting for applications that range from bioimaging to optoelectronics. For the same applications, engineering their luminescence lifetime, in particular, making it longer, would be as important; however, no rational approach to reach this goal is available to date. We describe a strategy to prolong the emission lifetime of QDs through electronic energy shuttling to the triplet excited state of a surface-bound molecular chromophore. To implement this idea, we made CdSe QDs of different sizes and carried out self-assembly with a pyrene derivative. We observed that the conjugates exhibit delayed luminescence, with emission decays that are prolonged by more than 3 orders of magnitude (lifetimes up to 330 μs) compared to the parent CdSe QDs. The mechanism invokes unprecedented reversible quantum dot to organic chromophore electronic energy transfer.


Ribosomal protein synthesis is not regulated at the translational level in Saccharomyces cerevisiae: balanced accumulation of ribosomal proteins L16 and rp59 is mediated by turnover of excess protein.
We have investigated the mechanisms whereby equimolar quantities of ribosomal proteins accumulate and assemble into ribosomes of the yeast Saccharomyces cerevisiae. Extra copies of the cry1 or RPL16 genes encoding ribosomal proteins rp59 or L16 were introduced into yeast by transformation. Excess cry1 or RPL16 mRNA accumulated in polyribosomes in these cells and was translated at wild-type rates into rp59 or L16 proteins. These excess proteins were degraded until their levels reached those of other ribosomal proteins. Identical results were obtained when the transcription of RPL16A was rapidly induced using GAL1-RPL16A promoter fusions, including a construct in which the entire RPL16A 5'-noncoding region was replaced with the GAL1 leader sequence. Our results indicate that posttranscriptional expression of the cry1 and RPL16 genes is regulated by turnover of excess proteins rather than autogenous regulation of mRNA splicing or translation. The turnover of excess rp59 or L16 is not affected directly by mutations that inactivate vacuolar hydrolases.


[Strategy for surgery in familial adenomatous polyposis patients with invasive colorectal cancer].
Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) has been established as the standard operative procedure for classic familial adenomatous polyposis( FAP). However, it is unclear which type of surgery should be undertaken for FAP patients with invasive colorectal cancer in clinical practice. This study evaluated the outcome of different surgeries performed in FAP patients with invasive colorectal cancer. The study included 21 classic FAP patients with or without invasive colorectal cancer, who underwent proctocolectomy at our institute between 2000 and 2013. Patient background, type of operation, and prognosis were retrospectively examined. In the non-invasive cancer group, total proctocolectomy with IPAA was performed in 7 patients, and colectomy with ileorectal anastomosis (IRA) was performed in 5 patients. Conversely, in the invasive cancer group, IPAA, proctocolectomy with end ileostomy (TPC), and IRA were performed in 2, 2, and 5 patients, respectively. Overall survival did not differ significantly between the 2 groups( 5 year survival, 88.9% vs 75.0%, p=0.48). These results suggest that IPAA, IRA, or TPC might contribute to survival time prolongation in patients with invasive colorectal cancer, as is the case for those without invasive colorectal cancer.


A phase II study of PALA (NSC 224131) in patients with advanced ovarian carcinoma. A Gynecologic Oncology Group study.
Pala, 5G /M2 i.v. every 3 weeks was given to 32 evaluable patients with ovarian carcinoma (31 previously treated). No complete or partial responses were noted. Ten patients had stable disease for a median progression-free interval of 4.7+ months, while the remainder had progression of disease from the start of therapy. The major toxicity was dermatologic, and five patients had severe skin rash with desquamation or ulceration. There was no substantial hematologic or gastrointestinal toxicity. PALA displays no useful activity in previously-treated patients with ovarian cancer.


Strategy for child immunization in Malaysian plantations.
An outline is given of a simple cost-effective strategy aimed at the immunization of all children and pregnant women residing in the plantation sector of Malaysia. It is based on a partnership between government, nongovernmental organizations and the private sector, and is supported by UNICEF.


The inpatient treatment of the borderline personality disorder: a critical review and discussion of aftercare implications.
The literature on inpatient treatment of adult borderline personality disorder is reviewed. The controversy regarding the use or avoidance of the regression which can accompany hospitalization is discussed. It is suggested that this literature is not specific enough. There is insufficient attention to definition of terms, clinical heterogeneity and the longitudinal course of the illness. As well, the ahistoric approach to the hospitalization of these patients serves to reinforce characteristic ego deficits. Recommendations regarding the use of long or short-term length of hospital stay are not substantiated by formal research. It is suggested that greater emphasis be placed on aftercare issues. The stabilization of the patient, outpatient therapist, and aftercare system are described as important goals of inhospital care.


Alternatives to randomized controlled trials in telemedicine.
Research designs other than true experiments may be useful in the evaluation of telemedicine. Potential methods include those that do not rely on randomization and tight control of the intervention, and analysis of existing administrative and clinical databases. Quasi-experimental designs may also be useful, especially when conducted in association with careful statistical methods that allow the investigator to control for certain differences between groups. Databases, such as those maintained by the Centers for Medicare and Medicaid Services, contain information on both outcomes and claims, as well as disease/procedure registries and electronic health records. This may provide a potential tool for understanding the effects of telemedicine on access to care in conjunction with costs and quality. These different approaches have advantages and disadvantages, but may be useful in telemedicine, where the conduct of randomized controlled trials is generally very expensive and frequently not feasible.


[Lower extremity amputations in diabetic patients: a case-control study].
Lower extremity amputation is an increasing problem among diabetic patients and an important public health problem. The study purpose was to identify factors associated with lower extremity amputation. A matched case-control study was carried out among diabetic patients. Cases were selected in public health programs of the city of São Paulo, Brazil. One hundred and seventeen cases of diabetics with lower extremity amputation were compared to 234 controls of diabetics without amputation, matched by sex, age, and duration of disease. Sociodemographic variables, life habits (smoking and alcohol drinking), clinical aspects, and health education in diabetes were included. Univariate analyses and conditional logistic regression method were applied to data. Data showed evidence of association for: smoking, last glucose test > or = 200 mg/dl, presence of peripheral somatic neuropathy and vibratory perception (tuning fork 128 Hz), and peripheral vascular disease. Diabetes treatment and attending nursing appointments for diabetes education were important factors for preventing lower extremity amputation in diabetic patients. The knowledge of determinants and intervening factors for this condition will lead to cost reduction and better quality of care delivered in public health services.


Personalized medicines - are pharmacists ready for the challenge?
The field of personalized medicine affords multiple opportunities to pharmacists, and pharmacists have specific knowledge, skills and abilities that make them uniquely suited to advance the use of personalized medicine as a clinical tool. The pharmacy profession as a whole, however, has been slow to embrace the concept of clinical pharmacogenetics and is now facing a critical juncture that can potentially redefine the professional identity of the pharmacist. Before practice transformation can occur, however, it is important for our profession to ask and fully explore the following question: Are pharmacists ready for the challenge of personalized medicine? When assessing the readiness of pharmacy for personalized medicine, one must consider factors that are specific to the individual pharmacist as well as systematic considerations that allow pharmacists to successfully integrate personalized medicine into their individual practice area. These include factors such as education and training, competency, an attitude of engagement and adequate support and guidance. Personnel, information technology and laboratory infrastructure are also critical elements that are required, and financially sustainable practice models must be developed. Successful advancement of clinical pharmacogenetics will also require the profession to clearly define their vision of what success looks like and where it wants to be at the end of the transformational journey. Without a clear destination, we will continue to move as individuals in different directions and fail to progress as a whole. While pharmacists might not be completely ready for the challenge of pharmacogenetics, they are most certainly up to facing the challenge. The time is right and the stage is set for pharmacy to embark on another transformative journey - a journey that will redefine the role of the pharmacist and will secure a place for pharmacy in the era of personalized medicine and beyond.


Validated Questionnaire of Maternal Attitude and Knowledge for Predicting Caries Risk in Children: Epidemiological Study in North Jakarta, Indonesia.
Predicting caries risk in children can be done by identifying caries risk factors. It is an important measure which contributes to best understanding of the cariogenic profile of the patient. Identification could be done by clinical examination and answering the questionnaire. We arrange the study to verify the questionnaire validation for predicting caries risk in children. The study was conducted on 62 pairs of mothers and their children, aged between 3 and 5 years. The questionnaire consists of 10 questions concerning mothers' attitude and knowledge about oral health. The reliability and validity test is based on Cronbach's alpha and correlation coefficient value. All question are reliable (Cronbach's alpha = 0.873) and valid (Corrected item-total item correlation >0.4). Five questionnaires of mother's attitude about oral health and five questionnaires of mother's knowledge about oral health are reliable and valid for predicting caries risk in children.


Relation between iron uptake, pH of growth medium, and penicillinase formation in Staphylococcus aureus.
The uptake of iron and the formation of penicillinase was examined in cultures of wild-type Staphylococcus aureus. Uptake of iron was about twice as great at pH 4.7 as at pH 7.4 At pH 4.7, increase in iron uptake in the range of 1.0 to 4.0 mug per mg of bacterial protein was associated with a progressive increase in the rate of penicillinase formation, but a direct correlation between cellular iron content and rate of enzyme formation was not demonstrated. Addition of iron to deferrated medium enhanced penicillinase formation at pH 6.5 to 7.4 two- to fourfold in cultures induced with benzylpenicillin and in uninduced cultures. To demonstrate an effect on the uninduced cells, it was necessary to increase iron uptake by preliminary incubation of cells with iron in buffer. Calcium and certain other ions depressed iron uptake at acidic and at neutral pH, and, presumably as a result of this action, depressed the formation of penicillinase. Iron did not enhance penicillinase formation at pH 4.7 by two penicillinase constitutive mutants nor by wild-type cells undergoing induction at pH 6.5 by cephalosporin C or methicillin. After removal of cephalosporin C or methicillin during an early phase of induction, residual synthesis of enzyme was increased by prior uptake of iron. The results are considered compatible with the concept that uptake of iron, especially at acidic pH, interferes with the formation or function of penicillinase repressor.


Identification of the endogenous cannabinoid system through integrative pharmacological approaches.
Scientific progress in the biological sciences increasingly relies on an integration of behavioral, pharmacological, cellular, and molecular approaches, particularly in translating basic research observations into therapeutic potential. The strength of in vivo model systems lies in the direct assessment of physiological function. However, they only allow indirect evidence for mechanism of action. Frequently, in vitro models provide just the opposite. A combination of both in vitro and in vivo approaches are often essential for establishing the underlying mechanisms of a specific pharmacological effect. In recent times, an endogenous cannabinoid system has been characterized due to the combined efforts of chemists, pharmacologists, molecular and cellular biologists, and biochemists. This endogenous cannabinoid system is providing a basis for systematically addressing the pharmacological controversies surrounding marijuana. The description of this endogenous cannabinoid system and the strategies for establishing the physiological function of this system are the subjects of this article.


Antiprotozoal activity against Entamoeba histolytica of plants used in northeast Mexican traditional medicine. Bioactive compounds from Lippia graveolens and Ruta chalepensis.
Amoebiasis caused by Entamoeba histolytica is associated with high morbidity and mortality is becoming a major public health problem worldwide, especially in developing countries. Because of the side-effects and the resistance that pathogenic protozoa build against the standard antiparasitic drugs, e.g., metronidazole, much recent attention has been paid to plants used in traditional medicine around the world in order to find new antiprotozoal agents. We collected 32 plants used in Northeast Mexican traditional medicine and the methanolic extracts of these species were screened for antiprotozoal activity against E. histolytica trophozoites using in vitro tests. Only 18 extracts showed a significant inhibiting activity and among them six plant extracts showed more than 80% growth inhibition against E. histolytica at a concentration of 150 µg/mL and the IC50 values of these extracts were determined. Lippia graveolens Kunth and Ruta chalepensis Pers. showed the more significant antiprotozoal activity (91.54% and 90.50% growth inhibition at a concentration of 150 µg/mL with IC50 values of 59.14 and 60.07 µg/mL, respectively). Bioassay-guided fractionation of the methanolic extracts from these two plants afforded carvacrol (1) and chalepensin (2), respectively, as bioactive compounds with antiprotozoal activity.


Evaluation of the abdomen using ultrasound following a ventral midline celiotomy.
Over the last 20 years, ultrasound has become a useful diagnostic tool in veterinary medicine. The purpose of this study was to use ultrasonographic examinations to determine if intra-abdominal contents could be visualized. Nineteen dogs, ranging from 8 months to 18 years of age were included. Each animal was evaluated sonographically prior to surgery, 24 h after surgery, and then 2-6 weeks following the surgical procedure. The results of our study suggest that ultrasound is an effective means for evaluation of the abdomen and surgery site following surgery. Both the abdomen and surgery site were clearly visualized in all dogs. In addition, subjective evaluation of the intra-abdominal contents was performed. The limiting factor in this study was not the presence of air, as was expected. Rather the limiting factor for appropriate visualization was pain. The information obtained could prove to be useful to surgeons and radiologists in assessing a patient's status postoperatively.


Efficacy of intravaginal electrical stimulation with different treatment frequency in women with refractory idiopathic overactive bladder.
The aim of this study is to evaluate the effect of intravaginal electrical stimulation (IVES) therapies with different treatment frequencies (two or five days in a week) added to bladder training (BT) on incontinence-related quality of life (QoL) and clinical parameters in women with refractory idiopathic overactive bladder (OAB). Fifty-two women with refractory idiopathic OAB were randomized into two groups as follows: Group 1 (n:26) received BT and IVES, two times in a week, for 10 weeks and Group 2 (n:26) received BT and IVES five times in a week, for 4 weeks. IVES was performed 20 minutes in a day, a total of 20 sessions for both groups. Women were evaluated for incontinence severity (24h pad test), pelvic floor muscles strength (perineometer), 3-day voiding diary (frequency of voiding, nocturia, incontinence episodes, and the number of pads), symptom severity (OAB-V8), quality of life (IIQ-7), treatment success (positive response rate), cure/improvement rate and treatment satisfaction (Likert scale). There was no statistically significant differences in all parameters between the two groups at the end of the treatment. It was found that the treatment satisfaction scores, cure/improvement and positive response rates were not significantly different between two groups (p>0.05). We concluded that the application of IVES twice a week or 5 times a week added to BT were both effective on incontinence-related QoL and clinical parameters in women with refractory idiopathic OAB. These two IVES frequencies had similar clinical efficacy and patient satisfaction with a slight difference between them; 5 times per week IVES has a shorter treatment duration.


Is military action ever justified? A physician defends the 'Responsibility to Protect'.
This article initially examines the moral dilemmas of war from personal and family experience, from the perspective of a family doctor trained to preserve life and a member of the peace movement. It then explores Just War from religious viewpoints and the challenges to pacifism from those living in war zones, and from human rights and human security perspectives. It concludes that the Responsibility to Protect reflects sound medical principles balancing the need to make war an extreme last resort with the responsibility of the international community to assist those unable to defend themselves.


Terephthalic Acid Copolyesters Containing Tetramethylcyclobutanediol for High-Performance Plastics.
There is a need for high-performance applications for terephthalic acid (TPA) polyesters with high heat resistance, impact toughness, and optical clarity. Bisphenol A (BPA) based polycarbonates and polyarylates have such properties, but BPA is an endocrine disruptor. Therefore, new TPA polyesters that are less hazardous to health and the environment are becoming popular. Tetramethylcyclobutanediol (TMCD) is a difunctional monomer that can be polymerized with TPA and other diols to yield copolyesters with superior properties to conventional TPA polyesters. It has a cyclobutyl ring that makes it more rigid than cyclohexanedimethanol (CHDM) and EG. Thus, TMCD containing TPA copolyesters can have high heat resistance and impact strength. TPA can be made from abundantly available upcycled polyethylene terephthalate (PET). Therefore, this review discusses the synthesis of monomers and copolyesters, the impact of diol composition on material properties, molecular weight, effects of photodegradation, health safety, and substitution of cyclobutane diols for future polyesters.


Neural control of vergence eye movements: convergence and divergence neurons in midbrain.
Animals with binocular single vision use disjunctive (vergence) eye movements to align the two eyes on a visual target. Several lines of evidence suggest that conjugate and vergence eye movement commands are generated independently and combined at the medial rectus motoneurons. If this were true, then a pure vergence eye-position signal should exist. This signal would be proportional to the horizontal angle between the eyes (vergence angle), without regard to the direction of conjugate gaze. The purpose of this experiment was to identify and study neurons that carry a pure vergence signal. Extracellular unit recordings were made from midbrain and pontine sites in monkeys trained to track visual targets moving in the horizontal, vertical, and depth (or target vergence) planes. The most commonly encountered neuron that had a vergence signal was the convergence cell. These units had a firing rate that was linearly proportional to the convergence angle; their activity was unaffected by changes in conjugate gaze. Changes in convergence cell activity preceded the change in vergence angle slightly. Convergence cell activity increased for increased convergence regardless of whether the change was in response to purely accommodative or disparity cues. Divergence cells were found far less frequently. These cells were similar to convergence cells except that they decreased their firing rate for increases in convergence. The activity of divergence cells was unaffected by changes in the direction of conjugate gaze. Both convergence and divergence cells were found, intermixed, in the mesencephalic reticular formation must outside the oculomotor nucleus. Most cells with a vergence signal were found within 1-2 mm of the nucleus. These results support the view that conjugate and vergence signals are generated independently and are combined at the extraocular motoneurons. Convergence cells seem ideally suited to provide the vergence signal required by the nearby medial rectus motoneurons.


[Drug-induced skin allergy].
Drug allergy is an important and increasing problem in everyday practice. It is estimated that about 15% of adverse side effects of drugs are of allergic nature. This kind of adverse reactions appear where antibodies or activated T cells are directed against drugs. The pathomechanism and symptoms of drug allergy may be connected with every of 4 types of hypersensitivity according to Gell and Coombs. Most frequently, drug allergy manifests as different forms of skin reactions. Some of them like urticaria and angioedema are IgE-related and appear rapidly after drug intake. Others appear as delayed-type reactions and manifest as maculopapular, pustular or bullous exanthema. The diagnosis of drug-induced skin allergy is based on history, clinical picture, in vitro laboratory tests and skin tests (prick, intradermal and patch). The treatment includes drug withdrawal and symptomatic pharmacotherapy.


Use of percutaneous cystolithotomy for removal of urethral uroliths in a pot-bellied pig.
A 6-month-old neutered male pot-bellied pig was presented for an obstructive urethral stone which was successfully removed by percutaneous cystolithotomy (PCCL). The pig recovered well although suspected urethral spasms and pollakiuria persisted for 2 weeks after surgery. The owner reported a good urine stream 2 months after discharge. This novel minimally invasive approach provided excellent visualization and allowed complete evaluation of the lower urinary tract. Percutaneous cystolithotomy holds great promise for the future treatment of various lower urinary tract disorders in this species.


Separating the effects of repulsive and attractive forces on the phase diagram, interfacial, and critical properties of simple fluids.
Molecular simulations in the canonical and isothermal-isobaric ensembles were performed to study the effect of varying the shape of the intermolecular potential on the phase diagram, critical, and interfacial properties of model fluids. The molecular interactions were modeled by the Approximate Non-Conformal (ANC) theory potentials. Unlike the Lennard-Jones or Morse potentials, the ANC interactions incorporate parameters (called softnesses) that modulate the steepness of the potential in their repulsive and attractive parts independently. This feature allowed us to separate unambiguously the role of each region of the potential on setting the thermophysical properties. In particular, we found positive linear correlation between all critical coordinates and the attractive and repulsive softness, except for the critical density and the attractive softness which are negatively correlated. Moreover, we found that the physical properties related to phase coexistence (such as span of the liquid phase between the critical and triple points, variations in the P-T vaporization curve, interface width, and surface tension) are more sensitive to changes in the attractive softness than to the repulsive one. Understanding the different roles of attractive and repulsive forces on phase coexistence may contribute to developing more accurate models of liquids and their mixtures.


Adding a Feature: Can a Pop-Up Chat Box Enhance Virtual Reference Services?
Online users seek help from virtual reference services via email, phone, texting, and live chat. Technologies have enabled new features in library websites to help make this service more accessible and effective. This article is an evaluation of an experimental pop-up live chat box on the website of a health sciences library to see whether the feature would enhance virtual reference services.


BIRB 796 has Distinctive Anti-inflammatory Effects on Different Cell Types.
The pro-inflammatory cytokines tumor necrosis factor-α (TNFα) and interleukin (IL)-1β are crucial mediators involved in chronic inflammatory diseases. Inflammatory signal pathways regulate inflammatory cytokine expression-mediated by p38 mitogen activated protein kinase (p38MAPK). Therefore, considerable attention has been given to p38MAPK as a target molecule for the development of a novel anti-inflammatory therapeutics. BIRB 796, one of p38MAPK inhibitor, is a candidate of therapeutic drug for chronic inflammatory diseases. In this study, we investigated the effect of BIRB 796 on inflammatory cytokine productions by lipopolysaccharide (LPS) in different immune cell types. BIRB 796 reduced LPS-mediated IL-8 production in THP-1 cells but not in Raw 264.7 cells. Further analysis of signal molecules by western blot revealed that BIRB 796 sufficiently suppressed LPS-mediated phosphorylation of p38MAPK in both cell types whereas it failed to block inhibitor of kappa B (I-κB) degradation in Raw 264.7 cells. Taken together, these results suggest that the anti-inflammatory function of BIRB 796 depends on cell types.


Homocysteine lowering interventions for peripheral arterial disease and bypass grafts.
Elevated plasma levels of the amino acid homocysteine (hyperhomocysteinaemia) are associated with narrowing or blocking of the arteries (atherosclerosis). Treatment to lower homocysteine levels has been shown to be both effective and cheap in healthy volunteers. However, the impact of reducing homocysteine levels on the progression of atherosclerosis and patency of the vessels after treatment for atherosclerosis is still unknown and forms the basis for this review. This is the second update of a review first published in 2002. To assess the effects of plasma homocysteine lowering therapy on the clinical progression of disease in people with peripheral arterial disease (PAD) and hyperhomocysteinaemia including, as a subset, those who have undergone surgical or radiological intervention. For this update, the Cochrane Peripheral Vascular Disease Group Trials Search Co-ordinator (TSC) searched the Specialised Register (last searched January 2013) and CENTRAL (2012, Issue 12). Trial databases were searched by the TSC (January 2013) for details of ongoing and unpublished studies. We also searched the reference lists of relevant articles. Randomised trials in which participants with PAD and hyperhomocysteinaemia were allocated to either homocysteine lowering therapy or no treatment, including participants before and after surgical or radiological interventions. Two review authors independently assessed trial quality and extracted the data. Information on adverse events was collected from the trials. Two randomised trials with a total of 161 participants were included in this review. The studies did not report on mortality and rate of limb loss. One randomised trial with a total of 133 participants showed that there was a significant improvement in ankle brachial index (ABI) in participants who received folic acid compared with placebo (mean difference (MD) 0.07, 95% confidence interval (CI) 0.04 to 0.11, P < 0.001) and in participants who received 5-methyltetrahydrofolate (5-MTHF) versus placebo (MD 0.05, 95% CI 0.01 to 0.10, P = 0.009). A second trial with a total of 18 participants showed that there was no difference (P non-significant) in ABI in participants who received a multivitamin B supplement (mean ± SEM: 0.7 ± 01) compared with placebo (mean ± SEM: 0.8 ± 0.1). No major events were reported. Currently, no recommendation can be made regarding the value of treatment of hyperhomocysteinaemia in peripheral arterial disease. Further, well constructed trials are urgently required.


Ursolic acid inhibits human dermal fibroblasts hyperproliferation, migration, and collagen deposition induced by TGF-β via regulating the Smad2/3 pathway.
Hypertrophic scar (HS) is a skin condition characterized by excessive fibrosis with disordered collagens from skin fibroblasts, which causes abnormal esthetic and even functional symptoms, thereby affecting millions of people. Ursolic acid (UA) is widely used in skincare and exerts anti-fibrotic effects. The present study aimed to delve into the impact of UA on HS and the mechanism. Fibroblasts (FBs) were incubated with TGF-β to investigate physiological characteristics compared with FBs isolated from normal skin (NSFBs) and hyperplastic scars (HSFBs). TGF-β-incubated FBs were subjected to treatment with UA (0-20 μM). The expressions of Vimentin, α-SMA, Collagen I, and Collagen III were examined using immunofluorescence, RT-qPCR, and western blot. Cell viability, proliferation, apoptosis, migration, and contractility were examined by CCK-8, EdU, Annexin V-FITC/PI, Transwell, and collagen gel contraction assays, respectively. The activation of Smad2/3 signaling was also determined by western blot. The binding sites for UA of TGF-βR1 (ALK5) were predicted by the Autodock tool. Compared with NSFBs, the cell proliferation, migration, and contractility of both HSFBs and TGF-β-incubated FBs were all significantly up-regulated. UA markedly impaired the TGF-β-induced increase in cell proliferation, migration, and contractility, α-SMA, collagen I, and Collagen III expression of FBs. UA significantly inhibited the phosphorylation levels of Smad2/3 in TGF-β-incubated FBs with no influence on TGF-βR1 and TGF-βR2 expressions, which might be because of the binding of UA to the catalytic domain of ALK5 protein. UA attenuated TGF-β1-induced hyperproliferation, migration, and collagen deposition in FBs via regulating the Smad2/3 pathway.


An efficient synthesis of porphyrins with different meso substituents that avoids scrambling in aqueous media.
We have developed new conditions that afford regioisomerically pure trans-A2B2-, A3B-, and trans-AB2C-porphyrins bearing aryl and arylethynyl substituents. The porphyrins were prepared by the acid-catalyzed condensation of dipyrromethanes with aldehydes followed by oxidation with p-chloranil or 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). Optimal conditions for the condensation were identified after examining various reaction parameters such as solvent composition, acid concentration, and reaction time. The conditions identified (for aromatic aldehydes: EtOH/H2O 4:1, [DPM] = 4 mM, [aldehyde] = 4 mM, [HCl] = 38 mM, 16 h; for arylethynyl aldehydes: THF/H2O 2:1, [DPM] = 13 mM, [aldehyde] = 13 mM, [HCl] = 150 mM, 3 h) resulted in the formation of porphyrins in yields of 9-38% without detectable scrambling. This synthesis is compatible with diverse functionalities such as ester or nitrile. In total, 20 new trans-A2B2-, A3B-, and trans-AB2C-porphyrins were prepared. The scope and limitations of the two sets of reaction conditions have been explored. The methodological advantage of this approach is its straightforward access to building blocks and the formation of the porphyrin core in higher yields than by any other methodology and by using environmentally benign and nonhazardous chemicals.


Update on Contact Sensitization in the Older Adult Population.
Little is known about the epidemiology of allergic contact dermatitis in the aging US population. The aim of this study was to describe patch test results in a cohort of older adult patients evaluated in a patch testing clinic in a tertiary medical center. This study was a retrospective analysis of patch test results of adults 65 years and older from February 2013 to December 2019. Data from a total of 169 patients 65 years and older were analyzed. Of these patients, 84.6% (143/169) had 1 or more positive reactions on patch testing, 84.6% (121/143) of which were felt to be clinically relevant and received a final diagnosis of allergic contact dermatitis. The most common allergen categories were fragrances (30.1%), preservatives (20.8%), metals (11.0%), medicaments (8.3%), and textile dyes (6.5%). The most common individual allergens were Myroxylon pereirae resin (balsam of Peru), hydroperoxide of linalool, methylisothiazolinone, nickel sulfate, and fragrance mix I. Personal products were by far the most common presumed source of allergen exposure. Allergic contact dermatitis is a common diagnosis in the older adult population, and patch testing with allergen avoidance counseling can be an important diagnostic step and potential cure for this allergic condition.


Long term survival after treatment of disseminated T cell lymphoma presenting with tracheal obstruction in a patient with coeliac disease.
A 46 year old man with coeliac disease and upper airway obstruction was thought to have undifferentiated carcinoma of the trachea. Subsequent immunohistological examination showed that the neoplasm was a T cell lymphoma. He had combination chemotherapy and is alive and well seven years after diagnosis.


Fatigue following Paediatric Acquired Brain Injury and its Impact on Functional Outcomes: A Systematic Review.
Fatigue is a commonly reported sequela following an acquired brain injury (ABI), and can have a negative impact on many areas of a child's life. However, there is minimal research that focuses on fatigue specifically, and so factors such as its occurrence, duration, and impact on functioning remain uncertain. This systematic review aims to provide a comprehensive summary of the research to date, bringing together a number of studies with a focus on paediatric ABI and fatigue. Terms were searched in relevant databases (PsycInfo, Medline, CINAHL), and articles were included or excluded based on specified criteria. Of the 1177 papers identified in the original search, a total of 9 papers met inclusion criteria, and were categorised as traumatic brain injury (TBI; n = 4), meningitis and meningococcal disease (n = 2), brain tumours (n = 2), and mixed ABI group (n = 1). Key findings suggest that fatigue is a problem encountered by a significant proportion of patients in all the studies reviewed, and often occurred regardless of the cause; fatigue was also associated with poor academic achievement, limited physical activity, and social and emotional problems. Injuries of greater severity were associated with higher levels of fatigue and worse outcomes. Several management options were suggested, though their efficacy was not reported. Future research is required with a suggested focus on using multiple time points to better understand the trajectories of fatigue following childhood ABI, and to build an evidence base to determine which management options are most suitable.


The Elevated Endogenous Reactive Oxygen Species Contribute to the Sensitivity of the Amphotericin B-Resistant Isolate of Aspergillus flavus to Triazoles and Echinocandins.
Aspergillus flavus has been frequently reported as the second cause of invasive aspergillosis (IA), as well as the leading cause in certain tropical countries. Amphotericin B (AMB) is a clinically important therapy option for a range of invasive fungal infections including invasive aspergillosis, and in vitro resistance to AMB was associated with poor outcomes in IA patients treated with AMB. Compared with the AMB-susceptible isolates of A. terreus, the AMB-resistant isolates of A. terreus showed a lower level of AMB-induced endogenous reactive oxygen species (ROS), which was an important cause of AMB resistance. In this study, we obtained one AMB-resistant isolate of A. flavus, with an AMB MIC of 32 μg/mL, which was sensitive to triazoles and echinocandins. This isolate presented elevated endogenous ROS levels, which strongly suggested that no contribution of decreased AMB-induced endogenous ROS for AMB-resistance, opposite to those observed in A. terreus. Further, we confirmed that the elevated endogenous ROS contributed to the sensitivity of the AMB-resistant A. flavus isolate to triazoles and echinocandins. Further investigation is needed to elucidate the causes of elevated endogenous ROS and the resistance mechanism to AMB in A. flavus.


Analysis of the recognition mechanism involved in the EcoRV catalyzed cleavage of DNA using modified oligodeoxynucleotides.
We have prepared a series of undecadeoxynucleotides that contain changes in the functional group pattern present within the EcoRV recognition site - GATATC-. Oligonucleotides were synthesized on solid phase using normal and modified beta-cyanoethylphosphoramidites and analyzed in steady state cleavage experiments with the EcoRV restriction endonuclease. The following groups appear to interact strongly with the enzyme, since their modification or substitution renders the oligonucleotides refractory to cleavage: the exocyclic NH2-groups of both A residues, the N7 of the first A residue, the exocyclic NH2-group of the C residue and the CH3-groups of both T residues. The exocyclic NH-group of the G residue supports effective recognition, since its absence lowers the kcat of the cleavage reaction. The N7 of the second A residue and the C5 position of the C residue apparently are not recognized by EcoRV; their substitution by -CH- or modification with -Br or -CH3, resp., does not considerably change the rate of cleavage. All oligonucleotides investigated compete with the unmodified substrate for binding to the enzyme. We conclude that EcoRV recognizes its substrate presumably through hydrogen bonds to the exocyclic NH2-group and the N7 of the first A residue, the exocyclic NH2-groups of the second A and the C residue, as well as through hydrophobic interactions with both T residues.


[Inoperable valve disease: should percutaneous valve replacement be an option?].
Surgical valve replacement is the treatment of choice in patients with severe valvular heart disease. However, published data clearly show that long-term survival is seriously compromised in those with a low inotropic reserve. In addition, a growing number of patients (estimated to be around 15% of those with aortic stenosis) present in such a poor and deteriorating clinical condition that they cannot be accepted for surgery because it involves a very high risk of death. Percutaneous balloon valvuloplasty is a less aggressive alternative which offers a form of palliative treatment that can increase the patient's life expectancy and bring about immediate hemodynamic and clinical improvement. It is in this context that the possibility of carrying out percutaneous valve replacement has become available as a novel therapeutic option since Cribier first reported using the procedure to treat a patient with severe aortic stenosis. Since this first operation, both the techniques employed and the material composition of the prosthesis have undergone substantial development. However, significant problems have been encountered in evaluating the safety and efficacy of percutaneous valve replacement. These, to a great extent, stem from the risks associated with treating elderly patients who have high morbidity and mortality. In the United States, one clinical study was even suspended because two of the first four patients undergoing treatment died. In contrast, studies carried out in other countries, although they have involved only a few patients, have produced more promising results. Moreover, because the cause of death in these series was frequently due to factors that were independent of good valvular function, the future of the technique is generally thought to be positive. Nevertheless, the results obtained with percutaneous mitral valve replacement have been poor. In conclusion, the technique of percutaneous valve replacement, although still undergoing development, is becoming established as a viable alternative for treating inoperable valve disease, at least in aortic valves.


0.3-V Voltage-Mode Versatile First-Order Analog Filter Using Multiple-Input DDTAs.
This paper presents a versatile first-order analog filter using differential difference transconductance amplifiers (DDTAs). The DDTA employs the bulk-driven (BD) multiple-input MOS transistors technique (MI-MOST) operating in the subthreshold region. This results in low-voltage and low-power operational capability. Therefore, the DDTA, designed using 130 nm CMOS technology from UMC in the Cadence environment, operates with 0.3 V and consumes 357.4 nW. Unlike previous works, the proposed versatile first-order analog filter provides first-order transfer functions of low-pass, high-pass, and all-pass filters within a single topology. The non-inverting, inverting, and voltage gain of the transfer functions are available for all filters. Furthermore, the proposed structure provides high-input and low-output impedance, which is required for voltage-mode circuits. The pole frequency and voltage gain of the filters can be electronically controlled. The total harmonic distortion of the low-pass filter was calculated as -39.97 dB with an applied sine wave input signal of 50 mVpp@ 50 Hz. The proposed filter has been used to realize a quadrature oscillator to confirm the advantages of the new structure.


Plasminogen activator receptor assemblies in cell signaling, innate immunity, and inflammation.
Tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) are serine proteases and major activators of fibrinolysis in mammalian systems. Because fibrinolysis is an essential component of the response to tissue injury, diverse cells, including cells that participate in the response to injury, have evolved receptor systems to detect tPA and uPA and initiate appropriate cell-signaling responses. Formation of functional receptor systems for the plasminogen activators requires assembly of diverse plasma membrane proteins, including but not limited to: the urokinase receptor (uPAR); integrins; N-formyl peptide receptor-2 (FPR2), receptor tyrosine kinases (RTKs), the N-methyl-d-aspartate receptor (NMDA-R), and low-density lipoprotein receptor-related protein-1 (LRP1). The cell-signaling responses elicited by tPA and uPA impact diverse aspects of cell physiology. This review describes rapidly evolving knowledge regarding the structure and function of plasminogen activator receptor assemblies. How these receptor assemblies regulate innate immunity and inflammation is then considered.


Identification and rapid mapping of a gene conferring broad-spectrum late blight resistance in the diploid potato species Solanum verrucosum through DNA capture technologies.
A broad-spectrum late blight disease-resistance gene from Solanum verrucosum has been mapped to potato chromosome 9. The gene is distinct from previously identified-resistance genes. We have identified and characterised a broad-spectrum resistance to Phytophthora infestans from the wild Mexican species Solanum verrucosum. Diagnostic resistance gene enrichment (dRenSeq) revealed that the resistance is not conferred by previously identified nucleotide-binding, leucine-rich repeat genes. Utilising the sequenced potato genome as a reference, two complementary enrichment strategies that target resistance genes (RenSeq) and single/low-copy number genes (Generic-mapping enrichment Sequencing; GenSeq), respectively, were deployed for the rapid, SNP-based mapping of the resistance through bulked-segregant analysis. Both approaches independently positioned the resistance, referred to as Rpi-ver1, to the distal end of potato chromosome 9. Stringent post-enrichment read filtering identified a total of 64 informative SNPs that corresponded to the expected ratio for significant polymorphisms in the parents as well as the bulks. Of these, 61 SNPs are located on potato chromosome 9 and reside within 27 individual genes, which in the sequenced potato clone DM locate to positions 45.9 to 60.9 Mb. RenSeq- and GenSeq-derived SNPs within the target region were converted into allele-specific PCR-based KASP markers and further defined the position of the resistance to a 4.3 Mb interval at the bottom end of chromosome 9 between positions 52.62-56.98 Mb.


Interoception and the uneasiness of the mind: affect as perceptual style.
Autonomous system models of interoception describe perception of bodily sensations as an active process in which the brain generates and tests hypotheses about the body on the basis of proximal information. This view of perception as inference allows a new perspective on the role of affect in perception. Affect and interoception are closely linked, but processes underlying this link are poorly understood. We suggest that a predictive coding perspective allows acknowledging affect as integral part of information processing. We outline how affect may intrinsically modify processes of interoception by acting as threshold mechanism in stimulus grouping and information compression. We outline how well-established methods, for example, from categorization research may allow quantifying this influence of affect on perception in empirical tests of predictive coding models. We discuss how this may enrich the study of the relationship between affect and interoception and may have important clinical relevance.


Plant genome editing: ever more precise and wide reaching.
Genome-editing technologies consisting of targeted mutagenesis and gene targeting enable us to modify genes of interest rapidly and precisely. The discovery in 2012 of CRISPR/Cas9 systems and their development as sequence-specific nucleases has brought about a paradigm shift in biology. Initially, CRISPR/Cas9 was applied in targeted mutagenesis to knock out a target gene. Thereafter, advances in genome-editing technologies using CRISPR/Cas9 developed rapidly, with base editing systems for transition substitution using a combination of Cas9 nickase and either cytidine or adenosine deaminase being reported in 2016 and 2017, respectively, and later in 2021 bringing reports of transversion substitution using Cas9 nickase, cytidine deaminase and uracil DNA glycosylase. Moreover, technologies for gene targeting and prime editing systems using DNA or RNA as donors have also been developed in recent years. Besides these precise genome-editing strategies, reports of successful chromosome engineering using CRISPR/Cas9 have been published recently. The application of genome editing to crop breeding has advanced in parallel with the development of these technologies. Genome-editing enzymes can be introduced into plant cells, and there are now many examples of crop breeding using genome-editing technologies. At present, it is no exaggeration to say that we are now in a position to be able to modify a gene precisely and rearrange genomes and chromosomes in a predicted way. In this review, we introduce and discuss recent highlights in the field of precise gene editing, chromosome engineering and genome engineering technology in plants.


[The role of extraperitoneoscopic adenomectomy in the management of benign prostatic hyperplasia greater than 80 cm3].
The current standard of surgery for benign prostatic hyperplasia (BPH) greater than 80 cm3 includes open adenomectomy and holmium enucleation. Transurethral resection and laser vaporization are second line interventions, while the role of laparoscopic extraperitoneal adenomectomy is not fully understood. To evaluate the role of laparoscopic technique as a surgical modality for BPH greater than 80 cm3. This study retrospectively evaluated the results of 79 patients (mean age 68 years) who underwent transcapsular extraperitoneoscopic adenomectomy from 2011 to 2016. The mean operative time was 206 (100-450) min; the prostate volume was 134 (80-300) cm3, blood loss was 256 (30-1200) ml. The I-PSS score after surgery decreased by an average of 18.3 points, the maximum urinary flow rate increased by 12 ml/s, the residual urine volume reduced from 147 to 28 ml. 35 (44%) patients underwent simultaneous operations (inguinal hernioplasty, cystolithotomy, etc.). There was one intraoperative complication, and 10 (12.6%) patients had postoperative complications. There were no conversions to open surgery. Incidental prostate cancer was detected in one patient. None of the patients required repeat surgery for infravesical obstruction. Extraperitoneoscopic adenomectomy is efficient, safe and reproducible surgical modality able to take the place of open surgery. There is a need for an evidence base to support the optimal choice between various minimally invasive techniques. Currently, laparoscopic procedure is more justified in patients with concomitant diseases, which can be simultaneously corrected.


The effect of uphill stride manipulation on race walking gait.
Stride length analysis represents an easy method for assessing race walking kinematics. However, the stride parameters emerging from such an analysis have never been used to design a training protocol aimed at increasing stride length. With this aim, we investigated the effects of stride frequency manipulation during three weeks of uphill (2%) training on stride length at iso-efficiency speed. Twelve male race walkers were randomly allocated to one of two training groups: stride frequency manipulation (RWM, n=6) and free stride frequency (RWF, n=6). Kinematic parameters measured before and after the 3-week training in RWM showed increased stride length (4.54%; p<0.0001) and contact time (4.58%; p<0.001); inversely, a decreased stride frequency (4.44%; p<0.0001) and internal work (7.09%; p<0.05) were found. In RWF the effect of the training showed a decrease in stride length (1.18%; p<0.0001) and contact time (<1%; p<0.0001) with respect to baseline conditions and an increased stride frequency and internal work of 1.19% (p<0.0001). These results suggest that using slopes (2%) as RWM could help coaches to provide some training methods that would improve an athlete's performance, through increasing stride length without altering his or her race walking technique or metabolic demands.


Scleral perforation. A complication of the soft contact lens.
A large area of conjunctiva and a smaller area of full thickness sclera eroded immediately adjacent to the edge of a soft contact lens. The soft lens was worn to protect the epithelium of a corneal graft in an alkali-burned eye. The conjunctiva-sclera necrosis appears to be a complication of a distorted and tightly fitting lens.


The Role of Interleukin-1 Inhibitors on Acute Myeloblastic Leukemia Blast Proliferation; Future Potential for Biotherapy.
The effect of interleukin-1 (IL-1) as an autocrine growth factor on the proliferation of the acute myeloblastic leukemia (AML) blasts was studied. Bone marrow specimens were obtained from nine patients with different subgroups of AML. IL-1 receptor antagonist (IL-1RA) and IL-1 ß neutralizing antibody (IL-1ß NA) alone or in combination were added to the culture mediums of the AML blast cultures for the detection of their inhibitory effect on AML blast cell proliferation and colony formation. Average colony numbers in the IL-RA, IL-ßNA, and IL-IRA plus IL-IßNA included culture flasks, were 63.7 ± 21.5 %, 69.5 ± 19 %, 53.4 ± 23.7 %, respectively, as compared to those of the control (p < 0.01). Inhibition of colony formation by IL-IRA plus IL-IßNA was more prominent than by IL-IßNA alone (p < 0.01). No correlation between the inhibition of AML blast colony ormation and FAB AML subgroups was seen. Both IL-1RA or IL-IßNA or in combination induced varying degrees of inhibition on blast colony formation. IL-I inhibitory molecules could be considered as an alternative therapy for AML in patients whose blast cells are sensitive to IL-1 inhibition.


Structural insights into photoactivation and signalling in plant phytochromes.
Plant phytochromes are red/far-red photochromic photoreceptors that act as master regulators of development, controlling the expression of thousands of genes. Here, we describe the crystal structures of four plant phytochrome sensory modules, three at about 2 Å resolution or better, including the first of an A-type phytochrome. Together with extensive spectral data, these structures provide detailed insight into the structure and function of plant phytochromes. In the Pr state, the substitution of phycocyanobilin and phytochromobilin cofactors has no structural effect, nor does the amino-terminal extension play a significant functional role. Our data suggest that the chromophore propionates and especially the phytochrome-specific domain tongue act differently in plant and prokaryotic phytochromes. We find that the photoproduct in period-ARNT-single-minded (PAS)-cGMP-specific phosphodiesterase-adenylyl cyclase-FhlA (GAF) bidomains might represent a novel intermediate between MetaRc and Pfr. We also discuss the possible role of a likely nuclear localization signal specific to and conserved in the phytochrome A lineage.


Rescue of hematopoietic stem/progenitor cells formation in plcg1 zebrafish mutant.
Hematopoietic stem/progenitor cells (HSPC) in zebrafish emerge from the aortic hemogenic endothelium (HE) and migrate towards the caudal hematopoietic tissue (CHT), where they expand and differentiate during definitive hematopoiesis. Phospholipase C gamma 1 (Plcγ1) has been implicated for hematopoiesis in vivo and in vitro and is also required to drive arterial and HSPC formation. Genetic mutation in plcg1-/- (y10 allele) completely disrupts the aortic blood flow, specification of arterial fate, and HSPC formation in zebrafish embryos. We previously demonstrated that ginger treatment promoted definitive hematopoiesis via Bmp signaling. In this paper, we focus on HSPC development in plcg1-/- mutants and show that ginger/10-gingerol (10-G) can rescue the expression of arterial and HSPC markers in the HE and CHT in plcg1-/- mutant embryos. We demonstrate that ginger can induce scl/runx1 expression, and that rescued HE fate is dependent on Bmp and Notch. Bmp and Notch are known to regulate nitric oxide (NO) production and NO can induce hematopoietic stem cell fate. We show that ginger produces a robust up-regulation of NO. Taken together, we suggest in this paper that Bmp, Notch and NO are potential players that mediate the effect of ginger/10-G for rescuing the genetic defects in blood vessel specification and HSPC formation in plcg1-/- mutants. Understanding the molecular mechanisms of HSPC development in vivo is critical for understanding HSPC expansion, which will have a positive impact in regenerative medicine.


Botulinum toxin treatment of apraxia of eyelid opening in progressive supranuclear palsy: report of two cases.
We report two patients, with postural instability and dystonic parkinsonism whose adjunctive disabling feature was blindness due to an inability to reopen the eyes after voluntary closure of the eyelids, as in apraxia of lid opening (ALO). Supranuclear downgaze paresis permitted the diagnosis of progressive supranuclear palsy (PSP) in one case. Electromyographic studies showed a loss of normal reciprocal inhibition between the levator palpebrae and the pretarsal portion of the orbicularis oculi, with a cocontraction of these two antagonist muscles. The evoked blink reflex, tested with the paired shock technique, showed enhanced recovery of R2 response. Botulinum toxin A injections directed toward the junction of the preseptal and pretarsal parts of the palpebral orbicularis oculi muscle improved eyelid motility in both patients. Successive static and dynamic balance training and development of compensatory strategies for visual scanning deficits reduced gait imbalance, the number of falls, and the disability level as measured on the Northwestern University Disability Scale.


Polymorphisms of the gene coding for copper/zinc superoxide dismutase (SOD1) in patients with Japanese encephalitis.
Japanese encephalitis is the commonest form of encephalitis globally. Most cases develop characteristic encephalitis but some also present with flaccid paralysis. The paralysis is secondary to damage at the alpha motor neurone, the site that is also damaged in amyotrophic lateral sclerosis (ALS). The gene coding for superoxide dismutase 1 (SOD1) is thought to be involved in ALS and may also be linked to susceptibility to Japanese encephalitis. To investigate this possibility, polymorphisms in the SOD1 gene were investigated, in 61 cases of Japanese encephalitis, 61 matched controls and 171 population controls, in Vietnam. Novel polymorphisms, found only in three of the cases and one of the population controls, may be involved with susceptibility to Japanese encephalitis and potentially to other flavivirus infections that lead to damage to the cells of the anterior horn. Further research on this possible association is required.


Robot-assisted cortical-sparing adrenalectomy in a patient with Von Hippel-Lindau disease and bilateral pheochromocytomas separated by 9 years.
Von Hippel-Lindau disease is a heritable syndrome that confers an increased risk of developing various benign and malignant tumors to those with a germline mutation of the tumor suppressor gene. We present a case of a male patient who initially presented at age 9 with headaches, fevers, and fatigue. He was found to have a left pheochromocytoma which was successfully managed with open total adrenalectomy. He presented again at age 18 with a second pheochromocytoma in the right adrenal gland. DNA analysis revealed a de novo Val84Leu mutation in the Von Hippel-Lindau gene, not seen in either parent. The challenge presented was that of balancing the obvious benefits of cortical- sparing adrenalectomy with the risk of tumor recurrence in spared tissue. Ultimately, management consisted of a robot-assisted laparoscopic partial right adrenalectomy with successful preservation of adrenocortical function.


Bilateral sacroiliac luxation fixation using a single transiliosacral pin: surgical technique and clinical outcomes in eight cats.
A very limited safe anatomical window for transiliosacral implant placement exists in cats (<0·5 cm2 ). Lag screw fixation requires multiple bilateral implants thus increasing the risk of iatrogenic trauma and implant interference. We describe a safe and effective method for bilateral sacroiliac fixation in cats using a single implant to minimise inadvertent iatrogenic damage to local structures and restore pelvic canal diameter. Eight cats underwent surgical fixation for traumatic bilateral sacroiliac luxation using a single smooth intramedullary pin. The pin spanned both ilial wings and sacrum. Implants were applied using a Universal C-guide. Pre- and postsurgery pelvic canal diameter ratios were calculated. Short-term follow-up was performed at 10 to 14 days postoperatively. Long-term follow-up was performed using the Feline Musculoskeletal Pain Index Questionnaire. Long-term radiographic assessment was available in two cases. The technique achieved safe and accurate implant position with precise sacroiliac joint reduction. Pelvic canal diameter ratios were restored to normal in all cases. Rapid return to normal hind leg function and excellent long-term clinical outcomes were achieved. This technique offers a simple, safe, repeatable and affordable technique for treating bilateral sacroiliac luxations in the cat without the aid of fluoroscopy. The procedure can be performed using surgical tools and inventory readily available in general small animal practices.


[Recurrent late hemarthrosis after total knee replacement].
A patient who had a successful total knee replacement for severe degenerative osteoarthritis of the right knee had an excellent functional result. 2 years after the operation there was spontaneous intra-articular bleeding that was treated successfully conservatively. Recurrent hemarthrosis 2 months later was treated similarly and also resolved without residual functional impairment after a follow-up of over 1 year. Recurrent late hemarthrosis in the knee is a fairly rare complication following total knee arthroplasty, but is amenable to conservative measures. Frequently, persistent recurrent hemarthrosis requires debridement of the bleeding synovium of the knee.


Bistable phase control via rocking in a nonlinear electronic oscillator.
We experimentally demonstrate the effective rocking [de Valcarcel and Staliunas, Phys. Rev. E 67, 026604 (2003)] of a nonlinear electronic circuit operating in a periodic regime. Namely, we show that by driving a Chua circuit with a periodic signal, whose phase alternates (also periodically) in time, we lock the oscillation frequency of the circuit to that of the driving signal, and its phase to one of two possible values shifted by pi, and lying between the alternating phases of the input signal. In this way, we show that a rocked nonlinear oscillator displays phase bistability. We interpret the experimental results via a theoretical analysis of rocking on a simple oscillator model, based on a normal form description (complex Landau equation) of the rocked Hopf bifurcation.


Arachidonic acid hyperpolarizes mesenchymal stromal cells from the human adipose tissue by stimulating TREK1 K+ channels.
The current knowledge of electrogenesis in mesenchymal stromal cells (MSCs) remains scarce. Earlier, we demonstrated that in MSCs from the human adipose tissue, transduction of certain agonists involved the phosphoinositide cascade. Its pivotal effector PLC generates DAG that can regulate ion channels directly or via its derivatives, including arachidonic acid (AA). Here we showed that AA strongly hyperpolarized MSCs by stimulating instantly activating, outwardly rectifying TEA-insensitive K+ channels. Among AA-regulated K+ channels, K2P channels from the TREK subfamily appeared to be an appropriate target. The expression of K2P channels in MSCs was verified by RT-PCR, which revealed TWIK-1, TREK-1, and TASK-5 transcripts. The TREK-1 inhibitor spadin antagonized the electrogenic action of AA, which was simulated by the channel activator BL 1249. This functional evidence suggested that TREK-1 channels mediated AA-dependent hyperpolarization of MSCs. Being mostly silent at rest, TREK-1 negligibly contributed to the "background" K+ current. The dramatic stimulation of TREK-1 channels by AA indicates their involvement in AA-dependent signaling in MSCs.


Disaggregating data on Asian and Pacific Islander women to assess cancer screening.
Although incidence of cancer is increasing among Asian-American and Pacific-Islander (AAPI) women, their low cancer screening rates are inadequately addressed. Furthermore, the traditional approach of studying the diverse AAPI nationalities as one group hides important intra- and inter-group ethnic differences in cancer screening, as well as lack of representativeness because the surveys are not administered in any AAPI language. To address these problems, this study compared cancer screening rates among particular AAPI groups and non-AAPIs living in an ethnically diverse region. This study was conducted in 2001-2002 using data from the 1999-2000 Los Angeles County Health Survey, a population-based telephone survey that relied on random-digit-dialing techniques. Cervical and breast cancer-screening rates were measured, and key determinants of screening using bivariate analyses and multivariate logistic regression were assessed. AAPIs had lower screening rates than whites, with significant variation among AAPI subgroups. Moreover, AAPI women were less likely to have undergone cervical cancer screening compared to white women, independent of major demographic, socioeconomic, and health status factors. Determinants for receipt of cancer screening differed for AAPIs and whites. Immigration factors were significant barriers to cancer screening for AAPIs. These findings support the evidence of disparities in receipt of cancer screening services among subgroups of AAPI women. Additionally, these findings highlight the importance of disaggregating the heterogeneous AAPI population to identify higher-risk subgroups and facilitate development of effective targeted interventions.


Modularity and intrinsic evolvability of Hsp90-buffered change.
Hsp90 controls dramatic phenotypic transitions in a wide array of morphological features of many organisms. The genetic-background dependence of specific abnormalities and their response to laboratory selection suggested Hsp90 could be an 'evolutionary capacitor', allowing developmental variation to accumulate as neutral alleles under normal conditions and manifest selectable morphological differences during environmental stress. The relevance of Hsp90-buffered variation for evolution has been most often challenged by the idea that large morphological changes controlled by Hsp90 are unconditionally deleterious. To address this issue, we tested an Hsp90-buffered abnormality in Drosophila for unselected pleiotropic effects and correlated fitness costs. Up to 120-fold differences in penetrance among six highly related selection lines, started from an initially small number of flies and rapidly selected for and against a deformed eye trait (dfe), did not translate into measurable differences in any of several tests of viability, lifespan or competitive fitness. Nor were 17 dfe Quantitative Trait Loci (QTL) associated with fitness effects in over 1,400 recombinant lines. Our ability to detect measurable effects of inbreeding, media environment and the white mutation in the selection line backgrounds independent of dfe penetrance suggests that, within the limitations of laboratory tests of fitness, this large morphological change controlled by Hsp90 was selectable independent of strong, correlated and unconditionally deleterious effects--abundant, polygenic variation hidden by Hsp90 allows potentially deleterious alleles to be readily replaced during selection by less deleterious alleles with similar phenotypic effects. Hsp90 links environmental stress with the expression of developmental variation controlling unprecedented morphological plasticity. As outlined here and in the companion paper of this issue, the complex genetic architecture of Hsp90-buffered variation supports a remarkable modularity of Hsp90 effects on quantitative and qualitative phenotypes, consistent with the 'Hsp90 capacitor hypothesis' and standard quantitative genetic models of threshold traits.


[Effects of disodium cromoglycate on the clinical manifestations of true and pseudo food allergies in adults (author's transl)].
The effects of disodium cromoglycate (DSCG) administered orally were compared in two groups of patients: 7 patients with urticaria, angioneurotic oedema, asthma or anaphylaxis due to type I allergy to 9 foodstuffs confirmed by skin tests, human basophil degranulation tests or Prausnitz-Küstner tests, and 9 patients with chronic urticaria and digestive disorders due to non-specific histamine reactions following food absorption. DSCG in aqueous solution was given in daily doses of 300 mg increased, if necessary, to 600 or 900 mg. After one month treatment was interrupted for 15 days, then replaced by a placebo for one month. Complete remission, lasting for up to 45 days after DSCG was discontinued, was observed in 5/7 patients of the first group, but in only 1/9 patients of the second group. The drug was well tolerated by 12/16 patients. Four patients presented with allergic or digestive reactions which obliged to withdraw treatment in two.


Checklist of decapods (Crustacea) from the coast of São Paulo State (Brazil) supported by integrative molecular and morphological data: II. Infraorder Caridea: family Alpheidae.
This study is part of a series of checklists resulting from a long-term multidisciplinary project on the biodiversity of decapod crustaceans from the marine and coastal environments (including estuaries) of São Paulo State (Brazil). For that, we integrated molecular techniques (mitochondrial DNA markers) and morphological analyses of adult specimens for an accurate and detailed identification. The DNA markers were used when the morphological identification was doubtful, particularly in the recognition of cryptic species. This second manuscript presents a checklist of the Alpheidae caridean shrimps from the coast of São Paulo. We report the occurrence of Alpheus cf. paracrinitus and Synalpheus townsendi for the first time in the region. Based on our survey, 39 species of Alpheidae are known for this region: Alpheus (21 spp.), Athanas (2 spp.), Automate (2 spp.), Leptalpheus (1 spp.), Salmoneus (3 spp.), and Synalpheus (10 spp.). We collected 28 species and obtained cytochrome oxidase subunit I (barcode region) and/or 16S partial sequences of 26 of them. These sequences may be used for phylogenetic and populational analyses in further studies.